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• What Is a Case Study? | Definition, Examples & Methods

What Is a Case Study? | Definition, Examples & Methods

Published on May 8, 2019 by Shona McCombes . Revised on November 20, 2023.

A case study is a detailed study of a specific subject, such as a person, group, place, event, organization, or phenomenon. Case studies are commonly used in social, educational, clinical, and business research.

A case study research design usually involves qualitative methods , but quantitative methods are sometimes also used. Case studies are good for describing , comparing, evaluating and understanding different aspects of a research problem .

Table of contents

When to do a case study, step 1: select a case, step 2: build a theoretical framework, step 3: collect your data, step 4: describe and analyze the case, other interesting articles.

A case study is an appropriate research design when you want to gain concrete, contextual, in-depth knowledge about a specific real-world subject. It allows you to explore the key characteristics, meanings, and implications of the case.

Case studies are often a good choice in a thesis or dissertation . They keep your project focused and manageable when you don’t have the time or resources to do large-scale research.

You might use just one complex case study where you explore a single subject in depth, or conduct multiple case studies to compare and illuminate different aspects of your research problem.

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Once you have developed your problem statement and research questions , you should be ready to choose the specific case that you want to focus on. A good case study should have the potential to:

• Provide new or unexpected insights into the subject
• Challenge or complicate existing assumptions and theories
• Propose practical courses of action to resolve a problem
• Open up new directions for future research

TipIf your research is more practical in nature and aims to simultaneously investigate an issue as you solve it, consider conducting action research instead.

Unlike quantitative or experimental research , a strong case study does not require a random or representative sample. In fact, case studies often deliberately focus on unusual, neglected, or outlying cases which may shed new light on the research problem.

Example of an outlying case studyIn the 1960s the town of Roseto, Pennsylvania was discovered to have extremely low rates of heart disease compared to the US average. It became an important case study for understanding previously neglected causes of heart disease.

However, you can also choose a more common or representative case to exemplify a particular category, experience or phenomenon.

Example of a representative case studyIn the 1920s, two sociologists used Muncie, Indiana as a case study of a typical American city that supposedly exemplified the changing culture of the US at the time.

While case studies focus more on concrete details than general theories, they should usually have some connection with theory in the field. This way the case study is not just an isolated description, but is integrated into existing knowledge about the topic. It might aim to:

• Exemplify a theory by showing how it explains the case under investigation
• Expand on a theory by uncovering new concepts and ideas that need to be incorporated
• Challenge a theory by exploring an outlier case that doesn’t fit with established assumptions

To ensure that your analysis of the case has a solid academic grounding, you should conduct a literature review of sources related to the topic and develop a theoretical framework . This means identifying key concepts and theories to guide your analysis and interpretation.

There are many different research methods you can use to collect data on your subject. Case studies tend to focus on qualitative data using methods such as interviews , observations , and analysis of primary and secondary sources (e.g., newspaper articles, photographs, official records). Sometimes a case study will also collect quantitative data.

Example of a mixed methods case studyFor a case study of a wind farm development in a rural area, you could collect quantitative data on employment rates and business revenue, collect qualitative data on local people’s perceptions and experiences, and analyze local and national media coverage of the development.

The aim is to gain as thorough an understanding as possible of the case and its context.

In writing up the case study, you need to bring together all the relevant aspects to give as complete a picture as possible of the subject.

How you report your findings depends on the type of research you are doing. Some case studies are structured like a standard scientific paper or thesis , with separate sections or chapters for the methods , results and discussion .

Others are written in a more narrative style, aiming to explore the case from various angles and analyze its meanings and implications (for example, by using textual analysis or discourse analysis ).

In all cases, though, make sure to give contextual details about the case, connect it back to the literature and theory, and discuss how it fits into wider patterns or debates.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

• Normal distribution
• Degrees of freedom
• Null hypothesis
• Discourse analysis
• Control groups
• Mixed methods research
• Non-probability sampling
• Quantitative research
• Ecological validity

Research bias

• Rosenthal effect
• Implicit bias
• Cognitive bias
• Selection bias
• Negativity bias
• Status quo bias

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Definition and Introduction

Case analysis is a problem-based teaching and learning method that involves critically analyzing complex scenarios within an organizational setting for the purpose of placing the student in a “real world” situation and applying reflection and critical thinking skills to contemplate appropriate solutions, decisions, or recommended courses of action. It is considered a more effective teaching technique than in-class role playing or simulation activities. The analytical process is often guided by questions provided by the instructor that ask students to contemplate relationships between the facts and critical incidents described in the case.

Cases generally include both descriptive and statistical elements and rely on students applying abductive reasoning to develop and argue for preferred or best outcomes [i.e., case scenarios rarely have a single correct or perfect answer based on the evidence provided]. Rather than emphasizing theories or concepts, case analysis assignments emphasize building a bridge of relevancy between abstract thinking and practical application and, by so doing, teaches the value of both within a specific area of professional practice.

Given this, the purpose of a case analysis paper is to present a structured and logically organized format for analyzing the case situation. It can be assigned to students individually or as a small group assignment and it may include an in-class presentation component. Case analysis is predominately taught in economics and business-related courses, but it is also a method of teaching and learning found in other applied social sciences disciplines, such as, social work, public relations, education, journalism, and public administration.

Ellet, William. The Case Study Handbook: A Student's Guide . Revised Edition. Boston, MA: Harvard Business School Publishing, 2018; Christoph Rasche and Achim Seisreiner. Guidelines for Business Case Analysis . University of Potsdam; Writing a Case Analysis . Writing Center, Baruch College; Volpe, Guglielmo. "Case Teaching in Economics: History, Practice and Evidence." Cogent Economics and Finance 3 (December 2015). doi:https://doi.org/10.1080/23322039.2015.1120977.

How to Approach Writing a Case Analysis Paper

The organization and structure of a case analysis paper can vary depending on the organizational setting, the situation, and how your professor wants you to approach the assignment. Nevertheless, preparing to write a case analysis paper involves several important steps. As Hawes notes, a case analysis assignment “...is useful in developing the ability to get to the heart of a problem, analyze it thoroughly, and to indicate the appropriate solution as well as how it should be implemented” [p.48]. This statement encapsulates how you should approach preparing to write a case analysis paper.

Before you begin to write your paper, consider the following analytical procedures:

• Review the case to get an overview of the situation . A case can be only a few pages in length, however, it is most often very lengthy and contains a significant amount of detailed background information and statistics, with multilayered descriptions of the scenario, the roles and behaviors of various stakeholder groups, and situational events. Therefore, a quick reading of the case will help you gain an overall sense of the situation and illuminate the types of issues and problems that you will need to address in your paper. If your professor has provided questions intended to help frame your analysis, use them to guide your initial reading of the case.
• Read the case thoroughly . After gaining a general overview of the case, carefully read the content again with the purpose of understanding key circumstances, events, and behaviors among stakeholder groups. Look for information or data that appears contradictory, extraneous, or misleading. At this point, you should be taking notes as you read because this will help you develop a general outline of your paper. The aim is to obtain a complete understanding of the situation so that you can begin contemplating tentative answers to any questions your professor has provided or, if they have not provided, developing answers to your own questions about the case scenario and its connection to the course readings,lectures, and class discussions.
• Determine key stakeholder groups, issues, and events and the relationships they all have to each other . As you analyze the content, pay particular attention to identifying individuals, groups, or organizations described in the case and identify evidence of any problems or issues of concern that impact the situation in a negative way. Other things to look for include identifying any assumptions being made by or about each stakeholder, potential biased explanations or actions, explicit demands or ultimatums , and the underlying concerns that motivate these behaviors among stakeholders. The goal at this stage is to develop a comprehensive understanding of the situational and behavioral dynamics of the case and the explicit and implicit consequences of each of these actions.
• Identify the core problems . The next step in most case analysis assignments is to discern what the core [i.e., most damaging, detrimental, injurious] problems are within the organizational setting and to determine their implications. The purpose at this stage of preparing to write your analysis paper is to distinguish between the symptoms of core problems and the core problems themselves and to decide which of these must be addressed immediately and which problems do not appear critical but may escalate over time. Identify evidence from the case to support your decisions by determining what information or data is essential to addressing the core problems and what information is not relevant or is misleading.
• Explore alternative solutions . As noted, case analysis scenarios rarely have only one correct answer. Therefore, it is important to keep in mind that the process of analyzing the case and diagnosing core problems, while based on evidence, is a subjective process open to various avenues of interpretation. This means that you must consider alternative solutions or courses of action by critically examining strengths and weaknesses, risk factors, and the differences between short and long-term solutions. For each possible solution or course of action, consider the consequences they may have related to their implementation and how these recommendations might lead to new problems. Also, consider thinking about your recommended solutions or courses of action in relation to issues of fairness, equity, and inclusion.
• Decide on a final set of recommendations . The last stage in preparing to write a case analysis paper is to assert an opinion or viewpoint about the recommendations needed to help resolve the core problems as you see them and to make a persuasive argument for supporting this point of view. Prepare a clear rationale for your recommendations based on examining each element of your analysis. Anticipate possible obstacles that could derail their implementation. Consider any counter-arguments that could be made concerning the validity of your recommended actions. Finally, describe a set of criteria and measurable indicators that could be applied to evaluating the effectiveness of your implementation plan.

Use these steps as the framework for writing your paper. Remember that the more detailed you are in taking notes as you critically examine each element of the case, the more information you will have to draw from when you begin to write. This will save you time.

NOTE : If the process of preparing to write a case analysis paper is assigned as a student group project, consider having each member of the group analyze a specific element of the case, including drafting answers to the corresponding questions used by your professor to frame the analysis. This will help make the analytical process more efficient and ensure that the distribution of work is equitable. This can also facilitate who is responsible for drafting each part of the final case analysis paper and, if applicable, the in-class presentation.

Framework for Case Analysis . College of Management. University of Massachusetts; Hawes, Jon M. "Teaching is Not Telling: The Case Method as a Form of Interactive Learning." Journal for Advancement of Marketing Education 5 (Winter 2004): 47-54; Rasche, Christoph and Achim Seisreiner. Guidelines for Business Case Analysis . University of Potsdam; Writing a Case Study Analysis . University of Arizona Global Campus Writing Center; Van Ness, Raymond K. A Guide to Case Analysis . School of Business. State University of New York, Albany; Writing a Case Analysis . Business School, University of New South Wales.

Structure and Writing Style

A case analysis paper should be detailed, concise, persuasive, clearly written, and professional in tone and in the use of language . As with other forms of college-level academic writing, declarative statements that convey information, provide a fact, or offer an explanation or any recommended courses of action should be based on evidence. If allowed by your professor, any external sources used to support your analysis, such as course readings, should be properly cited under a list of references. The organization and structure of case analysis papers can vary depending on your professor’s preferred format, but its structure generally follows the steps used for analyzing the case.

Introduction

The introduction should provide a succinct but thorough descriptive overview of the main facts, issues, and core problems of the case . The introduction should also include a brief summary of the most relevant details about the situation and organizational setting. This includes defining the theoretical framework or conceptual model on which any questions were used to frame your analysis.

Following the rules of most college-level research papers, the introduction should then inform the reader how the paper will be organized. This includes describing the major sections of the paper and the order in which they will be presented. Unless you are told to do so by your professor, you do not need to preview your final recommendations in the introduction. U nlike most college-level research papers , the introduction does not include a statement about the significance of your findings because a case analysis assignment does not involve contributing new knowledge about a research problem.

Background Analysis

Background analysis can vary depending on any guiding questions provided by your professor and the underlying concept or theory that the case is based upon. In general, however, this section of your paper should focus on:

• Providing an overarching analysis of problems identified from the case scenario, including identifying events that stakeholders find challenging or troublesome,
• Identifying assumptions made by each stakeholder and any apparent biases they may exhibit,
• Describing any demands or claims made by or forced upon key stakeholders, and
• Highlighting any issues of concern or complaints expressed by stakeholders in response to those demands or claims.

These aspects of the case are often in the form of behavioral responses expressed by individuals or groups within the organizational setting. However, note that problems in a case situation can also be reflected in data [or the lack thereof] and in the decision-making, operational, cultural, or institutional structure of the organization. Additionally, demands or claims can be either internal and external to the organization [e.g., a case analysis involving a president considering arms sales to Saudi Arabia could include managing internal demands from White House advisors as well as demands from members of Congress].

Throughout this section, present all relevant evidence from the case that supports your analysis. Do not simply claim there is a problem, an assumption, a demand, or a concern; tell the reader what part of the case informed how you identified these background elements.

Identification of Problems

In most case analysis assignments, there are problems, and then there are problems . Each problem can reflect a multitude of underlying symptoms that are detrimental to the interests of the organization. The purpose of identifying problems is to teach students how to differentiate between problems that vary in severity, impact, and relative importance. Given this, problems can be described in three general forms: those that must be addressed immediately, those that should be addressed but the impact is not severe, and those that do not require immediate attention and can be set aside for the time being.

All of the problems you identify from the case should be identified in this section of your paper, with a description based on evidence explaining the problem variances. If the assignment asks you to conduct research to further support your assessment of the problems, include this in your explanation. Remember to cite those sources in a list of references. Use specific evidence from the case and apply appropriate concepts, theories, and models discussed in class or in relevant course readings to highlight and explain the key problems [or problem] that you believe must be solved immediately and describe the underlying symptoms and why they are so critical.

Alternative Solutions

This section is where you provide specific, realistic, and evidence-based solutions to the problems you have identified and make recommendations about how to alleviate the underlying symptomatic conditions impacting the organizational setting. For each solution, you must explain why it was chosen and provide clear evidence to support your reasoning. This can include, for example, course readings and class discussions as well as research resources, such as, books, journal articles, research reports, or government documents. In some cases, your professor may encourage you to include personal, anecdotal experiences as evidence to support why you chose a particular solution or set of solutions. Using anecdotal evidence helps promote reflective thinking about the process of determining what qualifies as a core problem and relevant solution .

Throughout this part of the paper, keep in mind the entire array of problems that must be addressed and describe in detail the solutions that might be implemented to resolve these problems.

Recommended Courses of Action

In some case analysis assignments, your professor may ask you to combine the alternative solutions section with your recommended courses of action. However, it is important to know the difference between the two. A solution refers to the answer to a problem. A course of action refers to a procedure or deliberate sequence of activities adopted to proactively confront a situation, often in the context of accomplishing a goal. In this context, proposed courses of action are based on your analysis of alternative solutions. Your description and justification for pursuing each course of action should represent the overall plan for implementing your recommendations.

For each course of action, you need to explain the rationale for your recommendation in a way that confronts challenges, explains risks, and anticipates any counter-arguments from stakeholders. Do this by considering the strengths and weaknesses of each course of action framed in relation to how the action is expected to resolve the core problems presented, the possible ways the action may affect remaining problems, and how the recommended action will be perceived by each stakeholder.

In addition, you should describe the criteria needed to measure how well the implementation of these actions is working and explain which individuals or groups are responsible for ensuring your recommendations are successful. In addition, always consider the law of unintended consequences. Outline difficulties that may arise in implementing each course of action and describe how implementing the proposed courses of action [either individually or collectively] may lead to new problems [both large and small].

Throughout this section, you must consider the costs and benefits of recommending your courses of action in relation to uncertainties or missing information and the negative consequences of success.

The conclusion should be brief and introspective. Unlike a research paper, the conclusion in a case analysis paper does not include a summary of key findings and their significance, a statement about how the study contributed to existing knowledge, or indicate opportunities for future research.

Begin by synthesizing the core problems presented in the case and the relevance of your recommended solutions. This can include an explanation of what you have learned about the case in the context of your answers to the questions provided by your professor. The conclusion is also where you link what you learned from analyzing the case with the course readings or class discussions. This can further demonstrate your understanding of the relationships between the practical case situation and the theoretical and abstract content of assigned readings and other course content.

Problems to Avoid

The literature on case analysis assignments often includes examples of difficulties students have with applying methods of critical analysis and effectively reporting the results of their assessment of the situation. A common reason cited by scholars is that the application of this type of teaching and learning method is limited to applied fields of social and behavioral sciences and, as a result, writing a case analysis paper can be unfamiliar to most students entering college.

After you have drafted your paper, proofread the narrative flow and revise any of these common errors:

• Unnecessary detail in the background section . The background section should highlight the essential elements of the case based on your analysis. Focus on summarizing the facts and highlighting the key factors that become relevant in the other sections of the paper by eliminating any unnecessary information.
• Analysis relies too much on opinion . Your analysis is interpretive, but the narrative must be connected clearly to evidence from the case and any models and theories discussed in class or in course readings. Any positions or arguments you make should be supported by evidence.
• Analysis does not focus on the most important elements of the case . Your paper should provide a thorough overview of the case. However, the analysis should focus on providing evidence about what you identify are the key events, stakeholders, issues, and problems. Emphasize what you identify as the most critical aspects of the case to be developed throughout your analysis. Be thorough but succinct.
• Writing is too descriptive . A paper with too much descriptive information detracts from your analysis of the complexities of the case situation. Questions about what happened, where, when, and by whom should only be included as essential information leading to your examination of questions related to why, how, and for what purpose.
• Inadequate definition of a core problem and associated symptoms . A common error found in case analysis papers is recommending a solution or course of action without adequately defining or demonstrating that you understand the problem. Make sure you have clearly described the problem and its impact and scope within the organizational setting. Ensure that you have adequately described the root causes w hen describing the symptoms of the problem.
• Recommendations lack specificity . Identify any use of vague statements and indeterminate terminology, such as, “A particular experience” or “a large increase to the budget.” These statements cannot be measured and, as a result, there is no way to evaluate their successful implementation. Provide specific data and use direct language in describing recommended actions.
• Unrealistic, exaggerated, or unattainable recommendations . Review your recommendations to ensure that they are based on the situational facts of the case. Your recommended solutions and courses of action must be based on realistic assumptions and fit within the constraints of the situation. Also note that the case scenario has already happened, therefore, any speculation or arguments about what could have occurred if the circumstances were different should be revised or eliminated.

Bee, Lian Song et al. "Business Students' Perspectives on Case Method Coaching for Problem-Based Learning: Impacts on Student Engagement and Learning Performance in Higher Education." Education & Training 64 (2022): 416-432; The Case Analysis . Fred Meijer Center for Writing and Michigan Authors. Grand Valley State University; Georgallis, Panikos and Kayleigh Bruijn. "Sustainability Teaching using Case-Based Debates." Journal of International Education in Business 15 (2022): 147-163; Hawes, Jon M. "Teaching is Not Telling: The Case Method as a Form of Interactive Learning." Journal for Advancement of Marketing Education 5 (Winter 2004): 47-54; Georgallis, Panikos, and Kayleigh Bruijn. "Sustainability Teaching Using Case-based Debates." Journal of International Education in Business 15 (2022): 147-163; .Dean,  Kathy Lund and Charles J. Fornaciari. "How to Create and Use Experiential Case-Based Exercises in a Management Classroom." Journal of Management Education 26 (October 2002): 586-603; Klebba, Joanne M. and Janet G. Hamilton. "Structured Case Analysis: Developing Critical Thinking Skills in a Marketing Case Course." Journal of Marketing Education 29 (August 2007): 132-137, 139; Klein, Norman. "The Case Discussion Method Revisited: Some Questions about Student Skills." Exchange: The Organizational Behavior Teaching Journal 6 (November 1981): 30-32; Mukherjee, Arup. "Effective Use of In-Class Mini Case Analysis for Discovery Learning in an Undergraduate MIS Course." The Journal of Computer Information Systems 40 (Spring 2000): 15-23; Pessoa, Silviaet al. "Scaffolding the Case Analysis in an Organizational Behavior Course: Making Analytical Language Explicit." Journal of Management Education 46 (2022): 226-251: Ramsey, V. J. and L. D. Dodge. "Case Analysis: A Structured Approach." Exchange: The Organizational Behavior Teaching Journal 6 (November 1981): 27-29; Schweitzer, Karen. "How to Write and Format a Business Case Study." ThoughtCo. https://www.thoughtco.com/how-to-write-and-format-a-business-case-study-466324 (accessed December 5, 2022); Reddy, C. D. "Teaching Research Methodology: Everything's a Case." Electronic Journal of Business Research Methods 18 (December 2020): 178-188; Volpe, Guglielmo. "Case Teaching in Economics: History, Practice and Evidence." Cogent Economics and Finance 3 (December 2015). doi:https://doi.org/10.1080/23322039.2015.1120977.

Writing Tip

Ca se Study and Case Analysis Are Not the Same!

Confusion often exists between what it means to write a paper that uses a case study research design and writing a paper that analyzes a case; they are two different types of approaches to learning in the social and behavioral sciences. Professors as well as educational researchers contribute to this confusion because they often use the term "case study" when describing the subject of analysis for a case analysis paper. But you are not studying a case for the purpose of generating a comprehensive, multi-faceted understanding of a research problem. R ather, you are critically analyzing a specific scenario to argue logically for recommended solutions and courses of action that lead to optimal outcomes applicable to professional practice.

To avoid any confusion, here are twelve characteristics that delineate the differences between writing a paper using the case study research method and writing a case analysis paper:

• Case study is a method of in-depth research and rigorous inquiry ; case analysis is a reliable method of teaching and learning . A case study is a modality of research that investigates a phenomenon for the purpose of creating new knowledge, solving a problem, or testing a hypothesis using empirical evidence derived from the case being studied. Often, the results are used to generalize about a larger population or within a wider context. The writing adheres to the traditional standards of a scholarly research study. A case analysis is a pedagogical tool used to teach students how to reflect and think critically about a practical, real-life problem in an organizational setting.
• The researcher is responsible for identifying the case to study; a case analysis is assigned by your professor . As the researcher, you choose the case study to investigate in support of obtaining new knowledge and understanding about the research problem. The case in a case analysis assignment is almost always provided, and sometimes written, by your professor and either given to every student in class to analyze individually or to a small group of students, or students select a case to analyze from a predetermined list.
• A case study is indeterminate and boundless; a case analysis is predetermined and confined . A case study can be almost anything [see item 9 below] as long as it relates directly to examining the research problem. This relationship is the only limit to what a researcher can choose as the subject of their case study. The content of a case analysis is determined by your professor and its parameters are well-defined and limited to elucidating insights of practical value applied to practice.
• Case study is fact-based and describes actual events or situations; case analysis can be entirely fictional or adapted from an actual situation . The entire content of a case study must be grounded in reality to be a valid subject of investigation in an empirical research study. A case analysis only needs to set the stage for critically examining a situation in practice and, therefore, can be entirely fictional or adapted, all or in-part, from an actual situation.
• Research using a case study method must adhere to principles of intellectual honesty and academic integrity; a case analysis scenario can include misleading or false information . A case study paper must report research objectively and factually to ensure that any findings are understood to be logically correct and trustworthy. A case analysis scenario may include misleading or false information intended to deliberately distract from the central issues of the case. The purpose is to teach students how to sort through conflicting or useless information in order to come up with the preferred solution. Any use of misleading or false information in academic research is considered unethical.
• Case study is linked to a research problem; case analysis is linked to a practical situation or scenario . In the social sciences, the subject of an investigation is most often framed as a problem that must be researched in order to generate new knowledge leading to a solution. Case analysis narratives are grounded in real life scenarios for the purpose of examining the realities of decision-making behavior and processes within organizational settings. A case analysis assignments include a problem or set of problems to be analyzed. However, the goal is centered around the act of identifying and evaluating courses of action leading to best possible outcomes.
• The purpose of a case study is to create new knowledge through research; the purpose of a case analysis is to teach new understanding . Case studies are a choice of methodological design intended to create new knowledge about resolving a research problem. A case analysis is a mode of teaching and learning intended to create new understanding and an awareness of uncertainty applied to practice through acts of critical thinking and reflection.
• A case study seeks to identify the best possible solution to a research problem; case analysis can have an indeterminate set of solutions or outcomes . Your role in studying a case is to discover the most logical, evidence-based ways to address a research problem. A case analysis assignment rarely has a single correct answer because one of the goals is to force students to confront the real life dynamics of uncertainly, ambiguity, and missing or conflicting information within professional practice. Under these conditions, a perfect outcome or solution almost never exists.
• Case study is unbounded and relies on gathering external information; case analysis is a self-contained subject of analysis . The scope of a case study chosen as a method of research is bounded. However, the researcher is free to gather whatever information and data is necessary to investigate its relevance to understanding the research problem. For a case analysis assignment, your professor will often ask you to examine solutions or recommended courses of action based solely on facts and information from the case.
• Case study can be a person, place, object, issue, event, condition, or phenomenon; a case analysis is a carefully constructed synopsis of events, situations, and behaviors . The research problem dictates the type of case being studied and, therefore, the design can encompass almost anything tangible as long as it fulfills the objective of generating new knowledge and understanding. A case analysis is in the form of a narrative containing descriptions of facts, situations, processes, rules, and behaviors within a particular setting and under a specific set of circumstances.
• Case study can represent an open-ended subject of inquiry; a case analysis is a narrative about something that has happened in the past . A case study is not restricted by time and can encompass an event or issue with no temporal limit or end. For example, the current war in Ukraine can be used as a case study of how medical personnel help civilians during a large military conflict, even though circumstances around this event are still evolving. A case analysis can be used to elicit critical thinking about current or future situations in practice, but the case itself is a narrative about something finite and that has taken place in the past.
• Multiple case studies can be used in a research study; case analysis involves examining a single scenario . Case study research can use two or more cases to examine a problem, often for the purpose of conducting a comparative investigation intended to discover hidden relationships, document emerging trends, or determine variations among different examples. A case analysis assignment typically describes a stand-alone, self-contained situation and any comparisons among cases are conducted during in-class discussions and/or student presentations.

The Case Analysis . Fred Meijer Center for Writing and Michigan Authors. Grand Valley State University; Mills, Albert J. , Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010; Ramsey, V. J. and L. D. Dodge. "Case Analysis: A Structured Approach." Exchange: The Organizational Behavior Teaching Journal 6 (November 1981): 27-29; Yin, Robert K. Case Study Research and Applications: Design and Methods . 6th edition. Thousand Oaks, CA: Sage, 2017; Crowe, Sarah et al. “The Case Study Approach.” BMC Medical Research Methodology 11 (2011):  doi: 10.1186/1471-2288-11-100; Yin, Robert K. Case Study Research: Design and Methods . 4th edition. Thousand Oaks, CA: Sage Publishing; 1994.

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• Rajendra Baikady 5  

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This chapter reviews the strengths and limitations of case study as a research method in social sciences. It provides an account of an evidence base to justify why a case study is best suitable for some research questions and why not for some other research questions. Case study designing around the research context, defining the structure and modality, conducting the study, collecting the data through triangulation mode, analysing the data, and interpreting the data and theory building at the end give a holistic view of it. In addition, the chapter also focuses on the types of case study and when and where to use case study as a research method in social science research.

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Ang, C. S., Lee, K. F., & Dipolog-Ubanan, G. F. (2019). Determinants of first-year student identity and satisfaction in higher education: A quantitative case study. SAGE Open, 9 (2), 215824401984668. https://doi.org/10.1177/2158244019846689

Baxter, P., & Jack, S. (2015). Qualitative case study methodology: Study design and implementation for novice researchers. The Qualitative Report . Published. https://doi.org/10.46743/2160-3715/2008.1573

Bhatta, T. P. (2018). Case study research, philosophical position and theory building: A methodological discussion. Dhaulagiri Journal of Sociology and Anthropology, 12 , 72–79. https://doi.org/10.3126/dsaj.v12i0.22182

Article   Google Scholar  

Bromley, P. D. (1990). Academic contributions to psychological counselling. A philosophy of science for the study of individual cases. Counselling Psychology Quarterly , 3 (3), 299–307.

Google Scholar  

Crowe, S., Cresswell, K., Robertson, A., Huby, G., Avery, A., & Sheikh, A. (2011). The case study approach. BMC Medical Research Methodology, 11 (1), 1–9.

Grässel, E., & Schirmer, B. (2006). The use of volunteers to support family carers of dementia patients: Results of a prospective longitudinal study investigating expectations towards and experience with training and professional support. Zeitschrift Fur Gerontologie Und Geriatrie, 39 (3), 217–226.

Greenwood, D., & Lowenthal, D. (2005). Case study as a means of researching social work and improving practitioner education. Journal of Social Work Practice, 19 (2), 181–193. https://doi.org/10.1080/02650530500144782

Gülseçen, S., & Kubat, A. (2006). Teaching ICT to teacher candidates using PBL: A qualitative and quantitative evaluation. Journal of Educational Technology & Society, 9 (2), 96–106.

Gomm, R., Hammersley, M., & Foster, P. (2000). Case study and generalization. Case study method , 98–115.

Hamera, J., Denzin, N. K., & Lincoln, Y. S. (2011). Performance ethnography . SAGE.

Hayes, N. (2000). Doing psychological research (p. 133). Open University Press.

Harrison, H., Birks, M., Franklin, R., & Mills, J. (2017). Case study research: Foundations and methodological orientations. In Forum qualitative sozialforschung/forum: Qualitative social research (Vol. 18, No. 1).

Iwakabe, S., & Gazzola, N. (2009). From single-case studies to practice-based knowledge: Aggregating and synthesizing case studies. Psychotherapy Research, 19 (4–5), 601–611. https://doi.org/10.1080/10503300802688494

Johnson, M. P. (2006). Decision models for the location of community corrections centers. Environment and Planning b: Planning and Design, 33 (3), 393–412. https://doi.org/10.1068/b3125

Kaarbo, J., & Beasley, R. K. (1999). A practical guide to the comparative case study method in political psychology. Political Psychology, 20 (2), 369–391. https://doi.org/10.1111/0162-895x.00149

Lovell, G. I. (2006). Justice excused: The deployment of law in everyday political encounters. Law Society Review, 40 (2), 283–324. https://doi.org/10.1111/j.1540-5893.2006.00265.x

McDonough, S., & McDonough, S. (1997). Research methods as part of English language teacher education. English Language Teacher Education and Development, 3 (1), 84–96.

Meredith, J. (1998). Building operations management theory through case and field research. Journal of Operations Management, 16 (4), 441–454. https://doi.org/10.1016/s0272-6963(98)00023-0

Mills, A. J., Durepos, G., & Wiebe, E. (Eds.). (2009). Encyclopedia of case study research . Sage Publications.

Ochieng, P. A. (2009). An analysis of the strengths and limitation of qualitative and quantitative research paradigms. Problems of Education in the 21st Century , 13 , 13.

Page, E. B., Webb, E. J., Campell, D. T., Schwart, R. D., & Sechrest, L. (1966). Unobtrusive measures: Nonreactive research in the social sciences. American Educational Research Journal, 3 (4), 317. https://doi.org/10.2307/1162043

Rashid, Y., Rashid, A., Warraich, M. A., Sabir, S. S., & Waseem, A. (2019). Case study method: A step-by-step guide for business researchers. International Journal of Qualitative Methods, 18 , 160940691986242. https://doi.org/10.1177/1609406919862424

Ridder, H. G. (2017). The theory contribution of case study research designs. Business Research, 10 (2), 281–305. https://doi.org/10.1007/s40685-017-0045-z

Sadeghi Moghadam, M. R., Ghasemnia Arabi, N., & Khoshsima, G. (2021). A Review of case study method in operations management research. International Journal of Qualitative Methods, 20 , 160940692110100. https://doi.org/10.1177/16094069211010088

Sommer, B. B., & Sommer, R. (1997). A practical guide to behavioral research: Tools and techniques . Oxford University Press.

Stake, R. E. (2010). Qualitative research: Studying how things work .

Stake, R. E. (1995). The Art of Case Study Research . Sage Publications.

Stoecker, R. (1991). Evaluating and rethinking the case study. The Sociological Review, 39 (1), 88–112.

Suryani, A. (2013). Comparing case study and ethnography as qualitative research approaches .

Taylor, S., & Berridge, V. (2006). Medicinal plants and malaria: An historical case study of research at the London School of Hygiene and Tropical Medicine in the twentieth century. Transactions of the Royal Society of Tropical Medicine and Hygiene, 100 (8), 707–714. https://doi.org/10.1016/j.trstmh.2005.11.017

Tellis, W. (1997). Introduction to case study. The Qualitative Report . Published. https://doi.org/10.46743/2160-3715/1997.2024

Towne, L., & Shavelson, R. J. (2002). Scientific research in education . National Academy Press Publications Sales Office.

Widdowson, M. D. J. (2011). Case study research methodology. International Journal of Transactional Analysis Research, 2 (1), 25–34.

Yin, R. K. (2004). The case study anthology . Sage.

Yin, R. K. (2003). Design and methods. Case Study Research , 3 (9.2).

Yin, R. K. (1994). Case study research: Design and methods (2nd ed.). Sage Publishing.

Yin, R. (1984). Case study research: Design and methods . Sage Publications Beverly Hills.

Yin, R. (1993). Applications of case study research . Sage Publishing.

Zainal, Z. (2003). An investigation into the effects of discipline-specific knowledge, proficiency and genre on reading comprehension and strategies of Malaysia ESP Students. Unpublished Ph. D. Thesis. University of Reading , 1 (1).

Zeisel, J. (1984). Inquiry by design: Tools for environment-behaviour research (No. 5). CUP archive.

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The case study approach

• Sarah Crowe 1 ,
• Kathrin Cresswell 2 ,
• Ann Robertson 2 ,
• Guro Huby 3 ,
• Anthony Avery 1 &
• Aziz Sheikh 2  

BMC Medical Research Methodology volume  11 , Article number:  100 ( 2011 ) Cite this article

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The case study approach allows in-depth, multi-faceted explorations of complex issues in their real-life settings. The value of the case study approach is well recognised in the fields of business, law and policy, but somewhat less so in health services research. Based on our experiences of conducting several health-related case studies, we reflect on the different types of case study design, the specific research questions this approach can help answer, the data sources that tend to be used, and the particular advantages and disadvantages of employing this methodological approach. The paper concludes with key pointers to aid those designing and appraising proposals for conducting case study research, and a checklist to help readers assess the quality of case study reports.

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Introduction

The case study approach is particularly useful to employ when there is a need to obtain an in-depth appreciation of an issue, event or phenomenon of interest, in its natural real-life context. Our aim in writing this piece is to provide insights into when to consider employing this approach and an overview of key methodological considerations in relation to the design, planning, analysis, interpretation and reporting of case studies.

The illustrative 'grand round', 'case report' and 'case series' have a long tradition in clinical practice and research. Presenting detailed critiques, typically of one or more patients, aims to provide insights into aspects of the clinical case and, in doing so, illustrate broader lessons that may be learnt. In research, the conceptually-related case study approach can be used, for example, to describe in detail a patient's episode of care, explore professional attitudes to and experiences of a new policy initiative or service development or more generally to 'investigate contemporary phenomena within its real-life context' [ 1 ]. Based on our experiences of conducting a range of case studies, we reflect on when to consider using this approach, discuss the key steps involved and illustrate, with examples, some of the practical challenges of attaining an in-depth understanding of a 'case' as an integrated whole. In keeping with previously published work, we acknowledge the importance of theory to underpin the design, selection, conduct and interpretation of case studies[ 2 ]. In so doing, we make passing reference to the different epistemological approaches used in case study research by key theoreticians and methodologists in this field of enquiry.

This paper is structured around the following main questions: What is a case study? What are case studies used for? How are case studies conducted? What are the potential pitfalls and how can these be avoided? We draw in particular on four of our own recently published examples of case studies (see Tables 1 , 2 , 3 and 4 ) and those of others to illustrate our discussion[ 3 – 7 ].

What is a case study?

A case study is a research approach that is used to generate an in-depth, multi-faceted understanding of a complex issue in its real-life context. It is an established research design that is used extensively in a wide variety of disciplines, particularly in the social sciences. A case study can be defined in a variety of ways (Table 5 ), the central tenet being the need to explore an event or phenomenon in depth and in its natural context. It is for this reason sometimes referred to as a "naturalistic" design; this is in contrast to an "experimental" design (such as a randomised controlled trial) in which the investigator seeks to exert control over and manipulate the variable(s) of interest.

Stake's work has been particularly influential in defining the case study approach to scientific enquiry. He has helpfully characterised three main types of case study: intrinsic , instrumental and collective [ 8 ]. An intrinsic case study is typically undertaken to learn about a unique phenomenon. The researcher should define the uniqueness of the phenomenon, which distinguishes it from all others. In contrast, the instrumental case study uses a particular case (some of which may be better than others) to gain a broader appreciation of an issue or phenomenon. The collective case study involves studying multiple cases simultaneously or sequentially in an attempt to generate a still broader appreciation of a particular issue.

These are however not necessarily mutually exclusive categories. In the first of our examples (Table 1 ), we undertook an intrinsic case study to investigate the issue of recruitment of minority ethnic people into the specific context of asthma research studies, but it developed into a instrumental case study through seeking to understand the issue of recruitment of these marginalised populations more generally, generating a number of the findings that are potentially transferable to other disease contexts[ 3 ]. In contrast, the other three examples (see Tables 2 , 3 and 4 ) employed collective case study designs to study the introduction of workforce reconfiguration in primary care, the implementation of electronic health records into hospitals, and to understand the ways in which healthcare students learn about patient safety considerations[ 4 – 6 ]. Although our study focusing on the introduction of General Practitioners with Specialist Interests (Table 2 ) was explicitly collective in design (four contrasting primary care organisations were studied), is was also instrumental in that this particular professional group was studied as an exemplar of the more general phenomenon of workforce redesign[ 4 ].

What are case studies used for?

