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How to Write a Critique for a Case Analysis

Law, science, psychology, medicine, business and education -- these fields all use case studies to glean quantifiable data from anecdotal situations both in the classroom and professional world. A case analysis provides a review and interpretation, also known as an assessment, of the study results to draw conclusions and solutions that can be applied on a broader basis. It’s the job of the critique to investigate and evaluate the case analysis findings.

Case Details Overview

A critique of a case analysis must first delineate the details of the case study for readability and clarity. This includes all of the factual data produced by the original case study, such as the dates the study was conducted, significant statistical data and the impact of variables. The case overview may also need to address whether the case study data is qualitative or quantitative, which involves noting whether the information is mathematically measurable. The case overview should be a brief synopsis of the case study designed to provide information needed to understand the critique, not a full explanation.

Unbiased Interpretation of Analysis

A critique must also detail the findings of the case analysis using impartial language. Whether your critique questions or validates the analysis, calls the findings into question or simply suggests alternative viewpoints, the conclusions of the case analysis under evaluation must first be presented objectively. This means employing the use of objective language to avoid making personal, judgmental or emotive statements in the paragraphs presenting the findings.

Thesis Rationale

The thesis statement for a critique must address the fundamental issues being raised or questions being asked about the case analysis. Unlike pure analysis, a critique is influenced by personal opinions and beliefs, and the thesis statement should indicate the author’s rationale. The thesis must provide the critique writer’s position statement clearly and concisely. The thesis should also identify the intent of the critique, such as whether it aims to validate or question the case analysis.

Point and Counterpoint

Support for the opinions presented in the thesis statement are provided by counterpoints that address the points made in the case analysis. It’s important to provide a counterargument for all of the major arguments and findings in a case study analysis to prove the validity of your thesis statement. Critiques that gloss over or ignore significant data may be considered invalid for failing to address the full analysis.

Validation or Dissension

A critique is typically either a dissension or validation of the case study analysis, and it should avoid presenting new information from other sources, such as data from other case studies not addressed by the case analysis. In some instances, a critique may present new thoughts or ideas in the form of alternative interpretations of the original case study that the case analysis did not cover.

• Kansas State University: Criticism and Critical Analysis
• Nova Southeastern University: Introduction to Case Study
• Hobart and William Smith Colleges: Writing a Critique (Critical Analysis)
• The University of Adelaide: Objective Language

A former art instructor, high school counselor and party planner, Christine Bartsch writes fashion, travel, interior design, education and entertainment content. Bartsch earned a Bachelor of Fine Arts in communications/psychology/fine arts from Wisconsin Lutheran College and a creative writing Master of Fine Arts from Spalding University. She's written scripts for film/television productions and worked as the senior writer at a video game company.

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Home » Case Study – Methods, Examples and Guide

Case Study – Methods, Examples and Guide

Table of Contents

A case study is a research method that involves an in-depth examination and analysis of a particular phenomenon or case, such as an individual, organization, community, event, or situation.

It is a qualitative research approach that aims to provide a detailed and comprehensive understanding of the case being studied. Case studies typically involve multiple sources of data, including interviews, observations, documents, and artifacts, which are analyzed using various techniques, such as content analysis, thematic analysis, and grounded theory. The findings of a case study are often used to develop theories, inform policy or practice, or generate new research questions.

Types of Case Study

Types and Methods of Case Study are as follows:

Single-Case Study

A single-case study is an in-depth analysis of a single case. This type of case study is useful when the researcher wants to understand a specific phenomenon in detail.

For Example , A researcher might conduct a single-case study on a particular individual to understand their experiences with a particular health condition or a specific organization to explore their management practices. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of a single-case study are often used to generate new research questions, develop theories, or inform policy or practice.

Multiple-Case Study

A multiple-case study involves the analysis of several cases that are similar in nature. This type of case study is useful when the researcher wants to identify similarities and differences between the cases.

For Example, a researcher might conduct a multiple-case study on several companies to explore the factors that contribute to their success or failure. The researcher collects data from each case, compares and contrasts the findings, and uses various techniques to analyze the data, such as comparative analysis or pattern-matching. The findings of a multiple-case study can be used to develop theories, inform policy or practice, or generate new research questions.

Exploratory Case Study

An exploratory case study is used to explore a new or understudied phenomenon. This type of case study is useful when the researcher wants to generate hypotheses or theories about the phenomenon.

For Example, a researcher might conduct an exploratory case study on a new technology to understand its potential impact on society. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as grounded theory or content analysis. The findings of an exploratory case study can be used to generate new research questions, develop theories, or inform policy or practice.

Descriptive Case Study

A descriptive case study is used to describe a particular phenomenon in detail. This type of case study is useful when the researcher wants to provide a comprehensive account of the phenomenon.

For Example, a researcher might conduct a descriptive case study on a particular community to understand its social and economic characteristics. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of a descriptive case study can be used to inform policy or practice or generate new research questions.

Instrumental Case Study

An instrumental case study is used to understand a particular phenomenon that is instrumental in achieving a particular goal. This type of case study is useful when the researcher wants to understand the role of the phenomenon in achieving the goal.

For Example, a researcher might conduct an instrumental case study on a particular policy to understand its impact on achieving a particular goal, such as reducing poverty. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of an instrumental case study can be used to inform policy or practice or generate new research questions.

Case Study Data Collection Methods

Here are some common data collection methods for case studies:

Interviews involve asking questions to individuals who have knowledge or experience relevant to the case study. Interviews can be structured (where the same questions are asked to all participants) or unstructured (where the interviewer follows up on the responses with further questions). Interviews can be conducted in person, over the phone, or through video conferencing.

Observations

Observations involve watching and recording the behavior and activities of individuals or groups relevant to the case study. Observations can be participant (where the researcher actively participates in the activities) or non-participant (where the researcher observes from a distance). Observations can be recorded using notes, audio or video recordings, or photographs.

Documents can be used as a source of information for case studies. Documents can include reports, memos, emails, letters, and other written materials related to the case study. Documents can be collected from the case study participants or from public sources.

Surveys involve asking a set of questions to a sample of individuals relevant to the case study. Surveys can be administered in person, over the phone, through mail or email, or online. Surveys can be used to gather information on attitudes, opinions, or behaviors related to the case study.

Artifacts are physical objects relevant to the case study. Artifacts can include tools, equipment, products, or other objects that provide insights into the case study phenomenon.

How to conduct Case Study Research

Conducting a case study research involves several steps that need to be followed to ensure the quality and rigor of the study. Here are the steps to conduct case study research:

• Define the research questions: The first step in conducting a case study research is to define the research questions. The research questions should be specific, measurable, and relevant to the case study phenomenon under investigation.
• Select the case: The next step is to select the case or cases to be studied. The case should be relevant to the research questions and should provide rich and diverse data that can be used to answer the research questions.
• Collect data: Data can be collected using various methods, such as interviews, observations, documents, surveys, and artifacts. The data collection method should be selected based on the research questions and the nature of the case study phenomenon.
• Analyze the data: The data collected from the case study should be analyzed using various techniques, such as content analysis, thematic analysis, or grounded theory. The analysis should be guided by the research questions and should aim to provide insights and conclusions relevant to the research questions.
• Draw conclusions: The conclusions drawn from the case study should be based on the data analysis and should be relevant to the research questions. The conclusions should be supported by evidence and should be clearly stated.
• Validate the findings: The findings of the case study should be validated by reviewing the data and the analysis with participants or other experts in the field. This helps to ensure the validity and reliability of the findings.
• Write the report: The final step is to write the report of the case study research. The report should provide a clear description of the case study phenomenon, the research questions, the data collection methods, the data analysis, the findings, and the conclusions. The report should be written in a clear and concise manner and should follow the guidelines for academic writing.

Examples of Case Study

Here are some examples of case study research:

• The Hawthorne Studies : Conducted between 1924 and 1932, the Hawthorne Studies were a series of case studies conducted by Elton Mayo and his colleagues to examine the impact of work environment on employee productivity. The studies were conducted at the Hawthorne Works plant of the Western Electric Company in Chicago and included interviews, observations, and experiments.
• The Stanford Prison Experiment: Conducted in 1971, the Stanford Prison Experiment was a case study conducted by Philip Zimbardo to examine the psychological effects of power and authority. The study involved simulating a prison environment and assigning participants to the role of guards or prisoners. The study was controversial due to the ethical issues it raised.
• The Challenger Disaster: The Challenger Disaster was a case study conducted to examine the causes of the Space Shuttle Challenger explosion in 1986. The study included interviews, observations, and analysis of data to identify the technical, organizational, and cultural factors that contributed to the disaster.
• The Enron Scandal: The Enron Scandal was a case study conducted to examine the causes of the Enron Corporation’s bankruptcy in 2001. The study included interviews, analysis of financial data, and review of documents to identify the accounting practices, corporate culture, and ethical issues that led to the company’s downfall.
• The Fukushima Nuclear Disaster : The Fukushima Nuclear Disaster was a case study conducted to examine the causes of the nuclear accident that occurred at the Fukushima Daiichi Nuclear Power Plant in Japan in 2011. The study included interviews, analysis of data, and review of documents to identify the technical, organizational, and cultural factors that contributed to the disaster.

Application of Case Study

Case studies have a wide range of applications across various fields and industries. Here are some examples:

Business and Management

Case studies are widely used in business and management to examine real-life situations and develop problem-solving skills. Case studies can help students and professionals to develop a deep understanding of business concepts, theories, and best practices.

Case studies are used in healthcare to examine patient care, treatment options, and outcomes. Case studies can help healthcare professionals to develop critical thinking skills, diagnose complex medical conditions, and develop effective treatment plans.

Case studies are used in education to examine teaching and learning practices. Case studies can help educators to develop effective teaching strategies, evaluate student progress, and identify areas for improvement.

Social Sciences

Case studies are widely used in social sciences to examine human behavior, social phenomena, and cultural practices. Case studies can help researchers to develop theories, test hypotheses, and gain insights into complex social issues.

Law and Ethics

Case studies are used in law and ethics to examine legal and ethical dilemmas. Case studies can help lawyers, policymakers, and ethical professionals to develop critical thinking skills, analyze complex cases, and make informed decisions.

Purpose of Case Study

The purpose of a case study is to provide a detailed analysis of a specific phenomenon, issue, or problem in its real-life context. A case study is a qualitative research method that involves the in-depth exploration and analysis of a particular case, which can be an individual, group, organization, event, or community.

The primary purpose of a case study is to generate a comprehensive and nuanced understanding of the case, including its history, context, and dynamics. Case studies can help researchers to identify and examine the underlying factors, processes, and mechanisms that contribute to the case and its outcomes. This can help to develop a more accurate and detailed understanding of the case, which can inform future research, practice, or policy.

Case studies can also serve other purposes, including:

• Illustrating a theory or concept: Case studies can be used to illustrate and explain theoretical concepts and frameworks, providing concrete examples of how they can be applied in real-life situations.
• Developing hypotheses: Case studies can help to generate hypotheses about the causal relationships between different factors and outcomes, which can be tested through further research.
• Providing insight into complex issues: Case studies can provide insights into complex and multifaceted issues, which may be difficult to understand through other research methods.
• Informing practice or policy: Case studies can be used to inform practice or policy by identifying best practices, lessons learned, or areas for improvement.

Advantages of Case Study Research

There are several advantages of case study research, including:

• In-depth exploration: Case study research allows for a detailed exploration and analysis of a specific phenomenon, issue, or problem in its real-life context. This can provide a comprehensive understanding of the case and its dynamics, which may not be possible through other research methods.
• Rich data: Case study research can generate rich and detailed data, including qualitative data such as interviews, observations, and documents. This can provide a nuanced understanding of the case and its complexity.
• Holistic perspective: Case study research allows for a holistic perspective of the case, taking into account the various factors, processes, and mechanisms that contribute to the case and its outcomes. This can help to develop a more accurate and comprehensive understanding of the case.
• Theory development: Case study research can help to develop and refine theories and concepts by providing empirical evidence and concrete examples of how they can be applied in real-life situations.
• Practical application: Case study research can inform practice or policy by identifying best practices, lessons learned, or areas for improvement.
• Contextualization: Case study research takes into account the specific context in which the case is situated, which can help to understand how the case is influenced by the social, cultural, and historical factors of its environment.

Limitations of Case Study Research

There are several limitations of case study research, including:

• Limited generalizability : Case studies are typically focused on a single case or a small number of cases, which limits the generalizability of the findings. The unique characteristics of the case may not be applicable to other contexts or populations, which may limit the external validity of the research.
• Biased sampling: Case studies may rely on purposive or convenience sampling, which can introduce bias into the sample selection process. This may limit the representativeness of the sample and the generalizability of the findings.
• Subjectivity: Case studies rely on the interpretation of the researcher, which can introduce subjectivity into the analysis. The researcher’s own biases, assumptions, and perspectives may influence the findings, which may limit the objectivity of the research.
• Limited control: Case studies are typically conducted in naturalistic settings, which limits the control that the researcher has over the environment and the variables being studied. This may limit the ability to establish causal relationships between variables.
• Time-consuming: Case studies can be time-consuming to conduct, as they typically involve a detailed exploration and analysis of a specific case. This may limit the feasibility of conducting multiple case studies or conducting case studies in a timely manner.
• Resource-intensive: Case studies may require significant resources, including time, funding, and expertise. This may limit the ability of researchers to conduct case studies in resource-constrained settings.

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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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A case study research paper examines a person, place, event, condition, 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 research 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 more 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 the Organizing Your Social Sciences Research Paper writing guide. Review this page because it may help you identify a subject of analysis that can be investigated using a 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:

• The case represents 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.
• The case provides 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.
• The case challenges and offers 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 current practice. A case study analysis may offer 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 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.
• The case provides 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 so as to better warn drivers of an approaching train, particularly when visibility is hindered by heavy rain, fog, or at night.
• The case offers a new direction in future research? A case study can be used as a tool for an exploratory investigation that highlights the need for further research about the 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 east central Africa. A case study of how women contribute to saving water in a rural village of Uganda 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. This example of a case study could also point to the need for scholars to build new theoretical frameworks around the topic [e.g., applying 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 is being studied? Describe the research problem and describe the subject of analysis [the case] 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 is 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 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 involve 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 investigate 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 use of a 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 relation to explaining the relevance of the case in addressing the research problem.

III.  Method

In this section, you explain why you selected a particular case [i.e., subject of analysis] 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 constitutes 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; and, c) what were the consequences of the event in relation to the research problem.

If your subject of analysis is a person. Explain why you selected this particular individual to be studied and describe what experiences they have had that provide 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 their 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 them 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 [e.g., why is one politician in a particular local election used to show an increase in voter turnout from any other candidate running in the election]. Note that these issues apply to a specific group of people used as a case study unit of analysis [e.g., a classroom of students].

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, historical, cultural, economic, political], 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, explain why you are studying 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 suggests 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 off? How might knowing the suppliers of these trucks 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 clearly support investigation of the research problem and linked to key findings from your literature review. Be sure to cite any studies that helped you determine that the case you chose was appropriate for examining the 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 analysis of the 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 common to combine a description of the results 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 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 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 revealed by 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 if that is how the findings can be interpreted from your case.

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 any need for further research.

The function of your paper's conclusion is to: 1) reiterate the main argument supported by the findings from your case study; 2) state clearly 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 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 or the preferences of your professor, the concluding paragraph may contain your final reflections on the evidence presented as it applies 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 engaged with 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 more in terms of managing access rather 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 that leave the reader questioning the results.

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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What the Case Study Method Really Teaches

• Nitin Nohria

Seven meta-skills that stick even if the cases fade from memory.

It’s been 100 years since Harvard Business School began using the case study method. Beyond teaching specific subject matter, the case study method excels in instilling meta-skills in students. This article explains the importance of seven such skills: preparation, discernment, bias recognition, judgement, collaboration, curiosity, and self-confidence.

During my decade as dean of Harvard Business School, I spent hundreds of hours talking with our alumni. To enliven these conversations, I relied on a favorite question: “What was the most important thing you learned from your time in our MBA program?”

• Nitin Nohria is the George F. Baker Jr. and Distinguished Service University Professor. He served as the 10th dean of Harvard Business School, from 2010 to 2020.

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Writing a Case Study

What is a case study?

A Case study is: 

• An in-depth research design that primarily uses a qualitative methodology but sometimes​​ includes quantitative methodology.
• Used to examine an identifiable problem confirmed through research.
• Used to investigate an individual, group of people, organization, or event.
• Used to mostly answer "how" and "why" questions.

What are the different types of case studies?

Note: These are the primary case studies. As you continue to research and learn

about case studies you will begin to find a robust list of different types. 

Who are your case study participants?

What is triangulation ? 

Validity and credibility are an essential part of the case study. Therefore, the researcher should include triangulation to ensure trustworthiness while accurately reflecting what the researcher seeks to investigate.

How to write a Case Study?

When developing a case study, there are different ways you could present the information, but remember to include the five parts for your case study.

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How to Write a Case Study Analysis

Step-By-Step Instructions

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When writing a business case study analysis , you must first have a good understanding of the case study . Before you begin the steps below, read the business case carefully, taking notes all the while. It may be necessary to read the case several times to get all of the details and fully grasp the issues facing the group, company, or industry.

As you are reading, do your best to identify key issues, key players, and the most pertinent facts. After you are comfortable with the information, use the following step-by-step instructions (geared toward a single-company analysis) to write your report. To write about an industry, just adapt the steps listed here to discuss the segment as a whole.

Step 1: Investigate the Company’s History and Growth

A company’s past can greatly affect the present and future state of the organization. To begin, investigate the company’s founding, critical incidents, structure, and growth. Create a timeline of events, issues, and achievements. This timeline will come in handy for the next step. 

Step 2: Identify Strengths and Weaknesses

Using the information you gathered in step one, continue by examining and making a list of the value creation functions of the company. For example, the company may be weak in product development but strong in marketing. Make a list of problems that have occurred and note the effects they have had on the company. You should also list areas where the company has excelled. Note the effects of these incidents as well.

You're essentially conducting a partial SWOT analysis to get a better understanding of the company's strengths and weaknesses. A SWOT analysis involves documenting things like internal strengths (S) and weaknesses (W) and external opportunities (O) and threats (T). 

Step 3: Examine the External Environment

The third step involves identifying opportunities and threats within the company’s external environment. This is where the second part of the SWOT analysis (the O and the T) comes into play. Special items to note include competition within the industry, bargaining powers, and the threat of substitute products. Some examples of opportunities include expansion into new markets or new technology. Some examples of threats include increasing competition and higher interest rates.

Step 4: Analyze Your Findings

Using the information in steps 2 and 3, create an evaluation for this portion of your case study analysis. Compare the strengths and weaknesses within the company to the external threats and opportunities. Determine if the company is in a strong competitive position, and decide if it can continue at its current pace successfully.

Step 5: Identify Corporate-Level Strategy

To identify a company’s corporate-level strategy, identify and evaluate the company’s mission , goals, and actions toward those goals. Analyze the company’s line of business and its subsidiaries and acquisitions. You also want to debate the pros and cons of the company strategy to determine whether or not a change might benefit the company in the short or long term.​

Step 6: Identify Business-Level Strategy

Thus far, your case study analysis has identified the company’s corporate-level strategy. To perform a complete analysis, you will need to identify the company’s business-level strategy. (Note: If it is a single business, without multiple companies under one umbrella, and not an industry-wide review, the corporate strategy and the business-level strategy are the same.) For this part, you should identify and analyze each company’s competitive strategy, marketing strategy, costs, and general focus.