According to Yin, case studies can be used to explain, describe or explore events or phenomena in the everyday contexts in which they occur[ 1 ]. These can, for example, help to understand and explain causal links and pathways resulting from a new policy initiative or service development (see Tables 2 and 3 , for example)[ 1 ]. In contrast to experimental designs, which seek to test a specific hypothesis through deliberately manipulating the environment (like, for example, in a randomised controlled trial giving a new drug to randomly selected individuals and then comparing outcomes with controls),[ 9 ] the case study approach lends itself well to capturing information on more explanatory ' how ', 'what' and ' why ' questions, such as ' how is the intervention being implemented and received on the ground?'. The case study approach can offer additional insights into what gaps exist in its delivery or why one implementation strategy might be chosen over another. This in turn can help develop or refine theory, as shown in our study of the teaching of patient safety in undergraduate curricula (Table 4 )[ 6 , 10 ]. Key questions to consider when selecting the most appropriate study design are whether it is desirable or indeed possible to undertake a formal experimental investigation in which individuals and/or organisations are allocated to an intervention or control arm? Or whether the wish is to obtain a more naturalistic understanding of an issue? The former is ideally studied using a controlled experimental design, whereas the latter is more appropriately studied using a case study design.

Case studies may be approached in different ways depending on the epistemological standpoint of the researcher, that is, whether they take a critical (questioning one's own and others' assumptions), interpretivist (trying to understand individual and shared social meanings) or positivist approach (orientating towards the criteria of natural sciences, such as focusing on generalisability considerations) (Table 6 ). Whilst such a schema can be conceptually helpful, it may be appropriate to draw on more than one approach in any case study, particularly in the context of conducting health services research. Doolin has, for example, noted that in the context of undertaking interpretative case studies, researchers can usefully draw on a critical, reflective perspective which seeks to take into account the wider social and political environment that has shaped the case[ 11 ].

How are case studies conducted?

Here, we focus on the main stages of research activity when planning and undertaking a case study; the crucial stages are: defining the case; selecting the case(s); collecting and analysing the data; interpreting data; and reporting the findings.

Defining the case

Carefully formulated research question(s), informed by the existing literature and a prior appreciation of the theoretical issues and setting(s), are all important in appropriately and succinctly defining the case[ 8 , 12 ]. Crucially, each case should have a pre-defined boundary which clarifies the nature and time period covered by the case study (i.e. its scope, beginning and end), the relevant social group, organisation or geographical area of interest to the investigator, the types of evidence to be collected, and the priorities for data collection and analysis (see Table 7 )[ 1 ]. A theory driven approach to defining the case may help generate knowledge that is potentially transferable to a range of clinical contexts and behaviours; using theory is also likely to result in a more informed appreciation of, for example, how and why interventions have succeeded or failed[ 13 ].

For example, in our evaluation of the introduction of electronic health records in English hospitals (Table 3 ), we defined our cases as the NHS Trusts that were receiving the new technology[ 5 ]. Our focus was on how the technology was being implemented. However, if the primary research interest had been on the social and organisational dimensions of implementation, we might have defined our case differently as a grouping of healthcare professionals (e.g. doctors and/or nurses). The precise beginning and end of the case may however prove difficult to define. Pursuing this same example, when does the process of implementation and adoption of an electronic health record system really begin or end? Such judgements will inevitably be influenced by a range of factors, including the research question, theory of interest, the scope and richness of the gathered data and the resources available to the research team.

Selecting the case(s)

The decision on how to select the case(s) to study is a very important one that merits some reflection. In an intrinsic case study, the case is selected on its own merits[ 8 ]. The case is selected not because it is representative of other cases, but because of its uniqueness, which is of genuine interest to the researchers. This was, for example, the case in our study of the recruitment of minority ethnic participants into asthma research (Table 1 ) as our earlier work had demonstrated the marginalisation of minority ethnic people with asthma, despite evidence of disproportionate asthma morbidity[ 14 , 15 ]. In another example of an intrinsic case study, Hellstrom et al.[ 16 ] studied an elderly married couple living with dementia to explore how dementia had impacted on their understanding of home, their everyday life and their relationships.

For an instrumental case study, selecting a "typical" case can work well[ 8 ]. In contrast to the intrinsic case study, the particular case which is chosen is of less importance than selecting a case that allows the researcher to investigate an issue or phenomenon. For example, in order to gain an understanding of doctors' responses to health policy initiatives, Som undertook an instrumental case study interviewing clinicians who had a range of responsibilities for clinical governance in one NHS acute hospital trust[ 17 ]. Sampling a "deviant" or "atypical" case may however prove even more informative, potentially enabling the researcher to identify causal processes, generate hypotheses and develop theory.

In collective or multiple case studies, a number of cases are carefully selected. This offers the advantage of allowing comparisons to be made across several cases and/or replication. Choosing a "typical" case may enable the findings to be generalised to theory (i.e. analytical generalisation) or to test theory by replicating the findings in a second or even a third case (i.e. replication logic)[ 1 ]. Yin suggests two or three literal replications (i.e. predicting similar results) if the theory is straightforward and five or more if the theory is more subtle. However, critics might argue that selecting 'cases' in this way is insufficiently reflexive and ill-suited to the complexities of contemporary healthcare organisations.

The selected case study site(s) should allow the research team access to the group of individuals, the organisation, the processes or whatever else constitutes the chosen unit of analysis for the study. Access is therefore a central consideration; the researcher needs to come to know the case study site(s) well and to work cooperatively with them. Selected cases need to be not only interesting but also hospitable to the inquiry [ 8 ] if they are to be informative and answer the research question(s). Case study sites may also be pre-selected for the researcher, with decisions being influenced by key stakeholders. For example, our selection of case study sites in the evaluation of the implementation and adoption of electronic health record systems (see Table 3 ) was heavily influenced by NHS Connecting for Health, the government agency that was responsible for overseeing the National Programme for Information Technology (NPfIT)[ 5 ]. This prominent stakeholder had already selected the NHS sites (through a competitive bidding process) to be early adopters of the electronic health record systems and had negotiated contracts that detailed the deployment timelines.

It is also important to consider in advance the likely burden and risks associated with participation for those who (or the site(s) which) comprise the case study. Of particular importance is the obligation for the researcher to think through the ethical implications of the study (e.g. the risk of inadvertently breaching anonymity or confidentiality) and to ensure that potential participants/participating sites are provided with sufficient information to make an informed choice about joining the study. The outcome of providing this information might be that the emotive burden associated with participation, or the organisational disruption associated with supporting the fieldwork, is considered so high that the individuals or sites decide against participation.

In our example of evaluating implementations of electronic health record systems, given the restricted number of early adopter sites available to us, we sought purposively to select a diverse range of implementation cases among those that were available[ 5 ]. We chose a mixture of teaching, non-teaching and Foundation Trust hospitals, and examples of each of the three electronic health record systems procured centrally by the NPfIT. At one recruited site, it quickly became apparent that access was problematic because of competing demands on that organisation. Recognising the importance of full access and co-operative working for generating rich data, the research team decided not to pursue work at that site and instead to focus on other recruited sites.

Collecting the data

In order to develop a thorough understanding of the case, the case study approach usually involves the collection of multiple sources of evidence, using a range of quantitative (e.g. questionnaires, audits and analysis of routinely collected healthcare data) and more commonly qualitative techniques (e.g. interviews, focus groups and observations). The use of multiple sources of data (data triangulation) has been advocated as a way of increasing the internal validity of a study (i.e. the extent to which the method is appropriate to answer the research question)[ 8 , 18 – 21 ]. An underlying assumption is that data collected in different ways should lead to similar conclusions, and approaching the same issue from different angles can help develop a holistic picture of the phenomenon (Table 2 )[ 4 ].

Brazier and colleagues used a mixed-methods case study approach to investigate the impact of a cancer care programme[ 22 ]. Here, quantitative measures were collected with questionnaires before, and five months after, the start of the intervention which did not yield any statistically significant results. Qualitative interviews with patients however helped provide an insight into potentially beneficial process-related aspects of the programme, such as greater, perceived patient involvement in care. The authors reported how this case study approach provided a number of contextual factors likely to influence the effectiveness of the intervention and which were not likely to have been obtained from quantitative methods alone.

In collective or multiple case studies, data collection needs to be flexible enough to allow a detailed description of each individual case to be developed (e.g. the nature of different cancer care programmes), before considering the emerging similarities and differences in cross-case comparisons (e.g. to explore why one programme is more effective than another). It is important that data sources from different cases are, where possible, broadly comparable for this purpose even though they may vary in nature and depth.

Analysing, interpreting and reporting case studies

Making sense and offering a coherent interpretation of the typically disparate sources of data (whether qualitative alone or together with quantitative) is far from straightforward. Repeated reviewing and sorting of the voluminous and detail-rich data are integral to the process of analysis. In collective case studies, it is helpful to analyse data relating to the individual component cases first, before making comparisons across cases. Attention needs to be paid to variations within each case and, where relevant, the relationship between different causes, effects and outcomes[ 23 ]. Data will need to be organised and coded to allow the key issues, both derived from the literature and emerging from the dataset, to be easily retrieved at a later stage. An initial coding frame can help capture these issues and can be applied systematically to the whole dataset with the aid of a qualitative data analysis software package.

The Framework approach is a practical approach, comprising of five stages (familiarisation; identifying a thematic framework; indexing; charting; mapping and interpretation) , to managing and analysing large datasets particularly if time is limited, as was the case in our study of recruitment of South Asians into asthma research (Table 1 )[ 3 , 24 ]. Theoretical frameworks may also play an important role in integrating different sources of data and examining emerging themes. For example, we drew on a socio-technical framework to help explain the connections between different elements - technology; people; and the organisational settings within which they worked - in our study of the introduction of electronic health record systems (Table 3 )[ 5 ]. Our study of patient safety in undergraduate curricula drew on an evaluation-based approach to design and analysis, which emphasised the importance of the academic, organisational and practice contexts through which students learn (Table 4 )[ 6 ].

Case study findings can have implications both for theory development and theory testing. They may establish, strengthen or weaken historical explanations of a case and, in certain circumstances, allow theoretical (as opposed to statistical) generalisation beyond the particular cases studied[ 12 ]. These theoretical lenses should not, however, constitute a strait-jacket and the cases should not be "forced to fit" the particular theoretical framework that is being employed.

When reporting findings, it is important to provide the reader with enough contextual information to understand the processes that were followed and how the conclusions were reached. In a collective case study, researchers may choose to present the findings from individual cases separately before amalgamating across cases. Care must be taken to ensure the anonymity of both case sites and individual participants (if agreed in advance) by allocating appropriate codes or withholding descriptors. In the example given in Table 3 , we decided against providing detailed information on the NHS sites and individual participants in order to avoid the risk of inadvertent disclosure of identities[ 5 , 25 ].

What are the potential pitfalls and how can these be avoided?

The case study approach is, as with all research, not without its limitations. When investigating the formal and informal ways undergraduate students learn about patient safety (Table 4 ), for example, we rapidly accumulated a large quantity of data. The volume of data, together with the time restrictions in place, impacted on the depth of analysis that was possible within the available resources. This highlights a more general point of the importance of avoiding the temptation to collect as much data as possible; adequate time also needs to be set aside for data analysis and interpretation of what are often highly complex datasets.

Case study research has sometimes been criticised for lacking scientific rigour and providing little basis for generalisation (i.e. producing findings that may be transferable to other settings)[ 1 ]. There are several ways to address these concerns, including: the use of theoretical sampling (i.e. drawing on a particular conceptual framework); respondent validation (i.e. participants checking emerging findings and the researcher's interpretation, and providing an opinion as to whether they feel these are accurate); and transparency throughout the research process (see Table 8 )[ 8 , 18 – 21 , 23 , 26 ]. Transparency can be achieved by describing in detail the steps involved in case selection, data collection, the reasons for the particular methods chosen, and the researcher's background and level of involvement (i.e. being explicit about how the researcher has influenced data collection and interpretation). Seeking potential, alternative explanations, and being explicit about how interpretations and conclusions were reached, help readers to judge the trustworthiness of the case study report. Stake provides a critique checklist for a case study report (Table 9 )[ 8 ].

Conclusions

The case study approach allows, amongst other things, critical events, interventions, policy developments and programme-based service reforms to be studied in detail in a real-life context. It should therefore be considered when an experimental design is either inappropriate to answer the research questions posed or impossible to undertake. Considering the frequency with which implementations of innovations are now taking place in healthcare settings and how well the case study approach lends itself to in-depth, complex health service research, we believe this approach should be more widely considered by researchers. Though inherently challenging, the research case study can, if carefully conceptualised and thoughtfully undertaken and reported, yield powerful insights into many important aspects of health and healthcare delivery.

Yin RK: Case study research, design and method. 2009, London: Sage Publications Ltd., 4

Google Scholar  

Keen J, Packwood T: Qualitative research; case study evaluation. BMJ. 1995, 311: 444-446.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Sheikh A, Halani L, Bhopal R, Netuveli G, Partridge M, Car J, et al: Facilitating the Recruitment of Minority Ethnic People into Research: Qualitative Case Study of South Asians and Asthma. PLoS Med. 2009, 6 (10): 1-11.

Article   Google Scholar  

Pinnock H, Huby G, Powell A, Kielmann T, Price D, Williams S, et al: The process of planning, development and implementation of a General Practitioner with a Special Interest service in Primary Care Organisations in England and Wales: a comparative prospective case study. Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D (NCCSDO). 2008, [ http://www.sdo.nihr.ac.uk/files/project/99-final-report.pdf ]

Robertson A, Cresswell K, Takian A, Petrakaki D, Crowe S, Cornford T, et al: Prospective evaluation of the implementation and adoption of NHS Connecting for Health's national electronic health record in secondary care in England: interim findings. BMJ. 2010, 41: c4564-

Pearson P, Steven A, Howe A, Sheikh A, Ashcroft D, Smith P, the Patient Safety Education Study Group: Learning about patient safety: organisational context and culture in the education of healthcare professionals. J Health Serv Res Policy. 2010, 15: 4-10. 10.1258/jhsrp.2009.009052.

Article   PubMed   Google Scholar  

van Harten WH, Casparie TF, Fisscher OA: The evaluation of the introduction of a quality management system: a process-oriented case study in a large rehabilitation hospital. Health Policy. 2002, 60 (1): 17-37. 10.1016/S0168-8510(01)00187-7.

Stake RE: The art of case study research. 1995, London: Sage Publications Ltd.

Sheikh A, Smeeth L, Ashcroft R: Randomised controlled trials in primary care: scope and application. Br J Gen Pract. 2002, 52 (482): 746-51.

PubMed   PubMed Central   Google Scholar  

King G, Keohane R, Verba S: Designing Social Inquiry. 1996, Princeton: Princeton University Press

Doolin B: Information technology as disciplinary technology: being critical in interpretative research on information systems. Journal of Information Technology. 1998, 13: 301-311. 10.1057/jit.1998.8.

George AL, Bennett A: Case studies and theory development in the social sciences. 2005, Cambridge, MA: MIT Press

Eccles M, the Improved Clinical Effectiveness through Behavioural Research Group (ICEBeRG): Designing theoretically-informed implementation interventions. Implementation Science. 2006, 1: 1-8. 10.1186/1748-5908-1-1.

Article   PubMed Central   Google Scholar  

Netuveli G, Hurwitz B, Levy M, Fletcher M, Barnes G, Durham SR, Sheikh A: Ethnic variations in UK asthma frequency, morbidity, and health-service use: a systematic review and meta-analysis. Lancet. 2005, 365 (9456): 312-7.

Sheikh A, Panesar SS, Lasserson T, Netuveli G: Recruitment of ethnic minorities to asthma studies. Thorax. 2004, 59 (7): 634-

CAS   PubMed   PubMed Central   Google Scholar  

Hellström I, Nolan M, Lundh U: 'We do things together': A case study of 'couplehood' in dementia. Dementia. 2005, 4: 7-22. 10.1177/1471301205049188.

Som CV: Nothing seems to have changed, nothing seems to be changing and perhaps nothing will change in the NHS: doctors' response to clinical governance. International Journal of Public Sector Management. 2005, 18: 463-477. 10.1108/09513550510608903.

Lincoln Y, Guba E: Naturalistic inquiry. 1985, Newbury Park: Sage Publications

Barbour RS: Checklists for improving rigour in qualitative research: a case of the tail wagging the dog?. BMJ. 2001, 322: 1115-1117. 10.1136/bmj.322.7294.1115.

Mays N, Pope C: Qualitative research in health care: Assessing quality in qualitative research. BMJ. 2000, 320: 50-52. 10.1136/bmj.320.7226.50.

Mason J: Qualitative researching. 2002, London: Sage

Brazier A, Cooke K, Moravan V: Using Mixed Methods for Evaluating an Integrative Approach to Cancer Care: A Case Study. Integr Cancer Ther. 2008, 7: 5-17. 10.1177/1534735407313395.

Miles MB, Huberman M: Qualitative data analysis: an expanded sourcebook. 1994, CA: Sage Publications Inc., 2

Pope C, Ziebland S, Mays N: Analysing qualitative data. Qualitative research in health care. BMJ. 2000, 320: 114-116. 10.1136/bmj.320.7227.114.

Cresswell KM, Worth A, Sheikh A: Actor-Network Theory and its role in understanding the implementation of information technology developments in healthcare. BMC Med Inform Decis Mak. 2010, 10 (1): 67-10.1186/1472-6947-10-67.

Article   PubMed   PubMed Central   Google Scholar  

Malterud K: Qualitative research: standards, challenges, and guidelines. Lancet. 2001, 358: 483-488. 10.1016/S0140-6736(01)05627-6.

Article   CAS   PubMed   Google Scholar  

Yin R: Case study research: design and methods. 1994, Thousand Oaks, CA: Sage Publishing, 2

Yin R: Enhancing the quality of case studies in health services research. Health Serv Res. 1999, 34: 1209-1224.

Green J, Thorogood N: Qualitative methods for health research. 2009, Los Angeles: Sage, 2

Howcroft D, Trauth E: Handbook of Critical Information Systems Research, Theory and Application. 2005, Cheltenham, UK: Northampton, MA, USA: Edward Elgar

Book   Google Scholar  

Blakie N: Approaches to Social Enquiry. 1993, Cambridge: Polity Press

Doolin B: Power and resistance in the implementation of a medical management information system. Info Systems J. 2004, 14: 343-362. 10.1111/j.1365-2575.2004.00176.x.

Bloomfield BP, Best A: Management consultants: systems development, power and the translation of problems. Sociological Review. 1992, 40: 533-560.

Shanks G, Parr A: Positivist, single case study research in information systems: A critical analysis. Proceedings of the European Conference on Information Systems. 2003, Naples

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Acknowledgements

We are grateful to the participants and colleagues who contributed to the individual case studies that we have drawn on. This work received no direct funding, but it has been informed by projects funded by Asthma UK, the NHS Service Delivery Organisation, NHS Connecting for Health Evaluation Programme, and Patient Safety Research Portfolio. We would also like to thank the expert reviewers for their insightful and constructive feedback. Our thanks are also due to Dr. Allison Worth who commented on an earlier draft of this manuscript.

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Sarah Crowe & Anthony Avery

Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK

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AS conceived this article. SC, KC and AR wrote this paper with GH, AA and AS all commenting on various drafts. SC and AS are guarantors.

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How to write a case study — examples, templates, and tools

It’s a marketer’s job to communicate the effectiveness of a product or service to potential and current customers to convince them to buy and keep business moving. One of the best methods for doing this is to share success stories that are relatable to prospects and customers based on their pain points, experiences, and overall needs.

That’s where case studies come in. Case studies are an essential part of a content marketing plan. These in-depth stories of customer experiences are some of the most effective at demonstrating the value of a product or service. Yet many marketers don’t use them, whether because of their regimented formats or the process of customer involvement and approval.

A case study is a powerful tool for showcasing your hard work and the success your customer achieved. But writing a great case study can be difficult if you’ve never done it before or if it’s been a while. This guide will show you how to write an effective case study and provide real-world examples and templates that will keep readers engaged and support your business.

In this article, you’ll learn:

What is a case study?

How to write a case study, case study templates, case study examples, case study tools.

A case study is the detailed story of a customer’s experience with a product or service that demonstrates their success and often includes measurable outcomes. Case studies are used in a range of fields and for various reasons, from business to academic research. They’re especially impactful in marketing as brands work to convince and convert consumers with relatable, real-world stories of actual customer experiences.

The best case studies tell the story of a customer’s success, including the steps they took, the results they achieved, and the support they received from a brand along the way. To write a great case study, you need to:

• Celebrate the customer and make them — not a product or service — the star of the story.
• Craft the story with specific audiences or target segments in mind so that the story of one customer will be viewed as relatable and actionable for another customer.
• Write copy that is easy to read and engaging so that readers will gain the insights and messages intended.
• Follow a standardized format that includes all of the essentials a potential customer would find interesting and useful.
• Support all of the claims for success made in the story with data in the forms of hard numbers and customer statements.

Case studies are a type of review but more in depth, aiming to show — rather than just tell — the positive experiences that customers have with a brand. Notably, 89% of consumers read reviews before deciding to buy, and 79% view case study content as part of their purchasing process. When it comes to B2B sales, 52% of buyers rank case studies as an important part of their evaluation process.

Telling a brand story through the experience of a tried-and-true customer matters. The story is relatable to potential new customers as they imagine themselves in the shoes of the company or individual featured in the case study. Showcasing previous customers can help new ones see themselves engaging with your brand in the ways that are most meaningful to them.

Besides sharing the perspective of another customer, case studies stand out from other content marketing forms because they are based on evidence. Whether pulling from client testimonials or data-driven results, case studies tend to have more impact on new business because the story contains information that is both objective (data) and subjective (customer experience) — and the brand doesn’t sound too self-promotional.

Case studies are unique in that there’s a fairly standardized format for telling a customer’s story. But that doesn’t mean there isn’t room for creativity. It’s all about making sure that teams are clear on the goals for the case study — along with strategies for supporting content and channels — and understanding how the story fits within the framework of the company’s overall marketing goals.

Here are the basic steps to writing a good case study.

1. Identify your goal

Start by defining exactly who your case study will be designed to help. Case studies are about specific instances where a company works with a customer to achieve a goal. Identify which customers are likely to have these goals, as well as other needs the story should cover to appeal to them.

The answer is often found in one of the buyer personas that have been constructed as part of your larger marketing strategy. This can include anything from new leads generated by the marketing team to long-term customers that are being pressed for cross-sell opportunities. In all of these cases, demonstrating value through a relatable customer success story can be part of the solution to conversion.

2. Choose your client or subject

Who you highlight matters. Case studies tie brands together that might otherwise not cross paths. A writer will want to ensure that the highlighted customer aligns with their own company’s brand identity and offerings. Look for a customer with positive name recognition who has had great success with a product or service and is willing to be an advocate.

The client should also match up with the identified target audience. Whichever company or individual is selected should be a reflection of other potential customers who can see themselves in similar circumstances, having the same problems and possible solutions.

Some of the most compelling case studies feature customers who:

• Switch from one product or service to another while naming competitors that missed the mark.
• Experience measurable results that are relatable to others in a specific industry.
• Represent well-known brands and recognizable names that are likely to compel action.
• Advocate for a product or service as a champion and are well-versed in its advantages.

Whoever or whatever customer is selected, marketers must ensure they have the permission of the company involved before getting started. Some brands have strict review and approval procedures for any official marketing or promotional materials that include their name. Acquiring those approvals in advance will prevent any miscommunication or wasted effort if there is an issue with their legal or compliance teams.

3. Conduct research and compile data

Substantiating the claims made in a case study — either by the marketing team or customers themselves — adds validity to the story. To do this, include data and feedback from the client that defines what success looks like. This can be anything from demonstrating return on investment (ROI) to a specific metric the customer was striving to improve. Case studies should prove how an outcome was achieved and show tangible results that indicate to the customer that your solution is the right one.

This step could also include customer interviews. Make sure that the people being interviewed are key stakeholders in the purchase decision or deployment and use of the product or service that is being highlighted. Content writers should work off a set list of questions prepared in advance. It can be helpful to share these with the interviewees beforehand so they have time to consider and craft their responses. One of the best interview tactics to keep in mind is to ask questions where yes and no are not natural answers. This way, your subject will provide more open-ended responses that produce more meaningful content.

4. Choose the right format

There are a number of different ways to format a case study. Depending on what you hope to achieve, one style will be better than another. However, there are some common elements to include, such as:

• An engaging headline
• A subject and customer introduction
• The unique challenge or challenges the customer faced
• The solution the customer used to solve the problem
• The results achieved
• Data and statistics to back up claims of success
• A strong call to action (CTA) to engage with the vendor

It’s also important to note that while case studies are traditionally written as stories, they don’t have to be in a written format. Some companies choose to get more creative with their case studies and produce multimedia content, depending on their audience and objectives. Case study formats can include traditional print stories, interactive web or social content, data-heavy infographics, professionally shot videos, podcasts, and more.

5. Write your case study

We’ll go into more detail later about how exactly to write a case study, including templates and examples. Generally speaking, though, there are a few things to keep in mind when writing your case study.

• Be clear and concise. Readers want to get to the point of the story quickly and easily, and they’ll be looking to see themselves reflected in the story right from the start.
• Provide a big picture. Always make sure to explain who the client is, their goals, and how they achieved success in a short introduction to engage the reader.
• Construct a clear narrative. Stick to the story from the perspective of the customer and what they needed to solve instead of just listing product features or benefits.
• Leverage graphics. Incorporating infographics, charts, and sidebars can be a more engaging and eye-catching way to share key statistics and data in readable ways.
• Offer the right amount of detail. Most case studies are one or two pages with clear sections that a reader can skim to find the information most important to them.
• Include data to support claims. Show real results — both facts and figures and customer quotes — to demonstrate credibility and prove the solution works.

6. Promote your story

Marketers have a number of options for distribution of a freshly minted case study. Many brands choose to publish case studies on their website and post them on social media. This can help support SEO and organic content strategies while also boosting company credibility and trust as visitors see that other businesses have used the product or service.

Marketers are always looking for quality content they can use for lead generation. Consider offering a case study as gated content behind a form on a landing page or as an offer in an email message. One great way to do this is to summarize the content and tease the full story available for download after the user takes an action.

Sales teams can also leverage case studies, so be sure they are aware that the assets exist once they’re published. Especially when it comes to larger B2B sales, companies often ask for examples of similar customer challenges that have been solved.

Now that you’ve learned a bit about case studies and what they should include, you may be wondering how to start creating great customer story content. Here are a couple of templates you can use to structure your case study.

Template 1 — Challenge-solution-result format

• Start with an engaging title. This should be fewer than 70 characters long for SEO best practices. One of the best ways to approach the title is to include the customer’s name and a hint at the challenge they overcame in the end.
• Create an introduction. Lead with an explanation as to who the customer is, the need they had, and the opportunity they found with a specific product or solution. Writers can also suggest the success the customer experienced with the solution they chose.
• Present the challenge. This should be several paragraphs long and explain the problem the customer faced and the issues they were trying to solve. Details should tie into the company’s products and services naturally. This section needs to be the most relatable to the reader so they can picture themselves in a similar situation.
• Share the solution. Explain which product or service offered was the ideal fit for the customer and why. Feel free to delve into their experience setting up, purchasing, and onboarding the solution.
• Explain the results. Demonstrate the impact of the solution they chose by backing up their positive experience with data. Fill in with customer quotes and tangible, measurable results that show the effect of their choice.
• Ask for action. Include a CTA at the end of the case study that invites readers to reach out for more information, try a demo, or learn more — to nurture them further in the marketing pipeline. What you ask of the reader should tie directly into the goals that were established for the case study in the first place.

Template 2 — Data-driven format

• Start with an engaging title. Be sure to include a statistic or data point in the first 70 characters. Again, it’s best to include the customer’s name as part of the title.
• Create an overview. Share the customer’s background and a short version of the challenge they faced. Present the reason a particular product or service was chosen, and feel free to include quotes from the customer about their selection process.
• Present data point 1. Isolate the first metric that the customer used to define success and explain how the product or solution helped to achieve this goal. Provide data points and quotes to substantiate the claim that success was achieved.
• Present data point 2. Isolate the second metric that the customer used to define success and explain what the product or solution did to achieve this goal. Provide data points and quotes to substantiate the claim that success was achieved.
• Present data point 3. Isolate the final metric that the customer used to define success and explain what the product or solution did to achieve this goal. Provide data points and quotes to substantiate the claim that success was achieved.
• Summarize the results. Reiterate the fact that the customer was able to achieve success thanks to a specific product or service. Include quotes and statements that reflect customer satisfaction and suggest they plan to continue using the solution.
• Ask for action. Include a CTA at the end of the case study that asks readers to reach out for more information, try a demo, or learn more — to further nurture them in the marketing pipeline. Again, remember that this is where marketers can look to convert their content into action with the customer.

While templates are helpful, seeing a case study in action can also be a great way to learn. Here are some examples of how Adobe customers have experienced success.

Juniper Networks

One example is the Adobe and Juniper Networks case study , which puts the reader in the customer’s shoes. The beginning of the story quickly orients the reader so that they know exactly who the article is about and what they were trying to achieve. Solutions are outlined in a way that shows Adobe Experience Manager is the best choice and a natural fit for the customer. Along the way, quotes from the client are incorporated to help add validity to the statements. The results in the case study are conveyed with clear evidence of scale and volume using tangible data.

The story of Lenovo’s journey with Adobe is one that spans years of planning, implementation, and rollout. The Lenovo case study does a great job of consolidating all of this into a relatable journey that other enterprise organizations can see themselves taking, despite the project size. This case study also features descriptive headers and compelling visual elements that engage the reader and strengthen the content.

Tata Consulting

When it comes to using data to show customer results, this case study does an excellent job of conveying details and numbers in an easy-to-digest manner. Bullet points at the start break up the content while also helping the reader understand exactly what the case study will be about. Tata Consulting used Adobe to deliver elevated, engaging content experiences for a large telecommunications client of its own — an objective that’s relatable for a lot of companies.

Case studies are a vital tool for any marketing team as they enable you to demonstrate the value of your company’s products and services to others. They help marketers do their job and add credibility to a brand trying to promote its solutions by using the experiences and stories of real customers.

When you’re ready to get started with a case study:

• Think about a few goals you’d like to accomplish with your content.
• Make a list of successful clients that would be strong candidates for a case study.
• Reach out to the client to get their approval and conduct an interview.
• Gather the data to present an engaging and effective customer story.

Adobe can help

There are several Adobe products that can help you craft compelling case studies. Adobe Experience Platform helps you collect data and deliver great customer experiences across every channel. Once you’ve created your case studies, Experience Platform will help you deliver the right information to the right customer at the right time for maximum impact.

To learn more, watch the Adobe Experience Platform story .

Keep in mind that the best case studies are backed by data. That’s where Adobe Real-Time Customer Data Platform and Adobe Analytics come into play. With Real-Time CDP, you can gather the data you need to build a great case study and target specific customers to deliver the content to the right audience at the perfect moment.

Watch the Real-Time CDP overview video to learn more.

Finally, Adobe Analytics turns real-time data into real-time insights. It helps your business collect and synthesize data from multiple platforms to make more informed decisions and create the best case study possible.

Request a demo to learn more about Adobe Analytics.

https://business.adobe.com/blog/perspectives/b2b-ecommerce-10-case-studies-inspire-you

https://business.adobe.com/blog/basics/business-case

https://business.adobe.com/blog/basics/what-is-real-time-analytics

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What Is a Case Study?

Weighing the pros and cons of this method of research

Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

Cara Lustik is a fact-checker and copywriter.

Verywell / Colleen Tighe

• Pros and Cons

What Types of Case Studies Are Out There?

Where do you find data for a case study, how do i write a psychology case study.

A case study is an in-depth study of one person, group, or event. In a case study, nearly every aspect of the subject's life and history is analyzed to seek patterns and causes of behavior. Case studies can be used in many different fields, including psychology, medicine, education, anthropology, political science, and social work.

The point of a case study is to learn as much as possible about an individual or group so that the information can be generalized to many others. Unfortunately, case studies tend to be highly subjective, and it is sometimes difficult to generalize results to a larger population.

While case studies focus on a single individual or group, they follow a format similar to other types of psychology writing. If you are writing a case study, we got you—here are some rules of APA format to reference.  

At a Glance

A case study, or an in-depth study of a person, group, or event, can be a useful research tool when used wisely. In many cases, case studies are best used in situations where it would be difficult or impossible for you to conduct an experiment. They are helpful for looking at unique situations and allow researchers to gather a lot of˜ information about a specific individual or group of people. However, it's important to be cautious of any bias we draw from them as they are highly subjective.

What Are the Benefits and Limitations of Case Studies?

A case study can have its strengths and weaknesses. Researchers must consider these pros and cons before deciding if this type of study is appropriate for their needs.

One of the greatest advantages of a case study is that it allows researchers to investigate things that are often difficult or impossible to replicate in a lab. Some other benefits of a case study:

• Allows researchers to capture information on the 'how,' 'what,' and 'why,' of something that's implemented
• Gives researchers the chance to collect information on why one strategy might be chosen over another
• Permits researchers to develop hypotheses that can be explored in experimental research

On the other hand, a case study can have some drawbacks:

• It cannot necessarily be generalized to the larger population
• Cannot demonstrate cause and effect
• It may not be scientifically rigorous
• It can lead to bias

Researchers may choose to perform a case study if they want to explore a unique or recently discovered phenomenon. Through their insights, researchers develop additional ideas and study questions that might be explored in future studies.

It's important to remember that the insights from case studies cannot be used to determine cause-and-effect relationships between variables. However, case studies may be used to develop hypotheses that can then be addressed in experimental research.

Case Study Examples

There have been a number of notable case studies in the history of psychology. Much of  Freud's work and theories were developed through individual case studies. Some great examples of case studies in psychology include:

• Anna O : Anna O. was a pseudonym of a woman named Bertha Pappenheim, a patient of a physician named Josef Breuer. While she was never a patient of Freud's, Freud and Breuer discussed her case extensively. The woman was experiencing symptoms of a condition that was then known as hysteria and found that talking about her problems helped relieve her symptoms. Her case played an important part in the development of talk therapy as an approach to mental health treatment.
• Phineas Gage : Phineas Gage was a railroad employee who experienced a terrible accident in which an explosion sent a metal rod through his skull, damaging important portions of his brain. Gage recovered from his accident but was left with serious changes in both personality and behavior.
• Genie : Genie was a young girl subjected to horrific abuse and isolation. The case study of Genie allowed researchers to study whether language learning was possible, even after missing critical periods for language development. Her case also served as an example of how scientific research may interfere with treatment and lead to further abuse of vulnerable individuals.

Such cases demonstrate how case research can be used to study things that researchers could not replicate in experimental settings. In Genie's case, her horrific abuse denied her the opportunity to learn a language at critical points in her development.

This is clearly not something researchers could ethically replicate, but conducting a case study on Genie allowed researchers to study phenomena that are otherwise impossible to reproduce.

There are a few different types of case studies that psychologists and other researchers might use:

• Collective case studies : These involve studying a group of individuals. Researchers might study a group of people in a certain setting or look at an entire community. For example, psychologists might explore how access to resources in a community has affected the collective mental well-being of those who live there.
• Descriptive case studies : These involve starting with a descriptive theory. The subjects are then observed, and the information gathered is compared to the pre-existing theory.
• Explanatory case studies : These   are often used to do causal investigations. In other words, researchers are interested in looking at factors that may have caused certain things to occur.
• Exploratory case studies : These are sometimes used as a prelude to further, more in-depth research. This allows researchers to gather more information before developing their research questions and hypotheses .
• Instrumental case studies : These occur when the individual or group allows researchers to understand more than what is initially obvious to observers.
• Intrinsic case studies : This type of case study is when the researcher has a personal interest in the case. Jean Piaget's observations of his own children are good examples of how an intrinsic case study can contribute to the development of a psychological theory.

The three main case study types often used are intrinsic, instrumental, and collective. Intrinsic case studies are useful for learning about unique cases. Instrumental case studies help look at an individual to learn more about a broader issue. A collective case study can be useful for looking at several cases simultaneously.

The type of case study that psychology researchers use depends on the unique characteristics of the situation and the case itself.

There are a number of different sources and methods that researchers can use to gather information about an individual or group. Six major sources that have been identified by researchers are:

• Archival records : Census records, survey records, and name lists are examples of archival records.
• Direct observation : This strategy involves observing the subject, often in a natural setting . While an individual observer is sometimes used, it is more common to utilize a group of observers.
• Documents : Letters, newspaper articles, administrative records, etc., are the types of documents often used as sources.
• Interviews : Interviews are one of the most important methods for gathering information in case studies. An interview can involve structured survey questions or more open-ended questions.
• Participant observation : When the researcher serves as a participant in events and observes the actions and outcomes, it is called participant observation.
• Physical artifacts : Tools, objects, instruments, and other artifacts are often observed during a direct observation of the subject.

If you have been directed to write a case study for a psychology course, be sure to check with your instructor for any specific guidelines you need to follow. If you are writing your case study for a professional publication, check with the publisher for their specific guidelines for submitting a case study.

Here is a general outline of what should be included in a case study.

Section 1: A Case History

This section will have the following structure and content:

Background information : The first section of your paper will present your client's background. Include factors such as age, gender, work, health status, family mental health history, family and social relationships, drug and alcohol history, life difficulties, goals, and coping skills and weaknesses.

Description of the presenting problem : In the next section of your case study, you will describe the problem or symptoms that the client presented with.

Describe any physical, emotional, or sensory symptoms reported by the client. Thoughts, feelings, and perceptions related to the symptoms should also be noted. Any screening or diagnostic assessments that are used should also be described in detail and all scores reported.

Your diagnosis : Provide your diagnosis and give the appropriate Diagnostic and Statistical Manual code. Explain how you reached your diagnosis, how the client's symptoms fit the diagnostic criteria for the disorder(s), or any possible difficulties in reaching a diagnosis.