Step 7: Analyze Implementations

This portion requires that you identify and analyze the structure and control systems that the company is using to implement its business strategies. Evaluate organizational change, levels of hierarchy, employee rewards, conflicts, and other issues that are important to the company you are analyzing.

Step 8: Make Recommendations

The final part of your case study analysis should include your recommendations for the company. Every recommendation you make should be based on and supported by the context of your analysis. Never share hunches or make a baseless recommendation.

You also want to make sure that your suggested solutions are actually realistic. If the solutions cannot be implemented due to some sort of restraint, they are not realistic enough to make the final cut.

Finally, consider some of the alternative solutions that you considered and rejected. Write down the reasons why these solutions were rejected. 

Step 9: Review

Look over your analysis when you have finished writing. Critique your work to make sure every step has been covered. Look for grammatical errors , poor sentence structure, or other things that can be improved. It should be clear, accurate, and professional.

Business Case Study Analysis Tips

Keep these strategic tips in mind:

• Know the case study ​backward and forward before you begin your case study analysis.
• Give yourself enough time to write the case study analysis. You don't want to rush through it.
• Be honest in your evaluations. Don't let personal issues and opinions cloud your judgment.
• Be analytical, not descriptive.
• Proofread your work, and even let a test reader give it a once-over for dropped words or typos that you no longer can see.
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The Ultimate Guide to Qualitative Research - Part 1: The Basics

• Introduction and overview
• What is qualitative research?
• What is qualitative data?
• Examples of qualitative data
• Qualitative vs. quantitative research
• Mixed methods
• Qualitative research preparation
• Theoretical perspective
• Theoretical framework
• Literature reviews

Research question

• Conceptual framework
• Conceptual vs. theoretical framework

Data collection

• Qualitative research methods
• Focus groups
• Observational research

What is a case study?

Applications for case study research, what is a good case study, process of case study design, benefits and limitations of case studies.

• Ethnographical research
• Ethical considerations
• Confidentiality and privacy
• Power dynamics
• Reflexivity

Case studies

Case studies are essential to qualitative research , offering a lens through which researchers can investigate complex phenomena within their real-life contexts. This chapter explores the concept, purpose, applications, examples, and types of case studies and provides guidance on how to conduct case study research effectively.

Whereas quantitative methods look at phenomena at scale, case study research looks at a concept or phenomenon in considerable detail. While analyzing a single case can help understand one perspective regarding the object of research inquiry, analyzing multiple cases can help obtain a more holistic sense of the topic or issue. Let's provide a basic definition of a case study, then explore its characteristics and role in the qualitative research process.

Definition of a case study

A case study in qualitative research is a strategy of inquiry that involves an in-depth investigation of a phenomenon within its real-world context. It provides researchers with the opportunity to acquire an in-depth understanding of intricate details that might not be as apparent or accessible through other methods of research. The specific case or cases being studied can be a single person, group, or organization – demarcating what constitutes a relevant case worth studying depends on the researcher and their research question .

Among qualitative research methods , a case study relies on multiple sources of evidence, such as documents, artifacts, interviews , or observations , to present a complete and nuanced understanding of the phenomenon under investigation. The objective is to illuminate the readers' understanding of the phenomenon beyond its abstract statistical or theoretical explanations.

Characteristics of case studies

Case studies typically possess a number of distinct characteristics that set them apart from other research methods. These characteristics include a focus on holistic description and explanation, flexibility in the design and data collection methods, reliance on multiple sources of evidence, and emphasis on the context in which the phenomenon occurs.

Furthermore, case studies can often involve a longitudinal examination of the case, meaning they study the case over a period of time. These characteristics allow case studies to yield comprehensive, in-depth, and richly contextualized insights about the phenomenon of interest.

The role of case studies in research

Case studies hold a unique position in the broader landscape of research methods aimed at theory development. They are instrumental when the primary research interest is to gain an intensive, detailed understanding of a phenomenon in its real-life context.

In addition, case studies can serve different purposes within research - they can be used for exploratory, descriptive, or explanatory purposes, depending on the research question and objectives. This flexibility and depth make case studies a valuable tool in the toolkit of qualitative researchers.

Remember, a well-conducted case study can offer a rich, insightful contribution to both academic and practical knowledge through theory development or theory verification, thus enhancing our understanding of complex phenomena in their real-world contexts.

What is the purpose of a case study?

Case study research aims for a more comprehensive understanding of phenomena, requiring various research methods to gather information for qualitative analysis . Ultimately, a case study can allow the researcher to gain insight into a particular object of inquiry and develop a theoretical framework relevant to the research inquiry.

Why use case studies in qualitative research?

Using case studies as a research strategy depends mainly on the nature of the research question and the researcher's access to the data.

Conducting case study research provides a level of detail and contextual richness that other research methods might not offer. They are beneficial when there's a need to understand complex social phenomena within their natural contexts.

The explanatory, exploratory, and descriptive roles of case studies

Case studies can take on various roles depending on the research objectives. They can be exploratory when the research aims to discover new phenomena or define new research questions; they are descriptive when the objective is to depict a phenomenon within its context in a detailed manner; and they can be explanatory if the goal is to understand specific relationships within the studied context. Thus, the versatility of case studies allows researchers to approach their topic from different angles, offering multiple ways to uncover and interpret the data .

The impact of case studies on knowledge development

Case studies play a significant role in knowledge development across various disciplines. Analysis of cases provides an avenue for researchers to explore phenomena within their context based on the collected data.

This can result in the production of rich, practical insights that can be instrumental in both theory-building and practice. Case studies allow researchers to delve into the intricacies and complexities of real-life situations, uncovering insights that might otherwise remain hidden.

Types of case studies

In qualitative research , a case study is not a one-size-fits-all approach. Depending on the nature of the research question and the specific objectives of the study, researchers might choose to use different types of case studies. These types differ in their focus, methodology, and the level of detail they provide about the phenomenon under investigation.

Understanding these types is crucial for selecting the most appropriate approach for your research project and effectively achieving your research goals. Let's briefly look at the main types of case studies.

Exploratory case studies

Exploratory case studies are typically conducted to develop a theory or framework around an understudied phenomenon. They can also serve as a precursor to a larger-scale research project. Exploratory case studies are useful when a researcher wants to identify the key issues or questions which can spur more extensive study or be used to develop propositions for further research. These case studies are characterized by flexibility, allowing researchers to explore various aspects of a phenomenon as they emerge, which can also form the foundation for subsequent studies.

Descriptive case studies

Descriptive case studies aim to provide a complete and accurate representation of a phenomenon or event within its context. These case studies are often based on an established theoretical framework, which guides how data is collected and analyzed. The researcher is concerned with describing the phenomenon in detail, as it occurs naturally, without trying to influence or manipulate it.

Explanatory case studies

Explanatory case studies are focused on explanation - they seek to clarify how or why certain phenomena occur. Often used in complex, real-life situations, they can be particularly valuable in clarifying causal relationships among concepts and understanding the interplay between different factors within a specific context.

Intrinsic, instrumental, and collective case studies

These three categories of case studies focus on the nature and purpose of the study. An intrinsic case study is conducted when a researcher has an inherent interest in the case itself. Instrumental case studies are employed when the case is used to provide insight into a particular issue or phenomenon. A collective case study, on the other hand, involves studying multiple cases simultaneously to investigate some general phenomena.

Each type of case study serves a different purpose and has its own strengths and challenges. The selection of the type should be guided by the research question and objectives, as well as the context and constraints of the research.

The flexibility, depth, and contextual richness offered by case studies make this approach an excellent research method for various fields of study. They enable researchers to investigate real-world phenomena within their specific contexts, capturing nuances that other research methods might miss. Across numerous fields, case studies provide valuable insights into complex issues.

Critical information systems research

Case studies provide a detailed understanding of the role and impact of information systems in different contexts. They offer a platform to explore how information systems are designed, implemented, and used and how they interact with various social, economic, and political factors. Case studies in this field often focus on examining the intricate relationship between technology, organizational processes, and user behavior, helping to uncover insights that can inform better system design and implementation.

Health research

Health research is another field where case studies are highly valuable. They offer a way to explore patient experiences, healthcare delivery processes, and the impact of various interventions in a real-world context.

Case studies can provide a deep understanding of a patient's journey, giving insights into the intricacies of disease progression, treatment effects, and the psychosocial aspects of health and illness.

Asthma research studies

Specifically within medical research, studies on asthma often employ case studies to explore the individual and environmental factors that influence asthma development, management, and outcomes. A case study can provide rich, detailed data about individual patients' experiences, from the triggers and symptoms they experience to the effectiveness of various management strategies. This can be crucial for developing patient-centered asthma care approaches.

Other fields

Apart from the fields mentioned, case studies are also extensively used in business and management research, education research, and political sciences, among many others. They provide an opportunity to delve into the intricacies of real-world situations, allowing for a comprehensive understanding of various phenomena.

Case studies, with their depth and contextual focus, offer unique insights across these varied fields. They allow researchers to illuminate the complexities of real-life situations, contributing to both theory and practice.

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Understanding the key elements of case study design is crucial for conducting rigorous and impactful case study research. A well-structured design guides the researcher through the process, ensuring that the study is methodologically sound and its findings are reliable and valid. The main elements of case study design include the research question , propositions, units of analysis, and the logic linking the data to the propositions.

The research question is the foundation of any research study. A good research question guides the direction of the study and informs the selection of the case, the methods of collecting data, and the analysis techniques. A well-formulated research question in case study research is typically clear, focused, and complex enough to merit further detailed examination of the relevant case(s).

Propositions

Propositions, though not necessary in every case study, provide a direction by stating what we might expect to find in the data collected. They guide how data is collected and analyzed by helping researchers focus on specific aspects of the case. They are particularly important in explanatory case studies, which seek to understand the relationships among concepts within the studied phenomenon.

Units of analysis

The unit of analysis refers to the case, or the main entity or entities that are being analyzed in the study. In case study research, the unit of analysis can be an individual, a group, an organization, a decision, an event, or even a time period. It's crucial to clearly define the unit of analysis, as it shapes the qualitative data analysis process by allowing the researcher to analyze a particular case and synthesize analysis across multiple case studies to draw conclusions.

Argumentation

This refers to the inferential model that allows researchers to draw conclusions from the data. The researcher needs to ensure that there is a clear link between the data, the propositions (if any), and the conclusions drawn. This argumentation is what enables the researcher to make valid and credible inferences about the phenomenon under study.

Understanding and carefully considering these elements in the design phase of a case study can significantly enhance the quality of the research. It can help ensure that the study is methodologically sound and its findings contribute meaningful insights about the case.

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Conducting a case study involves several steps, from defining the research question and selecting the case to collecting and analyzing data . This section outlines these key stages, providing a practical guide on how to conduct case study research.

Defining the research question

The first step in case study research is defining a clear, focused research question. This question should guide the entire research process, from case selection to analysis. It's crucial to ensure that the research question is suitable for a case study approach. Typically, such questions are exploratory or descriptive in nature and focus on understanding a phenomenon within its real-life context.

Selecting and defining the case

The selection of the case should be based on the research question and the objectives of the study. It involves choosing a unique example or a set of examples that provide rich, in-depth data about the phenomenon under investigation. After selecting the case, it's crucial to define it clearly, setting the boundaries of the case, including the time period and the specific context.

Previous research can help guide the case study design. When considering a case study, an example of a case could be taken from previous case study research and used to define cases in a new research inquiry. Considering recently published examples can help understand how to select and define cases effectively.

Developing a detailed case study protocol

A case study protocol outlines the procedures and general rules to be followed during the case study. This includes the data collection methods to be used, the sources of data, and the procedures for analysis. Having a detailed case study protocol ensures consistency and reliability in the study.

The protocol should also consider how to work with the people involved in the research context to grant the research team access to collecting data. As mentioned in previous sections of this guide, establishing rapport is an essential component of qualitative research as it shapes the overall potential for collecting and analyzing data.

Collecting data

Gathering data in case study research often involves multiple sources of evidence, including documents, archival records, interviews, observations, and physical artifacts. This allows for a comprehensive understanding of the case. The process for gathering data should be systematic and carefully documented to ensure the reliability and validity of the study.

Analyzing and interpreting data

The next step is analyzing the data. This involves organizing the data , categorizing it into themes or patterns , and interpreting these patterns to answer the research question. The analysis might also involve comparing the findings with prior research or theoretical propositions.

Writing the case study report

The final step is writing the case study report . This should provide a detailed description of the case, the data, the analysis process, and the findings. The report should be clear, organized, and carefully written to ensure that the reader can understand the case and the conclusions drawn from it.

Each of these steps is crucial in ensuring that the case study research is rigorous, reliable, and provides valuable insights about the case.

The type, depth, and quality of data in your study can significantly influence the validity and utility of the study. In case study research, data is usually collected from multiple sources to provide a comprehensive and nuanced understanding of the case. This section will outline the various methods of collecting data used in case study research and discuss considerations for ensuring the quality of the data.

Interviews are a common method of gathering data in case study research. They can provide rich, in-depth data about the perspectives, experiences, and interpretations of the individuals involved in the case. Interviews can be structured , semi-structured , or unstructured , depending on the research question and the degree of flexibility needed.

Observations

Observations involve the researcher observing the case in its natural setting, providing first-hand information about the case and its context. Observations can provide data that might not be revealed in interviews or documents, such as non-verbal cues or contextual information.

Documents and artifacts

Documents and archival records provide a valuable source of data in case study research. They can include reports, letters, memos, meeting minutes, email correspondence, and various public and private documents related to the case.

These records can provide historical context, corroborate evidence from other sources, and offer insights into the case that might not be apparent from interviews or observations.

Physical artifacts refer to any physical evidence related to the case, such as tools, products, or physical environments. These artifacts can provide tangible insights into the case, complementing the data gathered from other sources.

Ensuring the quality of data collection

Determining the quality of data in case study research requires careful planning and execution. It's crucial to ensure that the data is reliable, accurate, and relevant to the research question. This involves selecting appropriate methods of collecting data, properly training interviewers or observers, and systematically recording and storing the data. It also includes considering ethical issues related to collecting and handling data, such as obtaining informed consent and ensuring the privacy and confidentiality of the participants.

Data analysis

Analyzing case study research involves making sense of the rich, detailed data to answer the research question. This process can be challenging due to the volume and complexity of case study data. However, a systematic and rigorous approach to analysis can ensure that the findings are credible and meaningful. This section outlines the main steps and considerations in analyzing data in case study research.

Organizing the data

The first step in the analysis is organizing the data. This involves sorting the data into manageable sections, often according to the data source or the theme. This step can also involve transcribing interviews, digitizing physical artifacts, or organizing observational data.

Categorizing and coding the data

Once the data is organized, the next step is to categorize or code the data. This involves identifying common themes, patterns, or concepts in the data and assigning codes to relevant data segments. Coding can be done manually or with the help of software tools, and in either case, qualitative analysis software can greatly facilitate the entire coding process. Coding helps to reduce the data to a set of themes or categories that can be more easily analyzed.

Identifying patterns and themes

After coding the data, the researcher looks for patterns or themes in the coded data. This involves comparing and contrasting the codes and looking for relationships or patterns among them. The identified patterns and themes should help answer the research question.

Interpreting the data

Once patterns and themes have been identified, the next step is to interpret these findings. This involves explaining what the patterns or themes mean in the context of the research question and the case. This interpretation should be grounded in the data, but it can also involve drawing on theoretical concepts or prior research.

Verification of the data

The last step in the analysis is verification. This involves checking the accuracy and consistency of the analysis process and confirming that the findings are supported by the data. This can involve re-checking the original data, checking the consistency of codes, or seeking feedback from research participants or peers.

Like any research method , case study research has its strengths and limitations. Researchers must be aware of these, as they can influence the design, conduct, and interpretation of the study.

Understanding the strengths and limitations of case study research can also guide researchers in deciding whether this approach is suitable for their research question . This section outlines some of the key strengths and limitations of case study research.

Benefits include the following:

• Rich, detailed data: One of the main strengths of case study research is that it can generate rich, detailed data about the case. This can provide a deep understanding of the case and its context, which can be valuable in exploring complex phenomena.
• Flexibility: Case study research is flexible in terms of design , data collection , and analysis . A sufficient degree of flexibility allows the researcher to adapt the study according to the case and the emerging findings.
• Real-world context: Case study research involves studying the case in its real-world context, which can provide valuable insights into the interplay between the case and its context.
• Multiple sources of evidence: Case study research often involves collecting data from multiple sources , which can enhance the robustness and validity of the findings.

On the other hand, researchers should consider the following limitations:

• Generalizability: A common criticism of case study research is that its findings might not be generalizable to other cases due to the specificity and uniqueness of each case.
• Time and resource intensive: Case study research can be time and resource intensive due to the depth of the investigation and the amount of collected data.
• Complexity of analysis: The rich, detailed data generated in case study research can make analyzing the data challenging.
• Subjectivity: Given the nature of case study research, there may be a higher degree of subjectivity in interpreting the data , so researchers need to reflect on this and transparently convey to audiences how the research was conducted.

Being aware of these strengths and limitations can help researchers design and conduct case study research effectively and interpret and report the findings appropriately.

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What is Case Study Analysis? (Explained With Examples)

Oct 11, 2023

Case Study Analysis is a widely used research method that examines in-depth information about a particular individual, group, organization, or event. It is a comprehensive investigative approach that aims to understand the intricacies and complexities of the subject under study. Through the analysis of real-life scenarios and inquiry into various data sources, Case Study Analysis provides valuable insights and knowledge that can be used to inform decision-making and problem-solving strategies.

1°) What is Case Study Analysis?

Case Study Analysis is a research methodology that involves the systematic investigation of a specific case or cases to gain a deep understanding of the subject matter. This analysis encompasses collecting and analyzing various types of data, including qualitative and quantitative information. By examining multiple aspects of the case, such as its context, background, influences, and outcomes, researchers can draw meaningful conclusions and provide valuable insights for various fields of study.

When conducting a Case Study Analysis, researchers typically begin by selecting a case or multiple cases that are relevant to their research question or area of interest. This can involve choosing a specific organization, individual, event, or phenomenon to study. Once the case is selected, researchers gather relevant data through various methods, such as interviews, observations, document analysis, and artifact examination.

The data collected during a Case Study Analysis is then carefully analyzed and interpreted. Researchers use different analytical frameworks and techniques to make sense of the information and identify patterns, themes, and relationships within the data. This process involves coding and categorizing the data, conducting comparative analysis, and drawing conclusions based on the findings.

One of the key strengths of Case Study Analysis is its ability to provide a rich and detailed understanding of a specific case. This method allows researchers to delve deep into the complexities and nuances of the subject matter, uncovering insights that may not be captured through other research methods. By examining the case in its natural context, researchers can gain a holistic perspective and explore the various factors and variables that contribute to the case.

1.1 - Definition of Case Study Analysis

Case Study Analysis can be defined as an in-depth examination and exploration of a particular case or cases to unravel relevant details and complexities associated with the subject being studied. It involves a comprehensive and detailed analysis of various factors and variables that contribute to the case, aiming to answer research questions and uncover insights that can be applied in real-world scenarios.