Section 2: Treatment Plan

This portion of the paper will address the chosen treatment for the condition. This might also include the theoretical basis for the chosen treatment or any other evidence that might exist to support why this approach was chosen.

• Cognitive behavioral approach : Explain how a cognitive behavioral therapist would approach treatment. Offer background information on cognitive behavioral therapy and describe the treatment sessions, client response, and outcome of this type of treatment. Make note of any difficulties or successes encountered by your client during treatment.
• Humanistic approach : Describe a humanistic approach that could be used to treat your client, such as client-centered therapy . Provide information on the type of treatment you chose, the client's reaction to the treatment, and the end result of this approach. Explain why the treatment was successful or unsuccessful.
• Psychoanalytic approach : Describe how a psychoanalytic therapist would view the client's problem. Provide some background on the psychoanalytic approach and cite relevant references. Explain how psychoanalytic therapy would be used to treat the client, how the client would respond to therapy, and the effectiveness of this treatment approach.
• Pharmacological approach : If treatment primarily involves the use of medications, explain which medications were used and why. Provide background on the effectiveness of these medications and how monotherapy may compare with an approach that combines medications with therapy or other treatments.

This section of a case study should also include information about the treatment goals, process, and outcomes.

When you are writing a case study, you should also include a section where you discuss the case study itself, including the strengths and limitiations of the study. You should note how the findings of your case study might support previous research. 

In your discussion section, you should also describe some of the implications of your case study. What ideas or findings might require further exploration? How might researchers go about exploring some of these questions in additional studies?

Need More Tips?

Here are a few additional pointers to keep in mind when formatting your case study:

• Never refer to the subject of your case study as "the client." Instead, use their name or a pseudonym.
• Read examples of case studies to gain an idea about the style and format.
• Remember to use APA format when citing references .

Crowe S, Cresswell K, Robertson A, Huby G, Avery A, Sheikh A. The case study approach .  BMC Med Res Methodol . 2011;11:100.

Crowe S, Cresswell K, Robertson A, Huby G, Avery A, Sheikh A. The case study approach . BMC Med Res Methodol . 2011 Jun 27;11:100. doi:10.1186/1471-2288-11-100

Gagnon, Yves-Chantal.  The Case Study as Research Method: A Practical Handbook . Canada, Chicago Review Press Incorporated DBA Independent Pub Group, 2010.

Yin, Robert K. Case Study Research and Applications: Design and Methods . United States, SAGE Publications, 2017.

By Kendra Cherry, MSEd Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

Do Your Students Know How to Analyze a Case—Really?

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• Case Teaching
• Student Engagement

J ust as actors, athletes, and musicians spend thousands of hours practicing their craft, business students benefit from practicing their critical-thinking and decision-making skills. Students, however, often have limited exposure to real-world problem-solving scenarios; they need more opportunities to practice tackling tough business problems and deciding on—and executing—the best solutions.

To ensure students have ample opportunity to develop these critical-thinking and decision-making skills, we believe business faculty should shift from teaching mostly principles and ideas to mostly applications and practices. And in doing so, they should emphasize the case method, which simulates real-world management challenges and opportunities for students.

To help educators facilitate this shift and help students get the most out of case-based learning, we have developed a framework for analyzing cases. We call it PACADI (Problem, Alternatives, Criteria, Analysis, Decision, Implementation); it can improve learning outcomes by helping students better solve and analyze business problems, make decisions, and develop and implement strategy. Here, we’ll explain why we developed this framework, how it works, and what makes it an effective learning tool.

The Case for Cases: Helping Students Think Critically

Business students must develop critical-thinking and analytical skills, which are essential to their ability to make good decisions in functional areas such as marketing, finance, operations, and information technology, as well as to understand the relationships among these functions. For example, the decisions a marketing manager must make include strategic planning (segments, products, and channels); execution (digital messaging, media, branding, budgets, and pricing); and operations (integrated communications and technologies), as well as how to implement decisions across functional areas.

Faculty can use many types of cases to help students develop these skills. These include the prototypical “paper cases”; live cases , which feature guest lecturers such as entrepreneurs or corporate leaders and on-site visits; and multimedia cases , which immerse students into real situations. Most cases feature an explicit or implicit decision that a protagonist—whether it is an individual, a group, or an organization—must make.

For students new to learning by the case method—and even for those with case experience—some common issues can emerge; these issues can sometimes be a barrier for educators looking to ensure the best possible outcomes in their case classrooms. Unsure of how to dig into case analysis on their own, students may turn to the internet or rely on former students for “answers” to assigned cases. Or, when assigned to provide answers to assignment questions in teams, students might take a divide-and-conquer approach but not take the time to regroup and provide answers that are consistent with one other.

To help address these issues, which we commonly experienced in our classes, we wanted to provide our students with a more structured approach for how they analyze cases—and to really think about making decisions from the protagonists’ point of view. We developed the PACADI framework to address this need.

PACADI: A Six-Step Decision-Making Approach

The PACADI framework is a six-step decision-making approach that can be used in lieu of traditional end-of-case questions. It offers a structured, integrated, and iterative process that requires students to analyze case information, apply business concepts to derive valuable insights, and develop recommendations based on these insights.

Prior to beginning a PACADI assessment, which we’ll outline here, students should first prepare a two-paragraph summary—a situation analysis—that highlights the key case facts. Then, we task students with providing a five-page PACADI case analysis (excluding appendices) based on the following six steps.

Step 1: Problem definition. What is the major challenge, problem, opportunity, or decision that has to be made? If there is more than one problem, choose the most important one. Often when solving the key problem, other issues will surface and be addressed. The problem statement may be framed as a question; for example, How can brand X improve market share among millennials in Canada? Usually the problem statement has to be re-written several times during the analysis of a case as students peel back the layers of symptoms or causation.

Step 2: Alternatives. Identify in detail the strategic alternatives to address the problem; three to five options generally work best. Alternatives should be mutually exclusive, realistic, creative, and feasible given the constraints of the situation. Doing nothing or delaying the decision to a later date are not considered acceptable alternatives.

Step 3: Criteria. What are the key decision criteria that will guide decision-making? In a marketing course, for example, these may include relevant marketing criteria such as segmentation, positioning, advertising and sales, distribution, and pricing. Financial criteria useful in evaluating the alternatives should be included—for example, income statement variables, customer lifetime value, payback, etc. Students must discuss their rationale for selecting the decision criteria and the weights and importance for each factor.

Step 4: Analysis. Provide an in-depth analysis of each alternative based on the criteria chosen in step three. Decision tables using criteria as columns and alternatives as rows can be helpful. The pros and cons of the various choices as well as the short- and long-term implications of each may be evaluated. Best, worst, and most likely scenarios can also be insightful.

Step 5: Decision. Students propose their solution to the problem. This decision is justified based on an in-depth analysis. Explain why the recommendation made is the best fit for the criteria.

Step 6: Implementation plan. Sound business decisions may fail due to poor execution. To enhance the likeliness of a successful project outcome, students describe the key steps (activities) to implement the recommendation, timetable, projected costs, expected competitive reaction, success metrics, and risks in the plan.

“Students note that using the PACADI framework yields ‘aha moments’—they learned something surprising in the case that led them to think differently about the problem and their proposed solution.”

PACADI’s Benefits: Meaningfully and Thoughtfully Applying Business Concepts

The PACADI framework covers all of the major elements of business decision-making, including implementation, which is often overlooked. By stepping through the whole framework, students apply relevant business concepts and solve management problems via a systematic, comprehensive approach; they’re far less likely to surface piecemeal responses.

As students explore each part of the framework, they may realize that they need to make changes to a previous step. For instance, when working on implementation, students may realize that the alternative they selected cannot be executed or will not be profitable, and thus need to rethink their decision. Or, they may discover that the criteria need to be revised since the list of decision factors they identified is incomplete (for example, the factors may explain key marketing concerns but fail to address relevant financial considerations) or is unrealistic (for example, they suggest a 25 percent increase in revenues without proposing an increased promotional budget).

In addition, the PACADI framework can be used alongside quantitative assignments, in-class exercises, and business and management simulations. The structured, multi-step decision framework encourages careful and sequential analysis to solve business problems. Incorporating PACADI as an overarching decision-making method across different projects will ultimately help students achieve desired learning outcomes. As a practical “beyond-the-classroom” tool, the PACADI framework is not a contrived course assignment; it reflects the decision-making approach that managers, executives, and entrepreneurs exercise daily. Case analysis introduces students to the real-world process of making business decisions quickly and correctly, often with limited information. This framework supplies an organized and disciplined process that students can readily defend in writing and in class discussions.

PACADI in Action: An Example

Here’s an example of how students used the PACADI framework for a recent case analysis on CVS, a large North American drugstore chain.

The CVS Prescription for Customer Value*

PACADI Stage

Summary Response

How should CVS Health evolve from the “drugstore of your neighborhood” to the “drugstore of your future”?

Alternatives

A1. Kaizen (continuous improvement)

A2. Product development

A3. Market development

A4. Personalization (micro-targeting)

Criteria (include weights)

C1. Customer value: service, quality, image, and price (40%)

C2. Customer obsession (20%)

C3. Growth through related businesses (20%)

C4. Customer retention and customer lifetime value (20%)

Each alternative was analyzed by each criterion using a Customer Value Assessment Tool

Alternative 4 (A4): Personalization was selected. This is operationalized via: segmentation—move toward segment-of-1 marketing; geodemographics and lifestyle emphasis; predictive data analysis; relationship marketing; people, principles, and supply chain management; and exceptional customer service.

Implementation

Partner with leading medical school

Curbside pick-up

Pet pharmacy

E-newsletter for customers and employees

Employee incentive program

CVS beauty days

Expand to Latin America and Caribbean

Healthier/happier corner

Holiday toy drives/community outreach

*Source: A. Weinstein, Y. Rodriguez, K. Sims, R. Vergara, “The CVS Prescription for Superior Customer Value—A Case Study,” Back to the Future: Revisiting the Foundations of Marketing from Society for Marketing Advances, West Palm Beach, FL (November 2, 2018).

Results of Using the PACADI Framework

When faculty members at our respective institutions at Nova Southeastern University (NSU) and the University of North Carolina Wilmington have used the PACADI framework, our classes have been more structured and engaging. Students vigorously debate each element of their decision and note that this framework yields an “aha moment”—they learned something surprising in the case that led them to think differently about the problem and their proposed solution.

These lively discussions enhance individual and collective learning. As one external metric of this improvement, we have observed a 2.5 percent increase in student case grade performance at NSU since this framework was introduced.

Tips to Get Started

The PACADI approach works well in in-person, online, and hybrid courses. This is particularly important as more universities have moved to remote learning options. Because students have varied educational and cultural backgrounds, work experience, and familiarity with case analysis, we recommend that faculty members have students work on their first case using this new framework in small teams (two or three students). Additional analyses should then be solo efforts.

To use PACADI effectively in your classroom, we suggest the following:

Advise your students that your course will stress critical thinking and decision-making skills, not just course concepts and theory.

Use a varied mix of case studies. As marketing professors, we often address consumer and business markets; goods, services, and digital commerce; domestic and global business; and small and large companies in a single MBA course.

As a starting point, provide a short explanation (about 20 to 30 minutes) of the PACADI framework with a focus on the conceptual elements. You can deliver this face to face or through videoconferencing.

Give students an opportunity to practice the case analysis methodology via an ungraded sample case study. Designate groups of five to seven students to discuss the case and the six steps in breakout sessions (in class or via Zoom).

Ensure case analyses are weighted heavily as a grading component. We suggest 30–50 percent of the overall course grade.

Once cases are graded, debrief with the class on what they did right and areas needing improvement (30- to 40-minute in-person or Zoom session).

Encourage faculty teams that teach common courses to build appropriate instructional materials, grading rubrics, videos, sample cases, and teaching notes.

When selecting case studies, we have found that the best ones for PACADI analyses are about 15 pages long and revolve around a focal management decision. This length provides adequate depth yet is not protracted. Some of our tested and favorite marketing cases include Brand W , Hubspot , Kraft Foods Canada , TRSB(A) , and Whiskey & Cheddar .

Art Weinstein , Ph.D., is a professor of marketing at Nova Southeastern University, Fort Lauderdale, Florida. He has published more than 80 scholarly articles and papers and eight books on customer-focused marketing strategy. His latest book is Superior Customer Value—Finding and Keeping Customers in the Now Economy . Dr. Weinstein has consulted for many leading technology and service companies.

Herbert V. Brotspies , D.B.A., is an adjunct professor of marketing at Nova Southeastern University. He has over 30 years’ experience as a vice president in marketing, strategic planning, and acquisitions for Fortune 50 consumer products companies working in the United States and internationally. His research interests include return on marketing investment, consumer behavior, business-to-business strategy, and strategic planning.

John T. Gironda , Ph.D., is an assistant professor of marketing at the University of North Carolina Wilmington. His research has been published in Industrial Marketing Management, Psychology & Marketing , and Journal of Marketing Management . He has also presented at major marketing conferences including the American Marketing Association, Academy of Marketing Science, and Society for Marketing Advances.

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Did an Unorthodox Therapist Drive a Woman to Suicide?

“Case Study,” by Graeme Macrae Burnet, is a novel of found documents detailing troubled lives and shifting identities.

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By Christian Lorentzen

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CASE STUDY, by Graeme Macrae Burnet

To get to Primrose Hill from central London, you take the Tube to Chalk Farm Station, exit to your right toward a cafe and an off-license, and climb a path to an overpass above train tracks. The path is called, rather unassumingly, Bridge Approach, and a five-minute walk leads to Primrose Hill. I happened to live in these parts for three years, and I crossed the overpass twice a day most days. Just to the south is the Pembroke Castle pub, where Liam Gallagher of Oasis was once arrested, in 1998. Another neighborhood tippler, Kingsley Amis, favored the Queen’s at the corner of St. George’s Terrace, according to his biographer Zachary Leader, who printed his monthly tab. From my balcony I could see the phone box where Sylvia Plath would desperately call Ted Hughes at his lover’s flat in her last days. It is a quiet neighborhood, but one dense with intrigue and peopled by famous, messy and tortured artistic personages.

The events of Graeme Macrae Burnet’s fourth novel, “Case Study,” are set off by a suicide in the 1960s by a young woman named Veronica, who jumps from the Bridge Approach overpass and is struck by the 4:45 train to High Barnet. (I am not sure that High Barnet trains, rather than Edgware-bound ones, run on this track, nor that the overpass itself, rather than just the path that approaches it, is called Bridge Approach, but these are the sorts of possible slight inaccuracies that Burnet and his not entirely reliable narrators relish.) An investigation into Veronica’s death and the man who might have been responsible for it — her therapist, Arthur Collins Braithwaite, whose office is on Primrose Hill — forms the substance of the narrative. Like Burnet’s previous novel, “ His Bloody Project ” (2016), “Case Study” was nominated for the Booker Prize and consists largely of purportedly found documents.

The would-be Miss Marple of Burnet’s loopy detective story is Veronica’s unnamed younger sister, who, under the alias Rebecca Smyth, becomes Braithwaite’s patient to find out if he drove Veronica to take her own life. Rebecca details her five sessions in notebooks that decades later end up in the hands of a writer named GMB, our frame narrator, who is researching Braithwaite for a potential biography. Now cast into obscurity, the (fictional) therapist was once a figure of note, appearing on BBC chat shows and publishing the books “Untherapy,” a best seller, and “Kill Your Self,” which Rebecca calls “a jumble of incomprehensible sentences, each having no discernible relationship to its neighbors.” Still, we are told by GMB, “Kill Your Self” “captured the zeitgeist,” acquired for its author a cult following from which he drew a lucrative pool of patients, and “if anything, the impenetrability of certain passages only served to confirm the author’s genius.”

“Case Study” consists of a preface, in which GMB explains how he received the notebooks (from Rebecca’s cousin, who noticed a blog post by GMB on Braithwaite); the five notebooks themselves, one of which includes a chapter clipped from “Untherapy” about a patient who is clearly Veronica; five biographical chapters about Braithwaite by GMB, inserted between the notebooks; and a postscript, in which GMB ventures south to pay a visit to the Pembroke Castle. The elegant nested structure is one of the novel’s chief appeals. So is the contrast between Rebecca’s narrative voice, characterized by what GMB calls “a certain kooky élan,” and the cool tone of GMB’s Life of Braithwaite. What emerges is a comedy of identities tried on and discarded. Given the number of suicides that mark the story, it’s a comedy with dark underpinnings.

Rebecca lives with her father, a retired engineer, and their housekeeper, and works as a receptionist for a talent agent. Her mother died when she was 15, falling off a cliff before her eyes, during a family holiday in Devon. Given that Rebecca is the only witness to the fall, and that she admits to fantasizing about pushing someone off the cliff the sentence before recounting her mother’s death, we can’t help suspecting that she might have done it herself. But we have no more reason to doubt it than the rest of her story, and that’s part of the fun: The whole tale might be a hoax.

Unlike Veronica, who was a doctoral student in mathematics at Cambridge, Rebecca is not very ambitious. She’s an erstwhile fiction writer, having given up on writing after the one story she published in Women’s Journal didn’t have editors banging down the door for more. She is a homebody, happy to tend to her father and not be a “Modern Independent Woman.” She attests to being a virgin, and so becoming Rebecca Smyth means becoming someone else: the sort of woman who puts on lipstick, attends glamorous parties and drinks gin with gentlemen at the Pembridge Castle (as she calls the Pembroke Castle). Since she is not really that sort of woman, drinking even a little gin causes her to vomit in the bathroom the first time she tries it.

Braithwaite is also someone who puts on new identities, but at the same time he’s a recognizable English type: the humble boy from northern England who goes down to Oxford after the war and reinvents himself as a kind of romantic rogue. “Case Study” has a lot in common with the novels of Vladimir Nabokov and Roberto Bolaño, in which invented characters pass through tumultuous episodes of literary history that never quite happened, though it seems as if they should have. Braithwaite brushes against real-life figures, engaging in hostile correspondence with the psychiatrist R.D. Laing and becoming a confidant of the actor Dirk Bogarde. After an overblown scandal consumes his therapeutic practice and sets him off on a bender, he winds up back at the home of his father (another suicide) in the North, where he writes his unpublished memoir, “My Self and Other Strangers.” It is the source, we are told, of GMB’s biographical reconstructions.

“Case Study” is a diverting novel, overflowing with clever plays on and inversions of tropes of English intellectual and social life during the postwar decades. As such, it is not exactly an excursion into undiscovered literary terrain. Reading Burnet’s doubly mediated metafiction of North London neurotics and decadents, I often longed to turn back to the shelf for the real thing: fictions by Doris Lessing, Kingsley and Martin Amis, Muriel Spark, Jenny Diski, Julian Barnes, Alan Hollinghurst, Zadie Smith or Rachel Cusk; biographies of Plath and Hughes; films of kitchen-sink realism starring Bogarde and Laurence Harvey, with scripts by Harold Pinter; or even the documentaries of Adam Curtis, in which Laing often makes a cameo. It’s a compliment to put “Case Study” in that company and no insult to say that Burnet must have done his homework to get there. I imagine he lives in a flat full of piles of yellowing copies of The Times Literary Supplement, every issue a catalog of obscurities from across time. Humble children from the provinces who want to reinvent themselves have to get the stuff of their daydreams from somewhere.

Christian Lorentzen’s work has appeared in The London Review of Books, Bookforum and Harper’s Magazine.

CASE STUDY | By Graeme Macrae Burnet | 278 pp. | Biblioasis | Paperback, $17.95

An earlier version of this review misstated R.D. Laing’s profession. He was a psychiatrist, not a psychologist.

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• Published: 17 February 2022

Effectiveness of problem-based learning methodology in undergraduate medical education: a scoping review

• Joan Carles Trullàs   ORCID: orcid.org/0000-0002-7380-3475 1 , 2 , 3 ,
• Carles Blay   ORCID: orcid.org/0000-0003-3962-5887 1 , 4 ,
• Elisabet Sarri   ORCID: orcid.org/0000-0002-2435-399X 3 &
• Ramon Pujol   ORCID: orcid.org/0000-0003-2527-385X 1  

BMC Medical Education volume  22 , Article number:  104 ( 2022 ) Cite this article

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Problem-based learning (PBL) is a pedagogical approach that shifts the role of the teacher to the student (student-centered) and is based on self-directed learning. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness of the method is still under discussion. The author’s purpose was to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs.

The authors applied the Arksey and O’Malley framework to undertake a scoping review. The search was carried out in February 2021 in PubMed and Web of Science including all publications in English and Spanish with no limits on publication date, study design or country of origin.

The literature search identified one hundred and twenty-four publications eligible for this review. Despite the fact that this review included many studies, their design was heterogeneous and only a few provided a high scientific evidence methodology (randomized design and/or systematic reviews with meta-analysis). Furthermore, most were single-center experiences with small sample size and there were no large multi-center studies. PBL methodology obtained a high level of satisfaction, especially among students. It was more effective than other more traditional (or lecture-based methods) at improving social and communication skills, problem-solving and self-learning skills. Knowledge retention and academic performance weren’t worse (and in many studies were better) than with traditional methods. PBL was not universally widespread, probably because requires greater human resources and continuous training for its implementation.

PBL is an effective and satisfactory methodology for medical education. It is likely that through PBL medical students will not only acquire knowledge but also other competencies that are needed in medical professionalism.

Peer Review reports

There has always been enormous interest in identifying the best learning methods. In the mid-twentieth century, US educator Edgar Dale proposed which actions would lead to deeper learning than others and published the well-known (and at the same time controversial) “Cone of Experience or Cone of Dale”. At the apex of the cone are oral representations (verbal descriptions, written descriptions, etc.) and at the base is direct experience (based on a person carrying out the activity that they aim to learn), which represents the greatest depth of our learning. In other words, each level of the cone corresponds to various learning methods. At the base are the most effective, participative methods (what we do and what we say) and at the apex are the least effective, abstract methods (what we read and what we hear) [ 1 ]. In 1990, psychologist George Miller proposed a framework pyramid to assess clinical competence. At the lowest level of the pyramid is knowledge (knows), followed by the competence (knows how), execution (shows how) and finally the action (does) [ 2 ]. Both Miller’s pyramid and Dale’s cone propose a very efficient way of training and, at the same time, of evaluation. Miller suggested that the learning curve passes through various levels, from the acquisition of theoretical knowledge to knowing how to put this knowledge into practice and demonstrate it. Dale stated that to remember a high percentage of the acquired knowledge, a theatrical representation should be carried out or real experiences should be simulated. It is difficult to situate methodologies such as problem-based learning (PBL), case-based learning (CBL) and team-based learning (TBL) in the context of these learning frameworks.

In the last 50 years, various university education models have emerged and have attempted to reconcile teaching with learning, according to the principle that students should lead their own learning process. Perhaps one of the most successful models is PBL that came out of the English-speaking environment. There are many descriptions of PBL in the literature, but in practice there is great variability in what people understand by this methodology. The original conception of PBL as an educational strategy in medicine was initiated at McMaster University (Canada) in 1969, leaving aside the traditional methodology (which is often based on lectures) and introducing student-centered learning. The new formulation of medical education proposed by McMaster did not separate the basic sciences from the clinical sciences, and partially abandoned theoretical classes, which were taught after the presentation of the problem. In its original version, PBL is a methodology in which the starting point is a problem or a problematic situation. The situation enables students to develop a hypothesis and identify learning needs so that they can better understand the problem and meet the established learning objectives [ 3 , 4 ]. PBL is taught using small groups (usually around 8–10 students) with a tutor. The aim of the group sessions is to identify a problem or scenario, define the key concepts identified, brainstorm ideas and discuss key learning objectives, research these and share this information with each other at subsequent sessions. Tutors are used to guide students, so they stay on track with the learning objectives of the task. Contemporary medical education also employs other small group learning methods including CBL and TBL. Characteristics common to the pedagogy of both CBL and TBL include the use of an authentic clinical case, active small-group learning, activation of existing knowledge and application of newly acquired knowledge. In CBL students are encouraged to engage in peer learning and apply new knowledge to these authentic clinical problems under the guidance of a facilitator. CBL encourages a structured and critical approach to clinical problem-solving, and, in contrast to PBL, is designed to allow the facilitator to correct and redirect students [ 5 ]. On the other hand, TBL offers a student-centered, instructional approach for large classes of students who are divided into small teams of typically five to seven students to solve clinically relevant problems. The overall similarities between PBL and TBL relate to the use of professionally relevant problems and small group learning, while the main difference relates to one teacher facilitating interactions between multiple self-managed teams in TBL, whereas each small group in PBL is facilitated by one teacher. Further differences are related to mandatory pre-reading assignments in TBL, testing of prior knowledge in TBL and activating prior knowledge in PBL, teacher-initiated clarifying of concepts that students struggled with in TBL versus students-generated issues that need further study in PBL, inter-team discussions in TBL and structured feedback and problems with related questions in TBL [ 6 ].

In the present study we have focused on PBL methodology, and, as attractive as the method may seem, we should consider whether it is really useful and effective as a learning method. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness (in terms of academic performance and/or skill improvement) of the method is still under discussion. This is due partly to the methodological difficulty in comparing PBL with traditional curricula based on lectures. To our knowledge, there is no systematic scoping review in the literature that has analyzed these aspects.

The main motivation for carrying out this research and writing this article was scientific but also professional interest. We believe that reviewing the state of the art of this methodology once it was already underway in our young Faculty of Medicine, could allow us to know if we were on the right track and if we should implement changes in the training of future doctors.

The primary goal of this study was to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs. As the intention was to synthesize the scattered evidence available, the option was to conduct a scoping review. A scoping study tends to address broader topics where many different study designs might be applicable. Scoping studies may be particularly relevant to disciplines, such as medical education, in which the paucity of randomized controlled trials makes it difficult for researchers to undertake systematic reviews [ 7 , 8 ]. Even though the scoping review methodology is not widely used in medical education, it is well established for synthesizing heterogeneous research evidence [ 9 ].

The specific aims were: 1) to determine the effectiveness of PBL in academic performance (learning and retention of knowledge) in medical education; 2) to determine the effectiveness of PBL in other skills (social and communication skills, problem solving or self-learning) in medical education; 3) to know the level of satisfaction perceived by the medical students (and/or tutors) when they are taught with the PBL methodology (or when they teach in case of tutors).

This review was guided by Arksey and O’Malley’s methodological framework for conducting scoping reviews. The five main stages of the framework are: (1) identifying the research question; (2) ascertaining relevant studies; (3) determining study selection; (4) charting the data; and (5) collating, summarizing and reporting the results [ 7 ]. We reported our process according to the PRISMA Extension for Scoping Reviews [ 10 ].

Stage 1: Identifying the research question

With the goals of the study established, the four members of the research team established the research questions. The primary research question was “What is the effectiveness of PBL methodology for learning in undergraduate medicine?” and the secondary question “What is the perception and satisfaction of medical students and tutors in relation to PBL methodology?”.

Stage 2: Identifying relevant studies

After the research questions and a search strategy were defined, the searches were conducted in PubMed and Web of Science using the MeSH terms “problem-based learning” and “Medicine” (the Boolean operator “AND” was applied to the search terms). No limits were set on language, publication date, study design or country of origin. The search was carried out on 14th February 2021. Citations were uploaded to the reference manager software Mendeley Desktop (version 1.19.8) for title and abstract screening, and data characterization.

Stage 3: Study selection

The searching strategy in our scoping study generated a total of 2399 references. The literature search and screening of title, abstract and full text for suitability was performed independently by one author (JCT) based on predetermined inclusion criteria. The inclusion criteria were: 1) PBL methodology was the major research topic; 2) participants were undergraduate medical students or tutors; 3) the main outcome was academic performance (learning and knowledge retention); 4) the secondary outcomes were one of the following: social and communication skills, problem solving or self-learning and/or student/tutor satisfaction; 5) all types of studies were included including descriptive papers, qualitative, quantitative and mixed studies methods, perspectives, opinion, commentary pieces and editorials. Exclusion criteria were studies including other types of participants such as postgraduate medical students, residents and other health non-medical specialties such as pharmacy, veterinary, dentistry or nursing. Studies published in languages other than Spanish and English were also excluded. Situations in which uncertainty arose, all authors (CB, ES, RP) discussed the publication together to reach a final consensus. The outcomes of the search results and screening are presented in Fig.  1 . One-hundred and twenty-four articles met the inclusion criteria and were included in the final analysis.

Study flow PRISMA diagram. Details the review process through the different stages of the review; includes the number of records identified, included and excluded

Stage 4: Charting the data

A data extraction table was developed by the research team. Data extracted from each of the 124 publications included general publication details (year, author, and country), sample size, study population, design/methodology, main and secondary outcomes and relevant results and/or conclusions. We compiled all data into a single spreadsheet in Microsoft Excel for coding and analysis. The characteristics and the study subject of the 124 articles included in this review are summarized in Tables 1 and 2 . The detailed results of the Microsoft Excel file is also available in Additional file 1 .

Stage 5: Collating, summarizing and reporting the results

As indicated in the search strategy (Fig.  1 ) this review resulted in the inclusion of 124 publications. Publication years of the final sample ranged from 1990 to 2020, the majority of the publications (51, 41%) were identified for the years 2010–2020 and the years in which there were more publications were 2001, 2009 and 2015. Countries from the six continents were represented in this review. Most of the publications were from Asia (especially China and Saudi Arabia) and North America followed by Europe, and few studies were from Africa, Oceania and South America. The country with more publications was the United States of America ( n  = 27). The most frequent designs of the selected studies were surveys or questionnaires ( n  = 45) and comparative studies ( n  = 48, only 16 were randomized) with traditional or lecture-based learning methodologies (in two studies the comparison was with simulation) and the most frequently measured outcomes were academic performance followed by student satisfaction (48 studies measured more than one outcome). The few studies with the highest level of scientific evidence (systematic review and meta-analysis and randomized studies) were conducted mostly in Asian countries (Tables  1 and 2 ). The study subject was specified in 81 publications finding a high variability but at the same time great representability of almost all disciplines of the medical studies.

The sample size was available in 99 publications and the median [range] of the participants was 132 [14–2061]. According to study population, there were more participants in the students’ focused studies (median 134 and range 16–2061) in comparison with the tutors’ studies (median 53 and range 14–494).

Finally, after reviewing in detail the measured outcomes (main and secondary) according to the study design (Table 2 and Additional file 1 ) we present a narrative overview and a synthesis of the main findings.

Main outcome: academic performance (learning and knowledge retention)

Seventy-one of the 124 publications had learning and/or knowledge retention as a measured outcome, most of them ( n  = 45) were comparative studies with traditional or lecture-based learning and 16 were randomized. These studies were varied in their methodology, were performed in different geographic zones, and normally analyzed the experience of just one education center. Most studies ( n  = 49) reported superiority of PBL in learning and knowledge acquisition [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] but there was no difference between traditional and PBL curriculums in another 19 studies [ 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. Only three studies reported that PBL was less effective [ 79 , 80 , 81 ], two of them were randomized (in one case favoring simulation-based learning [ 80 ] and another favoring lectures [ 81 ]) and the remaining study was based on tutors’ opinion rather than real academic performance [ 79 ]. It is noteworthy that the four systematic reviews and meta-analysis included in this scoping review, all carried out in China, found that PBL was more effective than lecture-based learning in improving knowledge and other skills (clinical, problem-solving, self-learning and collaborative) [ 40 , 51 , 53 , 58 ]. Another relevant example of the superiority of the PBL method over the traditional method is the experience reported by Hoffman et al. from the University of Missouri-Columbia. The authors analyzed the impact of implementing the PBL methodology in its Faculty of Medicine and revealed an improvement in the academic results that lasted for over a decade [ 31 ].

Secondary outcomes

Social and communication skills.

We found five studies in this scoping review that focused on these outcomes and all of them described that a curriculum centered on PBL seems to instill more confidence in social and communication skills among students. Students perceived PBL positively for teamwork, communication skills and interpersonal relations [ 44 , 45 , 67 , 75 , 82 ].

Student satisfaction

Sixty publications analyzed student satisfaction with PBL methodology. The most frequent methodology were surveys or questionnaires (30 studies) followed by comparative studies with traditional or lecture-based methodology (19 studies, 7 of them were randomized). Almost all the studies (51) have shown that PBL is generally well-received [ 11 , 13 , 18 , 19 , 20 , 21 , 22 , 26 , 29 , 34 , 37 , 39 , 41 , 42 , 46 , 50 , 56 , 58 , 63 , 64 , 66 , 78 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ] but in 9 studies the overall satisfaction scores for the PBL program were neutral [ 76 , 111 , 112 , 113 , 114 , 115 , 116 ] or negative [ 117 , 118 ]. Some factors that have been identified as key components for PBL to be successful include: a small group size, the use of scenarios of realistic cases and good management of group dynamics. Despite a mostly positive assessment of the PBL methodology by the students, there were some negative aspects that could be criticized or improved. These include unclear communication of the learning methodology, objectives and assessment method; bad management and organization of the sessions; tutors having little experience of the method; and a lack of standardization in the implementation of the method by the tutors.

Tutor satisfaction

There are only 15 publications that analyze the satisfaction of tutors, most of them surveys or questionnaires [ 85 , 88 , 92 , 98 , 108 , 110 , 119 ]. In comparison with the satisfaction of the students, here the results are more neutral [ 112 , 113 , 115 , 120 , 121 ] and even unfavorable to the PBL methodology in two publications [ 117 , 122 ]. PBL teaching was favored by tutors when the institutions train them in the subject, when there was administrative support and adequate infrastructure and coordination [ 123 ]. In some experiences, the PBL modules created an unacceptable toll of anxiety, unhappiness and strained relations.

Other skills (problem solving and self-learning)

The effectiveness of the PBL methodology has also been explored in other outcomes such as the ability to solve problems and to self-directed learning. All studies have shown that PBL is more effective than lecture-based learning in problem-solving and self-learning skills [ 18 , 24 , 40 , 48 , 67 , 75 , 93 , 104 , 124 ]. One single study found a poor accuracy of the students’ self-assessment when compared to their own performance [ 125 ]. In addition, there are studies that support PBL methodology for integration between basic and clinical sciences [ 126 ].

Finally, other publications have reported the experience of some faculties in the implementation of the PBL methodology. Different experiences have demonstrated that it is both possible and feasible to shift from a traditional curriculum to a PBL program, recognizing that PBL methodology is complex to plan and structure, needs a large number of human and material resources, requiring an immense teacher effort [ 28 , 31 , 94 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. In addition, and despite its cost implication, a PBL curriculum can be successfully implemented in resource-constrained settings [ 134 , 135 ].

We conducted this scoping review to explore the effectiveness and satisfaction of PBL methodology for teaching in undergraduate medicine and, to our knowledge, it is the only study of its kind (systematic scoping review) that has been carried out in the last years. Similarly, Vernon et al. conducted a meta-analysis of articles published between 1970 and 1992 and their results generally supported the superiority of the PBL approach over more traditional methods of medical education [ 136 ]. PBL methodology is implemented in medical studies on the six continents but there is more experience (or at least more publications) from Asian countries and North America. Despite its apparent difficulties on implementation, a PBL curriculum can be successfully implemented in resource-constrained settings [ 134 , 135 ]. Although it is true that the few studies with the highest level of scientific evidence (randomized studies and meta-analysis) were carried out mainly in Asian countries (and some in North America and Europe), there were no significant differences in the main results according to geographical origin.

In this scoping review we have included a large number of publications that, despite their heterogeneity, tend to show favorable results for the usefulness of the PBL methodology in teaching and learning medicine. The results tend to be especially favorable to PBL methodology when it is compared with traditional or lecture-based teaching methods, but when compared with simulation it is not so clear. There are two studies that show neutral [ 71 ] or superior [ 80 ] results to simulation for the acquisition of specific clinical skills. It seems important to highlight that the four meta-analysis included in this review, which included a high number of participants, show results that are clearly favorable to the PBL methodology in terms of knowledge, clinical skills, problem-solving, self-learning and satisfaction [ 40 , 51 , 53 , 58 ].

Regarding the level of satisfaction described in the surveys or questionnaires, the overall satisfaction rate was higher in the PBL students when compared with traditional learning students. Students work in small groups, allowing and promoting teamwork and facilitating social and communication skills. As sessions are more attractive and dynamic than traditional classes, this could lead to a greater degree of motivation for learning.

These satisfaction results are not so favorable when tutors are asked and this may be due to different reasons; first, some studies are from the 90s, when the methodology was not yet fully implemented; second, the number of tutors included in these studies is low; and third, and perhaps most importantly, the complaints are not usually due to the methodology itself, but rather due to lack of administrative support, and/or work overload. PBL methodology implies more human and material resources. The lack of experience in guided self-learning by lecturers requires more training. Some teachers may not feel comfortable with the method and therefore do not apply it correctly.

Despite how effective and/or attractive the PBL methodology may seem, some (not many) authors are clearly detractors and have published opinion articles with fierce criticism to this methodology. Some of the arguments against are as follows: clinical problem solving is the wrong task for preclinical medical students, self-directed learning interpreted as self-teaching is not appropriate in undergraduate medical education, relegation to the role of facilitators is a misuse of the faculty, small-group experience is inherently variable and sometimes dysfunctional, etc. [ 137 ].

In light of the results found in our study, we believe that PBL is an adequate methodology for the training of future doctors and reinforces the idea that the PBL should have an important weight in the curriculum of our medical school. It is likely that training through PBL, the doctors of the future will not only have great knowledge but may also acquire greater capacity for communication, problem solving and self-learning, all of which are characteristics that are required in medical professionalism. For this purpose, Koh et al. analyzed the effect that PBL during medical school had on physician competencies after graduation, finding a positive effect mainly in social and cognitive dimensions [ 138 ].