When conducting a Case Study Analysis, researchers employ a range of research methods and techniques to collect and analyze data. These methods can include interviews, surveys, observations, document analysis, and experiments, among others. By using multiple sources of data, researchers can triangulate their findings and ensure the validity and reliability of their analysis.

Furthermore, Case Study Analysis often involves the use of theoretical frameworks and models to guide the research process. These frameworks provide a structured approach to analyzing the case and help researchers make sense of the data collected. By applying relevant theories and concepts, researchers can gain a deeper understanding of the underlying factors and dynamics at play in the case.

1.2 - Advantages of Case Study Analysis

Case Study Analysis offers numerous advantages that make it a popular research method across different disciplines. One significant advantage is its ability to provide rich and detailed information about a specific case, allowing researchers to gain a holistic understanding of the subject matter. Additionally, Case Study Analysis enables researchers to explore complex issues and phenomena in their natural context, capturing the intricacies and nuances that may not be captured through other research methods.

Moreover, Case Study Analysis allows researchers to investigate rare or unique cases that may not be easily replicated or studied through experimental methods. This method is particularly useful when studying phenomena that are complex, multifaceted, or involve multiple variables. By examining real-world cases, researchers can gain insights that can be applied to similar situations or inform future research and practice.

Furthermore, this research method allows for the analysis of multiple sources of data, such as interviews, observations, documents, and artifacts, which can contribute to a comprehensive and well-rounded examination of the case. Case Study Analysis also facilitates the exploration and identification of patterns, trends, and relationships within the data, generating valuable insights and knowledge for future reference and application.

1.3 - Disadvantages of Case Study Analysis

While Case Study Analysis offers various advantages, it also comes with certain limitations and challenges. One major limitation is the potential for researcher bias, as the interpretation of data and findings can be influenced by preconceived notions and personal perspectives. Researchers must be aware of their own biases and take steps to minimize their impact on the analysis.

Additionally, Case Study Analysis may suffer from limited generalizability, as it focuses on specific cases and contexts, which might not be applicable or representative of broader populations or situations. The findings of a case study may not be easily generalized to other settings or individuals, and caution should be exercised when applying the results to different contexts.

Moreover, Case Study Analysis can require significant time and resources due to its in-depth nature and the need for meticulous data collection and analysis. This can pose challenges for researchers working with limited budgets or tight deadlines. However, the thoroughness and depth of the analysis often outweigh the resource constraints, as the insights gained from a well-conducted case study can be highly valuable.

Finally, ethical considerations also play a crucial role in Case Study Analysis, as researchers must ensure the protection of participant confidentiality and privacy. Researchers must obtain informed consent from participants and take measures to safeguard their identities and personal information. Ethical guidelines and protocols should be followed to ensure the rights and well-being of the individuals involved in the case study.

2°) Examples of Case Study Analysis

Real-world examples of Case Study Analysis demonstrate the method's practical application and showcase its usefulness across various fields. The following examples provide insights into different scenarios where Case Study Analysis has been employed successfully.

2.1 - Example in a Startup Context

In a startup context, a Case Study Analysis might explore the factors that contributed to the success of a particular startup company. It would involve examining the organization's background, strategies, market conditions, and key decision-making processes. This analysis could reveal valuable lessons and insights for aspiring entrepreneurs and those interested in understanding the intricacies of startup success.

2.2 - Example in a Consulting Context

In the consulting industry, Case Study Analysis is often utilized to understand and develop solutions for complex business problems. For instance, a consulting firm might conduct a Case Study Analysis on a company facing challenges in its supply chain management. This analysis would involve identifying the underlying issues, evaluating different options, and proposing recommendations based on the findings. This approach enables consultants to apply their expertise and provide practical solutions to their clients.

2.3 - Example in a Digital Marketing Agency Context

Within a digital marketing agency, Case Study Analysis can be used to examine successful marketing campaigns. By analyzing various factors such as target audience, message effectiveness, channel selection, and campaign metrics, this analysis can provide valuable insights into the strategies and tactics that contribute to successful marketing initiatives. Digital marketers can then apply these insights to optimize future campaigns and drive better results for their clients.

2.4 - Example with Analogies

Case Study Analysis can also be utilized with analogies to investigate specific scenarios and draw parallels to similar situations. For instance, a Case Study Analysis could explore the response of different countries to natural disasters and draw analogies to inform disaster management strategies in other regions. These analogies can help policymakers and researchers develop more effective approaches to mitigate the impact of disasters and protect vulnerable populations.

In conclusion, Case Study Analysis is a powerful research method that provides a comprehensive understanding of a particular individual, group, organization, or event. By analyzing real-life cases and exploring various data sources, researchers can unravel complexities, generate valuable insights, and inform decision-making processes. With its advantages and limitations, Case Study Analysis offers a unique approach to gaining in-depth knowledge and practical application across numerous fields.

About the author

Arnaud Belinga

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WCU » WCU Student Resources » Research and Writing » Writing a Case Study Analysis

Guidelines for Writing a Case Study Analysis

A case study analysis requires an investigation to a problem. Then, examine the alternative solutions. Next, propose the most effective solution using supporting evidence.

Preparing the Case

Before you begin writing, follow these guidelines to help you prepare and understand the case study:

• Read and examine the case thoroughly Take notes, highlight relevant facts, and underline key problems.
• Focus your analysis Identify key issues. Who or what are responsible?
• Detect solutions Review: course readings, discussions, outside research, and your experience.
• Select solution[s] Consider all supporting evidence, pros, and cons: is this solution genuine?

Drafting the Case

A draft of your analysis should include these sections:

• Introduction Identify the key problems and issues in the case study. • Formulate and include a thesis statement, summarizing the outcome of your analysis in 1–2 sentences.
• Background Set the scene: background information, relevant facts, and the most important issues. Demonstrate that you have researched the problems in this case study.
• Choices Explain why alternatives were rejected or not possible at this time.
• Solution[s] Provide one specific and realistic solution. Explain why this solution was chosen. Support this solution with solid evidence.
• Recommendations Determine and discuss specific strategies for accomplishing the proposed solution. What should be done and who should do it?

Finalizing the Case

Read through your work to check for any gaps or inconsistencies in content. I suggest reading it out loud. It can bring the inconsistencies or gaps to light much faster than reading it in silence to yourself.

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Case Study Analysis: Examples + How-to Guide & Writing Tips

A case study analysis is a typical assignment in business management courses. The task aims to show high school and college students how to analyze a current situation, determine what problems exist, and develop the best possible strategy to achieve the desired outcome.

Many students feel anxious about writing case analyses because being told to analyze a case study and provide a solution can seem like a big task. That is especially so when working with real-life scenarios. However, you can rest assured writing a case analysis paper is easier than you think. Just keep reading this article and you will find case study examples for students and the advice provided by Custom-writing experts!

• 👣 Main Steps
• 🕵 Preparing the Case

🔬 Analyzing the Case

• 📑 Format & Structure
• 🙅 Things to Avoid
• 🏁 Conclusion

🔗 References

👣 writing a case study analysis: main steps.

Business management is built on case analysis. Every single economic result shows that the methods and instruments employed were either well-timed and expedient, in the event of success, or not, in case of failure. These two options indicate whether the strategy is efficient (and should be followed) or requires corrections (or complete change). Such an approach to the case study will make your writing piece more proficient and valuable for the reader. The following steps will direct your plan for writing a case study analysis.

Step 1: Preliminary work

• Make notes and highlight the numbers and ideas that could be quoted.
• Single out as many problems as you can, and briefly mark their underlying issues. Then make a note of those responsible. In the report, you will use two to five of the problems, so you will have a selection to choose from.
• Outline a possible solution to each of the problems you found. Course readings and outside research shall be used here. Highlight your best and worst solution for further reference.

Step 2: Drafting the Case

• Provide a general description of the situation and its history.
• Name all the problems you are going to discuss.
• Specify the theory used for the analysis.
• Present the assumptions that emerged during the analysis, if any.
• Describe the detected problems in more detail.
• Indicate their link to, and effect on, the general situation.
• Explain why the problems emerged and persist.
• List realistic and feasible solutions to the problems you outlined, in the order of importance.
• Specify your predicted results of such changes.
• Support your choice with reliable evidence (i.e., textbook readings, the experience of famous companies, and other external research).
• Define the strategies required to fulfill your proposed solution.
• Indicate the responsible people and the realistic terms for its implementation.
• Recommend the issues for further analysis and supervision.

Step 3: Finalizing the Case

Like any other piece of writing, a case analysis requires post-editing. Carefully read it through, looking for inconsistencies and gaps in meaning. Your purpose is to make it look complete, precise, and convincing.

🕵 Preparing a Case for Analysis

Your professor might give you various case study examples from which to choose, or they may just assign you a particular case study. To conduct a thorough data analysis, you must first read the case study. This might appear to be obvious. However, you’d be surprised at how many students don’t take adequate time to complete this part.

Read the case study very thoroughly, preferably several times. Highlight, underline, flag key information, and make notes to refer to later when you are writing your analysis report.

If you don’t have a complete knowledge of the case study your professor has assigned, you won’t conduct a proper analysis of it. Even if you make use of a business case study template or refer to a sample analysis, it won’t help if you aren’t intimately familiar with your case study.

You will also have to conduct research. When it comes to research, you will need to do the following:

• Gather hard, quantitative data (e.g. 67% of the staff participated in the meeting).
• Design research tools , such as questionnaires and surveys (this will aid in gathering data).
• Determine and suggest the best specific, workable solutions.