Despite its defects and limitations, we must not abandon this methodology and, in any case, perhaps PBL should evolve, adapt, and improve to enhance its strengths and improve its weaknesses. It is likely that the new generations, trained in schools using new technologies and methodologies far from lectures, will feel more comfortable (either as students or as tutors) with methodologies more like PBL (small groups and work focused on problems or projects). It would be interesting to examine the implementation of technologies and even social media into PBL sessions, an issue that has been poorly explorer [ 139 ].

Limitations

Scoping reviews are not without limitations. Our review includes 124 articles from the 2399 initially identified and despite our efforts to be as comprehensive as possible, we may have missed some (probably few) articles. Even though this review includes many studies, their design is very heterogeneous, only a few include a large sample size and high scientific evidence methodology. Furthermore, most are single-center experiences and there are no large multi-center studies. Finally, the frequency of the PBL sessions (from once or twice a year to the whole curriculum) was not considered, in part, because most of the revised studies did not specify this information. This factor could affect the efficiency of PBL and the perceptions of students and tutors about PBL. However, the adoption of a scoping review methodology was effective in terms of summarizing the research findings, identifying limitations in studies’ methodologies and findings and provided a more rigorous vision of the international state of the art.

Conclusions

This systematic scoping review provides a broad overview of the efficacy of PBL methodology in undergraduate medicine teaching from different countries and institutions. PBL is not a new teaching method given that it has already been 50 years since it was implemented in medicine courses. It is a method that shifts the leading role from teachers to students and is based on guided self-learning. If it is applied properly, the degree of satisfaction is high, especially for students. PBL is more effective than traditional methods (based mainly on lectures) at improving social and communication skills, problem-solving and self-learning skills, and has no worse results (and in many studies better results) in relation to academic performance. Despite that, its use is not universally widespread, probably because it requires greater human resources and continuous training for its implementation. In any case, more comparative and randomized studies and/or other systematic reviews and meta-analysis are required to determine which educational strategies could be most suitable for the training of future doctors.

Abbreviations

• Problem-based learning

Case-based learning

Team-based learning

References:

Dale E. Methods for analyzing the content of motion pictures. J Educ Sociol. 1932;6:244–50.

Google Scholar  

Miller GE. The assessment of clinical skills/competence/performance. Acad Med. 1990;65(9 Suppl):S63–7. https://doi.org/10.1097/00001888-199009000-00045 .

Article   Google Scholar  

Bodagh N, Bloomfield J, Birch P, Ricketts W. Problem-based learning: a review. Br J Hosp Med (Lond). 2017;78:C167–70. https://doi.org/10.12968/hmed.2017.78.11.C167 .

- Branda LA. El abc del ABP: Lo esencial del aprendizaje basado en problemas. In: Fundación Dr. Esteve, Cuadernos de la fundación Dr. Antonio Esteve nº27: El aprendizaje basado en problemas en sus textos, pp.1–16. 2013. Barcelona.

Burgess A, Matar E, Roberts C, et al. Scaffolding medical student knowledge and skills: team-based learning (TBL) and case-based learning (CBL). BMC Med Educ. 2021;21:238. https://doi.org/10.1186/s12909-021-02638-3 .

Dolmans D, Michaelsen L, van Merriënboer J, van der Vleuten C. Should we choose between problem-based learning and team-based learning? No, combine the best of both worlds! Med Teach. 2015;37:354–9. https://doi.org/10.3109/0142159X.2014.948828 .

Arksey H, O’Malley L. Scoping studies: towards a methodological framework. In J Soc Res Methodol. 2005;8:19–32. https://doi.org/10.1080/1364557032000119616 .

Levac D, Colquhoun H, O’Brien KK. Scoping studies: advancing the methodology. Implement Sci. 2010;5:69. https://doi.org/10.1186/1748-5908-5-69 .

Pham MT, Rajić A, Greig JD, Sargeant JM, Papadopoulos A, McEwen SA. A scoping review of scoping reviews: advancing the approach and enhancing the consistency. Res Synth Methods. 2014;5:371–85. https://doi.org/10.1002/jrsm.1123 .

Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169:467–73. https://doi.org/10.7326/M18-0850 .

Sokas RK, Diserens D, Johnston MA. Integrating occupational-health into the internal medicine clerkship using problem-based learning. Clin Res. 1990;38:A735.

Richards BF, Ober KP, Cariaga-Lo L, et al. Ratings of students’ performances in a third-year internal medicine clerkship: a comparison between problem-based and lecture-based curricula. Acad Med. 1996;71:187–9. https://doi.org/10.1097/00001888-199602000-00028 .

Gresham CL, Philp JR. Problem-based learning in clinical medicine. Teach Learn Med. 1996;8:111–5. https://doi.org/10.1080/10401339609539776 .

Hill J, Rolfe IE, Pearson SA, Heathcote A. Do junior doctors feel they are prepared for hospital practice? A study of graduates from traditional and non-traditional medical schools. Med Educ. 1998;32:19–24. https://doi.org/10.1046/j.1365-2923.1998.00152.x .

Blake RL, Parkison L. Faculty evaluation of the clinical performances of students in a problem-based learning curriculum. Teach Learn Med. 1998;10:69–73. https://doi.org/10.1207/S15328015TLM1002\_3 .

Hmelo CE. Problem-based learning: effects on the early acquisition of cognitive skill in medicine. J Learn Sc. 1998;7:173–208. https://doi.org/10.1207/s15327809jls0702\_2 .

Finch PN. The effect of problem-based learning on the academic performance of students studying podiatric medicine in Ontario. Med Educ. 1999;33:411–7.

Casassus P, Hivon R, Gagnayre R, d’Ivernois JF. An initial experiment in haematology instruction using the problem-based learning method in third-year medical training in France. Hematol Cell Ther. 1999;41:137–44. https://doi.org/10.1007/s00282-999-0137-0 .

Purdy RA, Benstead TJ, Holmes DB, Kaufman DM. Using problem-based learning in neurosciences education for medical students. Can J Neurol Sci. 1999;26:211–6. https://doi.org/10.1017/S0317167100000287 .

Farrell TA, Albanese MA, Pomrehn PRJ. Problem-based learning in ophthalmology: a pilot program for curricular renewal. Arch Ophthalmol. 1999;117:1223–6. https://doi.org/10.1001/archopht.117.9.1223 .

Curtis JA, Indyk D, Taylor B. Successful use of problem-based learning in a third-year pediatric clerkship. Ambul Pediatr. 2001;1:132–5. https://doi.org/10.1367/1539-4409(2001)001%3c0132:suopbl%3e2.0.co;2 .

Trevena LJ, Clarke RM. Self-directed learning in population health. a clinically relevant approach for medical students. Am J Prev Med. 2002;22:59–65. https://doi.org/10.1016/s0749-3797(01)00395-6 .

Astin J, Jenkins T, Moore L. Medical students’ perspective on the teaching of medical statistics in the undergraduate medical curriculum. Stat Med. 2002;21:1003–7. https://doi.org/10.1002/sim.1132 .

Whitfield CR, Manger EA, Zwicker J, Lehman EB. Differences between students in problem-based and lecture-based curricula measured by clerkship performance ratings at the beginning of the third year. Teach Learn Med. 2002;14:211–7. https://doi.org/10.1207/S15328015TLM1404\_2 .

McParland M, Noble LM, Livingston G. The effectiveness of problem-based learning compared to traditional teaching in undergraduate psychiatry. Med Educ. 2004;38:859–67. https://doi.org/10.1111/j.1365-2929.2004.01818.x .

Casey PM, Magrane D, Lesnick TG. Improved performance and student satisfaction after implementation of a problem-based preclinical obstetrics and gynecology curriculum. Am J Obstet Gynecol. 2005;193:1874–8. https://doi.org/10.1016/j.ajog.2005.07.061 .

Gurpinar E, Musal B, Aksakoglu G, Ucku R. Comparison of knowledge scores of medical students in problem-based learning and traditional curriculum on public health topics. BMC Med Educ. 2005;5:7. https://doi.org/10.1186/1472-6920-5-7 .

Tamblyn R, Abrahamowicz M, Dauphinee D, et al. Effect of a community oriented problem based learning curriculum on quality of primary care delivered by graduates: historical cohort comparison study. BMJ. 2005;331:1002. https://doi.org/10.1136/bmj.38636.582546.7C .

Abu-Hijleh MF, Chakravarty M, Al-Shboul Q, Kassab S, Hamdy H. Integrating applied anatomy in surgical clerkship in a problem-based learning curriculum. Surg Radiol Anat. 2005;27:152–7. https://doi.org/10.1007/s00276-004-0293-4 .

Distlehorst LH, Dawson E, Robbs RS, Barrows HS. Problem-based learning outcomes: the glass half-full. Acad Med. 2005;80:294–9. https://doi.org/10.1097/00001888-200503000-00020 .

Hoffman K, Hosokawa M, Blake R Jr, Headrick L, Johnson G. Problem-based learning outcomes: ten years of experience at the University of Missouri-Columbia school of medicine. Acad Med. 2006;81:617–25. https://doi.org/10.1097/01.ACM.0000232411.97399.c6 .

Kong J, Li X, Wang Y, Sun W, Zhang J. Effect of digital problem-based learning cases on student learning outcomes in ophthalmology courses. Arch Ophthalmol. 2009;127:1211–4. https://doi.org/10.1001/archophthalmol.2009.110 .

Tsou KI, Cho SL, Lin CS, et al. Short-term outcomes of a near-full PBL curriculum in a new Taiwan medical school. Kaohsiung J Med Sci. 2009;25:282–93. https://doi.org/10.1016/S1607-551X(09)70075-0 .

Wang J, Zhang W, Qin L, et al. Problem-based learning in regional anatomy education at Peking University. Anat Sci Educ. 2010;3:121–6. https://doi.org/10.1002/ase.151 .

Abou-Elhamd KA, Rashad UM, Al-Sultan AI. Applying problem-based learning to otolaryngology teaching. J Laryngol Otol. 2011;125:117–20. https://doi.org/10.1017/S0022215110001702 .

Urrutia Aguilar ME, Hamui-Sutton A, Castaneda Figueiras S, van der Goes TI, Guevara-Guzman R. Impact of problem-based learning on the cognitive processes of medical students. Gac Med Mex. 2011;147:385–93.

Tian J-H, Yang K-H, Liu A-P. Problem-based learning in evidence-based medicine courses at Lanzhou University. Med Teach. 2012;34:341. https://doi.org/10.3109/0142159X.2011.531169 .

Hoover CR, Wong CC, Azzam A. From primary care to public health: using problem-based Learning and the ecological model to teach public health to first year medical students. J Community Health. 2012;37:647–52. https://doi.org/10.1007/s10900-011-9495-y .

Li J, Li QL, Li J, et al. Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China. Med Teach. 2013;35:e963–70. https://doi.org/10.3109/0142159X.2012.719651 .

Ding X, Zhao L, Chu H, et al. Assessing the effectiveness of problem-based learning of preventive medicine education in China. Sci Rep. 2014;4:5126. https://doi.org/10.1038/srep05126 .

Meo SA. Undergraduate medical student’s perceptions on traditional and problem based curricula: pilot study. J Pak Med Assoc. 2014;64:775–9.

Khoshnevisasl P, Sadeghzadeh M, Mazloomzadeh S, Hashemi Feshareki R, Ahmadiafshar A. Comparison of problem-based learning with lecture-based learning. Iran Red Crescent Med J. 2014;16: e5186. https://doi.org/10.5812/ircmj.5186 .

Al-Drees AA, Khalil MS, Irshad M, Abdulghani HM. Students’ perception towards the problem based learning tutorial session in a system-based hybrid curriculum. Saudi Med J. 2015;36:341–8. https://doi.org/10.15537/smj.2015.3.10216 .

Al-Shaikh G, Al Mussaed EM, Altamimi TN, Elmorshedy H, Syed S, Habib F. Perception of medical students regarding problem based learning. Kuwait Med J. 2015;47:133–8.

Hande S, Mohammed CA, Komattil R. Acquisition of knowledge, generic skills and attitudes through problem-based learning: student perspectives in a hybrid curriculum. J Taibah Univ Medical Sci. 2015;10:21–5. https://doi.org/10.1016/j.jtumed.2014.01.008 .

González Mirasol E, Gómez García MT, Lobo Abascal P, Moreno Selva R, Fuentes Rozalén AM, González MG. Analysis of perception of training in graduates of the faculty of medicine at Universidad de Castilla-Mancha. Eval Program Plann. 2015;52:169–75. https://doi.org/10.1016/j.evalprogplan.2015.06.001 .

Yanamadala M, Kaprielian VS, O’Connor Grochowski C, Reed T, Heflin MT. A problem-based learning curriculum in geriatrics for medical students. Gerontol Geriatr Educ. 2018;39:122–31. https://doi.org/10.1080/02701960.2016.1152268 .

Balendran K, John L. Comparison of learning outcomes in problem based learning and lecture based learning in teaching forensic medicine. J Evol Med Dent Sci. 2017;6:89–92. https://doi.org/10.14260/jemds/2017/22 .

Chang H-C, Wang N-Y, Ko W-R, Yu Y-T, Lin L-Y, Tsai H-F. The effectiveness of clinical problem-based learning model of medico-jurisprudence education on general law knowledge for obstetrics/gynecological interns. Taiwan J Obstet Gynecol. 2017;56:325–30. https://doi.org/10.1016/j.tjog.2017.04.011 .

Eltony SA, El-Sayed NH, El-Araby SE-S, Kassab SE. Implementation and evaluation of a patient safety course in a problem-based learning program. Educ Heal. 2017;30:44–9. https://doi.org/10.4103/1357-6283.210512 .

Zhang S, Xu J, Wang H, Zhang D, Zhang Q, Zou L. Effects of problem-based learning in Chinese radiology education: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97: e0069. https://doi.org/10.1097/MD.0000000000010069 .

Hincapie Parra DA, Ramos Monobe A, Chrino-Barcelo V. Problem based learning as an active learning strategy and its impact on academic performance and critical thinking of medical students. Rev Complut Educ. 2018;29:665–81. https://doi.org/10.5209/RCED.53581 .

Ma Y, Lu X. The effectiveness of problem-based learning in pediatric medical education in China: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98: e14052. https://doi.org/10.1097/MD.0000000000014052 .

Berger C, Brinkrolf P, Ertmer C, et al. Combination of problem-based learning with high-fidelity simulation in CPR training improves short and long-term CPR skills: a randomised single blinded trial. BMC Med Educ. 2019;19:180. https://doi.org/10.1186/s12909-019-1626-7 .

Aboonq M, Alquliti A, Abdulmonem I, Alpuq N, Jalali K, Arabi S. Students’ approaches to learning and perception of learning environment: a comparison between traditional and problem-based learning medical curricula. Indo Am J Pharm Sci. 2019;6:3610–9. https://doi.org/10.5281/zenodo.2562660 .

Li X, Xie F, Li X, et al. Development, application, and evaluation of a problem-based learning method in clinical laboratory education. Clin Chim ACTA. 2020;510:681–4. https://doi.org/10.1016/j.cca.2020.08.037 .

Zhao W, He L, Deng W, Zhu J, Su A, Zhang Y. The effectiveness of the combined problem-based learning (PBL) and case-based learning (CBL) teaching method in the clinical practical teaching of thyroid disease. BMC Med Educ. 2020;20:381. https://doi.org/10.1186/s12909-020-02306 .

Liu C-X, Ouyang W-W, Wang X-W, Chen D, Jiang Z-L. Comparing hybrid problem-based and lecture learning (PBL plus LBL) with LBL pedagogy on clinical curriculum learning for medical students in China: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2020;99:e19687. https://doi.org/10.1097/MD.0000000000019687 .

Margolius SW, Papp KK, Altose MD, Wilson-Delfosse AL. Students perceive skills learned in pre-clerkship PBL valuable in core clinical rotations. Med Teach. 2020;42:902–8. https://doi.org/10.1080/0142159X.2020.1762031 .

Schwartz RW, Donnelly MB, Nash PP, Young B. Developing students cognitive skills in a problem-based surgery clerkship. Acad Med. 1992;67:694–6. https://doi.org/10.1097/00001888-199210000-00016 .

Mennin SP, Friedman M, Skipper B, Kalishman S, Snyder J. Performances on the NBME-I, NBME-II, and NBME-III by medical-students in the problem-based learning and conventional tracks at the university-of-new-mexico. Acad Med. 1993;68:616–24. https://doi.org/10.1097/00001888-199308000-00012 .

Kaufman DM, Mann KV. Comparing achievement on the medical council of Canada qualifying examination part I of students in conventional and problem-based learning curricula. Acad Med. 1998;73:1211–3. https://doi.org/10.1097/00001888-199811000-00022 .

Kaufman DM, Mann KV. Achievement of students in a conventional and Problem-Based Learning (PBL) curriculum. Adv Heal Sci Educ. 1999;4:245–60. https://doi.org/10.1023/A:1009829831978 .

Antepohl W, Herzig S. Problem-based learning versus lecture-based learning in a course of basic pharmacology: a controlled, randomized study. Med Educ. 1999;33:106–13. https://doi.org/10.1046/j.1365-2923.1999.00289.x .

Dyke P, Jamrozik K, Plant AJ. A randomized trial of a problem-based learning approach for teaching epidemiology. Acad Med. 2001;76:373–9. https://doi.org/10.1097/00001888-200104000-00016 .

Brewer DW. Endocrine PBL in the year 2000. Adv Physiol Educ. 2001;25:249–55. https://doi.org/10.1152/advances.2001.25.4.249 .

Seneviratne RD, Samarasekera DD, Karunathilake IM, Ponnamperuma GG. Students’ perception of problem-based learning in the medical curriculum of the faculty of medicine, University of Colombo. Ann Acad Med Singapore. 2001;30:379–81.

Alleyne T, Shirley A, Bennett C, et al. Problem-based compared with traditional methods at the faculty of medical sciences, University of the West Indies: a model study. Med Teach. 2002;24:273–9. https://doi.org/10.1080/01421590220125286 .

Norman GR, Wenghofer E, Klass D. Predicting doctor performance outcomes of curriculum interventions: problem-based learning and continuing competence. Med Educ. 2008;42:794–9. https://doi.org/10.1111/j.1365-2923.2008.03131.x .

Cohen-Schotanus J, Muijtjens AMM, Schoenrock-Adema J, Geertsma J, van der Vleuten CPM. Effects of conventional and problem-based learning on clinical and general competencies and career development. Med Educ. 2008;42:256–65. https://doi.org/10.1111/j.1365-2923.2007.02959.x .

Wenk M, Waurick R, Schotes D, et al. Simulation-based medical education is no better than problem-based discussions and induces misjudgment in self-assessment. Adv Health Sci Educ Theory Pract. 2009;14:159–71. https://doi.org/10.1007/s10459-008-9098-2 .

Collard A, Gelaes S, Vanbelle S, et al. Reasoning versus knowledge retention and ascertainment throughout a problem-based learning curriculum. Med Educ. 2009;43:854–65. https://doi.org/10.1111/j.1365-2923.2009.03410.x .

Nouns Z, Schauber S, Witt C, Kingreen H, Schuettpelz-Brauns K. Development of knowledge in basic sciences: a comparison of two medical curricula. Med Educ. 2012;46:1206–14. https://doi.org/10.1111/medu.12047 .

Saloojee S, van Wyk J. The impact of a problem-based learning curriculum on the psychiatric knowledge and skills of final-year students at the Nelson R Mandela school of medicine. South African J Psychiatry. 2012;18:116.

Mughal AM, Shaikh SH. Assessment of collaborative problem solving skills in undergraduate medical students at Ziauddin college of medicine. Karachi Pakistan J Med Sci. 2018;34:185–9. https://doi.org/10.12669/pjms.341.13485 .

Hu X, Zhang H, Song Y, et al. Implementation of flipped classroom combined with problem-based learning: an approach to promote learning about hyperthyroidism in the endocrinology internship. BMC Med Educ. 2019;19:290. https://doi.org/10.1186/s12909-019-1714-8 .

Thompson KL, Gendreau JL, Strickling JE, Young HE. Cadaveric dissection in relation to problem-based learning case sequencing: a report of medical student musculoskeletal examination performances and self-confidence. Anat Sci Educ. 2019;12:619–26. https://doi.org/10.1002/ase.1891 .

Chang G, Cook D, Maguire T, Skakun E, Yakimets WW, Warnock GL. Problem-based learning: its role in undergraduate surgical education. Can J Surg. 1995;38:13–21.

Vernon DTA, Hosokawa MC. Faculty attitudes and opinions about problem-based learning. Acad Med. 1996;71:1233–8. https://doi.org/10.1097/00001888-199611000-00020 .

Steadman RH, Coates WC, Huang YM, et al. Simulation-based training is superior to problem-based learning for the acquisition of critical assessment and management skills. Crit Care Med. 2006;34:151–7. https://doi.org/10.1097/01.CCM.0000190619.42013.94 .

Johnston JM, Schooling CM, Leung GM. A randomised-controlled trial of two educational modes for undergraduate evidence-based medicine learning in Asia. BMC Med Educ. 2009;9:63. https://doi.org/10.1186/1472-6920-9-63 .

Suleman W, Iqbal R, Alsultan A, Baig SM. Perception of 4(th) year medical students about problem based learning. Pakistan J Med Sci. 2010;26:871–4.

Blosser A, Jones B. Problem-based learning in a surgery clerkship. Med Teach. 1991;13:289–93. https://doi.org/10.3109/01421599109089907 .

Usherwood T, Joesbury H, Hannay D. Student-directed problem-based learning in general-practice and public-health medicine. Med Educ. 1991;25:421–9. https://doi.org/10.1111/j.1365-2923.1991.tb00090.x .

Bernstein P, Tipping J, Bercovitz K, Skinner HA. Shifting students and faculty to a PBL curriculum - attitudes changed and lessons learned. Acad Med. 1995;70:245–7. https://doi.org/10.1097/00001888-199503000-00019 .

Kaufman DM, Mann KV. Comparing students’ attitudes in problem-based and conventional curricula. Acad Med. 1996;71:1096–9. https://doi.org/10.1097/00001888-199610000-00018 .

Kalaian HA, Mullan PB. Exploratory factor analysis of students’ ratings of a problem-based learning curriculum. Acad Med. 1996;71:390–2. https://doi.org/10.1097/00001888-199604000-00019 .

Vincelette J, Lalande R, Delorme P, Goudreau J, Lalonde V, Jean P. A pilot course as a model for implementing a PBL curriculum. Acad Med. 1997;72:698–701. https://doi.org/10.1097/00001888-199708000-00015 .

Ghosh S, Dawka V. Combination of didactic lecture with problem-based learning sessions in physiology teaching in a developing medical college in Nepal. Adv Physiol Educ. 2000;24:8–12.

Walters MR. Problem-based learning within endocrine physiology lectures. Adv Physiol Educ. 2001;25:225–7. https://doi.org/10.1152/advances.2001.25.4.225 .

Leung GM, Lam TH, Hedley AJ. Problem-based public health learning - from the classroom to the community. Med Educ. 2001;35:1071–2.

Khoo HE, Chhem RK, Gwee MCE, Balasubramaniam P. Introduction of problem-based learning in a traditional medical curriculum in Singapore - students’ and tutors’ perspectives. Ann Acad Med Singapore. 2001;30:371–4.

Villamor MCA. Problem-based learning (PBL) as an approach in the teaching of biochemistry of the endocrine system at the Angeles University College of Medicine. Ann Acad Med Singapore. 2001;30:382–6.

Chang C-H, Yang C-Y, See L-C, Lui P-W. High satisfaction with problem-based learning for anesthesia. Chang Gung Med J. 2004;27:654–62.

McLean M. A comparison of students who chose a traditional or a problem-based learning curriculum after failing year 2 in the traditional curriculum: a unique case study at the Nelson R. Mandela school of medicine. Teach Learn Med. 2004;16:301–3. https://doi.org/10.1207/s15328015tlm1603\_15 .

Lucas M, García Guasch R, Moret E, Llasera R, Melero A. Canet J [Problem-based learning in an undergraduate medical school course on anesthesiology, recovery care, and pain management]. Rev Esp Anestesiol Reanim. 2006;53:419–25.

Burgun A, Darmoni S, Le Duff F, Weber J. Problem-based learning in medical informatics for undergraduate medical students: an experiment in two medical schools. Int J Med Inform. 2006;75:396–402. https://doi.org/10.1016/j.ijmedinf.2005.07.014 .

Gurpinar E, Senol Y, Aktekin MR. Evaluation of problem based learning by tutors and students in a medical faculty of Turkey. Kuwait Med J. 2009;41:123–7.

Elzubeir MA. Teaching of the renal system in an integrated, problem-based curriculum. Saudi J Kidney Dis Transpl. 2012;23:93–8.

Sulaiman N, Hamdy H. Problem-based learning: where are we now? Guide supplement 36.3–practical application. Med Teach. 2013;35:160–2. https://doi.org/10.3109/0142159X.2012.737965 .

Albarrak AI, Mohammed R, Abalhassan MF, Almutairi NK. Academic satisfaction among traditional and problem based learning medical students a comparative study. Saudi Med J. 2013;34:1179–88.

Nosair E, Mirghani Z, Mostafa RM. Measuring students’ perceptions of educational environment in the PBL program of Sharjah Medical College. J Med Educ Curric Dev. 2015;2:71–9. https://doi.org/10.4137/JMECDECDECD.S29926 .

Tshitenge ST, Ndhlovu CE, Ogundipe R. Evaluation of problem-based learning curriculum implementation in a clerkship rotation of a newly established African medical training institution: lessons from the University of Botswana. Pan Afr Med J. 2017;27:13. https://doi.org/10.11604/pamj.2017.27.13.10623 .

Yadav RL, Piryani RM, Deo GP, Shah DK, Yadav LK, Islam MN. Attitude and perception of undergraduate medical students toward the problem-based learning in Chitwan Medical College. Nepal Adv Med Educ Pract. 2018;9:317–22. https://doi.org/10.2147/AMEP.S160814 .

Asad MR, Tadvi N, Amir KM, Afzal K, Irfan A, Hussain SA. Medical student’s feedback towards problem based learning and interactive lectures as a teaching and learning method in an outcome-based curriculum. Int J Med Res & Heal Sci. 2019;8:78–84. https://doi.org/10.33844/ijol.2019.60392 .

Mpalanyi M, Nalweyiso ID, Mubuuke AG. Perceptions of radiography students toward problem-based learning almost two decades after its introduction at Makerere University. Uganda J Med imaging Radiat Sci. 2020;51:639–44. https://doi.org/10.1016/j.jmir.2020.06.009 .

Korkmaz NS, Ozcelik S. Evaluation of the opinions of the first, second and third term medical students about problem based learning sessions in Bezmialem Vakif University. Bezmialem Sci. 2020;8:144–9. https://doi.org/10.14235/bas.galenos.2019.3471 .

McGrew MC, Skipper B, Palley T, Kaufman A. Student and faculty perceptions of problem-based learning on a family medicine clerkship. Fam Med. 1999;31:171–6.

Kelly AM. A problem-based learning resource in emergency medicine for medical students. J Accid Emerg Med. 2000;17:320–3. https://doi.org/10.1136/emj.17.5.320 .

Bui-Mansfield LT, Chew FS. Radiologists as clinical tutors in a problem-based medical school curriculum. Acad Radiol. 2001;8:657–63. https://doi.org/10.1016/S1076-6332(03)80693-1 .

Macallan DC, Kent A, Holmes SC, Farmer EA, McCrorie P. A model of clinical problem-based learning for clinical attachments in medicine. Med Educ. 2009;43:799–807. https://doi.org/10.1111/j.1365-2923.2009.03406.x .

Grisham JW, Martiniuk ALC, Negin J, Wright EP. Problem-based learning (PBL) and public health: an initial exploration of perceptions of PBL in Vietnam. Asia-Pacific J public Heal. 2015;27:NP2019-27. https://doi.org/10.1177/1010539512436875 .

Khan IA, Al-Swailmi FK. Perceptions of faculty and students regarding Problem Based Learning: a mixed methods study. J Pak Med Assoc. 2015;65:1334–8.

Alduraywish AA, Mohager MO, Alenezi MJ, Nail AM, Aljafari AS. Evaluation of students’ experience with Problem-based Learning (PBL) applied at the College of Medicine, Al-Jouf University. Saudi Arabia J Pak Med Assoc. 2017;67:1870–3.

Yoo DM, Cho AR, Kim S. Satisfaction with and suitability of the problem-based learning program at the Catholic University of Korea College of Medicine. J Educ Eval Health Prof. 2019;16:20. https://doi.org/10.3352/jeehp.2019.16.20 .

Aldayel AA, Alali AO, Altuwaim AA, et al. Problem-based learning: medical students’ perception toward their educational environment at Al-Imam Mohammad Ibn Saud Islamic University. Adv Med Educ Pract. 2019;10:95–104. https://doi.org/10.2147/AMEP.S189062 .

DeLowerntal E. An evaluation of a module in problem-based learning. Int J Educ Dev. 1996;16:303–7. https://doi.org/10.1016/0738-0593(96)00001-6 .

Tufts MA, Higgins-Opitz SB. What makes the learning of physiology in a PBL medical curriculum challenging? Student perceptions. Adv Physiol Educ. 2009;33:187–95. https://doi.org/10.1152/advan.90214.2008 .

Aboonq M. Perception of the faculty regarding problem-based learning as an educational approach in Northwestern Saudi Arabia. Saudi Med J. 2015;36:1329–35. https://doi.org/10.15537/smj.2015.11.12263 .

Subramaniam RM, Scally P, Gibson R. Problem-based learning and medical student radiology teaching. Australas Radiol. 2004;48:335–8. https://doi.org/10.1111/j.0004-8461.2004.01317.x .

Chang BJ. Problem-based learning in medical school: a student’s perspective. Ann Med Surg. 2016;12:88–9. https://doi.org/10.1016/j.amsu.2016.11.011 .

Griffith CD, Blue AV, Mainous AG, DeSimone PA. Housestaff attitudes toward a problem-based clerkship. Med Teach. 1996;18:133–4. https://doi.org/10.3109/01421599609034147 .

Navarro HN, Zamora SJ. The opinion of teachers about tutorial problem based learning. Rev Med Chil. 2014;142:989–97. https://doi.org/10.4067/S0034-98872014000800006 .

Demiroren M, Turan S, Oztuna D. Medical students’ self-efficacy in problem-based learning and its relationship with self-regulated learning. Med Educ Online. 2016;21:30049. https://doi.org/10.3402/meo.v21.30049 .

Tousignant M, DesMarchais JE. Accuracy of student self-assessment ability compared to their own performance in a problem-based learning medical program: a correlation study. Adv Heal Sci Educ. 2002;7:19–27. https://doi.org/10.1023/A:1014516206120 .

Brynhildsen J, Dahle LO, Behrbohm Fallsberg M, Rundquist I, Hammar M. Attitudes among students and teachers on vertical integration between clinical medicine and basic science within a problem-based undergraduate medical curriculum. Med Teach. 2002;24:286–8. https://doi.org/10.1080/01421590220134105 .

Desmarchais JE. A student-centered, problem-based curriculum - 5 years experience. Can Med Assoc J. 1993;148:1567–72.

Doig K, Werner E. The marriage of a traditional lecture-based curriculum and problem-based learning: are the offspring vigorous? Med Teach. 2000;22:173–8.

Kemahli S. Hematology education in a problem-based curriculum. Hematology. 2005;10(Suppl 1):161–3. https://doi.org/10.1080/10245330512331390267 .

Grkovic I. Transition of the medical curriculum from classical to integrated: problem-based approach and Australian way of keeping academia in medicine. Croat Med J. 2005;46:16–20.

Bosch-Barrera J, Briceno Garcia HC, Capella D, et al. Teaching bioethics to students of medicine with Problem-Based Learning (PBL). Cuad Bioet. 2015;26:303–9.

Lin Y-C, Huang Y-S, Lai C-S, Yen J-H, Tsai W-C. Problem-based learning curriculum in medical education at Kaohsiung Medical University. Kaohsiung J Med Sci. 2009;25:264–9. https://doi.org/10.1016/S1607-551X(09)70072-5 .

Salinas Sánchez AS, Hernández Millán I, Virseda Rodríguez JA, et al. Problem-based learning in urology training the faculty of medicine of the Universidad de Castilla-La Mancha model. Actas Urol Esp. 2005;29:8–15. https://doi.org/10.1016/s0210-4806(05)73193-4 .

Amoako-Sakyi D, Amonoo-Kuofi H. Problem-based learning in resource-poor settings: lessons from a medical school in Ghana. BMC Med Educ. 2015;15:221. https://doi.org/10.1186/s12909-015-0501-4 .

Carrera LI, Tellez TE, D’Ottavio AE. Implementing a problem-based learning curriculum in an Argentinean medical school: implications for developing countries. Acad Med. 2003;78:798–801. https://doi.org/10.1097/00001888-200308000-00010 .

Vernon DT, Blake RL. Does problem-based learning work? A meta-analysis of evaluative research. Acad Med. 1993;68:550–63. https://doi.org/10.1097/00001888-199307000-00015 .

Shanley PF. Viewpoint: leaving the “empty glass” of problem-based learning behind: new assumptions and a revised model for case study in preclinical medical education. Acad Med. 2007;82:479–85. https://doi.org/10.1097/ACM.0b013e31803eac4c .

Koh GC, Khoo HE, Wong ML, Koh D. The effects of problem-based learning during medical school on physician competency: a systematic review. CMAJ. 2008;178:34–41. https://doi.org/10.1503/cmaj.070565 .

Awan ZA, Awan AA, Alshawwa L, Tekian A, Park YS. Assisting the integration of social media in problem-based learning sessions in the faculty of medicine at King Abdulaziz University. Med Teach. 2018;40:S37–42. https://doi.org/10.1080/0142159X.2018.1465179 .

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Characteristics ofthe 124 included studies.

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Trullàs, J.C., Blay, C., Sarri, E. et al. Effectiveness of problem-based learning methodology in undergraduate medical education: a scoping review. BMC Med Educ 22 , 104 (2022). https://doi.org/10.1186/s12909-022-03154-8

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Post-bariatric pregnancy is associated with vitamin K1 deficiency, a case control study

• Brit Torunn Bechensteen 1 , 2 ,
• Cindhya Sithiravel 3 ,
• Ellen Marie Strøm-Roum 4 ,
• Heidi Kathrine Ruud 2 ,
• Gunnhild Kravdal 3 ,
• Jacob A. Winther 1 &
• Tone G. Valderhaug 1  

BMC Pregnancy and Childbirth volume  24 , Article number:  229 ( 2024 ) Cite this article

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Maternal obesity is associated with adverse outcome for pregnancy and childbirths. While bariatric surgery may improve fertility and reduce the risk of certain pregnancy-related complications such as hypertension and gestational diabetes mellitus, there is a lack of evidence on the optimal nutritional monitoring and supplementation strategies in pregnancy following bariatric surgery. We aimed to assess the impact of bariatric surgery on micronutrients in post-bariatric pregnancy and possible differences between gastric bypass surgery and sleeve gastrectomy.

In this prospective case control study, we recruited 204 pregnant women (bariatric surgery n  = 59 [gastric bypass surgery n  = 26, sleeve gastrectomy n  = 31, missing n  = 2] and controls n  = 145) from Akershus university hospital in Norway. Women with previous bariatric surgery were consecutively invited to study participation at referral to the clinic for morbid obesity and the controls were recruited from the routine ultrasound screening in gestational week 17–20. A clinical questionnaire was completed and blood samples were drawn at mean gestational week 20.4 (SD 4.5).

The women with bariatric surgery had a higher pre-pregnant BMI than controls (30.8 [SD 6.0] vs. 25.2 [5.4] kg/m2, p  < 0.001). There were no differences between groups regarding maternal weight gain (bariatric surgery 13.3 kg (9.6) vs. control 14.8 kg (6.5), p  = 0.228) or development of gestational diabetes ( n  = 3 [5%] vs. n  = 7 [5%], p  = 1.000). Mean levels of vitamin K1 was lower after bariatric surgery compared with controls (0.29 [0.35] vs. 0.61 [0.65] ng/mL, p  < 0.001). Multiadjusted regression analyses revealed an inverse relationship between bariatric surgery and vitamin K1 (B -0.26 ng/mL [95% CI -0.51, -0.04], p  = 0.047) with a fivefold increased risk of vitamin K1 deficiency in post-bariatric pregnancies compared with controls (OR 5.69 [1.05, 30.77] p  = 0.044). Compared with sleeve gastrectomy, having a previous gastric bypass surgery was associated with higher risk of vitamin K1 deficiency (OR 17.1 [1.31, 223.3], p  = 0.030).

Post-bariatric pregnancy is negatively associated with vitamin K1 with a higher risk of vitamin K1 deficiency in pregnancies after gastric bypass surgery compared with after sleeve gastrectomy. Vitamin K1 deficiency in post-bariatric pregnancy have potential risk of hypocoaguble state in mother and child and should be explored in future studies.

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Obesity is common in women of reproductive age, increasing the risk of several complications for mother and child [ 1 , 2 ]. Maternal metabolism in obesity may reduce the likelihood of successful pregnancy [ 3 ]. Moreover, given that weight loss before pregnancy mitigates the adverse outcomes of pregnancy related outcomes from obesity, bariatric surgery in women of reproductive age in increasing [ 4 , 5 ]. However, although bariatric surgery may reduce the risks of certain obesity related complications in pregnancy, pregnancy after bariatric surgery may carry adverse events such as malnutrition, vitamin deficiencies and inadequate weight gain as well as changes in endocrine and metabolic homeostasis [ 6 , 7 , 8 , 9 , 10 ]. Pregnancy following bariatric surgery has been associated with increased risk of preterm birth, nutritional deficiency and small for gestational age [ 7 , 8 , 11 , 12 , 13 , 14 ]. The causality of these effects are not known, but personalized nutritional counseling during post-bariatric pregnancy has been shown to improve nutrient intake of mothers and may contribute to higher weight of offspring [ 15 ].