It would be best if you also learned how to analyze a case study. Once you have read through the case study, you need to determine the focus of your analysis. You can do this by doing the following:

Compare your chosen solutions to the solutions offered by the experts who analyzed the case study you were given or to online assignments for students who were dealing with a similar task. The experts’ solutions will probably be more advanced than yours simply because these people are more experienced. However, don’t let this discourage you; the whole point of doing this analysis is to learn. Use the opportunity to learn from others’ valuable experience, and your results will be better next time.

If you are still in doubt, the University of South Carolina offers a great guide on forming a case study analysis.

📑 Case Analysis Format & Structure

When you are learning how to write a case study analysis, it is important to get the format of your analysis right. Understanding the case study format is vital for both the professor and the student. The person planning and handing out such an assignment should ensure that the student doesn’t have to use any external sources .

In turn, students have to remember that a well-written case analysis provides all the data, making it unnecessary for the reader to go elsewhere for information.

Regardless of whether you use a case study template, you will need to follow a clear and concise format when writing your analysis report. There are some possible case study frameworks available. Still, a case study should contain eight sections laid out in the following format:

• Describe the purpose of the current case study;
• Provide a summary of the company;
• Briefly introduce the problems and issues found in the case study
• Discuss the theory you will be using in the analysis;
• Present the key points of the study and present any assumptions made during the analysis.
• Present each problem you have singled out;
• Justify your inclusion of each problem by providing supporting evidence from the case study and by discussing relevant theory and what you have learned from your course content;
• Divide the section (and following sections) into subsections, one for each of your selected problems.
• Present a summary of each problem you have identified;
• Present plausible solutions for each of the problems, keeping in mind that each problem will likely have more than one possible solution;
• Provide the pros and cons of each solution in a way that is practical.
• Conclusion . This is a summary of your findings and discussion.
• Decide which solution best fits each of the issues you identified;
• Explain why you chose this solution and how it will effectively solve the problem;
• Be persuasive when you write this section so that you can drive your point home;
• Be sure to bring together theory and what you have learned throughout your course to support your recommendations.
• Provide an explanation of what must be done, who should take action, and when the solution should be carried out;
• Where relevant, you should provide an estimate of the cost in implementing the solution, including both the financial investment and the cost in terms of time.
• References. While you generally do not need to refer to many external sources when writing a case study analysis, you might use a few. When you do, you will need to properly reference these sources, which is most often done in one of the main citation styles, including APA, MLA, or Harvard. There is plenty of help when citing references, and you can follow these APA guidelines , these MLA guidelines , or these Harvard guidelines .
• Appendices. This is the section you include after your case study analysis if you used any original data in the report. These data, presented as charts, graphs, and tables, are included here because to present them in the main body of the analysis would be disruptive to the reader. The University of Southern California provides a great description of appendices and when to make use of them.

When you’ve finished your first draft, be sure to proofread it. Look not only for potential grammar and spelling errors but also for discrepancies or holes in your argument.

You should also know what you need to avoid when writing your analysis.

🙅 Things to Avoid in Case Analysis

Whenever you deal with a case study, remember that there are some pitfalls to avoid! Beware of the following mistakes:

• Excessive use of colloquial language . Even though it is a study of an actual case, it should sound formal.
• Lack of statistical data . Give all the important data, both in percentages and in numbers.
• Excessive details. State only the most significant facts, rather than drowning the reader in every fact you find.
• Inconsistency in the methods you have used . In a case study, theory plays a relatively small part, so you must develop a specific case study research methodology.
• Trivial means of research . It is critical that you design your own case study research method in whatever form best suits your analysis, such as questionnaires and surveys.

It is useful to see a few examples of case analysis papers. After all, a sample case study report can provide you with some context so you can see how to approach each aspect of your paper.

👀 Case Study Examples for Students

It might be easier to understand how a case study analysis works if you have an example to look at. Fortunately, examples of case studies are easy to come by. Take a look at this video for a sample case study analysis for the Coca-Cola Company.

If you want another example, then take a look at the one below!

Business Case Analysis: Example

CRM’s primary focus is customers and customer perception of the brand or the company. The focus may shift depending on customers’ needs. The main points that Center Parcs should consider are an increase in customer satisfaction and its market share. Both of these points will enhance customer perception of the product as a product of value. Increased customer satisfaction will indicate that the company provides quality services, and increased market share can reduce the number of switching (or leaving) customers, thus fostering customer loyalty.

Case Study Topics

• Equifax case study: the importance of cybersecurity measures. 
• Study a case illustrating ethical issues of medical research.
• Examine the case describing the complications connected with nursing and residential care.
• Analyze the competitive strategy of Delta Airlines .
• Present a case study of an ethical dilemma showing the conflict between the spirit and the letter of the law.  
• Explore the aspects of Starbucks’ marketing strategyin a case study.  
• Research a case of community-based clinic organization and development.
• Customer service of United Airlines: a case study .
• Analyze a specific schizophrenia case and provide your recommendations.
• Provide a case study of a patient with hyperglycemia.
• Examine the growth strategy of United Healthcare.
• Present a case study demonstrating ethical issues in business.
• Study a case of the 5% shareholding rule application and its impact on the company.
• Case study of post-traumatic stress disorder .
• Analyze a case examining the issues of cross-cultural management .
• Write a case study exploring the ethical issues the finance manager of a long-term care facility can face and the possible reaction to them.
• Write a case study analyzing the aspects of a new president of a firm election.
• Discuss the specifics of supply chain management in the case of Tehindo company.
• Study a case of a life crisis in a family and the ways to cope with it.
• Case study of Tea Leaves and More: supply chain issues.   
• Explore the case of ketogenic diet implementation among sportspeople.  
• Analyze the case of Webster Jewelry shop and suggest some changes.  
• Examine the unique aspects of Tea and More brand management.  
• Adidas case study: an ethical dilemma .
• Research the challenges of Brazos Valley Food Bank and suggest possible solutions.  
• Describe the case of dark web monitoring for business.  
• Study a case of permissive parenting style .
• Case study of Starbucks employees.
• Analyze a case of workplace discrimination and suggest a strategy to avoid it.
• Examine a case of the consumer decision-making process and define the factors that influence it.
• Present a case study of Netflix illustrating the crucial role of management innovation for company development.  
• Discuss a case describing a workplace ethical issue and propose ways to resolve it.
• Case study of the 2008 financial crisis: Graham’s value investing principles in the modern economic climate.
• Write a case study analyzing the harmful consequences of communication issues in a virtual team.
• Analyze a case that highlights the importance of a proper functional currency choice. 
• Examine the case of Hitachi Power Systems management.  
• Present a case study of medication research in a healthcare facility.
• Study the case of Fiji Water and the challenges the brand faces.  
• Research a social problem case and suggest a solution.
• Analyze a case that reveals the connection between alcohol use and borderline personality disorder.
• Transglobal Airline case study: break-even analysis.
• Examine the case of Chiquita Brands International from the moral and business ethics points of view.
• Present a case study of applying for Social Security benefits. 
• Study the case of a mass hacker attack on Microsoft clients and suggest possible ways to prevent future attacks.
• Case study of leadership effectiveness. 
• Analyze a case presenting a clinical moral dilemma and propose ways to resolve it. 
• Describe the case of Cowbell Brewing Company and discuss the strategy that made them successful.
• Write a case study of WeWork company and analyze the strengths and weaknesses of its strategy.
• Case study of medical ethical decision-making.
• Study the case of The Georges hotel and suggest ways to overcome its managerial issues.

🏁 Concluding Remarks

Writing a case study analysis can seem incredibly overwhelming, especially if you have never done it before. Just remember, you can do it provided you follow a plan, keep to the format described here, and study at least one case analysis example.

If you still need help analyzing a case study, your professor is always available to answer your questions and point you in the right direction. You can also get help with any aspect of the project from a custom writing company. Just tackle the research and hand over the writing, write a rough draft and have it checked by a professional, or completely hand the project off to an expert writer.

Regardless of the path you choose, you will turn in something of which you can be proud!

✏️ Case Study Analysis FAQ

Students (especially those who study business) often need to write a case study analysis. It is a kind of report that describes a business case. It includes multiple aspects, for example, the problems that exist, possible solutions, forecasts, etc.

There should be 3 main points covered in a case study analysis:

• The challenge(s) description,
• Possible solutions,
• Outcomes (real and/or foreseen).

Firstly, study some examples available online and in the library. Case study analysis should be a well-structured paper with all the integral components in place. Thus, you might want to use a template and/or an outline to start correctly.

A case study analysis is a popular task for business students. They typically hand it in the format of a paper with several integral components:

• Description of the problem
• Possible ways out
• Results and/or forecasts

Students sometimes tell about the outcome of their research within an oral presentation.

• Case Study: Academia
• Windows of vulnerability: a case study analysis (IEEE)
• A (Very) Brief Refresher on the Case Study Method: SAGE
• The case study approach: Medical Research Methodology
• Strengths and Limitations of Case Studies: Stanford University
• A Sample APA Paper: Radford University
• How to Write a Case Study APA Style: Seattle PI
• The Case Analysis: GVSU
• How to Outline: Purdue OWL
• Incorporating Interview Data: UW-Madison Writing Center
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How to Analyse a Case Study

Last Updated: April 13, 2024 Fact Checked

This article was co-authored by Sarah Evans . Sarah Evans is a Public Relations & Social Media Expert based in Las Vegas, Nevada. With over 14 years of industry experience, Sarah is the Founder & CEO of Sevans PR. Her team offers strategic communications services to help clients across industries including tech, finance, medical, real estate, law, and startups. The agency is renowned for its development of the "reputation+" methodology, a data-driven and AI-powered approach designed to elevate brand credibility, trust, awareness, and authority in a competitive marketplace. Sarah’s thought leadership has led to regular appearances on The Doctors TV show, CBS Las Vegas Now, and as an Adobe influencer. She is a respected contributor at Entrepreneur magazine, Hackernoon, Grit Daily, and KLAS Las Vegas. Sarah has been featured in PR Daily and PR Newswire and is a member of the Forbes Agency Council. She received her B.A. in Communications and Public Relations from Millikin University. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 414,012 times.