There is a growing body of evidence suggesting that maternal nutrition and lifestyle affect fetal growth and development [ 16 , 17 ]. Micronutrients are vitamins and minerals that enable the body to produce enzymes, hormones and other substances essential for normal growth and development [ 18 ]. Micronutrient deficiencies contribute to poor growth, intellectual impairments and increased risk of morbidity and mortality [ 19 ]. Widespread global micronutrient deficiencies exist, with pregnant women and young children at highest risk [ 19 ]. Micronutrient interventions such as supplementation of folate to prevent neural tube defects zinc to reduce risk of preterm birth, and iron to reduce the risk of low birthweight are established [ 20 , 21 , 22 ]. The micronutritional deficiencies seen after bariatric surgery might be explained by poor dietary pattern in combination with gastrointestinal modification and reduced intestinal transit time [ 23 , 24 , 25 , 26 , 27 ]. Deficiencies of fatty soluble vitamins seem to be particularly prevalent in post-bariatric pregnancies, with potential risks of impaired vision, neuronal disorders, impairment of the immune system and hypocoagulability for mother and child [ 24 , 28 , 29 , 30 ].

While sleeve gastrectomy is the most common surgical procedure for the treatment of obesity worldwide, there is conflicting evidence on the optimal surgical procedure before subsequent pregnancy [ 10 , 31 ]. A large registry study showed no difference between gastric bypass and sleeve gastrectomy for preterm birth or small for gestational age [ 12 ]. Studies indicates increased risk of prematurity in pregnancy occurring less than 2 years after bariatric surgery [ 12 , 32 ]. However, other studies have not confirmed increased risks in pregnancies related to time-interval between bariatric surgery and conception [ 13 , 33 ]. As such, there is an evident knowledge gap on the impact of bariatric surgery on micronutrient status in pregnancies as well as outcomes for mother and child in order to provide optimal obstetric care in this group.

The aim of this study was to assess the impact of bariatric surgery on concentrations of micronutrients in post-bariatric pregnancies compared with non-surgical controls. Specifically, we hypothesized that fatty soluble micronutrients, including vitamin K1, was impaired after bariatric surgery. We also wanted to assess differences in maternal micronutrients concentrations following sleeve gastrectomy versus gastric bariatric surgery.

Materials and methods

Design and study population.

This observational case control study compared micronutritional status in pregnancy after bariatric surgery with non-surgical controls. Study participants were recruited from Akershus university hospital, between October 18th 2018 and December 9th 2022. Pregnant women with previous bariatric surgery were consecutively invited to study participation at referral to the clinic for morbid obesity and the controls were recruited from the routine ultrasound screening in gestational week 17–20. A total of 59 women with a previous bariatric surgery was included in the study and information on surgical procedure was available for 57 women (gastric bypass surgery n  = 26 and sleeve gastrectomy n  = 31). All women with post-bariatric pregnancies were closely monitored individually by a clinical doctor and a registered clinical dietitian focusing on micronutrient status and gestational weight gain. The controls received standard hospital care and dietary advice with additional advice if the blood samples revealed deficiencies.

A total of 204 women were included in this study with 92% of Caucasian ethnicity ( n  = 185). We compared micronutrient status in pregnancy in women with previous bariatric surgery ( n  = 59) to controls ( n  = 145). Women with known intestinal conditions (i.e. known inflammatory bowel disease, uncontrolled coeliac disease) were not included in the study. The study was approved by the Regional Committee for Medical and Health Research Ethics (reference 25829). All study participants provided written informed consent before study commencement, and the study was performed in accordance with the Declaration of Helsinki [ 34 ].

Definitions

The reference intervals for micronutrients in non-pregnant women and the chosen cut-offs defining micronutrient deficiencies in pregnancy are presented in Table  1 . We defined micronutrient deficiency according to known physiological changes in blood during pregnancy combined with established reference intervals in a non-pregnant population [ 30 , 35 , 36 , 37 ]. Time interval between bariatric surgery and conception was categorized into < 18 and ≥ 18 months.

Data collection

Clinical and laboratory data were retrieved at mean gestational week 20.4 (SD 4.5) (Bariatric surgery 23.9 [6.5] vs. controls 19.0 [2.0] weeks, p  < 0.001). Follow-up blood sample was available in a subgroup of 32 women with post-bariatric pregnancies at mean 30.4 (SD 5.6) gestational week. All patients completed a questionnaire on comorbidities, medications and dietary supplements. Additional information including maximum weight, time of bariatric surgery, type of bariatric surgery was retrieved during the first visit.

Blood samples and analysis

The blood samples were obtained by venipuncture and collected in Vacuette® tubes. EDTA tubes were used for analysis of hemoglobin, hemoglobin A1c and thiamine (vitamin B1). Lithium heparin gel tubes were used for analysis of zinc and selenium, and serum gel tubes for the remaining analyses. All the blood samples were non-fasting. After blood collection, all tubes were handled according to established procedures. The standard clinical chemistry parameters were analysed at the laboratory at Akershus University Hospital. Hemoglobin was analysed on Sysmex instruments (Sysmex Corporation, Kobe, Japan) and hemoglobin A1c on Tosoh instruments (Tosoh Corporation, Tokyo, Japan). Magnesium and homocysteine were analysed on Vitros 5.1 FS (Ortho Clinical Diagnostics, Raritan, NJ) until May 2021, thereafter on cobas c503 (Roche Diagnostics, Mannheim, Germany). Folate, cobalamin, ferritin and vitamin D were analysed on cobas e801 (Roche Diagnostics). Zinc and selenium were analysed using inductive coupled plasma – mass spectrometry (ICP-MS) and methylmalonic acid (MMA) with a liquid chromatography – mass spectrometry method (LC-MS/MS). Thiamine, pyridoxal 5-phosphate (vitamin B6), vitamin A and vitamin E were analysed at Oslo University Hospital, Aker and vitamin K1 was analysed at Fürst Medical Laboratorium, Oslo, all with chromatographic methods.

Statistical analysis

We estimated that the prevalence of micronutrient deficiency would be 30% in post-bariatric pregnancies and 5% in controls. To confirm a similar difference with a statistical power of more than 80% and a significance level (α) of 0.05, a total of 200 patients had to be included in the study with a 4:1 ratio of cases vs. controls (40 post-bariatric pregnancies and 160 controls). Proportions are reported as numbers with percent, continuous variables as mean ± standard deviation (SD) as appropriate. Differences between treatment groups were analysed using Pearson’s chi-square test or Fishers exact test for categorical data and Student’s t-test for continuous data. Paired sample t-test was used to assess paired observations of micronutrients in baseline and follow-up blood samples. Skewed distributed data were log-transformed to achieve normal distribution. Correlations between possible confounders and vitamin K1 variables were assessed by Spearman’s correlation (rho). Two-sided P values < 0.05 were considered statistically significant. The Bonferroni Holm correction was applied to mitigate the risk of type 1 statistical error. We used linear regression analyses to explore possible associations between bariatric surgery and vitamin K1 and logistic regression analyses to explore possible associations between bariatric surgery and vitamin K1 deficiency. Possible confounders were identified using a stepwise selection approach in which variables with p-values below 0.10 were included along with clinically significant confounders. Coefficients and odds ratio (OR) from regression analysis are presented with 95% confidence interval (CI). The analyses were performed using IBM SPSS Statistics (version 729.0.0).

We included 204 women in the study (bariatric surgery n  = 59 and controls n  = 145). Data on the specific type of surgical procedure were available for 57 women who had undergone bariatric surgery prior to conception (gastric bypass surgery n  = 26 and sleeve gastrectomy = 31). The women in the surgical group lost on average 39.0 (16.9) kg from the time of surgery to the start of pregnancy and the time interval from bariatric surgery to pregnancy was mean 63.7 (39.2) months. Patients’ characteristics by surgical status are presented in Table  2 .

The women with bariatric surgery had a higher pre-pregnant body mass index (BMI) compared with controls (30.8 [SD 6.0] vs. 25.2 [5.4] kg/m 2 , p  < 0.001). There was no difference between groups regarding age (32.1 [5.7] vs. 31.2 [4.2] years, p  = 0.215), maternal weight gain (13.3 [9.6] vs. 14.8 [6.5] kg, p  = 0.228), HbA1c (30.2 [7.1] vs. 31.1[3.6] mmol/mol, p  = 0.234) or development of gestational diabetes (5% vs. 5%, p  = 1.000). Fewer women with bariatric surgery had completed higher education and more women with bariatric surgery currently smoked compared with controls (24 [43%] vs. 103 [72%], p  < 0.001 and 5 [9%] vs. 0, p  = 0.001, respectively. Children of post-bariatric pregnancies had lower gestational age and lower birthweight, however neither reached statistical significance (38.5[3.1] vs. 39.3[2.1] weeks, p  = 0.054 and 3363 [624] vs. 3520 [521] g, p  = 0.081, respectively).

Dietary supplements and micronutrient status by surgical status are presented in Table  3 . Concentrations of ferritin, magnesium, pyridoxal 5-phosphate, vitamin A, E and K1 and selenium were significantly lower post-bariatric pregnancies compared with controls. Using micronutrients as categorical variables (deficiency yes/no) conferred a higher prevalence of micronutrient deficiencies such as iron, magnesium, pyridoxal 5-phosphate, vitamin K1 and selenium in pregnancies after bariatric surgery compared with controls and a higher prevalence of vitamin K1 deficiency after gastric bariatric surgery vs. sleeve gastrectomy (Fig.  1 ). The distribution of vitamin K1 concentrations in women with post-bariatric pregnancies and controls is presented in Fig.  2 . Paired sample t-test showed increased concentrations vitamin K1 in a subgroup of women with post-bariatric pregnancies (0.29 [0.29] ng/mL to 0.64 [0.92] ng/mL, p  = 0.070).

Micronutritional deficiency in pregnancy. A : pregnancy following bariatric surgery vs. non-surgical controls. B : pregnancy after gastric bypass surgery vs. sleeve gastrectomy. * denotes statistically significance after corrections for multiple comparisons

Distribution of vitamin K1 concentrations in women with post-bariatric pregnancies and controls

The women with gastric bariatric surgery underwent surgery at a younger age and with a longer time-interval between surgery and conception compared with the women with sleeve gastrectomy (23.5 vs. 27.5 years, p  = 0.002 and 85 [40] vs. 45 [28] months, p = < 0.001, respectively). One woman (4%) after gastric bariatric surgery and five women (16%) after sleeve gastrectomy, p  = 0.205 became pregnant < 18 months after surgery. Both surgical groups had lost comparable weight since surgery (gastric bypass surgery 41.4 [17.1] vs. sleeve gastrectomy 37.0 [16.8] kg, p  = 0.342) and they had comparable pre-pregnant BMI (gastric bypass surgery 31.9 [5.5] vs. sleeve gastrectomy 29.9 [6.4] kg/m 2 , p  = 0.222). The proportion of women with vitamin K1 deficiency was higher after gastric bariatric surgery compared with sleeve gastrectomy (gastric bypass surgery 9 [38%] vs. 1 [3%], p  = 0.003 and Fig.  1 ).

Univariate linear regression analysis showed that bariatric surgery was inversely associated with vitamin K1 levels (B -0.33 [95% CI -0.51, -0.15, p  < 0.001]. The result remained statistically significant after multivariable adjustments (-0.26 ng/mL [-0.51, -0.04], p  = 0.047) (Table  4 A). In addition, compared with sleeve gastrectomy, gastric bariatric surgery was inversely associated with vitamin K1 in univariate linear regression analysis (0.20 [0.019, 0.387], p  = 0.031), but not after multivariate adjustment (Table  4 B). Using vitamin K1 as a categorical variable (deficiency yes/no), bariatric surgery was associated with a fivefold increased risk of vitamin K1 deficiency compared with controls and that gastric bariatric surgery was associated with higher adjusted risk of vitamin K1 deficiency compared with sleeve gastrectomy (Table  5 ).

In this study, we compare micronutrient concentrations in post-bariatric pregnancy with matched non-surgical controls. The study shows that the concentrations of vitamin K1, magnesium, and selenium were significantly impaired in post-bariatric pregnancies vs. controls. Moreover, our results show that bariatric surgery was consistently associated with vitamin K1 levels, both as a continuous outcome variable and as a categorical variable (vitamin K1 deficiency) in post-bariatric pregnancy compared with controls. Moreover, the associations might be driven by gastric bariatric surgery rather than sleeve gastrectomy. However, the number of pregnant women with vitamin K1 concentration below the lower reference limit was overall small and the confidence intervals were large. Thus, these results should be interpreted with caution.

Maternal nutrition and micronutrients in pregnancy after bariatric surgery

In pregnancy, there is an increased need for nutrients to support fetal and placental growth and development [ 20 ]. A detailed dietary information was not available in this study and we cannot exclude that the women with bariatric surgery had a different nutritional composition compared with controls. In a subgroup of women with post-bariatric pregnancies, an increment in vitamin K was seen. However, the changes did not reach statistical significance. Follow-up blood samples for the controls were not available. A healthy diet after bariatric surgery may differ from the general population in the composition of lean protein, fruits and vegetables and starchy carbohydrates. Nonetheless, the combination of diet, intestinal modifications and increased metabolism in pregnancy might explain the deficiencies in fatty soluble vitamins seen in this study [ 23 , 24 , 25 , 26 , 27 ]. Improved nutrient intake of mothers was seen after personalized nutritional counseling during post-bariatric pregnancy and might contribute to higher birth weight of offspring [ 15 ]. Given the complexity and heterogeneity of nutritional status in post-bariatric pregnancies, focusing on sub-groups including pre-gestational nutritional deficiencies, and type of surgery performed is of vital importance. A recent consensus report recommended specialized care in pregnancies after bariatric surgery [ 38 ]. There is however a paucity of data to support clinical practice [ 38 , 39 ]. As such, there is an imperative need to identify pregnancy and trimester specific reference intervals and clinical decision limits in order to help clinical advice on dietary supplement.

Lifelong dietary supplement is recommended after bariatric surgery, however adherence to adequate dietary supplements seems to decrease over time [ 26 , 40 , 41 ]. Our study also confers inadequate use of dietary supplements in pregnancy after bariatric surgery with 30–70% of the women not taking recommended post-bariatric surgery dietary supplements (Table  3 ). Thus, a need for increased awareness to ensure adequate microntutrional care before, during and after pregnancy is imperative.

The role of vitamin K1 in pregnancy after bariatric surgery

In line with our results, a systematic review on vitamin K1 concentrations in patients with a history of bariatric surgery reported high risk of vitamin K1 deficiency after bariatric surgery and opted for better monitoring [ 23 ]. Our results also cohere with another study of 49 pregnant women with previous bariatric surgery, showing that vitamin K1 concentrations were lower in women with a history of bariatric surgery compared with 27 controls [ 30 ]. The increased fat storage in pregnancy may lead to less bioavailability for activation of fatty soluble vitamins [ 42 ]. Furthermore, the highly fat-soluble vitamin K1 depend upon conjugated bile salts for adequate absorption. Consequently, reduced stomach acid production, reduced absorption surface and shorter interaction time between conjugated bile salts and vitamin K1 might explain the lower serum concentrations of vitamin K1 after bariatric surgery [ 43 ]. Screening for vitamin K1 deficiency is usually recommended after malabsorptive surgical procedures including biliopancreatic diversion with or without duodenal switch [ 43 ]. However, restrictive procedures may also cause vitamin deficiencies due to digestive symptoms such as vomiting and food intolerance. Interestingly, lower levels of vitamin K1 were found in the first trimester compared to a control group of women without bariatric surgery [ 30 ]. Vomiting and food intolerance may also be the main symptoms of hyperemesis gravidarum, which calls for increased vigilance of vitamin K1 insufficiency in post-bariatric pregnancies in women with symptoms of hyperemesis in pregnancy.

The impact of vitamin K1 deficiency in post-bariatric pregnancies is not clear. Low circulating levels of vitamin K1 might lead to a hypocoaguble state in mother and child [ 30 ]. Some cases of neonatal intracranial bleeding have been reported, possible due to vitamin K1 deficiency [ 44 ]. Another study reported that obesity had stronger impact on hypercoagulability than pregnancy itself [ 45 ]. Nonetheless, insufficient data exist in order to recommend interventions of vitamin K1 deficiency in post-bariatric pregnancy [ 38 ]. While optimal monitoring of vitamin K1 during pregnancy following bariatric surgery remains unclear, a major concern is raised about the consistent finding of vitamin K1 deficiency in post-bariatric pregnancy.

Bariatric surgery before pregnancy: timing and selection of procedure – dose it matter?

Few studies have assessed the impact of different surgical procedures before pregnancy. One study of 119 pregnant women found no effect of maternal weight gain on maternal and perinatal outcome after sleeve gastrectomy [ 46 ]. However, the study did not include pregnancies after gastric bariatric surgery for comparison. Another retrospective observational study showed no differences between gastric bariatric surgery and sleeve gastrectomy regarding re-interventions or obstetric outcomes [ 4 ]. Conflicting evidence exists on the possible adverse effects of sleeve gastrectomy such as dyspepsia and weight regain as compared with gastric bariatric surgery [ 47 , 48 , 49 ]. Our study adds important knowledge about the different surgical procedures, suggesting that gastric bariatric surgery holds greater risk of vitamin K1 deficiency compared with sleeve gastrectomy. The optimal surgical procedure for obesity treatment in women of reproductive age is however not clear and a person-centered approach should be advocated in future guidelines.

The timing of pregnancy after bariatric surgery is moreover under debate. Current recommendations suggest waiting at least 12 months after bariatric surgery before planning a pregnancy [ 12 , 38 , 50 ]. In our study, women with previous sleeve gastrectomy had a shorter time interval between surgery and conception than the women with gastric bariatric surgery. This might reflect that the women who underwent gastric bariatric surgery underwent surgery in an era where gastric bariatric surgery was the most common surgical procedure for weight loss [ 31 ]. Interestingly, after adjustments for the time interval since bariatric surgery, gastric bariatric surgery was not associated with vitamin K1 in the linear regression model (Table  4 B). Thus, as adherence to dietary supplements is reduced with time after bariatric surgery, we cannot rule out that patient’ adherence to dietary supplement might have influenced the differences between surgical procedure seen in the present study [ 26 , 40 , 41 ]. On the other hand, the time interval between sleeve gastrectomy and conception did not impact maternal and neonatal outcomes in a study of 15 women conceived > 18 months after surgery. The authors concluded that pregnancy after sleeve gastrectomy was overall safe and well-tolerated [ 33 ]. Furthermore, a study of 30 women who became pregnant within a mean time of 17 months after gastric bariatric surgery did not appear to confer any serious risks in pregnancy with 90% of the children were born at term with normal birthweight [ 13 ]. In our study, only six patients (11%) became pregnant earlier than 18 months after surgery and the study was not designed to assess pregnancy or birth related complications.

Future implications?

The results of this study underscore the need for increased awareness of nutritional and microntutrional status to ensure adequate obstetric care both before and during post-bariatric pregnancies. Also, this study present important information on adherence to dietary supplement that should be considered in the planning of post-bariatric pregnancies. Moreover, the results of our study rises important questions on the impact of micronutrients deficiencies on future child development.

Strengths and limitations

The strengths of this study include the prospective design with matched controls. Moreover, definitions for the chosen cut-offs for micronutrient deficiency were chosen according to pregnancy specific reference intervals if established. However, we cannot rule out that the concentrations of the micronutrients change in pregnancy. Thus, the validity of the chosen cut-offs for defining micronutrient deficiency should be assessed in future studies. This study was a small single center study and did not have the statistical power to assess pregnancy related or birth related complications. The majority of the women in this study was Caucasian and the results may not be valid in populations of other ethnicities. The observational design does not provide any causality between variables. Also, we cannot rule out if the difference in gestational week for blood sampling or non-fasting blood samples might have influenced the micronutrient analyses. Finally, use of dietary supplements was self-reported and we cannot be sure that all the study participants adhered with the recommendation.

This study shows that concentrations of the micronutrients vitamin K1, magnesium, and selenium were significantly impaired in post-bariatric pregnancies compared with controls. We found a negative association between bariatric surgery and vitamin K1 and a higher risk of vitamin K1 deficiency after gastric bariatric surgery compared with sleeve gastrectomy. Vitamin K1 deficiency in post-bariatric pregnancy have potential risk of hypocoaguble state in mother and child and should be assessed in future studies.

Data availability

The data used in the present study is not open access or publicly available. The datasets are available from the corresponding author on reasonable request.

Abbreviations

Body mass index

Confidence interval

Standard deviation

Obesity in Pregnancy. ACOG Practice Bulletin, Number 230. Obstet Gynecol. 2021;137(6):e128–44.

Article   Google Scholar  

Marchi J, Berg M, Dencker A, Olander EK, Begley C. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews. Obes Rev. 2015;16(8):621–38.

Article   CAS   PubMed   Google Scholar  

Bou Nemer L, Shi H, Carr BR, Word RA, Bukulmez O. Effect of Body Weight on metabolic hormones and fatty acid metabolism in follicular fluid of women undergoing in Vitro fertilization: a pilot study. Reprod Sci. 2019;26(3):404–11.

Chao GF, Yang J, Peahl AF, Thumma JR, Dimick JB, Arterburn DE, Telem DA. Comparative effectiveness of sleeve gastrectomy vs Roux-en-Y gastric bypass in patients giving birth after bariatric surgery: reinterventions and obstetric outcomes. Surg Endosc. 2022;36(9):6954–68.

Article   PubMed   Google Scholar  

Fisher SA, Stetson BT, Kominiarek MA. Pregnancy after bariatric surgery. JAMA. 2023;329(9):758–9.

Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, Navaneethan SD, Singh RP, Pothier CE, Nissen SE, et al. Bariatric surgery versus Intensive Medical Therapy for diabetes – 5-Year outcomes. N Engl J Med. 2017;376(7):641–51.

Article   PubMed   PubMed Central   Google Scholar  

Johansson K, Cnattingius S, Näslund I, Roos N, Trolle Lagerros Y, Granath F, Stephansson O, Neovius M. Outcomes of pregnancy after bariatric surgery. N Engl J Med. 2015;372(9):814–24.

Bloomberg RD, Fleishman A, Nalle JE, Herron DM, Kini S. Nutritional deficiencies following bariatric surgery: what have we learned? Obes Surg. 2005;15(2):145–54.

Yi XY, Li QF, Zhang J, Wang ZH. A meta-analysis of maternal and fetal outcomes of pregnancy after bariatric surgery. Int J Gynaecol Obstet. 2015;130(1):3–9.

Akhter Z, Rankin J, Ceulemans D, Ngongalah L, Ackroyd R, Devlieger R, Vieira R, Heslehurst N. Pregnancy after bariatric surgery and adverse perinatal outcomes: a systematic review and meta-analysis. PLoS Med. 2019;16(8):e1002866.

Stephansson O, Johansson K, Näslund I, Neovius M. Bariatric surgery and Preterm Birth. N Engl J Med. 2016;375(8):805–6.

Roos N, Neovius M, Cnattingius S, Trolle Lagerros Y, Sääf M, Granath F, Stephansson O. Perinatal outcomes after bariatric surgery: nationwide population based matched cohort study. BMJ. 2013;347:f6460.

Chagas C, Saunders C, Pereira S, Silva J, Saboya C, Ramalho A. Perinatal outcomes and the influence of maternal characteristics after Roux-en-Y gastric bypass surgery. J Womens Health (Larchmt). 2017;26(1):71–5.

Hammeken LH, Betsagoo R, Jensen AN, Sørensen AN, Overgaard C. Nutrient deficiency and obstetrical outcomes in pregnant women following Roux-en-Y gastric bypass: a retrospective Danish cohort study with a matched comparison group. Eur J Obstet Gynecol Reprod Biol. 2017;216:56–60.

Araki S, Shani Levi C, Abutbul Vered S, Solt I, Rozen GS. Pregnancy after bariatric surgery: effects of personalized nutrition counseling on pregnancy outcomes. Clin Nutr. 2022;41(2):288–97.

Barker M, Dombrowski SU, Colbourn T, Fall CHD, Kriznik NM, Lawrence WT, Norris SA, Ngaiza G, Patel D, Skordis-Worrall J, et al. Intervention strategies to improve nutrition and health behaviours before conception. Lancet. 2018;391(10132):1853–64.

Jain S, Maheshwari A, Jain SK. Maternal Nutrition and Fetal/Infant development. Clin Perinatol. 2022;49(2):313–30.

Tam E, Keats EC, Rind F, Das JK, Bhutta AZA. Micronutrient Supplementation and Fortification interventions on Health and Development outcomes among children under-five in low- and Middle-Income countries: a systematic review and Meta-analysis. Nutrients 2020, 12(2).

Bailey RL, West KP Jr., Black RE. The epidemiology of global micronutrient deficiencies. Ann Nutr Metab. 2015;66(Suppl 2):22–33.

Gernand AD, Schulze KJ, Stewart CP, West KP Jr., Christian P. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat Rev Endocrinol. 2016;12(5):274–89.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Carducci B, Keats EC, Bhutta ZA. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 2021;3(3):Cd000230.

PubMed   Google Scholar  

Kaska L, Kobiela J, Abacjew-Chmylko A, Chmylko L, Wojanowska-Pindel M, Kobiela P, Walerzak A, Makarewicz W, Proczko-Markuszewska M, Stefaniak T. Nutrition and pregnancy after bariatric surgery. ISRN Obes. 2013;2013:492060.

PubMed   PubMed Central   Google Scholar  

Sherf-Dagan S, Goldenshluger A, Azran C, Sakran N, Sinai T, Ben-Porat T. Vitamin K-what is known regarding bariatric surgery patients: a systematic review. Surg Obes Relat Dis. 2019;15(8):1402–13.

Sherf-Dagan S, Buch A, Ben-Porat T, Sakran N, Sinai T. Vitamin E status among bariatric surgery patients: a systematic review. Surg Obes Relat Dis. 2021;17(4):816–30.

Lewis CA, de Jersey S, Hopkins G, Hickman I, Osland E. Does bariatric surgery cause vitamin A, B1, C or E Deficiency? A systematic review. Obes Surg. 2018;28(11):3640–57.

Krzizek EC, Brix JM, Stöckl A, Parzer V, Ludvik B. Prevalence of Micronutrient Deficiency after bariatric surgery. Obes Facts. 2021;14(2):197–204.

Guelinckx I, Devlieger R, Donceel P, Bel S, Pauwels S, Bogaerts A, Thijs I, Schurmans K, Deschilder P, Vansant G. Lifestyle after bariatric surgery: a multicenter, prospective cohort study in pregnant women. Obes Surg. 2012;22(9):1456–64.

Falcone V, Stopp T, Feichtinger M, Kiss H, Eppel W, Husslein PW, Prager G, Göbl CS. Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome. BMC Pregnancy Childbirth. 2018;18(1):507.

Devlieger R, Guelinckx I, Jans G, Voets W, Vanholsbeke C, Vansant G. Micronutrient levels and supplement intake in pregnancy after bariatric surgery: a prospective cohort study. PLoS ONE. 2014;9(12):e114192.

Jans G, Guelinckx I, Voets W, Galjaard S, Van Haard PM, Vansant GM, Devlieger R. Vitamin K1 monitoring in pregnancies after bariatric surgery: a prospective cohort study. Surg Obes Relat Dis. 2014;10(5):885–90.

English WJ, DeMaria EJ, Brethauer SA, Mattar SG, Rosenthal RJ, Morton JM. American Society for Metabolic and bariatric surgery estimation of metabolic and bariatric procedures performed in the United States in 2016. Surg Obes Relat Dis. 2018;14(3):259–63.

Parent B, Martopullo I, Weiss NS, Khandelwal S, Fay EE, Rowhani-Rahbar A. Bariatric surgery in women of Childbearing Age, timing between an operation and birth, and Associated Perinatal complications. JAMA Surg. 2017;152(2):128–35.

Sancak S, Çeler Ö, Çırak E, Karip AB, Tumiçin Aydın M, Esen Bulut N, Mahir Fersahoğlu M, Altun H, Memişoğlu K. Timing of Gestation after laparoscopic sleeve gastrectomy (LSG): does it influence obstetrical and neonatal outcomes of pregnancies? Obes Surg. 2019;29(5):1498–505.

Association WM. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2000;284(23):3043–5.

Means RT. Iron Deficiency and Iron Deficiency Anemia: implications and impact in pregnancy, Fetal Development, and early childhood parameters. Nutrients 2020, 12(2).

Berger MM, Shenkin A, Schweinlin A, Amrein K, Augsburger M, Biesalski HK, Bischoff SC, Casaer MP, Gundogan K, Lepp HL, et al. ESPEN micronutrient guideline. Clin Nutr. 2022;41(6):1357–424.

Nasjonal brukerhåndbok i medisinsk biokjemi. Available from https://metodebok.no/index.php?action=book&book=biokjemi . Version 2.4. Last updated 23.06.2022. Accessed 20.06.2023.

Shawe J, Ceulemans D, Akhter Z, Neff K, Hart K, Heslehurst N, Stotl I, Agrawal S, Steegers-Theunissen R, Taheri S, et al. Pregnancy after bariatric surgery: Consensus recommendations for periconception, antenatal and postnatal care. Obes Rev. 2019;20(11):1507–22.

Makrides M, Crosby DD, Bain E, Crowther CA. Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. 2014;2014(4):Cd000937.

Smelt HJM, Pouwels S, Smulders JF, Hazebroek EJ. Patient adherence to multivitamin supplementation after bariatric surgery: a narrative review. J Nutr Sci. 2020;9:e46.

Ben-Porat T, Elazary R, Goldenshluger A, Sherf Dagan S, Mintz Y, Weiss R. Nutritional deficiencies four years after laparoscopic sleeve gastrectomy-are supplements required for a lifetime? Surg Obes Relat Dis. 2017;13(7):1138–44.

Weissgerber TL, Wolfe LA. Physiological adaptation in early human pregnancy: adaptation to balance maternal-fetal demands. Appl Physiol Nutr Metab. 2006;31(1):1–11.

Pournaras DJ, le Roux CW. After bariatric surgery, what vitamins should be measured and what supplements should be given? Clin Endocrinol (Oxf). 2009;71(3):322–5.

Eerdekens A, Debeer A, Van Hoey G, De Borger C, Sachar V, Guelinckx I, Devlieger R, Hanssens M, Vanhole C. Maternal bariatric surgery: adverse outcomes in neonates. Eur J Pediatr. 2010;169(2):191–6.

Sharma S, Uprichard J, Moretti A, Boyce H, Szydlo R, Stocks G. Use of thromboelastography to assess the combined role of pregnancy and obesity on coagulation: a prospective study. Int J Obstet Anesth. 2013;22(2):113–8.

Sancak S, Altun H, Çeler Ö, Çırak E, Er C, Karip AB, Okuroğlu N, Bulut NE, Fersahoğlu MM, Sertbaş Y, et al. Impact of Gestational Weight Gain on maternal and perinatal outcomes after laparoscopic sleeve Gastrectomy. Obes Surg. 2022;32(12):4007–14.

Carabotti M, Silecchia G, Greco F, Leonetti F, Piretta L, Rengo M, Rizzello M, Osborn J, Corazziari E, Severi C. Impact of laparoscopic sleeve gastrectomy on upper gastrointestinal symptoms. Obes Surg. 2013;23(10):1551–7.

Mandeville Y, Van Looveren R, Vancoillie PJ, Verbeke X, Vandendriessche K, Vuylsteke P, Pattyn P, Smet B. Moderating the enthusiasm of Sleeve Gastrectomy: up to 50% of reflux symptoms after ten years in a Consecutive Series of one hundred laparoscopic sleeve gastrectomies. Obes Surg. 2017;27(7):1797–803.

Silveira FC, Poa-Li C, Pergamo M, Gujral A, Kolli S, Fielding GA, Ren-Fielding CJ, Schwack BF. The effect of laparoscopic sleeve gastrectomy on gastroesophageal reflux disease. Obes Surg. 2021;31(3):1139–46.

Ciangura C, Coupaye M, Deruelle P, Gascoin G, Calabrese D, Cosson E, Ducarme G, Gaborit B, Lelièvre B, Mandelbrot L, et al. Clinical practice guidelines for childbearing female candidates for bariatric surgery, pregnancy, and Post-partum Management after bariatric surgery. Obes Surg. 2019;29(11):3722–34.

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We acknowledge the work of the staff at the Section for Morbid Obesity at Akershus University Hospital HF for the persistent effort of data collection.

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Brit Torunn Bechensteen, Jacob A. Winther & Tone G. Valderhaug

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TGV and EMRS designed the study. BTB, EMRS and TGV collected the data for the study. TGV analysed the data. BTB and TGV drafted the manuscript. CS ad GK were responsible for the laboratory analyses. TGV and JAW were responsible for the statistical analyses. All authors contributed to the interpretation of data, reviewed and edited the manuscript and gave their final approval of the final version to be published.

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Bechensteen, B.T., Sithiravel, C., Strøm-Roum, E.M. et al. Post-bariatric pregnancy is associated with vitamin K1 deficiency, a case control study. BMC Pregnancy Childbirth 24 , 229 (2024). https://doi.org/10.1186/s12884-024-06407-0

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The term case study refers to both a method of analysis and a specific research design for examining a problem, both of which are used in most circumstances to generalize across populations. This tab focuses on the latter--how to design and organize a research paper in the social sciences that analyzes a specific case.

A case study research paper examines a person, place, event, phenomenon, or other type of subject of analysis in order to extrapolate  key themes and results that help predict future trends, illuminate previously hidden issues that can be applied to practice, and/or provide a means for understanding an important research problem with greater clarity. A case study paper usually examines a single subject of analysis, but case study papers can also be designed as a comparative investigation that shows relationships between two or among more than two subjects. The methods used to study a case can rest within a quantitative, qualitative, or mixed-method investigative paradigm.

Case Studies . Writing@CSU. Colorado State University; Mills, Albert J. , Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010 ; “What is a Case Study?” In Swanborn, Peter G. Case Study Research: What, Why and How? London: SAGE, 2010.

How to Approach Writing a Case Study Research Paper

General information about how to choose a topic to investigate can be found under the " Choosing a Research Problem " tab in this writing guide. Review this page because it may help you identify a subject of analysis that can be investigated using a single case study design.

However, identifying a case to investigate involves more than choosing the research problem . A case study encompasses a problem contextualized around the application of in-depth analysis, interpretation, and discussion, often resulting in specific recommendations for action or for improving existing conditions. As Seawright and Gerring note, practical considerations such as time and access to information can influence case selection, but these issues should not be the sole factors used in describing the methodological justification for identifying a particular case to study. Given this, selecting a case includes considering the following:

• Does the case represent an unusual or atypical example of a research problem that requires more in-depth analysis? Cases often represent a topic that rests on the fringes of prior investigations because the case may provide new ways of understanding the research problem. For example, if the research problem is to identify strategies to improve policies that support girl's access to secondary education in predominantly Muslim nations, you could consider using Azerbaijan as a case study rather than selecting a more obvious nation in the Middle East. Doing so may reveal important new insights into recommending how governments in other predominantly Muslim nations can formulate policies that support improved access to education for girls.
• Does the case provide important insight or illuminate a previously hidden problem? In-depth analysis of a case can be based on the hypothesis that the case study will reveal trends or issues that have not been exposed in prior research or will reveal new and important implications for practice. For example, anecdotal evidence may suggest drug use among homeless veterans is related to their patterns of travel throughout the day. Assuming prior studies have not looked at individual travel choices as a way to study access to illicit drug use, a case study that observes a homeless veteran could reveal how issues of personal mobility choices facilitate regular access to illicit drugs. Note that it is important to conduct a thorough literature review to ensure that your assumption about the need to reveal new insights or previously hidden problems is valid and evidence-based.
• Does the case challenge and offer a counter-point to prevailing assumptions? Over time, research on any given topic can fall into a trap of developing assumptions based on outdated studies that are still applied to new or changing conditions or the idea that something should simply be accepted as "common sense," even though the issue has not been thoroughly tested in practice. A case may offer you an opportunity to gather evidence that challenges prevailing assumptions about a research problem and provide a new set of recommendations applied to practice that have not been tested previously. For example, perhaps there has been a long practice among scholars to apply a particular theory in explaining the relationship between two subjects of analysis. Your case could challenge this assumption by applying an innovative theoretical framework [perhaps borrowed from another discipline] to the study a case in order to explore whether this approach offers new ways of understanding the research problem. Taking a contrarian stance is one of the most important ways that new knowledge and understanding develops from existing literature.
• Does the case provide an opportunity to pursue action leading to the resolution of a problem? Another way to think about choosing a case to study is to consider how the results from investigating a particular case may result in findings that reveal ways in which to resolve an existing or emerging problem. For example, studying the case of an unforeseen incident, such as a fatal accident at a railroad crossing, can reveal hidden issues that could be applied to preventative measures that contribute to reducing the chance of accidents in the future. In this example, a case study investigating the accident could lead to a better understanding of where to strategically locate additional signals at other railroad crossings in order to better warn drivers of an approaching train, particularly when visibility is hindered by heavy rain, fog, or at night.
• Does the case offer a new direction in future research? A case study can be used as a tool for exploratory research that points to a need for further examination of the research problem. A case can be used when there are few studies that help predict an outcome or that establish a clear understanding about how best to proceed in addressing a problem. For example, after conducting a thorough literature review [very important!], you discover that little research exists showing the ways in which women contribute to promoting water conservation in rural communities of Uganda. A case study of how women contribute to saving water in a particular village can lay the foundation for understanding the need for more thorough research that documents how women in their roles as cooks and family caregivers think about water as a valuable resource within their community throughout rural regions of east Africa. The case could also point to the need for scholars to apply feminist theories of work and family to the issue of water conservation.

Eisenhardt, Kathleen M. “Building Theories from Case Study Research.” Academy of Management Review 14 (October 1989): 532-550; Emmel, Nick. Sampling and Choosing Cases in Qualitative Research: A Realist Approach . Thousand Oaks, CA: SAGE Publications, 2013; Gerring, John. “What Is a Case Study and What Is It Good for?” American Political Science Review 98 (May 2004): 341-354; Mills, Albert J. , Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010; Seawright, Jason and John Gerring. "Case Selection Techniques in Case Study Research." Political Research Quarterly 61 (June 2008): 294-308.

Structure and Writing Style

The purpose of a paper in the social sciences designed around a case study is to thoroughly investigate a subject of analysis in order to reveal a new understanding about the research problem and, in so doing, contributing new knowledge to what is already known from previous studies. In applied social sciences disciplines [e.g., education, social work, public administration, etc.], case studies may also be used to reveal best practices, highlight key programs, or investigate interesting aspects of professional work. In general, the structure of a case study research paper is not all that different from a standard college-level research paper. However, there are subtle differences you should be aware of. Here are the key elements to organizing and writing a case study research paper.

I.  Introduction

As with any research paper, your introduction should serve as a roadmap for your readers to ascertain the scope and purpose of your study . The introduction to a case study research paper, however, should not only describe the research problem and its significance, but you should also succinctly describe why the case is being used and how it relates to addressing the problem. The two elements should be linked. With this in mind, a good introduction answers these four questions:

• What was I studying? Describe the research problem and describe the subject of analysis you have chosen to address the problem. Explain how they are linked and what elements of the case will help to expand knowledge and understanding about the problem.
• Why was this topic important to investigate? Describe the significance of the research problem and state why a case study design and the subject of analysis that the paper is designed around is appropriate in addressing the problem.
• What did we know about this topic before I did this study? Provide background that helps lead the reader into the more in-depth literature review to follow. If applicable, summarize prior case study research applied to the research problem and why it fails to adequately address the research problem. Describe why your case will be useful. If no prior case studies have been used to address the research problem, explain why you have selected this subject of analysis.
• How will this study advance new knowledge or new ways of understanding? Explain why your case study will be suitable in helping to expand knowledge and understanding about the research problem.

Each of these questions should be addressed in no more than a few paragraphs. Exceptions to this can be when you are addressing a complex research problem or subject of analysis that requires more in-depth background information.

II.  Literature Review

The literature review for a case study research paper is generally structured the same as it is for any college-level research paper. The difference, however, is that the literature review is focused on providing background information and  enabling historical interpretation of the subject of analysis in relation to the research problem the case is intended to address . This includes synthesizing studies that help to:

• Place relevant works in the context of their contribution to understanding the case study being investigated . This would include summarizing studies that have used a similar subject of analysis to investigate the research problem. If there is literature using the same or a very similar case to study, you need to explain why duplicating past research is important [e.g., conditions have changed; prior studies were conducted long ago, etc.].
• Describe the relationship each work has to the others under consideration that informs the reader why this case is applicable . Your literature review should include a description of any works that support using the case to study the research problem and the underlying research questions.
• Identify new ways to interpret prior research using the case study . If applicable, review any research that has examined the research problem using a different research design. Explain how your case study design may reveal new knowledge or a new perspective or that can redirect research in an important new direction.
• Resolve conflicts amongst seemingly contradictory previous studies . This refers to synthesizing any literature that points to unresolved issues of concern about the research problem and describing how the subject of analysis that forms the case study can help resolve these existing contradictions.
• Point the way in fulfilling a need for additional research . Your review should examine any literature that lays a foundation for understanding why your case study design and the subject of analysis around which you have designed your study may reveal a new way of approaching the research problem or offer a perspective that points to the need for additional research.
• Expose any gaps that exist in the literature that the case study could help to fill . Summarize any literature that not only shows how your subject of analysis contributes to understanding the research problem, but how your case contributes to a new way of understanding the problem that prior research has failed to do.
• Locate your own research within the context of existing literature [very important!] . Collectively, your literature review should always place your case study within the larger domain of prior research about the problem. The overarching purpose of reviewing pertinent literature in a case study paper is to demonstrate that you have thoroughly identified and synthesized prior studies in the context of explaining the relevance of the case in addressing the research problem.

III.  Method

In this section, you explain why you selected a particular subject of analysis to study and the strategy you used to identify and ultimately decide that your case was appropriate in addressing the research problem. The way you describe the methods used varies depending on the type of subject of analysis that frames your case study.

If your subject of analysis is an incident or event . In the social and behavioral sciences, the event or incident that represents the case to be studied is usually bounded by time and place, with a clear beginning and end and with an identifiable location or position relative to its surroundings. The subject of analysis can be a rare or critical event or it can focus on a typical or regular event. The purpose of studying a rare event is to illuminate new ways of thinking about the broader research problem or to test a hypothesis. Critical incident case studies must describe the method by which you identified the event and explain the process by which you determined the validity of this case to inform broader perspectives about the research problem or to reveal new findings. However, the event does not have to be a rare or uniquely significant to support new thinking about the research problem or to challenge an existing hypothesis. For example, Walo, Bull, and Breen conducted a case study to identify and evaluate the direct and indirect economic benefits and costs of a local sports event in the City of Lismore, New South Wales, Australia. The purpose of their study was to provide new insights from measuring the impact of a typical local sports event that prior studies could not measure well because they focused on large "mega-events." Whether the event is rare or not, the methods section should include an explanation of the following characteristics of the event: a) when did it take place; b) what were the underlying circumstances leading to the event; c) what were the consequences of the event.

If your subject of analysis is a person. Explain why you selected this particular individual to be studied and describe what experience he or she has had that provides an opportunity to advance new understandings about the research problem. Mention any background about this person which might help the reader understand the significance of his/her experiences that make them worthy of study. This includes describing the relationships this person has had with other people, institutions, and/or events that support using him or her as the subject for a case study research paper. It is particularly important to differentiate the person as the subject of analysis from others and to succinctly explain how the person relates to examining the research problem.

If your subject of analysis is a place. In general, a case study that investigates a place suggests a subject of analysis that is unique or special in some way and that this uniqueness can be used to build new understanding or knowledge about the research problem. A case study of a place must not only describe its various attributes relevant to the research problem [e.g., physical, social, cultural, economic, political, etc.], but you must state the method by which you determined that this place will illuminate new understandings about the research problem. It is also important to articulate why a particular place as the case for study is being used if similar places also exist [i.e., if you are studying patterns of homeless encampments of veterans in open spaces, why study Echo Park in Los Angeles rather than Griffith Park?]. If applicable, describe what type of human activity involving this place makes it a good choice to study [e.g., prior research reveals Echo Park has more homeless veterans].

If your subject of analysis is a phenomenon. A phenomenon refers to a fact, occurrence, or circumstance that can be studied or observed but with the cause or explanation to be in question. In this sense, a phenomenon that forms your subject of analysis can encompass anything that can be observed or presumed to exist but is not fully understood. In the social and behavioral sciences, the case usually focuses on human interaction within a complex physical, social, economic, cultural, or political system. For example, the phenomenon could be the observation that many vehicles used by ISIS fighters are small trucks with English language advertisements on them. The research problem could be that ISIS fighters are difficult to combat because they are highly mobile. The research questions could be how and by what means are these vehicles used by ISIS being supplied to the militants and how might supply lines to these vehicles be cut? How might knowing the suppliers of these trucks from overseas reveal larger networks of collaborators and financial support? A case study of a phenomenon most often encompasses an in-depth analysis of a cause and effect that is grounded in an interactive relationship between people and their environment in some way.

NOTE:   The choice of the case or set of cases to study cannot appear random. Evidence that supports the method by which you identified and chose your subject of analysis should be linked to the findings from the literature review. Be sure to cite any prior studies that helped you determine that the case you chose was appropriate for investigating the research problem.

IV.  Discussion

The main elements of your discussion section are generally the same as any research paper, but centered around interpreting and drawing conclusions about the key findings from your case study. Note that a general social sciences research paper may contain a separate section to report findings. However, in a paper designed around a case study, it is more common to combine a description of the findings with the discussion about their implications. The objectives of your discussion section should include the following:

Reiterate the Research Problem/State the Major Findings Briefly reiterate the research problem you are investigating and explain why the subject of analysis around which you designed the case study were used. You should then describe the findings revealed from your study of the case using direct, declarative, and succinct proclamation of the study results. Highlight any findings that were unexpected or especially profound.

Explain the Meaning of the Findings and Why They are Important Systematically explain the meaning of your case study findings and why you believe they are important. Begin this part of the section by repeating what you consider to be your most important or surprising finding first, then systematically review each finding. Be sure to thoroughly extrapolate what your analysis of the case can tell the reader about situations or conditions beyond the actual case that was studied while, at the same time, being careful not to misconstrue or conflate a finding that undermines the external validity of your conclusions.

Relate the Findings to Similar Studies No study in the social sciences is so novel or possesses such a restricted focus that it has absolutely no relation to previously published research. The discussion section should relate your case study results to those found in other studies, particularly if questions raised from prior studies served as the motivation for choosing your subject of analysis. This is important because comparing and contrasting the findings of other studies helps to support the overall importance of your results and it highlights how and in what ways your case study design and the subject of analysis differs from prior research about the topic.

Consider Alternative Explanations of the Findings It is important to remember that the purpose of social science research is to discover and not to prove. When writing the discussion section, you should carefully consider all possible explanations for the case study results, rather than just those that fit your hypothesis or prior assumptions and biases. Be alert to what the in-depth analysis of the case may reveal about the research problem, including offering a contrarian perspective to what scholars have stated in prior research.

Acknowledge the Study's Limitations You can state the study's limitations in the conclusion section of your paper but describing the limitations of your subject of analysis in the discussion section provides an opportunity to identify the limitations and explain why they are not significant. This part of the discussion section should also note any unanswered questions or issues your case study could not address. More detailed information about how to document any limitations to your research can be found here .

Suggest Areas for Further Research Although your case study may offer important insights about the research problem, there are likely additional questions related to the problem that remain unanswered or findings that unexpectedly revealed themselves as a result of your in-depth analysis of the case. Be sure that the recommendations for further research are linked to the research problem and that you explain why your recommendations are valid in other contexts and based on the original assumptions of your study.

V.  Conclusion

As with any research paper, you should summarize your conclusion in clear, simple language; emphasize how the findings from your case study differs from or supports prior research and why. Do not simply reiterate the discussion section. Provide a synthesis of key findings presented in the paper to show how these converge to address the research problem. If you haven't already done so in the discussion section, be sure to document the limitations of your case study and needs for further research.

The function of your paper's conclusion is to: 1)  restate the main argument supported by the findings from the analysis of your case; 2) clearly state the context, background, and necessity of pursuing the research problem using a case study design in relation to an issue, controversy, or a gap found from reviewing the literature; and, 3) provide a place for you to persuasively and succinctly restate the significance of your research problem, given that the reader has now been presented with in-depth information about the topic.

Consider the following points to help ensure your conclusion is appropriate:

• If the argument or purpose of your paper is complex, you may need to summarize these points for your reader.
• If prior to your conclusion, you have not yet explained the significance of your findings or if you are proceeding inductively, use the conclusion of your paper to describe your main points and explain their significance.
• Move from a detailed to a general level of consideration of the case study's findings that returns the topic to the context provided by the introduction or within a new context that emerges from your case study findings.

Note that, depending on the discipline you are writing in and your professor's preferences, the concluding paragraph may contain your final reflections on the evidence presented applied to practice or on the essay's central research problem. However, the nature of being introspective about the subject of analysis you have investigated will depend on whether you are explicitly asked to express your observations in this way.

Problems to Avoid

Overgeneralization One of the goals of a case study is to lay a foundation for understanding broader trends and issues applied to similar circumstances. However, be careful when drawing conclusions from your case study. They must be evidence-based and grounded in the results of the study; otherwise, it is merely speculation. Looking at a prior example, it would be incorrect to state that a factor in improving girls access to education in Azerbaijan and the policy implications this may have for improving access in other Muslim nations is due to girls access to social media if there is no documentary evidence from your case study to indicate this. There may be anecdotal evidence that retention rates were better for girls who were on social media, but this observation would only point to the need for further research and would not be a definitive finding if this was not a part of your original research agenda.

Failure to Document Limitations No case is going to reveal all that needs to be understood about a research problem. Therefore, just as you have to clearly state the limitations of a general research study , you must describe the specific limitations inherent in the subject of analysis. For example, the case of studying how women conceptualize the need for water conservation in a village in Uganda could have limited application in other cultural contexts or in areas where fresh water from rivers or lakes is plentiful and, therefore, conservation is understood differently than preserving access to a scarce resource.

Failure to Extrapolate All Possible Implications Just as you don't want to over-generalize from your case study findings, you also have to be thorough in the consideration of all possible outcomes or recommendations derived from your findings. If you do not, your reader may question the validity of your analysis, particularly if you failed to document an obvious outcome from your case study research. For example, in the case of studying the accident at the railroad crossing to evaluate where and what types of warning signals should be located, you failed to take into consideration speed limit signage as well as warning signals. When designing your case study, be sure you have thoroughly addressed all aspects of the problem and do not leave gaps in your analysis.

Case Studies . Writing@CSU. Colorado State University; Gerring, John. Case Study Research: Principles and Practices . New York: Cambridge University Press, 2007; Merriam, Sharan B. Qualitative Research and Case Study Applications in Education . Rev. ed. San Francisco, CA: Jossey-Bass, 1998; Miller, Lisa L. “The Use of Case Studies in Law and Social Science Research.” Annual Review of Law and Social Science 14 (2018): TBD; Mills, Albert J., Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010; Putney, LeAnn Grogan. "Case Study." In Encyclopedia of Research Design , Neil J. Salkind, editor. (Thousand Oaks, CA: SAGE Publications, 2010), pp. 116-120; Simons, Helen. Case Study Research in Practice . London: SAGE Publications, 2009;  Kratochwill,  Thomas R. and Joel R. Levin, editors. Single-Case Research Design and Analysis: New Development for Psychology and Education .  Hilldsale, NJ: Lawrence Erlbaum Associates, 1992; Swanborn, Peter G. Case Study Research: What, Why and How? London : SAGE, 2010; Yin, Robert K. Case Study Research: Design and Methods . 6th edition. Los Angeles, CA, SAGE Publications, 2014; Walo, Maree, Adrian Bull, and Helen Breen. “Achieving Economic Benefits at Local Events: A Case Study of a Local Sports Event.” Festival Management and Event Tourism 4 (1996): 95-106.

Writing Tip

At Least Five Misconceptions about Case Study Research

Social science case studies are often perceived as limited in their ability to create new knowledge because they are not randomly selected and findings cannot be generalized to larger populations. Flyvbjerg examines five misunderstandings about case study research and systematically "corrects" each one. To quote, these are:

Misunderstanding 1 :  General, theoretical [context-independent knowledge is more valuable than concrete, practical (context-dependent) knowledge. Misunderstanding 2 :  One cannot generalize on the basis of an individual case; therefore, the case study cannot contribute to scientific development. Misunderstanding 3 :  The case study is most useful for generating hypotheses; that is, in the first stage of a total research process, whereas other methods are more suitable for hypotheses testing and theory building. Misunderstanding 4 :  The case study contains a bias toward verification, that is, a tendency to confirm the researcher’s preconceived notions. Misunderstanding 5 :  It is often difficult to summarize and develop general propositions and theories on the basis of specific case studies [p. 221].

While writing your paper, think introspectively about how you addressed these misconceptions because to do so can help you strengthen the validity and reliability of your research by clarifying issues of case selection, the testing and challenging of existing assumptions, the interpretation of key findings, and the summation of case outcomes. Think of a case study research paper as a complete, in-depth narrative about the specific properties and key characteristics of your subject of analysis applied to the research problem.

Flyvbjerg, Bent. “Five Misunderstandings About Case-Study Research.” Qualitative Inquiry 12 (April 2006): 219-245.

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• Open access
• Published: 04 April 2024

Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature

• Ken-ichiro Sakata 1 ,
• Ayako Hashimoto 2 ,
• Taiho Kambe 3 ,
• Jun Sato 1 ,
• Noritaka Ohga 1 ,
• Yutaka Yamazaki 4 ,
• Masahide Koyachi 5 ,
• Itagaki Tatsuki 1 ,
• Mai Okada 1 ,
• Okura Taro 1 ,
• Hiroshi Hikasa 1 &
• Yoshimasa Kitagawa 1  

Journal of Medical Case Reports volume  18 , Article number:  198 ( 2024 ) Cite this article

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The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels.

Case presentation

This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc.

Conclusions

Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels.

Peer Review reports

Zinc deficiency in humans was recognized for the first time in 1961 [ 1 ]. Studies have reported that zinc deficiency is associated with taste disorder and glossodynia [ 2 , 3 , 4 ]. There are several other symptoms, such as bedsores, skin symptoms, delayed wound healing, fetal growth restriction, chronic diarrhea, anemia, and altered mental status [ 5 ]. The Zincage Project (research on the relationship between health/aging and zinc), an epidemiological survey in Europe, has shown that health status of older adults is positively associated with the amount of zinc in the body [ 6 ]. In the basic research field, zinc is considered an essential trace metal element, with approximately 2 g being present in the body. Zinc plays a role as the active center of 3000 types of enzymes and bioactive substances [ 7 ]. Recent human genome decoding projects have indicated that approximately 10% of genes have zinc-binding domains. Hence, researchers have focused their attention on the relationship between zinc and diverse physiological functions, including zinc transporters and zinc signals [ 8 ]. Sequelae of oral diseases caused by zinc deficiency lead to a frailty cycle. This cycle stems from appetite loss and decreased food consumption, causing undernutrition. This state results in weight loss and sarcopenia onset (Fig.  1 ).

Hypozincemia leads to frailty

To address this issue, accurate measurement of the zinc content in the body is required in clinical practice, highlighting the need to develop a method for accurate and rapid diagnosis of zinc deficiency. Zinc deficiency is known as the main factor contributing to taste disorder [ 9 ]. However, it is not well known that zinc deficiency can also cause several oral diseases, such as mouth ulcers and glossodynia, posing a diagnostic and treatment challenge in many cases [ 10 ]. Serum zinc levels are a commonly used indicator of zinc assessment in clinical practice. However, they do not accurately reflect the zinc content in the body, because they account for only less than 0.1% of the total zinc in the body [ 3 ]. Furthermore, they exhibit circadian rhythms and are easily influenced by several conditions. Owing to such disadvantages, they are not considered an absolute indicator [ 11 ]. In this study, we attempted to identify an indicator other than serum zinc levels for accurately measuring the amount of zinc in the body, focusing our attention on zinc-requiring enzymes, which show zinc-dependent activity. Zinc-requiring enzymes are activated after binding to zinc. The activity level of alkaline phosphatase (ALP), a zinc-requiring enzyme in the serum, is used as an indicator of zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. To accurately evaluate the zinc nutritional status, we shifted our focus from serum ALP to total alkaline phosphatase [ 12 , 13 ]. Four ALP isozymes are  broadly expressed in various cells (Table  1 ). Previous studies using cultured cells and animals have shown that ALP, an enzyme that is activated by coordinating zinc at the active center, plays a role in suppressing inflammation by hydrolyzing adenosine triphosphate (ATP), which serves as a danger signal extracellularly, into adenosine. The results demonstrate that ALP is a zinc-requiring enzyme (zinc marker enzyme), enabling the accurate measurement of zinc content in the body [ 14 ].

Objective: Intervention is required to break the frailty cycle; however, the following questions remain unsolved: “Which indicators should be used for zinc supplementation?”, “How long should zinc supplementation be continued?”, and “How much zinc is required for the supplementation?” We raised the possibility of conducting translational research in which basic scientific findings are translated into clinical practice, with the aim of attaining a society where “older adults can enjoy meals.” This study aimed to evaluate total ALP activity levels in the saliva, serum zinc levels, and subjective symptoms before and after zinc supplementation in patients with oral diseases caused by zinc deficiency.

Patients and methods

Saliva samples were used because they can be collected repeatedly in a noninvasive manner. They were collected before and after zinc supplementation, and subjective symptoms of taste disorder and serum zinc levels were simultaneously evaluated. Saliva sample collection and blood tests were performed only in the morning. The gustatory testing (whole mouth) results are as follows: Four types of taste solutions [sucrose (S), sodium chloride (NaCl; N), tartaric acid (T), and quinine hydrochloride dihydrate (Q)] were dropped on the dorsum of the tongue at the following concentrations (No. 1: 2.9 μmol, No. 1.5: 5.8 μmol, No. 2: 8.8 μmol, No. 2.5: 17.5 μmol, No. 3: 29.2 μmol, No. 4: 58.4 μmol, and No. 5: 2337 μmol), and cognitive thresholds were tested by tasting the samples within 2–3 seconds. Taste perception threshold testing followed the criteria in the table below, and when No. 5 could not be recognized, it was considered taste loss. The efficacy of zinc supplementation in patients with taste disorder and those with burning mouth syndrome (BMS) was evaluated using the Visual Analog Scale [ 15 ] and Numerical Rating Scale [ 16 ], respectively. Zinc content was measured using ACCURAS AUTO Zn (Shino-Test Corporation, Osaka, Japan).

Zinc was measured using the Acurus Auto Zn (Shino-Test Corporation, Tokyo, Japan) based on the colorimetric method using an automated analyzer (Hitachi 7700 series; Hitachi High-technology Corporation, Tokyo, Japan). Measurement of ALP activity in saliva was performed as follows: 5 µl of saliva was used to measure ALP activity. A total of 100 μl of substrate solution [2 mg/ml disodium  p -nitrophenylphosphate hexahydrate ( p NPP); Wako Pure Chemicals in 1 M diethanolamine buffer pH 9.8 containing 0.5 mM MgCl 2 ] was added and incubated at 37 ℃ for 1 hour. The released  p -nitrophenol product was quantified by measuring the absorbance at 405 nm.

Calf intestinal ALP (Promega) was used to generate a standard curve. This study was approved by the Hokkaido University Hospital Independent Clinical Research Review Committee (Approval No. 019-0337) and approved by the Ethics Committee of Kyoto, University Graduate School and Faculty of Medicine (Approval No. R3275).

All study procedures were performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.

Two patients experiencing hypozincemia were included. Patient 1 was a 69-year-old Japanese woman (Fig.  2 ). The patient presented to the Dentistry Center, Hokkaido University Hospital, with the chief complaint of hypogeusia. In addition to routine intraoral examination, the patient received gustatory testing, oral bacteria testing, blood tests, and chewing gum test. Intraoral examination showed mild xerostomia and tongue coating. The results of gustatory testing (whole mouth) were sweet (2.5), salty (4), sour (2), and bitter (2), indicating hypogeusia. Oral bacteria testing was unremarkable. The volume of saliva collected using the chewing gum test was 17.8 mL. Blood tests at the initial visit showed a serum zinc level of 65.6 μg/dL. Based on this low serum zinc level, the patient was diagnosed with zinc-deficient taste disorder. The total ALP activity level was 0.072 mU/5 μL. Zinc supplementation was continued for 2 months using zinc acetate hydrate. After the patient orally took zinc acetate hydrate 50 mg for 1 month, the serum zinc level improved to 115.3 μg/dL, and the total ALP activity level increased to 0.102 mU/5 μL. After the zinc acetate hydrate dose was reduced to 25 mg, the serum zinc level slightly decreased to 86 μg/dL. However, the total ALP activity level remained almost the same at 0.1 mU/5 μL.

69-year-old woman with taste disorder

Patient 2 was an 82-year-old Japanese woman (Fig.  3 ). The patient presented to the Dentistry Center, Hokkaido University Hospital, with the chief complaint of glossodynia. In addition to routine intraoral examination, she received gustatory testing, oral bacteria testing, and blood tests. Intraoral examination showed mild tongue coating. The results of gustatory testing (whole mouth) were sweet (1.5), salty (2.5), sour (2.5), and bitter (2), indicating hypogeusia. Results of oral bacteria testing were positive for Candida albicans . Administration of amphotericin B gargles eradicated C. albicans . However, glossodynia persisted after the eradication; therefore, the patient was diagnosed with BMS secondary to zinc deficiency. Blood tests at the initial visit showed a serum zinc level of 51.9 μg/dL. On the basis of this low serum zinc level, the patient was diagnosed with BMS secondary to zinc deficiency. The total ALP activity level was 0.045 mU/5 μL. Zinc supplementation was continued for 5 months using zinc acetate hydrate. After the patient orally took zinc acetate hydrate 50 mg for 1 month, the serum zinc level improved to 113.3 μg/dL, and the total ALP activity level increased to 0.05 mU/5 μL. The patient received a reduced zinc acetate hydrate dose of 25 mg for the subsequent month of zinc supplementation, and the serum zinc level and total ALP activity level 2 months after treatment initiation were 126.6 μg/dL and 0.03 mU/5 μL, respectively. Zinc acetate hydrate 25 mg was administered every other day over the third and fourth months after the initiation of zinc supplementation. Serum zinc and total ALP activity levels 4 months after treatment initiation were 71.3 μg/dL and 0.049 mU/5 μL, respectively. Zinc acetate hydrate 50 mg was administered for the fifth month after the initiation of zinc supplementation. Serum zinc and total ALP activity level 5 months after treatment initiation were 116.6 μg/dL and 0.056 mU/5 μL, respectively. The serum zinc level decreased transiently, but the total ALP activity level remained almost the same.

An 82-year-old woman with glossodynia

Discussion and conclusions

Unstable serum zinc levels.

Currently, zinc supplementation is performed on patients with taste disorder and glossodynia due to zinc deficiency based on serum zinc levels. Our previous study showed that the mean serum zinc level was 72 μg/dL in the taste disorder group and 74 μg/dL in the control group, with no relationship between taste disorder and serum zinc levels [ 17 ]. The proportion of patients with zinc deficiency in the taste disorder group was significantly higher ( p  < 0.05) only when a serum zinc level of < 60 μg/dL (that is, severe zinc deficiency) was used to identify patients with zinc deficiency. Possible explanations for the absence of an association between clinical symptoms and serum zinc levels include: (1) Serum zinc levels do not accurately reflect the zinc content in the body; (2) serum zinc levels exhibit a large fluctuation of circadian rhythms and are easily influenced by meals, stress, and hormone conditions, therefore making them problematic as an indicator of zinc deficiency; and (3) differences in serum zinc levels between laboratories (serum zinc levels tend to show a higher value in outsourcing examination than in-hospital examination owing to hemolysis). These disadvantages suggest that serum zinc levels may not reflect the bioavailability of zinc in the body in some cases. Thus, selecting an appropriate sample and developing a method to analyze the sample are important issues.

Taste disorder and zinc

The relationship between taste disorder and zinc deficiency plays an important role in regenerating taste bud cells. Taste buds, or taste sensors, are actively regenerated approximately every 10 days. Normal regeneration of taste bud cells is required to correctly recognize different tastes. Insufficient regeneration of taste bud cells due to zinc deficiency is associated with a decrease in the number of these cells, causing impairment of taste sensor function. Zinc plays an important role in protein formation that is required for cell regeneration and transmission of genetic information.

Glossodynia and zinc

Glossodynia is a traditionally well-known symptom of hypozincemia in clinical practice; however, its evident cause is unknown [ 18 ]. Zinc exerts analgesic effects when administered locally to the spinal nerves or peripheral nerves or systemically in patients with chronic pain in areas other than in the oral area, renal dysfunction, anemia, and itchy sensation on the skin [ 19 , 20 ]. The mechanism of this analgesic effect was reported in a study in 2011 [ 21 ]. In the said study, increased sensitivity to pain was observed in knockout mice whose zinc ion binding to the NMDA-type glutamate receptor was inactivated. The authors reported that C fibers were particularly affected as compared with Aδ fibers, resulting in difficulty in suppressing chronic pain. Chronic glossodynia signals are transmitted to the brain mainly via C fibers, suggesting that the association between hypozincemia and glossodynia may be mediated by NMDA receptors, although the details remain to be clarified.

Total ALP activity levels

Both patients experienced a transient decrease in serum zinc levels, but total ALP activity levels did not change. Total ALP activity is involved in the dephosphorylation of various physiological substrates and has vital physiological functions, including extraskeletal functions such as neuronal development, detoxification of lipopolysaccharide, an anti-inflammatory role, bile pH regulation, and maintenance of the blood–brain barrier. Total ALP activity has also been reported to be involved in cardiovascular calcification, chronic kidney disease, and type 2 diabetes [ 22 ]. In particular, it is a logical clinical target to attenuate vascular calcification. Total ALP activity has gained attention as a clinical marker in several diseases. The relationship between total ALP activity levels and changes in zinc content in the body has been evaluated only in studies using cultured cells and animals. Thus, this is the first study to report the relationship in humans. Furthermore, this study used saliva samples; therefore, the results are extremely useful because these samples can be collected repeatedly in a noninvasive manner. Further cross-sectional or cohort studies are required to clarify the relationship between serum zinc levels and zinc-requiring enzymes, including total ALP activity, to interrupt the disease cycle due to zinc deficiency and improve the health status. This study suggests that total ALP activity may be a new diagnostic marker alternative to serum zinc levels. Furthermore, it may be used as an indicator when assessing the efficacy of zinc supplementation.

Availability of data and materials

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Abbreviations

Alkaline phosphatase

Prasad AS, Halsted JA, Nadimi M. Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am J Med. 1961;31:532–46.

Article   CAS   PubMed   Google Scholar  

Sakata KI, Hato H, Sato J, Iori T, Ohga N, Watanabe H, et al . Ethyl loflazepate as a treatment for patients with idiopathic and psychogenic taste disorder. Biopsychosoc Med. 2022;16:16.

Article   PubMed   PubMed Central   Google Scholar  

Yutaka Y, Ken-Ichiro S, Jun S, Manabu O, Hironobu H, Atsushi M. Clinical study of 210 cases of taste disorder. J Jpn Stomatol Soc. 2013;62:247–53.

Google Scholar  

Ohga N, Yamazaki Y, Sato J, Hata H, Murata T, Sakata K, et al . Dose escalation effectiveness and tolerability of paroxetine in patients with burning mouth syndrome and depressive conditions. J Oral Maxillofac Surg Med Pathol. 2015;27:402–6.

Article   Google Scholar  

Ogawa Y, Kinoshita M, Shimada S, Kawamura T. Zinc and skin disorders. Nutrients. 2018;10:199.

Haase H, Mocchegiani E, Rink L. Correlation between zinc status and immune function in the elderly. Biogerontology. 2006;7:421–8.

Andreini C, Banci L, Bertini I, Rosato A. Zinc through the three domains of life. J Proteome Res. 2006;5:3173–8.

Kambe T, Taylor KM, Fu D. Zinc transporters and their functional integration in mammalian cells. J Biol Chem. 2021;296: 100320.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Nin T, Tsuzuki K. Diagnosis and treatment of taste disorders in Japan. Auris Nasus Larynx. 2023. https://doi.org/10.1016/j.anl.2023.04.002 .

Article   PubMed   Google Scholar  

Hewlings S, Kalman D. A review of zinc-L-carnosine and its positive effects on oral mucositis, taste disorders, and gastrointestinal disorders. Nutrients. 2020;12:665.

Sakata K, Yamazaki Y, Sato J, Hata H, Mizutani A, Oouchi M, et al . Study on association between subjective symptoms of the taste disorder and serum zinc level. J Jpn Oral Med. 2012;18:39–43.

Rocha ÉD, de Brito NJ, Dantas MM, Silva A, Almeida Md, Brandão-Neto J. Effect of zinc supplementation on GH, IGF1, IGFBP3, OCN, and ALP in non-zinc-deficient children. J Am Coll Nutr. 2015;34:290–9.

Sato M, Saitoh I, Kiyokawa Y, Iwase Y, Kubota N, Ibano N, et al . Tissue-nonspecific alkaline phosphatase, a possible mediator of cell maturation: towards a new paradigm. Cells. 2021;10:3338.

Hashimoto A, Nakagawa M, Tsujimura N, Miyazaki S, Kizu K, Goto T, et al . Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation. Am J Physiol Regul Integr Comp Physiol. 2016;310:R459–68.

McCormack HM, Horne DJ, Sheather S. Clinical applications of visual analogue scales: a critical review. Psychol Med. 1988;18:1007–19.

Wikström L, Nilsson M, Broström A, Eriksson K. Patients’ self-reported nausea: validation of the numerical rating scale and of a daily summary of repeated numerical rating scale scores. J Clin Nurs. 2019;28:959–68.

Sakata KI, Yamazaki Y, Sato J, Hata H, Mizutani A, Oouchi M. Yoshimasa Kitagawa study on association between subjective symptoms of the taste disorder and serum zinc. J Jpn Oral Med. 2012;18:39–43.

Cho GS, Han MW, Lee B, Roh JL, Choi SH, Cho KJ, et al . Zinc deficiency may be a cause of burning mouth syndrome as zinc replacement therapy has therapeutic effects. J Oral Pathol Med. 2010;39:722–7.

Larson AA, Kitto KF. Manipulations of zinc in the spinal cord, by intrathecal injection of zinc chloride, disodium-calcium-EDTA, or dipicolinic acid, alter nociceptive activity in mice. J Pharmacol Exp Ther. 1997;282:1319–25.

CAS   PubMed   Google Scholar  

Liu T, Walker JS, Tracey DJ. Zinc alleviates thermal hyperalgesia due to partial nerve injury. NeuroReport. 1999;10:1619–23.

Nozaki C, Vergnano AM, Filliol D, Ouagazzal AM, Le Goff AL, Carvalho S, et al . Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nat Neurosci. 2011;14:1017–22.

Sekaran S, Vimalraj S, Thangavelu L. The physiological and pathological role of tissue nonspecific alkaline phosphatase beyond mineralization. Biomolecules. 2021;11:1564.

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Acknowledgements

I would like to give my heartfelt thanks to Prof. Kitagawa whose comments and suggestions were immeasurably valuable throughout the course of my study. I am also in debt to Prof. Yamazaki whose meticulous comments were enormously helpful. I would like to express my gratitude to Mr. Taiho Kambe and Ayako Hashimoto, for the valuable advice for evaluating zinc content in the body. I would also like to thank my family for their moral support and warm encouragement.

This study was partially supported by Lotte Co., Ltd., Tokyo, Japan.

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Department of Oral Diagnosis and Medicine, Division of Oral Pathobiological Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan

Ken-ichiro Sakata, Jun Sato, Noritaka Ohga, Itagaki Tatsuki, Mai Okada, Okura Taro, Hiroshi Hikasa & Yoshimasa Kitagawa

Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women’s University, Kyoto, Japan

Ayako Hashimoto

Department of Applied Molecular Biology, Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan

Taiho Kambe

Department of Gerodontology, Division of Oral Health Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan

Yutaka Yamazaki

Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Tokyo, Japan

Masahide Koyachi

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Contributions

Conceptualization: KS and JS. Methodology/formal analysis: AH and TK. Investigation: OT and TI. Resources: KS and NP. Data curation: KS. Writing—original draft preparation: KS. Writing—review and editing: YY. Visualization: NO, MO, and HH. Supervision: YK. Project administration: KM. All authors have read and agreed to the published version of the manuscript.

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In this report, we anonymized personal information and ensured the protection of privacy. This study was approved by the Hokkaido University Hospital Independent Clinical Research Review Committee (Approval No. 019–0337) and approved by the Ethics Committee of Kyoto, University Graduate School and Faculty of Medicine (Approval No. R3275). Written informed consent was obtained from all participants.

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Sakata, Ki., Hashimoto, A., Kambe, T. et al. Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature. J Med Case Reports 18 , 198 (2024). https://doi.org/10.1186/s13256-024-04463-w

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For more than a century, the pharmaceutical company Roche has been headquartered in Basel, Switzerland. It’s one of more than a dozen pharmaceutical companies that have long been based there.

Howard Yu , Lego Professor of Management and Innovation at IMD Business School in Switzerland, discusses how this industrial cluster is a unique example of enduring competitive advantage. He explains how these companies offer a counter-narrative to the pessimistic view that you can’t stay ahead of the competition for long.

In this episode, you’ll learn how these historic companies began as makers of chemical dyes and later evolved into microbiology. You’ll also learn how to repackage your company’s existing knowledge to pioneer new products and services. And you’ll learn why persistence and experimentation over the long term are prerequisites for innovation.

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For more than a century, the pharmaceutical company Roche has been headquartered in Basel, Switzerland. It’s just one of more than A dozen pharma companies who have long been based in the historic city, which sits at the crossroads of Switzerland, Germany, and France.  Innovation expert Howard Yu says that this industrial cluster is a unique example of enduring competitive advantage.

Yu is the Lego Professor of Management and Innovation at IMD Business School in Switzerland. He explains that the story of these enduring companies offers a counter-narrative to the pessimistic view that you can’t stay ahead of the competition for long. In this episode, you’ll learn how these historic companies began not as pharmaceutical companies, but as makers of chemical dyes. Their transition from organic chemistry to microbiology was an enormous change that ensured the longevity of their businesses.

You’ll also learn how to rethink and repackage your company’s existing knowledge in order to pioneer new products and services – and you’ll learn why persistence and experimentation over the long term are pre-requisites for innovation.  

This episode originally aired on HBR IdeaCast in July 2018. Here it is.