Case studies are used in many professional education programs, primarily in business school, to present real-world situations to students and to assess their ability to parse out the important aspects of a given dilemma. In general, a case study should include, in order: background on the business environment, description of the given business, identification of a key problem or issue, steps taken to address the issue, your assessment of that response, and suggestions for better business strategy. The steps below will guide you through the process of analyzing a business case study in this way.

• Describe the nature of the organization under consideration and its competitors. Provide general information about the market and customer base. Indicate any significant changes in the business environment or any new endeavors upon which the business is embarking.

• Analyze its management structure, employee base, and financial history. Describe annual revenues and profit. Provide figures on employment. Include details about private ownership, public ownership, and investment holdings. Provide a brief overview of the business's leaders and command chain.

• In all likelihood, there will be several different factors at play. Decide which is the main concern of the case study by examining what most of the data talks about, the main problems facing the business, and the conclusions at the end of the study. Examples might include expansion into a new market, response to a competitor's marketing campaign, or a changing customer base. [3] X Research source

• Draw on the information you gathered and trace a chronological progression of steps taken (or not taken). Cite data included in the case study, such as increased marketing spending, purchasing of new property, changed revenue streams, etc.

• Indicate whether or not each aspect of the response met its goal and whether the response overall was well-crafted. Use numerical benchmarks, like a desired customer share, to show whether goals were met; analyze broader issues, like employee management policies, to talk about the response as a whole. [4] X Research source

• Suggest alternative or improved measures that could have been taken by the business, using specific examples and backing up your suggestions with data and calculations.

Community Q&A

• Always read a case study several times. At first, you should read just for the basic details. On each subsequent reading, look for details about a specific topic: competitors, business strategy, management structure, financial loss. Highlight phrases and sections relating to these topics and take notes. Thanks Helpful 0 Not Helpful 0
• In the preliminary stages of analyzing a case study, no detail is insignificant. The biggest numbers can often be misleading, and the point of an analysis is often to dig deeper and find otherwise unnoticed variables that drive a situation. Thanks Helpful 0 Not Helpful 0
• If you are analyzing a case study for a consulting company interview, be sure to direct your comments towards the matters handled by the company. For example, if the company deals with marketing strategy, focus on the business's successes and failures in marketing; if you are interviewing for a financial consulting job, analyze how well the business keeps their books and their investment strategy. Thanks Helpful 0 Not Helpful 0

• Do not use impassioned or emphatic language in your analysis. Business case studies are a tool for gauging your business acumen, not your personal beliefs. When assigning blame or identifying flaws in strategy, use a detached, disinterested tone. Thanks Helpful 16 Not Helpful 4

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Expert Interview

Thanks for reading our article! If you’d like to learn more about business writing, check out our in-depth interview with Sarah Evans .

• ↑ https://www.gvsu.edu/cms4/asset/CC3BFEEB-C364-E1A1-A5390F221AC0FD2D/business_case_analysis_gg_final.pdf
• ↑ https://bizfluent.com/12741914/how-to-analyze-a-business-case-study
• ↑ http://www.business-fundas.com/2009/how-to-analyze-business-case-studies/
• ↑ https://writingcenter.uagc.edu/writing-case-study-analysis
• http://college.cengage.com/business/resources/casestudies/students/analyzing.htm

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How to write an effective case study: A comprehensive guide

Case studies are powerful tools for analyzing real-life situations, making informed decisions, and applying theoretical knowledge to practical problems.

Whether used in business, education, healthcare, or other fields, case studies require a deep understanding of the context, key players, and the complex dynamics at play.

This guide will walk you through the essential steps for developing a comprehensive and effective case study, from defining the objective to presenting a well-supported resolution.

Table of Contents

What is a case study?

A case study is a written summary or synthesis of a real-life situation, typically based on data and research.

Unlike hypothetical scenarios, case studies deal with actual events and decisions that need to be analyzed against both theoretical frameworks and the broader comparative environment.

The goal of a case study is to isolate key issues, evaluate potential strategies for resolving these issues, and recommend the best course of action with a solid rationale.

Considering this, case studies often involve:

• Isolating Key Issues : Identifying the most critical challenges or problems in the case.
• Evaluating Strategies : Weighing the pros and cons of various remedial options or strategies.
• Making Recommendations : Presenting a well-reasoned solution that addresses the key issues effectively.

10 steps to develop a case study

Creating a comprehensive case study involves a systematic process of investigation, analysis, and presentation.

Below are the key steps to follow when developing a case study:

1. Define the objective

The first step in developing a case study is to clearly define its objective.

What are you trying to achieve with this case study?

Are you aiming to solve a specific problem, understand the impact of certain decisions, or explore the dynamics within an organization?

Defining the objective will guide the direction of your analysis and help you focus on the most relevant issues.

2. Identify key players and stakeholders

Next, identify the important players within the organization or scenario you are studying. These could include:

• Internal Stakeholders : Such as management, employees, and decision-makers who have a direct impact on the situation.
• External Stakeholders : Such as clients, suppliers, and partners who are affected by the organization’s decisions.

Understanding who the stakeholders are and what their interests are is crucial for analyzing the situation accurately.

Additionally, scale the importance of these stakeholders based on their influence in decision-making and the consequences they may face.

3. Explore the organizational context

Studies have shown that organizations with clearly defined and well-communicated missions are more likely to experience alignment among stakeholders.

So guess what?

To fully grasp the situation in your case study, it’s crucial to dive into the organizational context.

This involves examining the official mission of the organization — what it publicly aims to achieve — as well as its historical mission, which can shed light on how its goals and strategies have evolved over time.

It’s also important to understand how different stakeholders perceive the organization’s mission.

These varied perspectives often influence decisions and outcomes, revealing potential areas of conflict or alignment within the organization.

What’s more, considering the competitive landscape will help you see where the organization stands in its industry and what external pressures it faces.

4. Map out the decision-making process

Understanding how decisions are made within the organization is key to analyzing the case.

Start by mapping out the formal decision-making processes, such as structured meetings, documented procedures, and official protocols.

However, don’t overlook the informal processes that often play a significant role, such as personal relationships, unwritten rules, and back-channel communications.

These informal elements can heavily influence outcomes, often in ways that aren’t immediately apparent.

Recognizing both formal and informal processes will give you a clearer picture of how decisions are truly made and the factors that impact them.

5. Analyze production and service delivery

The next step is to delve into the nuts and bolts of how the organization operates by examining its production or service delivery processes.

In general, this includes looking at the resources, technologies, and methods the organization uses to create its products or deliver its services.

Ideally, you should identify any challenges or inefficiencies that might be hindering performance, as well as the support mechanisms in place — like training programs, technology, or workflow systems — that help maintain or improve operations.

6. Pinpoint and investigate problems

Did you know that conducting a thorough root cause analysis is crucial for long-term problem resolution?

That’s why you should clearly articulate the primary problem or set of problems that the case presents.

Go beyond surface issues to explore underlying causes and subsequent challenges that arise from the main problem.

For example, a decline in customer satisfaction might lead to secondary issues like increased return rates or damaged brand reputation.

Investigating these interconnected problems helps to build a comprehensive understanding of the situation, allowing you to trace the ripple effects of the core issue and anticipate future complications.

7. Assess strategic issues and risks

Identify the strategic issues at the heart of the case, which require thoughtful decision-making.

These might include questions of resource allocation, market strategy, or operational changes.

Once these issues are identified, assess the associated risks—be they financial, reputational, or operational.

Evaluating both the strategic implications and the potential risks is crucial for understanding the stakes involved in any decision and for proposing solutions that are both effective and feasible.

8. Weigh remedial options

After identifying the strategic issues, it’s time to consider the different remedial options available.

For each option, assess the advantages and disadvantages, taking into account how each aligns with theoretical frameworks, the potential risks, and the practicalities of implementation.

Comparing these options helps you determine which course of action is most likely to succeed given the specific context and constraints of the case.

This comparative analysis forms the basis for your final recommendation.

9. Make a well-supported recommendation

Finally, based on your comprehensive analysis, make a clear and actionable recommendation.

Your recommendation should directly address the identified issues and be backed by a strong rationale.

It’s important to justify why this solution is the best, referencing the analysis you’ve conducted, the pros and cons of other options, and the potential risks.

This well-supported recommendation not only solves the problem at hand but also stands up to scrutiny from others who may review your case study.

10. Craft an executive summary

Now, the only thing you’ve left to do is to wrap up your case study with an executive summary that highlights the key elements of your analysis.

The executive summary should be concise, providing a quick overview of the major issues, the solutions considered, and the recommended course of action.

This section is designed to give readers a snapshot of your findings and conclusions, enabling them to grasp the essence of your case study without delving into the full report.

Writing an effective case study requires a systematic approach to identifying key issues, analyzing potential solutions, and making well-supported recommendations.

By following the steps outlined in this guide, you can develop a comprehensive and insightful case study that not only addresses the problems at hand but also provides valuable lessons for future situations.

Whether you’re a student, a professional, or a researcher, mastering the art of case study writing will enhance your ability to think critically, solve problems, and communicate your findings effectively.

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• Writing well

How to write a critique

• Starting well
• How to write an annotated bibliography
• How to write a case study response
• How to write an empirical article
• How to write an essay
• How to write a literature review
• How to write a reflective task
• How to write a report
• Finishing well

Before you start writing, it is important to have a thorough understanding of the work that will be critiqued.

• Study the work under discussion.
• Make notes on key parts of the work.
• Develop an understanding of the main argument or purpose being expressed in the work.
• Consider how the work relates to a broader issue or context.