CURT NICKISCH: Welcome to the HBR IdeaCast from Harvard Business Review. I’m Curt Nickisch. Float down the Rhine River through the City of Basel in Switzerland and the murky water will carry you past the red sandstone cathedral up on the hill, along old stone embankments and under a medieval bridge. You’ll also pass the gleaming Roche Tower jetting diagonally into the sky like an optimistic sales forecast. And outside the old city, you’ll drift past the shiny new sculptured glass offices of Novartis. These global pharmaceutical companies here have rich corporate campuses.

HOWARD YU: At Novartis for example, the campus looks almost like a modern museum in many ways. There are stone gardens. There are major art installations all across the campus and the buildings were designed by a famous architect.

CURT NICKISCH: Speaking there is Howard Yu. He’s a management and innovation professor at IMD Business School in Switzerland. And what really impresses him is that these enterprises have been on the shore of the Rhine River for the better part of two centuries. After all, Yu grew up in Hong Kong where he saw industries rise and fall in short order. He says this enduring industrial cluster in Basel is unique.

HOWARD YU: And it’s just interesting element around how a city, a cluster industry can enjoy so much bountiful prosperity that really tricked me to go explore this particular city.

CURT NICKISCH: How these companies have stayed on top for so long is the subject of his new book. It’s called Leap: How Businesses Thrive in a World Where Everything Can Be Copied.  I spoke to Yu recently on a day when my seasonal allergies were pretty bad, maybe something that those drug companies in Basel could help with. Howard, thanks so much for talking with the HBR IdeaCast.

HOWARD YU: My pleasure.

CURT NICKISCH: You have this title, Leap for your book, but when you talk about the pharmaceutical companies in Basel, there’re companies that have been in one place for a long time. They look like they’ve just stayed the same and endured. So, how do you explain that these pharmaceutical companies in Basel have lept ahead?

HOWARD YU: Yeah. The pharmaceutical cluster in Basel, Switzerland is sort of an anomaly because, in the field of competitive strategy, I think we are so well trained and thinking is so entrenched that you want to build up a defense for competitive possession. That you want to build a structural barrier to protect your businesses against competition over a long period of time. That seems to be the dominant thinking among executives and manager. That is a mirage. Because no value proposition can stay unique forever. Any blue ocean may turn red over time. If we were to look at different industries for a moment from automotive to textile, for example, to heavy machinery, personal computers, all the way to the mobile phone, inevitably what we see is expertise and capital and know how to migrate from one country to another. This anomaly in Basel kind of jumped out at me. And they’ve been settling in the same location for almost close to 200 years.

CURT NICKISCH: So, what is the conventional thinking, at least in Switzerland or elsewhere about how these drug companies have endured there?

HOWARD YU: Yeah. The usual response I get is, an executive would say, well, drug discovery is very high-tech. Or, drugs are subject to FDA approval, which is hard to get and as patent right. And yet, personal computers once upon a time, also have a lot of IP. Automotive has a lot of IP. And even the textile industry, 200 hundred years ago is the high-tech of the day. And yet they couldn’t stay away unscathed by global competition. What’s really interesting about Basel is how do these drug companies continue to reinvent itself? So, I decided to spend some time to just to understand from a historical development, a historical perspective what have these pharmaceutical companies have been doing throughout its long history of time, 200 years or so, to stay competitive, to fend off other low-cost competition differently than other industry we’ve seen.

CURT NICKISCH: What did you find?

HOWARD YU: Yeah, so it turns out at first they were actually old chemical dye maker for the textile industry. Now, some of these chemists, somehow they discovered there are medicinal benefits of the chemical dye. So, the first blockbuster in the world in the 19th Century is actually is antipyretic. It’s a fever-reducing drug. So, in many ways, organic chemistry is the hotbed for innovation. Now, we all remember back in high school, Alexander Fleming who discovered antibiotics, penicillin. So, after the Second World War, all the pharmaceutical companies essentially begins to study intensively around microbiology. They sent in a few workers to go down mineshafts. They sent a balloon to collect air samples. They called employees to ask them to look at the back of the fridge to look at an interesting mold.

CURT NICKISCH: Really?

HOWARD YU: Yes, in search of the next pay dirt. So, essentially the innovation discipline gradually moved away from organic chemistry to microbiology. Now of course, now these states, if we ask anybody what is the hotbed for innovation for medicine, its genomics.  So, if you’re looking at pharmaceutical co-industry, what’s really interesting is for these pioneers to discover new drugs, essentially they need to leap from one knowledge discipline to the next, starting from organic chemistry to microbiology’s and then today, it’s genomics. And I believe it is because the recurring, or the continuous leap from one discipline to another that allows the pioneering company, such as the one in Basel that is able to stay on top of the competition. And it’s essentially leaping to a new discipline that opens up new paths for growth, so that the latecomer, the copycats always have a hard time in catching them up.

CURT NICKISCH: Got it. They essentially have to be pioneers and then become pioneers again and then become pioneers again.

HOWARD YU: That’s right.

CURT NICKISCH: You said this is different from other industries.

HOWARD YU: Yep. That is a sort of stark contrast and that really draw my interest to understand what causes some company to stay pioneering and prosper long period of time, versus others kind of being swept away.

CURT NICKISCH: Yeah. You also went to Harvard Business School where your dissertation advisor was Clayton Christensen and so, you studied disruptive innovation as well. The name of your book is Leap: How to Thrive in a World Where Everything Can Be Copied. But I think a lot of people think of disruption or companies going out of business, not having their stuff copied, but having other people basically, rather than copy them it’s more like they pull the rug out from under them. Is this a world where everything can be copied or something a little different?

HOWARD YU: That’s a great question. What we see in my research is disruption oftentimes is a real threat, but that’s not the only threat. In fact, even when an industry seemingly stays constant, nothing changes, the pioneering company, if it doesn’t leap to a new knowledge discipline, sooner or later its financial resources or its market positioning will get threatened. The latecomer will catch up. Let me give you an analogy here. Competition, industry competition is always like mountaineering. Meaning, every company tries to reach the mountain peak. Now, if the knowledge discipline stays stagnate from automotive to textile, to piano making, sooner or later the latecomer will reach the same height. However, if the knowledge discipline evolves from organic chemistry to biology’s to genomics such as the one we explore in pharmaceuticals, then the mountains almost feeling like there’s a constant mudslide that pushes everyone downwards. In those situation,s it turns out it’s the most experienced one, the most early one that has mastered the old knowledge that withstands a better chance to stay on top of this game. And which is why if you’re looking at industry such as solar panel manufacturing, mobile phone making, and wind turbine, and heavy machinery, the latecomer i.e., the Asian competitor, they all have pretty much a meaningful or even formidable position in the global market versus drug discovery. The Western company paradoxically still leads the pack in leading drug discovery itself. And I think it’s because this leap of knowledge discipline that pushed out the latecomers so much that they had a hard time in catching up.

CURT NICKISCH: For now.

HOWARD YU: For now.

CURT NICKISCH: Yeah. That’s so interesting. I like how you reference the mastery of the old because it sounds like it’s not just about focusing on the new or leaping to someplace new. Can you help explain why that mastery is so important?

HOWARD YU: If we go back to the study of microbes or microbiology, in fact at that time the scientists and the engineers, they were pouring different dyes and acid onto bacteria, to understand the mechanism and the reaction. In fact, the discovery of chromosome is because some of these chemists actually pouring dye, to dye the nuclear of the cell, then they see the structure of a chromosome. As cell divided, was the roll. So, it’s this idea that what you know in the past is the pre-knowledge for you to understand the future. And I think there is a lot of fear about disjoint or discontinuous disruption that causes people to completely disregard about the past. Now, sometimes this continuous change does hit an industry in a very big way. But complete disregarding the past, and forget about everything that you have as a unique asset and never reimagine how to repackage this unique asset for future use, that’s a big pity.

CURT NICKISCH: So, what’s an example of a company outside of Switzerland that you think has done this well, sort of in modern times where they’ve been able to use their pre-knowledge of where they’ve been to make leaps into new places and stay experts and stay ahead of the followers?

HOWARD YU: I deliberately tried to find international examples, seemingly impossible examples during my research and one company that I came across is from Japan. Its name is Recruit Holdings and it used to be a classified post publisher. So, they make a print magazine, like the Yellow Pages. And I thought this company should have died a long time ago because of their obsolete business model. Interestingly enough, Recruit Holdings was able to reinvent itself, leaping into new knowledge discipline and today is an international service provider for small, medium-size companies across Japan that today if you’re looking at a PE ratio, price per earnings ratio, or revenue or sales per spot price, they were at the same range as Google and Facebook.

CURT NICKISCH: How specifically did they do that?

HOWARD YU: Yeah, so when Recruit begins to notice the emergence of the internet, one thing that they’ve done is to do small-scale experiments. They moved one of the magazines online and provide all those contents for free. Now, they don’t turn profitable overnight. In fact, they suffered some corporate loss over the course of three years and it’s only the fourth year then they see their online magazine to begin to rake in revenue.

CURT NICKISCH: Right. This sounds, I mean this sounds like a classic job of managing disruption of your industry.

HOWARD YU: Absolutely right. Because in many ways they don’t know what they don’t know and you have to go into the field and do it by yourself, rather than outsource to a management consultant, in order to gain that early experience. Because this is, we’re talking about the early 2000s. No one had worked out the internet rules. It was at the time that even academic research about platform strategies, still very little. But what they have learned over time, a lot of the customers are putting ads on their magazine, a small time proprietor, mom and pop store, beauty salon, small-time restaurants. They don’t just want sales, but in fact, there are a host of administrative tasks that were distracting. For example, if you are a beauty salon, the last thing you want is to have double book your customers who are trying to get a haircut at the same slot. But yet, at the same time all the small time proprietors, they continue to do a lot of these booking systems on paper. Very labor intensive, using, taking up a lot of time that distracts them from serving the customer better. And so, Recruit Holdings begins to experiment beyond just selling advertising space online. They provide an internet-based solution such as a booking system for customers, such as table reservations at restaurants. The interesting thing for Recruit is they never just stopped from one single service, but the moved into a vertical stack. Meaning every time they encountered and discovered ping pong of their customer, they think about a new solution and provide that solution to wrap it around job to be done so well that their customer finds it very hard to resist. Now, eventually, they begin to change their business model from simply selling advertisement space online, too much more akin to a subscription base for services and so on. And so today, what they have been doing is to really thinking about how can we harness our database through artificial intelligence? So, again a new knowledge frontier.

CURT NICKISCH: So, that’s a pretty remarkable digital transformation. To go from being a classified company on printed pages to a company that’s working in new forms of artificial intelligence to stay ahead as a tech company. How did they do that? How did they know to make the transformation as they did and not go the route that most companies did?

HOWARD YU: Yeah, that’s a very important question because in many ways when companies leap the investment it represents or the payoff of these investment represents is very, very hard to translate into a financial or conventional financial analysis. And I think this is actually the root cause of why we see so few companies are successfully able to leap into the new knowledge frontier. If I take a broad view of Recruit Holdings as I go through the whole corporate archives, two things jumped out. One is the company has a buyer’s for experimentation. And in many ways that is the only way to reduce the dark space of ignorance because we can debate all day long whether this is our strategic intent, whether this should be going forward or not, but unless the company really tries things out on the ground, they don’t know what they’re doing, they know. And so, one is the idea of empowering middle manager to experiment with different initiatives around a new knowledge discipline, that’s absolutely paramount. However, that’s not sufficient because time and time again, I have observed companies who are quite happy to do small-scale experimentation, but no one finally makes the call of pulling the trigger and move from an emerging strategy into a deliberate strategy. This is really important because from R&D to product development, into scale and commercialization, it requires major double down of the investment amount. Yet again, what we see from Recruit to other companies who are able to leap forward is that at some point the senior management team will essentially review all the early evidence and at some point, they will pull the trigger despite the short-term payoff doesn’t look very favorable.

CURT NICKISCH: How rare is this organizational skill and insight and commitment?

HOWARD YU: You know, I thought it was pretty rare at first, but it’s actually more common as my research continued to unfold. I saw that type of CEO behavior also from companies such as Proctor & Gamble, Apple is another example, Amazon is another example, even NGOs, and others. The CEO, once he understands the new knowledge discipline, actually could reconfigure how the company brings drugs to the market, he essentially tells his direct reports, quote, money doesn’t matter. Let’s go ahead. Now it does require the senior leader to say something like of that kind of nature. Money doesn’t matter. Full steam ahead. And so it’s this idea of a combination of experimentation of the middle manager who is close to the market, close to the ground and gets the learning. But at the same time, at some point, you do require a senior executive to move from an experimentation mode into a deliberate mod and to make that resource allocation accordingly. That would result in a leap of an organization. I admit it’s rare, but rare not in the sense that it’s not a learnable skill. But it requires executives and senior managers to really change the way they spend their time and delegate as much as possible of their main business to people who can pick up that responsibility, but also use more time in understanding the new business, the new knowledge discipline which requires personal learning. And I think it’s this disjoint between the two, as a result, we see less occurrence than we hoped to have observed.

CURT NICKISCH: How do you know if you work at one of these companies?

HOWARD YU: One key element that could be quite obvious would be whenever the company suffers some short-term ups and downs in terms of earnings or revenue, would they immediately cut off all the initiative regardless of early traction or not? That start, stop, start, stop usually is a very, very dangerous sign that a company doesn’t take the initiatives or the importance of leaping forward seriously enough. On the contrary, there are times that when companies suffer a short-term hit of the mainstream business, they continue to persist certain element of the experimentation inside a firm and that’s usually a good sign. This ability to acknowledge when things don’t work out, it’s OK to exit. When things are still persistent we will continue to reinvest. And when the signal is right, then there would be a pull of the trigger and move the organization along through a deliberate strategy. That is the usual signal whether these companies take it seriously or not. And that’s usually quite obvious once we zoom into that level.

CURT NICKISCH: Yeah. Well, the same way an animal leaps you can sort of see if an organization’s really sort of coiling up for the jump.

CURT NICKISCH: Howard, what’s your hope for writing this book that illuminating these companies and clusters that have sort of defied the usual track record?

HOWARD YU: When I talk to managers and executives around the topic of innovation, oftentimes there is almost this inevitable pessimism going on. It’s almost this declaration that if you’re not Google, if you’re not Facebook, if you’re not like an internet company, our future will be inevitably threatened. And as an industry incumbent, we are trapped in this inevitable downward spiral. And the reason that I write this book is to provide a counter-narrative with evidence. In fact, if you are able to repackage what you know, in fact, the art of success is even higher. So, I think it’s this type of example and knowhow and framework that we need so that manager would no longer condemn their own industry collapse into something of an external factor, but in fact, we can shape the environment and shape the future of one’s company.

CURT NICKISCH: Howard, this has been great. I want to thank you for showing a better way up and over, I guess. A good way to leap and move ahead.

HOWARD YU: Thank you so much, Curt. It’s been wonderful talking to you.

HANNAH BATES: That was Howard Yu, Lego Professor of Management and Innovation at IMD Business School in Switzerland – in conversation with Curt Nickisch on the HBR IdeaCast . Yu is the author of the book Leap: How to Thrive in a World Where Everything Can Be Copied .  

We’ll be back next Wednesday with another hand-picked conversation about business strategy from the Harvard Business Review. If you found this episode helpful, share it with your friends and colleagues, and follow our show on Apple Podcasts, Spotify, or wherever you get your podcasts. While you’re there, be sure to leave us a review.

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This episode was produced by Curt Nickisch, Anne Saini, and me, Hannah Bates. Ian Fox is our editor. Special thanks to Rob Eckhardt, Adam Buchholz, Maureen Hoch, Adi Ignatius, Karen Player, Ramsey Khabbaz, Nicole Smith, Anne Bartholomew, and you – our listener.

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• Published: 03 April 2024

Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study

• Mahendra Atlani 1   na1 ,
• Ashok Kumar 2   na1 ,
• Rajesh Ahirwar 3 ,
• M. N. Meenu 1 ,
• Sudhir K. Goel 2 ,
• Ravita Kumari 2 ,
• Athira Anirudhan 1 ,
• Saikrishna Vallamshetla 4 &
• G. Sai Tharun Reddy 4  

BMC Nephrology volume  25 , Article number:  120 ( 2024 ) Cite this article

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Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India.

The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases ( n  = 60) were compared with CKD ( n  = 62) and healthy subjects ( n  = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test.

CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3–132.7) µg/L compared to CKD 4.5 (0.0–58.8) µg/L and healthy subjects 39.01 (4.8–67.4) µg/L ( p  < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003–1.024) P  < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu ( p  > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects ( P  = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029–9.818) p  < .05).

The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.

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Chronic kidney disease of unknown cause (CKDu) has been reported in various parts of the world (i.e., Nicaragua, El Salvador, Sri Lanka), including India, as an endemic disease. The disease is a diagnosis of exclusion, made when a patient fulfils the Kidney Disease Improving Global Outcomes (KDIGO) CKD criteria but without the evidence of a recognized cause such as diabetes, hypertension, or glomerulonephritis [ 1 ]. No uniform and definite cause has yet been identified, though various environmental factors have been associated with and suggested to play a role in the pathogenesis. For example, heat stress, strenuous exercise, agrochemicals, and heavy metals have been held responsible for Mesoamerican nephropathy [ 2 ]. Mixed evidence has been reported for association with agrochemicals, heavy metals, and genetic variability for CKDu in Sri Lanka [ 3 , 4 , 5 ]. In India, one small study reported an association of heavy metals with CKD [ 6 ]. A study done on groundwater samples from the Uddanam region of Andhra Pradesh (India), which has a high prevalence of CKDu reported water as acidic (pH < 6.5) and to contain higher silica and lead in wet and dry seasons, respectively. Phthalates were also detected in the groundwater [ 7 ]. Previous studies have attempted to find a correlation between heavy metals and CKDu by comparing cases and endemic and nonendemic controls [ 4 ]. No study has yet tried to find the association of heavy metals comparing CKDu with CKD. Furthermore, previous studies have used urinary metal levels as a biomarker of metal exposure. There is an inherent issue of reverse causality i.e., reduced excretion of metals in urine with a reduction in glomerular filtration rate (GFR) [ 8 ]. Measurement of metals in blood has also been reported to be a promising biomarker of metal exposure [ 9 , 10 ]. Some studies have employed urine to blood ratio for deciding whether urine or blood levels should be used for a particular metal. For metals with urine/blood ratio more than one blood metal levels, whereas for metals with urine/blood ratio less than one, urine metal levels were used in estimation analysis [ 11 ]. The purpose of this study was to test hypothesis whether heavy metals i.e. Arsenic (As), Cadmium (Cd), Lead (Pb) and Chromium (Cr) are associated with CKDu, in central India using blood and urine levels as biomarker of metal exposure.

Materials and methods

Study setting and population.

Study was conducted in a tertiary care hospital setting in the Department of Nephrology in India in a case-control design between December 2019 to June 2022. Participants were enrolled between December 2019 -December 2021. The data collection was done simultaneously. The sample analysis was carried out between January to June-2022. The study was performed according to the guidelines of the Declaration of Helsinki. The study objective was to compare CKDu cases with CKD and healthy controls with regard to biomarkers of exposure of heavy metals [blood and urine levels of cadmium (Cd), lead (Pb), arsenic (As) and chromium (Cr)]. The study included adults aged 18–70 years with CKDu and two groups of the control population, one with CKD and another group of healthy controls without evidence of CKD.

The CKDu and CKD cases were inducted among the patients visiting the nephrology outpatient department and based on pre-defined criteria. At the same time, healthy controls were inducted among the healthy relatives accompanying the patients visiting other departments of the institute for treatment. Written informed consent was obtained from all the participants.

The case definition of CKDu was based on criteria proposed by the Indian Society of Nephrology for the diagnosis of CKDu [ 12 ]. The inclusion criteria included- eGFR < 60 mL/min/1.73m2 (CKD-EPI) [ 13 ] and albumin-to-creatinine ratio (ACR) > 30 mg/g for more than 3 months with:

Urine protein creatinine ratio(PCR) less than 2g/g.

No history of glomerulonephritis, pyelonephritis, renal calculi, polycystic kidneys or obstruction on renal ultrasound.

Not on treatment for diabetes and HbA1c less than 6.5%.

Blood pressure less than 140/90 if CKD stage 1 and 2; and less than 160/100 if CKD stage 3,4, and 5 and on a single drug for blood pressure control.

Case definition of CKD was based on: eGFR < 60 mL/min/1.73m2 (CKD-EPI) and albumin-to-creatinine ratio > 30 mg/g for more than 3 months. Patients were included in the CKD group only if PCR > 2g/g. Hypertension with BP > 140/90 in stages 1–2 and > 160/100 in stages 3–5 or on two or more drugs for BP control.

CKD staging was based on the KDIGO-2008 classification [ 1 ]. The same stages were applied to categorize the renal functions of subjects with CKDu.

Inclusion criteria for healthy controls included: Absence of CKD as evidenced by eGFR more than 90 ml/min/1.73m2, ACR < 30mg/g and lack of anatomical renal disease, obstruction or stone on renal ultrasound, no history of diabetes, HbA1C less than 6.5 and BP less than 140/90.

Biases were kept a minimum by adhering to the case definition described above, and study exposures are mainly objectively assessed with very less dependency on recall i.e. for pesticide or painkiller use. The urine metal levels were adjusted for urine dilution by estimating metals per gram of creatinine in urine.

Sample size

Assuming a difference of moderate effect size (0.25), between three groups (CKDu cases, CKD Controls, Normal Controls) with a confidence level of 95% and power of 80%, the calculated sample size was 159. The final sample size estimated, including a 10% non-response rate, was 180 (60 per group).

Specimen collection and analysis

For the analysis of heavy metals, venous blood (2 ml) was collected in trace element free Trace Element K2-EDTA Vacutainer (Cat# BD 368381). Whole blood was stored at -40 °C until analysis. Ten millilitres (10 ml) of first-morning urine was collected in 50 ml polypropylene tubes. Urine was stored at -40 °C in aliquots until analysis. Serum and urine creatinine was measured using a modified kinetic Jaffe’s method using a Random Access Fully Automated Chemistry Analyzer (Beckman Coulter). Urinary protein and urine albumin were estimated using a colorimetric and immune-turbidimetric methods, respectively, using a Random Access Fully Automated Chemistry Analyzer (Beckman Coulter). HbA1c was analyzed by ion-exchange high pressure liquid chromatography method using a D10 Haemoglobin testing system (BioRad Laboratories). eGFR was calculated from serum creatinine and CKD -EPI equation (Ref). A kidney ultrasound was performed in standard B Mode grey scale in 3.5–5 MHz, the longitudinal length was measured along with the width and thickness of the kidney, renal stones, and any other anatomical abnormality.

Estimation of heavy metals in blood and urine

Levels of Cd, Pb, Cr and As were measured in whole blood and urine. Urinary spot sample results of metal analysis were adjusted for dilution by urine creatinine. Metal analysis was carried out at NIREH, Bhopal (India).

Levels of various heavy metals, viz. Cd, Pb, Cr, As in the collected blood and urine samples were analyzed through inductively coupled plasma optical emission spectroscopy (iCAP® 7400 Duo ICP-OES, ThermoFisher Scientific® Pvt. Ltd). Blood and urine samples were acid-digested in a microwave oven prior to metal detection on ICP-OES. For blood digestion, 1 mL of whole blood sample was mixed with 6 ml of a freshly prepared mixture of concentrated trace metal grade nitric acid (HNO3) and hydrogen peroxide (H2O2) in a ratio 2:1 (v/v) in high-purity polytetrafluoroethylene (PTFE-TFM) vessels. For urine digestion, 5 mL of urine sample was mixed with 6 ml of a freshly prepared mixture of HNO3 and H2O2 in a ratio of 2:1. After gentle mixing of these reactants with blood, the PTFE-TFM vessels were arranged in the rotor (24HVT80, Anton PAAR) and digestion was carried out in the Anton Paar, multi microwave PRO Reaction System at 200 C for 15 min. Digested samples were cooled to 40°C and diluted to 30 ml with distilled water. Blank was prepared for each cycle of digestion using distilled water, nitric acid, and hydrogen peroxide mixture. All the chemicals were trace-element free.

Before the analysis of metal ions in processed blood and urine samples, calibration standards for each element were prepared from multi-element stock solutions (1000 mg L − 1) in triple distilled water. Detection of Cd, Pb, and Cr was performed using a standard sample introduction setup, whereas for As, the hydride generation sample introduction system was utilized. Online hydride generation for As was achieved with an Enhanced Vapor System sample introduction kit using 0.5% m/v sodium tetrahydroborate (NaBH4) stabilized in 0.5% m/v NaOH and 50% v/v HCl solution. Emission data acquisition was performed using the Qtegra ISDS Software at interference-free wavelengths.

Statistical analysis

Statistical analyses were performed with R version 4.2 (R Foundation for Statistical Computing, Vienna, Austria) and IBM SPSS 26 version. The distribution of data in groups was evaluated with Shapiro-Wilk, kurtosis, skewness, and histograms. Skewed data for three groups was compared with the Kruskal-Wallis test. Subgroup analysis in three groups was performed with pairwise comparisons by Dunn test. Parameters with homogeneous distribution were compared with the chi-square test. Data are presented as %, for categorical variables or as median (Q1-Q3) for continuous variables.

Detection rates for blood and urinary metal levels were calculated. For urine metal levels, all statistical analyses were performed with creatinine-adjusted metal concentrations.

Urine to blood ratio was calculated for all metal levels. Spearman correlation coefficient was used to find the association between blood and urine metal levels of individual metals as well as for the association between different metals both in blood and urine. Correlation of blood and urine As with GFR was also performed.

We performed multinominal regression analysis for significantly different metal level in CKDu cases with respect to CKD and healthy controls. We included age and gender (confounding factors) in the model to see the y independence of association and effect estimate of the factor associated with CKDu. Regression model matrices and goodness-of-fit were also determined by the pseudo R 2 coefficient and Hosmer-Lemeshow goodness-of-fit test.

For all analyses, we have considered a p -value less than 0.05 as statistically significant.

A total of 568 patients who visited Nephrology OPD during the study period were screened for inclusion in the study. Out of these, 66 CKDu and 70 CKD cases were found eligible to enroll in the study. Eight patients withdrew consent in the CKD group, whereas four patients in the CKDu group had uncontrolled blood pressure with a single drug, and two withdrew consent. Finally, 60 CKDu and 62 CKD cases were included in the study for outcome analysis. We have approached 120 relatives of patients attending other OPDs and screened them for eligibility criteria of the healthy control group. Out of these, 60 were eligible, and 54 provided consent for participation in the study.

Demography and lab parameters

The CKD and CKDu subjects were similar in demographics for age and sex. However, healthy subjects were younger (Table  1 ). There was no significant difference between CKDu and CKD with reference to stage V (32 vs. 44, P-0.107).There were 05 diabetic kidney disease 04 CKD due to secondary glomerular disease patients (3-lupus nephritis, 1-FSGS), 12 hypertension-associated renal disease, 01 ADPKD, 36 Chronic glomerulonephritis patients, and 04 Chronic pyelonephritis patients in the CKD group. Use of smoking, Alcohol, and painkillers was similar across the three groups (Table  1 ). A significant difference was found between the three study groups with respect to the source of drinking water (ground or surface water). A significantly higher number of CKDu subjects used surface water as a source of drinking water (Table  1 and Table-S 1 and Fig-S 1 ) and a higher number of CKDu subjects reported pesticide usage. As shown in Table  1 , blood pressures were significantly higher in CKD subjects compared to CKDu and healthy subjects and reflect the inclusion criteria with appropriate patient inclusion in three groups. Both ACR and PCR were also significantly different between CKD and CKDu. The eGFR was calculated based on the CKD-EPI formula and was not significantly different between the CKD and CKDu subjects, however, CKD subjects had lower median eGFR compared to CKDu subjects. The healthy subjects had significantly higher eGFR compared to both groups. HbA1c, were similar across the three groups (Table  1 ).

Analytical results

The urinary and blood levels of As, Cd, Pb, and Cr (Table  2 ) were measured in ppb (micrograms per litre), and median with interquartile ranges were reported. Urinary metal levels were also measured in ppb (micrograms per liter) and then adjusted for urinary dilution by urine creatinine value and were finally expressed as micrograms/grams of urine creatinine (Table  2 ).

Detection limits

The lowest detectable concentrations of various heavy metals analyzed on ICP OES with a signal-to-noise ratio of 1 were as follows: As (193.759 nm) - 0.191 ppb; Cd (214.438 nm) - 0 ppb; Pb (220.353 nm) - 0.822 ppb; Cr (283.563 nm) - 3.156 ppb (Table  2 , Figs-S 2 -S 5 ).

Detection percentage

The number of subjects with blood and urine metal levels above the respective detection limits in each study group is reported in Table  2 .

Urine to blood ratio

A urine/blood ratio for each metal in all study groups was calculated for patients with metal levels above the detection limit. The distribution of urine/blood ratios for all metals is presented in Table  2 . Ratios were different between healthy and subjects with deranged kidney functions i.e. low GFR (CKD and CKDu). Median urine/blood Ratio for As was > 1 in healthy subjects and < 1 in CKD and CKDu, reflecting higher urinary levels compared to blood in healthy and reverse in CKD and CKDu subjects. For Pb, it was < 1 in healthy subjects and > 1 in subjects with CKD and CKDu, reflecting higher blood levels compared to urine in healthy and reverse in CKD and CKDu subjects. For Cd and Cr the ratio were < 1 across all three groups suggesting higher urine levels compared to blood levels.

Correlation

A spearman correlation (ρ) was also performed to see the association between each urine and blood metal and among the metals with each other as well. In CKDu, UAs were negatively associated with BAs (ρ-0.260, p -0.11) and in CKD positively (0.138, p -0.37). There was a positive association between urine and blood levels of As,Pb, and Cr and negative association of urine and blood Cd in CKD. In CKDu, a positive association was found in blood and urine Cd,Pb and Cr. In addition, there was a strong correlation of blood Cd, Pb, and Cr ( p  < 0.01) [ρ = 0.68 (BCd and BPb), 0.88 (BCd and BCr), 0.71 (BPb and BCr) in CKDu and [ρ = 0.55 (BCd and BPb), 0.82 (BCd and BCr), 0.65 (BPb and BCr) in CKD. The Urine Cd, Pb, and Cr also had strong correlations [ρ = 0.33 (UCd and UPb), and 0.48(UPb and UCr)] in CKD and [ρ = 0.19(UCd and UPb), 0.67 (UCd and UCr), and 0.69 (UPb and UCr)] in CKDu < 0.05 (Table-S 2 -S 4 and Fig-S 6 ). Association of Blood and urine As with GFR was also evaluated, and BAs were found to be negatively associated with GFR (ρ = -0.097, p  = 0.56), whereas UAs were positively associated (ρ = 0.14, p  = 0.25) with GFR (Table-S 5 ). Metal levels: Blood As: was significantly higher in CKDu ( n  = 37) subjects compared to CKD ( n  = 41) and healthy ( n  = 53) subjects (Table  2 ). On the other hand, the urinary As (UAs) was significantly low in CKD ( n  = 50) and CKDu ( n  = 48) subjects compared to healthy subjects ( n  = 38) and was non significantly higher in CKD subjects compared to CKDu subjects (Fig.  1 , Table  2 ).The blood and urine As values were below detection limits in 21.6%, 35.7%, and 18.8% and in 6%, 16.6%, and 0% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine arsenic according to diagnosis categories. Median; microgram/Lt (blood); microgram/gm(urine); UAs- Urine arsenic;CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

Blood Cd also was significantly higher in CKD and CKDu subjects compared to healthy subjects. Urinary Cd (UCd) levels were significantly higher in CKD and CKDu subjects compared to healthy subjects,. There was a weak association of ( p  = 0.06) UCd with CKD subjects compared to CKDu subjects.UCd was higher in CKD subjects compared to CKDu (Fig.  2 , Table  2 ). The blood and urine Cd values were below detection limits in 8.3%, 8.1%, and 0% and 37.2%, 19.3%, and 75.9% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine cadmium according to diagnosis categories. Median, microgram/Lt (blood); micrograms/gm (urine); UCd- Urine cadmium;CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

Pb levels in the blood of CKD and CKDu as well as in urine of CKD and CKDu subjects were significantly higher compared to healthy subjects. The Pb levels were higher in CKD subjects compared to CKDu subjects, but it was not statistically significant (Fig.  3 , Table  2 ). The blood and urine Pb values were below detection limits in 15%, 20%, and 25.9% and 23.3%, 19.4% and 70.4% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine lead according to diagnosis categories. microgram/Lt (blood); microgram/gm(urine); UPb- Urine lead;CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

As shown in Table  2 and Fig.  4 , urinary and blood Cr was significantly higher in CKD, and CKDu patients than healthy subjects. The blood and urine Cr values were below detection limits in 13%, 0%, and 0% and 13.3%, 14.5% and 85.2% of subjects in CKDu, CKD, and healthy groups, respectively.

Box plot for distribution of blood and urine chromium according to diagnosis categories. Median; microgram/Lt(blood); microgram/gm(urine); UCr-urine chromium, CKDu-Chronic kidney disease of unknown cause; CKD-Chronic kidney disease

Multinominal regression

Though age, gender, were not significantly different between CKDu and CKD, on univariate analysis, we included these In the multinominal regression analysis between CKDu and CKD in reference to healthy subjects in addition to factors found significantly different ( p  < 0.01 on univariate analysis) i.e. blood As and source of drinking water.After the final model, gender had no association with CKDu. Blood As, surface water as drinking water source and age were independently associated with CKDu. Age was associated independently with CKD also (Table  3 ).

To the best of our knowledge, this is the first study wherein an attempt has been made to analyze the association of heavy metals with CKDu in central India, using blood and urine levels as biomarkers of metal exposure. In addition, CKD and healthy subjects have been used as control groups.

The current study showed that blood and urine creatinine-adjusted urinary levels of heavy metals Cd, Pb and Cr were significantly higher in patients with CKD and CKDu as compared to healthy subjects. The urinary levels of the above metals were undetectable in healthy subjects. The study also showed a weak association of ( p  = < 0.06) higher urinary Cd in CKD subjects compared to CKDu subjects of this Indian cohort.

The study also showed that Blood As was significantly higher in CKDu subjects compared to CKD and healthy subjects. On multinominalregression, blood As was independently ( p  < 0.05) associated with CKDu after age adjustment.

In our study, median GFR was rather high in CKDu subjects [14.5 (7.0, 34.2)] compared to GFR in CKD subjects [9.0 (6.0, 17.0)ml/min/1.73m 2 )] and it was non significantly different between the two groups. On correlation analysis, there was a negative correlation between Blood As and GFR and a positive correlation of urine As with GFR. Based on this, the higher blood As in CKDu with higher GFR appears to be truly elevated.

Previously a study from Sri Lanka has also reported an association of CKDu with chronic As toxicity. In that study, 48% of CKDu patients and 17.4% of the control subjects fulfilled the criteria to be diagnosed with chronic arsenical toxicity(CAT), indicating the potential link between CAT and CKDu and suggesting agrochemicals could be the possible source [ 14 ]. Later, it was reported that glyphosate was the most widely used pesticide in Sri Lanka, which contains an average of 1.9 mg/kg arsenic. Findings suggest that agrochemicals, especially phosphate fertilizers, are a major source of inorganic arsenic in CKDu endemic areas [ 15 ]. However, another study from Sri Lanka did not find any difference in UAs levels in patients of CKDu in endemic areas and controls from endemic and nonendemic areas [ 4 ].

Some other studies have reported associations of As with CKD. A study from Taiwan found total UAs to be associated with a four-fold risk of CKD [ 6 ]. Another study reported an association of MMA V (mono methyl arsenate pentavalent) and DMA V (dimethyl arsenate pentavalent) in urine with prevalence of CKD [ 16 ]. However, in both studies, the type of CKD was not reported.

The higher blood As in CKDu compared to CKD may be associated with exposures in our study; a significantly higher number of subjects in CKDu group reported use of pesticides, surface water as a source of drinking water in CKDu subjects.On regression analysis also, surface water was independently associated with CKDu.

A study from north India reported increased levels of OCPs, namely α-HCH, aldrin, and β-endosulfan, in CKDu patients as compared to healthy control and CKD patients of known etiology [ 17 ] and it is also known that arsenic is an important component of pesticides [ 18 ]. The contamination of surface water with various pollutants i.e. pesticides, is common [ 19 ]. Arsenic is a known nephrotoxin, and one of the case reports where kidney histopathology was evaluated reported As causes tubulointerstitial disease (TID) [ 20 ]. The difference in methylation processes of As has also been found responsible for various diseases associated with As i.e. for example, high proportions of urinary MMAs (%U-MMAs) have been associated with a higher risk of cancers and skin lesions [ 21 ]. In contrast, high %U-DMAs has been associated with diabetes risk [ 22 ]. We have measured only iAs in our study. Whether methylation resulting in various metabolite species has different associations with CKDu or CKD should be explored further. We recently found a significant association of single nucleotide polymorphism in a gene coding for sodium-dependent dicarboxylate transporter (SLC13A3) with the susceptibility to CKDu [ 23 ].

In the current study, the UAs results suggest that As levels of 97 µg/gm of creatinine in healthy subjects were not associated with decreased GFR or proteinuria. Similar results were reported by a study from China where researchers found a lower confidence limit on the benchmark dose (LBMD) of 102 and 0.88 µg/gm creatinine for As and Cd, respectively, in order to prevent renal damage in the general population co-exposed to arsenic and cadmium [ 24 ]. The UAs in healthy subjects in our study were nearly similar to the LBMD reference and, not surprisingly, not to be associated with CKD or proteinuria.

Some studies have reported lead to be associated with CKDu. An Indian study reported high levels of lead and silicon concentrations in Indian groundwater in the endemic Uddanam area [ 7 ]. Jaysuman et al. also reported higher levels of Pb (26.5 µg/gm) in the urine of patients with Sri Lankan agricultural nephropathy compared to endemic and nonendemic control [ 25 ].

In the current study, although the median level of blood Pb was almost double in CKD patients compared to CKDu, the result was not statistically significant.

Our study showed that Cd was significantly associated with renal disease. Blood Cd and urine Cd (UCd) levels were significantly higher in patients with renal disease (CKD and CKDu) as compared to healthy subjects. The findings of UCd also showed a weak association (p-0.06) of Cd with CKD compared to CKDu among patients with renal diseases. There are some concerns that UCd may not be truly reflective of metal burden in patients with advanced CKD [ 26 ], because initially, in the course of Cd toxicity with early tubular damage, the normal reabsorption of cadmium-metallothionein decreases, and the UCd concentration increases. However, in the long run, cadmium-induced kidney damage gives rise to low Cd concentrations in both the kidney and urine, while the tubular damage remains [ 27 ]. The U/B ratio of < 1 for Cd in our study supports the above findings.

The mean eGFR in our CKD cohort was lower compared to CKDu; despite this, higher UCd values in patients with CKD compared to CKDu in our study indicate a potential association of Cd with CKD.

Studies have reported variable association of Cd with CKDu when compared to healthy subjects. Nanayakkara et al. [ 28 ] did not find an association of UCd with CKDu in stages 1–4 compared to healthy controls. Whereas another Sri Lankan [ 4 ] study found significantly high UCd in patients with CKDu against the endemic and nonendemic controls. We also observed significantly higher UCd in CKDu vs. healthy controls.

In the current study, urinary Cr (UCr) was not detected in healthy subjects, whereas it was significantly higher in patients with CKD and CKDu as compared to healthy subjects. UCr levels were higher in CKD compared to CKDu. Epidemiologically, Cr exposure has been reported to be associated with kidney damage in occupational populations [ 26 ]. Recently, a study from Taiwan reported that a significant and independent association between Cr exposure and decreased renal function in the general population, and co-exposure to Cr with Pb and Cd is potentially associated with an additional decline in the GFR in Taiwanese adults [ 27 ]. A study from Bangladesh reported outcomes similar to our study; however, the study included only CKD ( n  = 30) patients and compared them with healthy subjects ( n  = 20). In that study, compared to the controls, CKD patients exhibited significantly higher levels of Pb, Cd, and Cr levels in their urine samples. This signifies a potential association between heavy metal co-exposure and CKD [ 29 ]. In the current study a significant correlation between blood Cd, Pb, and Cr and urine Cd, Pb, and Cr were found in CKDu and CKD subjects compared to healthy subjects. The levels of UCd, UPb, and UCr in CKD and CKDu patients were significantly higher compared to healthy controls; The possibility of the combined effect of Cd, Pb, and Cr in the causation of renal diseases could be evaluated further in future studies. As CKDu is an endemic disease, the results of our study suggest an association of arsenic with CKDu in the Indian population, and so the generalizability of the result should be used with caution.

Strengths and limitations

This is the first study which has included two controls (CKD and healthy) and compared metal levels in patients with CKDu. In addition, the comparison of metals in both blood and urine is another advantage, as falling GFR levels and urine levels of several metals do not reflect true metal burden in patients. Inclusion of CKDu patients, as per the suggested definition by the Indian society of Nephrology, is another strength of our study.

The small sample size of our study may be a limitation of our study though it was calculated scientifically. The study involved Indian patients and controls only so the generalization of the results should be with caution. Healthy controls were of younger age is also a limitation of the study.

Also the study included patients from central India, comparatively a larger area and does not points out endemicity.

The study finds an association of environmental toxins with CKDu and CKD. The age and sex-adjusted As were observed to have an independent association with CKDu. A weak association of Cd with CKD was also observed in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were observed to have a significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu patients may have higher exposure to As via pesticides, surface water usage, or both.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Chronic Kidney Disease of unknown cause

Chronic Kidney Disease

Kidney Disease Improving Global Outcomes

Glomerular filteration rate

Institutional Human Ethics committee

Concentrated trace metal grade nitric acid

Hydrogen peroxide

High-purity polytetrafluoroethylene

Inorganic As

Tubulo-interstitial disease

Pentavalent monomethylarsonic acid

Pentavalent dimethylarsinic acid

Methylarsenous acid

Sodium-dependent dicarboxylate transporter

Limit on the benchmark dose

Arsenobetaine

Urinary MMAs

Urinary DMAs

Blood lead levels

End-stage kidney disease

Chapter 1: definition and classification of CKD. Kidney Int Suppl (2011). 2013;3(1):19–62. https://doi.org/10.1038/kisup.2012.64 .

Gifford FJ, Gifford RM, Eddleston M, Dhaun N. Endemic nephropathy around the world. Kidney Int Rep. 2017;2(2):282–92. https://doi.org/10.1016/j.ekir.2016.11.003 .

Article   PubMed   Google Scholar  

Nanayakkara S, Senevirathna S, Parahitiyawa NB, et al. Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka. Environ Health Prev Med. 2015;20(5):354–9. https://doi.org/10.1007/s12199-015-0475-1 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Jayatilake N, Mendis S, Maheepala P, Mehta FR. Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country. BMC Nephrol. 2013;14(1):180. https://doi.org/10.1186/1471-2369-14-180 .

Article   PubMed   PubMed Central   Google Scholar  

Jayasumana C, Gunatilake S, Senanayake P. Glyphosate, hard water and nephrotoxic metals: are they the culprits behind the epidemic of chronic kidney disease of unknown etiology in Sri Lanka? Int J Environ Res Public Health. 2014;11(2):2125–47. https://doi.org/10.3390/ijerph110202125 .

Bawaskar HS, HimmatraoBawaskar P, Himmatrao BP. Chronic renal failure associated with heavy metal contamination of drinking water: a clinical report from a small village in Maharashtra. Clin Toxicol. 2010;48(7):768–768. https://doi.org/10.3109/15563650.2010.497763 .

Article   Google Scholar  

Lal K, Sehgal M, Gupta V, et al. Assessment of groundwater quality of CKDu affected Uddanam region in Srikakulam district and across Andhra Pradesh, India. Groundw Sustain Dev. 2020;11:100432. https://doi.org/10.1016/j.gsd.2020.100432 .

Zhang X, Cornelis R, de Kimpe J, et al. Accumulation of arsenic species in serum of patients with chronic renal disease. Clin Chem. 1996;42(8):1231–7. https://doi.org/10.1093/clinchem/42.8.1231 .

Article   CAS   PubMed   Google Scholar  

Bommarito PA, Beck R, Douillet C, et al. Evaluation of plasma arsenicals as potential biomarkers of exposure to inorganic arsenic. J Expo Sci Environ Epidemiol. 2019;29(5):718–29. https://doi.org/10.1038/s41370-019-0121-x .

Environmental Health Criteria 165. Joint sponsorship of The United Nations Environment Programme, The International Labour Organization, and The World Health Organization. 1995. https://apps.who.int/iris/bitstream/handle/10665/37241/9241571659-eng.pdf?sequence=1 . Accessed 10 Nov 2022.

Ashrap P, Watkins DJ, Mukherjee B, et al. Predictors of urinary and blood Metal(loid) concentrations among pregnant women in Northern Puerto Rico. Environ Res. 2020;183:109178. https://doi.org/10.1016/j.envres.2020.109178 .

Anupama Y, Sankarasubbaiyan S, Taduri G. Chronic kidney disease of unknown etiology: case definition for India – a perspective. Indian J Nephrol. 2019. https://doi.org/10.4103/ijn.IJN_327_18 .

Levey AS, Stevens LA, Schmid CH, et al. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006 .

Jayasumana MACS, Paranagama PA, Amarasinghe KMRC, et al. Possible link of chronic arsenic toxicity with chronic kidney disease of unknown etiology in Sri Lanka. J Nat Sci Res. 2013;3(1). www.iiste.org ISSN 2224-3186 (Paper) ISSN 2225-0921 (Online).

Jayasumana C, Fonseka S, Fernando A, et al. Phosphate fertilizer is a main source of arsenic in areas affected with chronic kidney disease of unknown etiology in Sri Lanka. Springerplus. 2015;4:90. https://doi.org/10.1186/s40064-015-0868-z .

Zheng LY, Umans JG, Yeh F, et al. The association of urine arsenic with prevalent and incident chronic kidney disease. Epidemiology. 2015;26(4):601–12. https://doi.org/10.1097/EDE.0000000000000313 .

Ghosh R, Siddarth M, Singh N, et al. Organochlorine pesticide level in patients with chronic kidney disease of unknown etiology and its association with renal function. Environ Health Prev Med. 2017;22(1):49. https://doi.org/10.1186/s12199-017-0660-5 . Published 2017 May 26.

Li Y, Ye F, Wang A, et al. Chronic arsenic poisoning probably caused by arsenic-based pesticides: findings from an investigation study of a household. Int J Environ Res Public Health. 2016;13(1):133. https://doi.org/10.3390/ijerph13010133 .

Agrawal A, Pandey R, Sharma B. Water pollution with special reference to pesticide contamination in India. J Water Resource Prot. 2010;2(5):432–48. https://doi.org/10.4236/jwarp.2010.25050 .

Prasad GVR, Rossi NF. Arsenic intoxication associated with tubulointerstitial nephritis. Am J Kidney Dis. 1995;26(2):373–6. https://doi.org/10.1016/0272-6386(95)90660-6 .

Kuo CC, Moon KA, Wang SL, Silbergeld E, Navas-Acien A. The association of arsenic metabolism with cancer, cardiovascular disease, and diabetes: a systematic review of the epidemiological evidence. Environ Health Perspect. 2017;125(8):087001. https://doi.org/10.1289/EHP577 .

del Razo LM, García-Vargas GG, Valenzuela OL, et al. Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico. Environ Health. 2011;10(1):73. https://doi.org/10.1186/1476-069X-10-73 .

Kumari R, Tiwari S, Atlani M, et al. Association of single nucleotide polymorphisms in KCNA10 and SLC13A3 genes with the susceptibility to chronic kidney disease of unknown etiology in central Indian patients [published online ahead of print, 2023 Jan 25]. Biochem Genet. 2023. https://doi.org/10.1007/s10528-023-10335-7 .

Hong F, Jin T, Zhang A. Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese population. Biometals. 2004;17(5):573–80. https://doi.org/10.1023/B:BIOM.0000045741.22924.d .

Jayasumana C, Gunatilake S, Siribaddana S. Simultaneous exposure to multiple heavy metals and glyphosate may contribute to Sri Lankan agricultural nephropathy. BMC Nephrol. 2015;16(1):103. https://doi.org/10.1186/s12882-015-0109-2 .

Wilbur S, Abadin H, Fay M, et al. Toxicological profile for chromium. Atlanta: Agency for Toxic Substances and Disease Registry (US); 2012.

Google Scholar  

Tsai TL, Kuo CC, Pan WH, et al. The decline in kidney function with chromium exposure is exacerbated with co-exposure to lead and cadmium. Kidney Int. 2017;92(3):710–20. https://doi.org/10.1016/j.kint.2017.03.013 .

Nanayakkara S, Senevirathna STMLD, Karunaratne U, et al. evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross-sectional study. Environ Health Prev Med. 2012;17(2):109–17. https://doi.org/10.1007/s12199-011-0224-z .

Choudhury TR, Zaman SKZ, Chowdhury TI, Begum BA, Islam MDA, Rahman MDM. Status of metals in serum and urine samples of chronic kidney disease patients in a rural area of Bangladesh: an observational study. Heliyon. 2021;7(11):e08382. https://doi.org/10.1016/j.heliyon.2021.e08382 .

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Acknowledgements

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The Study was funded by Indian council of Medical Research (ICMR),New Delhi, India. Sanction no.:5/4/7-14/2019-NCD-II.

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Mahendra Atlani and Ashok Kumar contributed equally to this work.

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Department of Nephrology, All India Institute of Medical Sciences (AIIMS), Room No-3022, Academic Block, 3rd Floor, Saket Nagar, Bhopal, Madhya Pradesh, 462020, India

Mahendra Atlani, M. N. Meenu & Athira Anirudhan

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Saket Nagar, Bhopal, Madhya Pradesh, 462020, India

Ashok Kumar, Sudhir K. Goel & Ravita Kumari

Department of Environmental Biochemistry, ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, Madhya Pradesh, India

Rajesh Ahirwar

All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India

Saikrishna Vallamshetla & G. Sai Tharun Reddy

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MA and AK were equally involved in conceptualising the study, winning the grant, analyzing the results, monitoring the progress of study. MA prepared the manuscript. AK and SKG did the editing. RA supervised analysis of metal levels, sample collection done by MMN, RK. Metal analysis done by AA. Data entry and file preparation for results done by MMN, AA, SKV and STR.

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Atlani, M., Kumar, A., Ahirwar, R. et al. Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study. BMC Nephrol 25 , 120 (2024). https://doi.org/10.1186/s12882-024-03564-4

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The case study approach

Sarah crowe.

1 Division of Primary Care, The University of Nottingham, Nottingham, UK

Kathrin Cresswell

2 Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK

Ann Robertson

3 School of Health in Social Science, The University of Edinburgh, Edinburgh, UK

Anthony Avery

Aziz sheikh.

The case study approach allows in-depth, multi-faceted explorations of complex issues in their real-life settings. The value of the case study approach is well recognised in the fields of business, law and policy, but somewhat less so in health services research. Based on our experiences of conducting several health-related case studies, we reflect on the different types of case study design, the specific research questions this approach can help answer, the data sources that tend to be used, and the particular advantages and disadvantages of employing this methodological approach. The paper concludes with key pointers to aid those designing and appraising proposals for conducting case study research, and a checklist to help readers assess the quality of case study reports.

Introduction

The case study approach is particularly useful to employ when there is a need to obtain an in-depth appreciation of an issue, event or phenomenon of interest, in its natural real-life context. Our aim in writing this piece is to provide insights into when to consider employing this approach and an overview of key methodological considerations in relation to the design, planning, analysis, interpretation and reporting of case studies.

The illustrative 'grand round', 'case report' and 'case series' have a long tradition in clinical practice and research. Presenting detailed critiques, typically of one or more patients, aims to provide insights into aspects of the clinical case and, in doing so, illustrate broader lessons that may be learnt. In research, the conceptually-related case study approach can be used, for example, to describe in detail a patient's episode of care, explore professional attitudes to and experiences of a new policy initiative or service development or more generally to 'investigate contemporary phenomena within its real-life context' [ 1 ]. Based on our experiences of conducting a range of case studies, we reflect on when to consider using this approach, discuss the key steps involved and illustrate, with examples, some of the practical challenges of attaining an in-depth understanding of a 'case' as an integrated whole. In keeping with previously published work, we acknowledge the importance of theory to underpin the design, selection, conduct and interpretation of case studies[ 2 ]. In so doing, we make passing reference to the different epistemological approaches used in case study research by key theoreticians and methodologists in this field of enquiry.

This paper is structured around the following main questions: What is a case study? What are case studies used for? How are case studies conducted? What are the potential pitfalls and how can these be avoided? We draw in particular on four of our own recently published examples of case studies (see Tables ​ Tables1, 1 , ​ ,2, 2 , ​ ,3 3 and ​ and4) 4 ) and those of others to illustrate our discussion[ 3 - 7 ].

Example of a case study investigating the reasons for differences in recruitment rates of minority ethnic people in asthma research[ 3 ]

Example of a case study investigating the process of planning and implementing a service in Primary Care Organisations[ 4 ]

Example of a case study investigating the introduction of the electronic health records[ 5 ]

Example of a case study investigating the formal and informal ways students learn about patient safety[ 6 ]

What is a case study?

A case study is a research approach that is used to generate an in-depth, multi-faceted understanding of a complex issue in its real-life context. It is an established research design that is used extensively in a wide variety of disciplines, particularly in the social sciences. A case study can be defined in a variety of ways (Table ​ (Table5), 5 ), the central tenet being the need to explore an event or phenomenon in depth and in its natural context. It is for this reason sometimes referred to as a "naturalistic" design; this is in contrast to an "experimental" design (such as a randomised controlled trial) in which the investigator seeks to exert control over and manipulate the variable(s) of interest.

Definitions of a case study

Stake's work has been particularly influential in defining the case study approach to scientific enquiry. He has helpfully characterised three main types of case study: intrinsic , instrumental and collective [ 8 ]. An intrinsic case study is typically undertaken to learn about a unique phenomenon. The researcher should define the uniqueness of the phenomenon, which distinguishes it from all others. In contrast, the instrumental case study uses a particular case (some of which may be better than others) to gain a broader appreciation of an issue or phenomenon. The collective case study involves studying multiple cases simultaneously or sequentially in an attempt to generate a still broader appreciation of a particular issue.

These are however not necessarily mutually exclusive categories. In the first of our examples (Table ​ (Table1), 1 ), we undertook an intrinsic case study to investigate the issue of recruitment of minority ethnic people into the specific context of asthma research studies, but it developed into a instrumental case study through seeking to understand the issue of recruitment of these marginalised populations more generally, generating a number of the findings that are potentially transferable to other disease contexts[ 3 ]. In contrast, the other three examples (see Tables ​ Tables2, 2 , ​ ,3 3 and ​ and4) 4 ) employed collective case study designs to study the introduction of workforce reconfiguration in primary care, the implementation of electronic health records into hospitals, and to understand the ways in which healthcare students learn about patient safety considerations[ 4 - 6 ]. Although our study focusing on the introduction of General Practitioners with Specialist Interests (Table ​ (Table2) 2 ) was explicitly collective in design (four contrasting primary care organisations were studied), is was also instrumental in that this particular professional group was studied as an exemplar of the more general phenomenon of workforce redesign[ 4 ].

What are case studies used for?

According to Yin, case studies can be used to explain, describe or explore events or phenomena in the everyday contexts in which they occur[ 1 ]. These can, for example, help to understand and explain causal links and pathways resulting from a new policy initiative or service development (see Tables ​ Tables2 2 and ​ and3, 3 , for example)[ 1 ]. In contrast to experimental designs, which seek to test a specific hypothesis through deliberately manipulating the environment (like, for example, in a randomised controlled trial giving a new drug to randomly selected individuals and then comparing outcomes with controls),[ 9 ] the case study approach lends itself well to capturing information on more explanatory ' how ', 'what' and ' why ' questions, such as ' how is the intervention being implemented and received on the ground?'. The case study approach can offer additional insights into what gaps exist in its delivery or why one implementation strategy might be chosen over another. This in turn can help develop or refine theory, as shown in our study of the teaching of patient safety in undergraduate curricula (Table ​ (Table4 4 )[ 6 , 10 ]. Key questions to consider when selecting the most appropriate study design are whether it is desirable or indeed possible to undertake a formal experimental investigation in which individuals and/or organisations are allocated to an intervention or control arm? Or whether the wish is to obtain a more naturalistic understanding of an issue? The former is ideally studied using a controlled experimental design, whereas the latter is more appropriately studied using a case study design.

Case studies may be approached in different ways depending on the epistemological standpoint of the researcher, that is, whether they take a critical (questioning one's own and others' assumptions), interpretivist (trying to understand individual and shared social meanings) or positivist approach (orientating towards the criteria of natural sciences, such as focusing on generalisability considerations) (Table ​ (Table6). 6 ). Whilst such a schema can be conceptually helpful, it may be appropriate to draw on more than one approach in any case study, particularly in the context of conducting health services research. Doolin has, for example, noted that in the context of undertaking interpretative case studies, researchers can usefully draw on a critical, reflective perspective which seeks to take into account the wider social and political environment that has shaped the case[ 11 ].

Example of epistemological approaches that may be used in case study research

How are case studies conducted?

Here, we focus on the main stages of research activity when planning and undertaking a case study; the crucial stages are: defining the case; selecting the case(s); collecting and analysing the data; interpreting data; and reporting the findings.

Defining the case

Carefully formulated research question(s), informed by the existing literature and a prior appreciation of the theoretical issues and setting(s), are all important in appropriately and succinctly defining the case[ 8 , 12 ]. Crucially, each case should have a pre-defined boundary which clarifies the nature and time period covered by the case study (i.e. its scope, beginning and end), the relevant social group, organisation or geographical area of interest to the investigator, the types of evidence to be collected, and the priorities for data collection and analysis (see Table ​ Table7 7 )[ 1 ]. A theory driven approach to defining the case may help generate knowledge that is potentially transferable to a range of clinical contexts and behaviours; using theory is also likely to result in a more informed appreciation of, for example, how and why interventions have succeeded or failed[ 13 ].

Example of a checklist for rating a case study proposal[ 8 ]

For example, in our evaluation of the introduction of electronic health records in English hospitals (Table ​ (Table3), 3 ), we defined our cases as the NHS Trusts that were receiving the new technology[ 5 ]. Our focus was on how the technology was being implemented. However, if the primary research interest had been on the social and organisational dimensions of implementation, we might have defined our case differently as a grouping of healthcare professionals (e.g. doctors and/or nurses). The precise beginning and end of the case may however prove difficult to define. Pursuing this same example, when does the process of implementation and adoption of an electronic health record system really begin or end? Such judgements will inevitably be influenced by a range of factors, including the research question, theory of interest, the scope and richness of the gathered data and the resources available to the research team.

Selecting the case(s)

The decision on how to select the case(s) to study is a very important one that merits some reflection. In an intrinsic case study, the case is selected on its own merits[ 8 ]. The case is selected not because it is representative of other cases, but because of its uniqueness, which is of genuine interest to the researchers. This was, for example, the case in our study of the recruitment of minority ethnic participants into asthma research (Table ​ (Table1) 1 ) as our earlier work had demonstrated the marginalisation of minority ethnic people with asthma, despite evidence of disproportionate asthma morbidity[ 14 , 15 ]. In another example of an intrinsic case study, Hellstrom et al.[ 16 ] studied an elderly married couple living with dementia to explore how dementia had impacted on their understanding of home, their everyday life and their relationships.

For an instrumental case study, selecting a "typical" case can work well[ 8 ]. In contrast to the intrinsic case study, the particular case which is chosen is of less importance than selecting a case that allows the researcher to investigate an issue or phenomenon. For example, in order to gain an understanding of doctors' responses to health policy initiatives, Som undertook an instrumental case study interviewing clinicians who had a range of responsibilities for clinical governance in one NHS acute hospital trust[ 17 ]. Sampling a "deviant" or "atypical" case may however prove even more informative, potentially enabling the researcher to identify causal processes, generate hypotheses and develop theory.

In collective or multiple case studies, a number of cases are carefully selected. This offers the advantage of allowing comparisons to be made across several cases and/or replication. Choosing a "typical" case may enable the findings to be generalised to theory (i.e. analytical generalisation) or to test theory by replicating the findings in a second or even a third case (i.e. replication logic)[ 1 ]. Yin suggests two or three literal replications (i.e. predicting similar results) if the theory is straightforward and five or more if the theory is more subtle. However, critics might argue that selecting 'cases' in this way is insufficiently reflexive and ill-suited to the complexities of contemporary healthcare organisations.

The selected case study site(s) should allow the research team access to the group of individuals, the organisation, the processes or whatever else constitutes the chosen unit of analysis for the study. Access is therefore a central consideration; the researcher needs to come to know the case study site(s) well and to work cooperatively with them. Selected cases need to be not only interesting but also hospitable to the inquiry [ 8 ] if they are to be informative and answer the research question(s). Case study sites may also be pre-selected for the researcher, with decisions being influenced by key stakeholders. For example, our selection of case study sites in the evaluation of the implementation and adoption of electronic health record systems (see Table ​ Table3) 3 ) was heavily influenced by NHS Connecting for Health, the government agency that was responsible for overseeing the National Programme for Information Technology (NPfIT)[ 5 ]. This prominent stakeholder had already selected the NHS sites (through a competitive bidding process) to be early adopters of the electronic health record systems and had negotiated contracts that detailed the deployment timelines.

It is also important to consider in advance the likely burden and risks associated with participation for those who (or the site(s) which) comprise the case study. Of particular importance is the obligation for the researcher to think through the ethical implications of the study (e.g. the risk of inadvertently breaching anonymity or confidentiality) and to ensure that potential participants/participating sites are provided with sufficient information to make an informed choice about joining the study. The outcome of providing this information might be that the emotive burden associated with participation, or the organisational disruption associated with supporting the fieldwork, is considered so high that the individuals or sites decide against participation.

In our example of evaluating implementations of electronic health record systems, given the restricted number of early adopter sites available to us, we sought purposively to select a diverse range of implementation cases among those that were available[ 5 ]. We chose a mixture of teaching, non-teaching and Foundation Trust hospitals, and examples of each of the three electronic health record systems procured centrally by the NPfIT. At one recruited site, it quickly became apparent that access was problematic because of competing demands on that organisation. Recognising the importance of full access and co-operative working for generating rich data, the research team decided not to pursue work at that site and instead to focus on other recruited sites.

Collecting the data

In order to develop a thorough understanding of the case, the case study approach usually involves the collection of multiple sources of evidence, using a range of quantitative (e.g. questionnaires, audits and analysis of routinely collected healthcare data) and more commonly qualitative techniques (e.g. interviews, focus groups and observations). The use of multiple sources of data (data triangulation) has been advocated as a way of increasing the internal validity of a study (i.e. the extent to which the method is appropriate to answer the research question)[ 8 , 18 - 21 ]. An underlying assumption is that data collected in different ways should lead to similar conclusions, and approaching the same issue from different angles can help develop a holistic picture of the phenomenon (Table ​ (Table2 2 )[ 4 ].

Brazier and colleagues used a mixed-methods case study approach to investigate the impact of a cancer care programme[ 22 ]. Here, quantitative measures were collected with questionnaires before, and five months after, the start of the intervention which did not yield any statistically significant results. Qualitative interviews with patients however helped provide an insight into potentially beneficial process-related aspects of the programme, such as greater, perceived patient involvement in care. The authors reported how this case study approach provided a number of contextual factors likely to influence the effectiveness of the intervention and which were not likely to have been obtained from quantitative methods alone.

In collective or multiple case studies, data collection needs to be flexible enough to allow a detailed description of each individual case to be developed (e.g. the nature of different cancer care programmes), before considering the emerging similarities and differences in cross-case comparisons (e.g. to explore why one programme is more effective than another). It is important that data sources from different cases are, where possible, broadly comparable for this purpose even though they may vary in nature and depth.

Analysing, interpreting and reporting case studies

Making sense and offering a coherent interpretation of the typically disparate sources of data (whether qualitative alone or together with quantitative) is far from straightforward. Repeated reviewing and sorting of the voluminous and detail-rich data are integral to the process of analysis. In collective case studies, it is helpful to analyse data relating to the individual component cases first, before making comparisons across cases. Attention needs to be paid to variations within each case and, where relevant, the relationship between different causes, effects and outcomes[ 23 ]. Data will need to be organised and coded to allow the key issues, both derived from the literature and emerging from the dataset, to be easily retrieved at a later stage. An initial coding frame can help capture these issues and can be applied systematically to the whole dataset with the aid of a qualitative data analysis software package.

The Framework approach is a practical approach, comprising of five stages (familiarisation; identifying a thematic framework; indexing; charting; mapping and interpretation) , to managing and analysing large datasets particularly if time is limited, as was the case in our study of recruitment of South Asians into asthma research (Table ​ (Table1 1 )[ 3 , 24 ]. Theoretical frameworks may also play an important role in integrating different sources of data and examining emerging themes. For example, we drew on a socio-technical framework to help explain the connections between different elements - technology; people; and the organisational settings within which they worked - in our study of the introduction of electronic health record systems (Table ​ (Table3 3 )[ 5 ]. Our study of patient safety in undergraduate curricula drew on an evaluation-based approach to design and analysis, which emphasised the importance of the academic, organisational and practice contexts through which students learn (Table ​ (Table4 4 )[ 6 ].

Case study findings can have implications both for theory development and theory testing. They may establish, strengthen or weaken historical explanations of a case and, in certain circumstances, allow theoretical (as opposed to statistical) generalisation beyond the particular cases studied[ 12 ]. These theoretical lenses should not, however, constitute a strait-jacket and the cases should not be "forced to fit" the particular theoretical framework that is being employed.

When reporting findings, it is important to provide the reader with enough contextual information to understand the processes that were followed and how the conclusions were reached. In a collective case study, researchers may choose to present the findings from individual cases separately before amalgamating across cases. Care must be taken to ensure the anonymity of both case sites and individual participants (if agreed in advance) by allocating appropriate codes or withholding descriptors. In the example given in Table ​ Table3, 3 , we decided against providing detailed information on the NHS sites and individual participants in order to avoid the risk of inadvertent disclosure of identities[ 5 , 25 ].

What are the potential pitfalls and how can these be avoided?

The case study approach is, as with all research, not without its limitations. When investigating the formal and informal ways undergraduate students learn about patient safety (Table ​ (Table4), 4 ), for example, we rapidly accumulated a large quantity of data. The volume of data, together with the time restrictions in place, impacted on the depth of analysis that was possible within the available resources. This highlights a more general point of the importance of avoiding the temptation to collect as much data as possible; adequate time also needs to be set aside for data analysis and interpretation of what are often highly complex datasets.

Case study research has sometimes been criticised for lacking scientific rigour and providing little basis for generalisation (i.e. producing findings that may be transferable to other settings)[ 1 ]. There are several ways to address these concerns, including: the use of theoretical sampling (i.e. drawing on a particular conceptual framework); respondent validation (i.e. participants checking emerging findings and the researcher's interpretation, and providing an opinion as to whether they feel these are accurate); and transparency throughout the research process (see Table ​ Table8 8 )[ 8 , 18 - 21 , 23 , 26 ]. Transparency can be achieved by describing in detail the steps involved in case selection, data collection, the reasons for the particular methods chosen, and the researcher's background and level of involvement (i.e. being explicit about how the researcher has influenced data collection and interpretation). Seeking potential, alternative explanations, and being explicit about how interpretations and conclusions were reached, help readers to judge the trustworthiness of the case study report. Stake provides a critique checklist for a case study report (Table ​ (Table9 9 )[ 8 ].

Potential pitfalls and mitigating actions when undertaking case study research

Stake's checklist for assessing the quality of a case study report[ 8 ]

Conclusions

The case study approach allows, amongst other things, critical events, interventions, policy developments and programme-based service reforms to be studied in detail in a real-life context. It should therefore be considered when an experimental design is either inappropriate to answer the research questions posed or impossible to undertake. Considering the frequency with which implementations of innovations are now taking place in healthcare settings and how well the case study approach lends itself to in-depth, complex health service research, we believe this approach should be more widely considered by researchers. Though inherently challenging, the research case study can, if carefully conceptualised and thoughtfully undertaken and reported, yield powerful insights into many important aspects of health and healthcare delivery.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

AS conceived this article. SC, KC and AR wrote this paper with GH, AA and AS all commenting on various drafts. SC and AS are guarantors.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1471-2288/11/100/prepub

Acknowledgements

We are grateful to the participants and colleagues who contributed to the individual case studies that we have drawn on. This work received no direct funding, but it has been informed by projects funded by Asthma UK, the NHS Service Delivery Organisation, NHS Connecting for Health Evaluation Programme, and Patient Safety Research Portfolio. We would also like to thank the expert reviewers for their insightful and constructive feedback. Our thanks are also due to Dr. Allison Worth who commented on an earlier draft of this manuscript.

• Yin RK. Case study research, design and method. 4. London: Sage Publications Ltd.; 2009. [ Google Scholar ]
• Keen J, Packwood T. Qualitative research; case study evaluation. BMJ. 1995; 311 :444–446. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Sheikh A, Halani L, Bhopal R, Netuveli G, Partridge M, Car J. et al. Facilitating the Recruitment of Minority Ethnic People into Research: Qualitative Case Study of South Asians and Asthma. PLoS Med. 2009; 6 (10):1–11. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Pinnock H, Huby G, Powell A, Kielmann T, Price D, Williams S, The process of planning, development and implementation of a General Practitioner with a Special Interest service in Primary Care Organisations in England and Wales: a comparative prospective case study. Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D (NCCSDO) 2008. http://www.sdo.nihr.ac.uk/files/project/99-final-report.pdf
• Robertson A, Cresswell K, Takian A, Petrakaki D, Crowe S, Cornford T. et al. Prospective evaluation of the implementation and adoption of NHS Connecting for Health's national electronic health record in secondary care in England: interim findings. BMJ. 2010; 41 :c4564. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Pearson P, Steven A, Howe A, Sheikh A, Ashcroft D, Smith P. the Patient Safety Education Study Group. Learning about patient safety: organisational context and culture in the education of healthcare professionals. J Health Serv Res Policy. 2010; 15 :4–10. doi: 10.1258/jhsrp.2009.009052. [ PubMed ] [ CrossRef ] [ Google Scholar ]
• van Harten WH, Casparie TF, Fisscher OA. The evaluation of the introduction of a quality management system: a process-oriented case study in a large rehabilitation hospital. Health Policy. 2002; 60 (1):17–37. doi: 10.1016/S0168-8510(01)00187-7. [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Stake RE. The art of case study research. London: Sage Publications Ltd.; 1995. [ Google Scholar ]
• Sheikh A, Smeeth L, Ashcroft R. Randomised controlled trials in primary care: scope and application. Br J Gen Pract. 2002; 52 (482):746–51. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• King G, Keohane R, Verba S. Designing Social Inquiry. Princeton: Princeton University Press; 1996. [ Google Scholar ]
• Doolin B. Information technology as disciplinary technology: being critical in interpretative research on information systems. Journal of Information Technology. 1998; 13 :301–311. doi: 10.1057/jit.1998.8. [ CrossRef ] [ Google Scholar ]
• George AL, Bennett A. Case studies and theory development in the social sciences. Cambridge, MA: MIT Press; 2005. [ Google Scholar ]
• Eccles M. the Improved Clinical Effectiveness through Behavioural Research Group (ICEBeRG) Designing theoretically-informed implementation interventions. Implementation Science. 2006; 1 :1–8. doi: 10.1186/1748-5908-1-1. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Netuveli G, Hurwitz B, Levy M, Fletcher M, Barnes G, Durham SR, Sheikh A. Ethnic variations in UK asthma frequency, morbidity, and health-service use: a systematic review and meta-analysis. Lancet. 2005; 365 (9456):312–7. [ PubMed ] [ Google Scholar ]
• Sheikh A, Panesar SS, Lasserson T, Netuveli G. Recruitment of ethnic minorities to asthma studies. Thorax. 2004; 59 (7):634. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hellström I, Nolan M, Lundh U. 'We do things together': A case study of 'couplehood' in dementia. Dementia. 2005; 4 :7–22. doi: 10.1177/1471301205049188. [ CrossRef ] [ Google Scholar ]
• Som CV. Nothing seems to have changed, nothing seems to be changing and perhaps nothing will change in the NHS: doctors' response to clinical governance. International Journal of Public Sector Management. 2005; 18 :463–477. doi: 10.1108/09513550510608903. [ CrossRef ] [ Google Scholar ]
• Lincoln Y, Guba E. Naturalistic inquiry. Newbury Park: Sage Publications; 1985. [ Google Scholar ]
• Barbour RS. Checklists for improving rigour in qualitative research: a case of the tail wagging the dog? BMJ. 2001; 322 :1115–1117. doi: 10.1136/bmj.322.7294.1115. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Mays N, Pope C. Qualitative research in health care: Assessing quality in qualitative research. BMJ. 2000; 320 :50–52. doi: 10.1136/bmj.320.7226.50. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Mason J. Qualitative researching. London: Sage; 2002. [ Google Scholar ]
• Brazier A, Cooke K, Moravan V. Using Mixed Methods for Evaluating an Integrative Approach to Cancer Care: A Case Study. Integr Cancer Ther. 2008; 7 :5–17. doi: 10.1177/1534735407313395. [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Miles MB, Huberman M. Qualitative data analysis: an expanded sourcebook. 2. CA: Sage Publications Inc.; 1994. [ Google Scholar ]
• Pope C, Ziebland S, Mays N. Analysing qualitative data. Qualitative research in health care. BMJ. 2000; 320 :114–116. doi: 10.1136/bmj.320.7227.114. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Cresswell KM, Worth A, Sheikh A. Actor-Network Theory and its role in understanding the implementation of information technology developments in healthcare. BMC Med Inform Decis Mak. 2010; 10 (1):67. doi: 10.1186/1472-6947-10-67. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Malterud K. Qualitative research: standards, challenges, and guidelines. Lancet. 2001; 358 :483–488. doi: 10.1016/S0140-6736(01)05627-6. [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Yin R. Case study research: design and methods. 2. Thousand Oaks, CA: Sage Publishing; 1994. [ Google Scholar ]
• Yin R. Enhancing the quality of case studies in health services research. Health Serv Res. 1999; 34 :1209–1224. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Green J, Thorogood N. Qualitative methods for health research. 2. Los Angeles: Sage; 2009. [ Google Scholar ]
• Howcroft D, Trauth E. Handbook of Critical Information Systems Research, Theory and Application. Cheltenham, UK: Northampton, MA, USA: Edward Elgar; 2005. [ Google Scholar ]
• Blakie N. Approaches to Social Enquiry. Cambridge: Polity Press; 1993. [ Google Scholar ]
• Doolin B. Power and resistance in the implementation of a medical management information system. Info Systems J. 2004; 14 :343–362. doi: 10.1111/j.1365-2575.2004.00176.x. [ CrossRef ] [ Google Scholar ]
• Bloomfield BP, Best A. Management consultants: systems development, power and the translation of problems. Sociological Review. 1992; 40 :533–560. [ Google Scholar ]
• Shanks G, Parr A. Proceedings of the European Conference on Information Systems. Naples; 2003. Positivist, single case study research in information systems: A critical analysis. [ Google Scholar ]