Example template

There are a variety of ways to structure a critique. You should always check your unit materials or Canvas site for guidance from your lecturer. The following template, which showcases the main features of a critique, is provided as one example.

Introduction

Typically, the introduction is short (less than 10% of the word length) and you should:

• name the work being reviewed as well as the date it was created and the name of the author/creator
• describe the main argument or purpose of the work
• explain the context in which the work was created - this could include the social or political context, the place of the work in a creative or academic tradition, or the relationship between the work and the creator’s life experience
• have a concluding sentence that signposts what your evaluation of the work will be - for instance, it may indicate whether it is a positive, negative, or mixed evaluation.

Briefly summarise the main points and objectively describe how the creator portrays these by using techniques, styles, media, characters or symbols. This summary should not be the focus of the critique and is usually shorter than the critical evaluation.

Critical evaluation

This section should give a systematic and detailed assessment of the different elements of the work, evaluating how well the creator was able to achieve the purpose through these. For example: you would assess the plot structure, characterisation and setting of a novel; an assessment of a painting would look at composition, brush strokes, colour and light; a critique of a research project would look at subject selection, design of the experiment, analysis of data and conclusions.

A critical evaluation does not simply highlight negative impressions. It should deconstruct the work and identify both strengths and weaknesses. It should examine the work and evaluate its success, in light of its purpose.

Examples of key critical questions that could help your assessment include:

• Who is the creator? Is the work presented objectively or subjectively?
• What are the aims of the work? Were the aims achieved?
• What techniques, styles, media were used in the work? Are they effective in portraying the purpose?
• What assumptions underlie the work? Do they affect its validity?
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Methodologic and Data-Analysis Triangulation in Case Studies: A Scoping Review

Margarithe charlotte schlunegger.

1 Department of Health Professions, Applied Research & Development in Nursing, Bern University of Applied Sciences, Bern, Switzerland

2 Faculty of Health, School of Nursing Science, Witten/Herdecke University, Witten, Germany

Maya Zumstein-Shaha

Rebecca palm.

3 Department of Health Care Research, Carl von Ossietzky University Oldenburg, Oldenburg, Germany

Associated Data

Supplemental material, sj-docx-1-wjn-10.1177_01939459241263011 for Methodologic and Data-Analysis Triangulation in Case Studies: A Scoping Review by Margarithe Charlotte Schlunegger, Maya Zumstein-Shaha and Rebecca Palm in Western Journal of Nursing Research

We sought to explore the processes of methodologic and data-analysis triangulation in case studies using the example of research on nurse practitioners in primary health care.

Design and methods:

We conducted a scoping review within Arksey and O’Malley’s methodological framework, considering studies that defined a case study design and used 2 or more data sources, published in English or German before August 2023.

Data sources:

The databases searched were MEDLINE and CINAHL, supplemented with hand searching of relevant nursing journals. We also examined the reference list of all the included studies.

In total, 63 reports were assessed for eligibility. Ultimately, we included 8 articles. Five studies described within-method triangulation, whereas 3 provided information on between/across-method triangulation. No study reported within-method triangulation of 2 or more quantitative data-collection procedures. The data-collection procedures were interviews, observation, documentation/documents, service records, and questionnaires/assessments. The data-analysis triangulation involved various qualitative and quantitative methods of analysis. Details about comparing or contrasting results from different qualitative and mixed-methods data were lacking.

Conclusions:

Various processes for methodologic and data-analysis triangulation are described in this scoping review but lack detail, thus hampering standardization in case study research, potentially affecting research traceability. Triangulation is complicated by terminological confusion. To advance case study research in nursing, authors should reflect critically on the processes of triangulation and employ existing tools, like a protocol or mixed-methods matrix, for transparent reporting. The only existing reporting guideline should be complemented with directions on methodologic and data-analysis triangulation.

Case study research is defined as “an empirical method that investigates a contemporary phenomenon (the ‘case’) in depth and within its real-world context, especially when the boundaries between phenomenon and context may not be clearly evident. A case study relies on multiple sources of evidence, with data needing to converge in a triangulating fashion.” 1 (p15) This design is described as a stand-alone research approach equivalent to grounded theory and can entail single and multiple cases. 1 , 2 However, case study research should not be confused with single clinical case reports. “Case reports are familiar ways of sharing events of intervening with single patients with previously unreported features.” 3 (p107) As a methodology, case study research encompasses substantially more complexity than a typical clinical case report. 1 , 3

A particular characteristic of case study research is the use of various data sources, such as quantitative data originating from questionnaires as well as qualitative data emerging from interviews, observations, or documents. Therefore, a case study always draws on multiple sources of evidence, and the data must converge in a triangulating manner. 1 When using multiple data sources, a case or cases can be examined more convincingly and accurately, compensating for the weaknesses of the respective data sources. 1 Another characteristic is the interaction of various perspectives. This involves comparing or contrasting perspectives of people with different points of view, eg, patients, staff, or leaders. 4 Through triangulation, case studies contribute to the completeness of the research on complex topics, such as role implementation in clinical practice. 1 , 5 Triangulation involves a combination of researchers from various disciplines, of theories, of methods, and/or of data sources. By creating connections between these sources (ie, investigator, theories, methods, data sources, and/or data analysis), a new understanding of the phenomenon under study can be obtained. 6 , 7

This scoping review focuses on methodologic and data-analysis triangulation because concrete procedures are missing, eg, in reporting guidelines. Methodologic triangulation has been called methods, mixed methods, or multimethods. 6 It can encompass within-method triangulation and between/across-method triangulation. 7 “Researchers using within-method triangulation use at least 2 data-collection procedures from the same design approach.” 6 (p254) Within-method triangulation is either qualitative or quantitative but not both. Therefore, within-method triangulation can also be considered data source triangulation. 8 In contrast, “researchers using between/across-method triangulation employ both qualitative and quantitative data-collection methods in the same study.” 6 (p254) Hence, methodologic approaches are combined as well as various data sources. For this scoping review, the term “methodologic triangulation” is maintained to denote between/across-method triangulation. “Data-analysis triangulation is the combination of 2 or more methods of analyzing data.” 6 (p254)

Although much has been published on case studies, there is little consensus on the quality of the various data sources, the most appropriate methods, or the procedures for conducting methodologic and data-analysis triangulation. 5 According to the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) clearinghouse for reporting guidelines, one standard exists for organizational case studies. 9 Organizational case studies provide insights into organizational change in health care services. 9 Rodgers et al 9 pointed out that, although high-quality studies are being funded and published, they are sometimes poorly articulated and methodologically inadequate. In the reporting checklist by Rodgers et al, 9 a description of the data collection is included, but reporting directions on methodologic and data-analysis triangulation are missing. Therefore, the purpose of this study was to examine the process of methodologic and data-analysis triangulation in case studies. Accordingly, we conducted a scoping review to elicit descriptions of and directions for triangulation methods and analysis, drawing on case studies of nurse practitioners (NPs) in primary health care as an example. Case studies are recommended to evaluate the implementation of new roles in (primary) health care, such as that of NPs. 1 , 5 Case studies on new role implementation can generate a unique and in-depth understanding of specific roles (individual), teams (smaller groups), family practices or similar institutions (organization), and social and political processes in health care systems. 1 , 10 The integration of NPs into health care systems is at different stages of progress around the world. 11 Therefore, studies are needed to evaluate this process.

The methodological framework by Arksey and O’Malley 12 guided this scoping review. We examined the current scientific literature on the use of methodologic and data-analysis triangulation in case studies on NPs in primary health care. The review process included the following stages: (1) establishing the research question; (2) identifying relevant studies; (3) selecting the studies for inclusion; (4) charting the data; (5) collating, summarizing, and reporting the results; and (6) consulting experts in the field. 12 Stage 6 was not performed due to a lack of financial resources. The reporting of the review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review) guideline by Tricco et al 13 (guidelines for reporting systematic reviews and meta-analyses [ Supplementary Table A ]). Scoping reviews are not eligible for registration in PROSPERO.

Stage 1: Establishing the Research Question

The aim of this scoping review was to examine the process of triangulating methods and analysis in case studies on NPs in primary health care to improve the reporting. We sought to answer the following question: How have methodologic and data-analysis triangulation been conducted in case studies on NPs in primary health care? To answer the research question, we examined the following elements of the selected studies: the research question, the study design, the case definition, the selected data sources, and the methodologic and data-analysis triangulation.

Stage 2: Identifying Relevant Studies

A systematic database search was performed in the MEDLINE (via PubMed) and CINAHL (via EBSCO) databases between July and September 2020 to identify relevant articles. The following terms were used as keyword search strategies: (“Advanced Practice Nursing” OR “nurse practitioners”) AND (“primary health care” OR “Primary Care Nursing”) AND (“case study” OR “case studies”). Searches were limited to English- and German-language articles. Hand searches were conducted in the journals Nursing Inquiry , BMJ Open , and BioMed Central ( BMC ). We also screened the reference lists of the studies included. The database search was updated in August 2023. The complete search strategy for all the databases is presented in Supplementary Table B .

Stage 3: Selecting the Studies

Inclusion and exclusion criteria.

We used the inclusion and exclusion criteria reported in Table 1 . We included studies of NPs who had at least a master’s degree in nursing according to the definition of the International Council of Nurses. 14 This scoping review considered studies that were conducted in primary health care practices in rural, urban, and suburban regions. We excluded reviews and study protocols in which no data collection had occurred. Articles were included without limitations on the time period or country of origin.

Inclusion and Exclusion Criteria.

Screening process

After the search, we collated and uploaded all the identified records into EndNote v.X8 (Clarivate Analytics, Philadelphia, Pennsylvania) and removed any duplicates. Two independent reviewers (MCS and SA) screened the titles and abstracts for assessment in line with the inclusion criteria. They retrieved and assessed the full texts of the selected studies while applying the inclusion criteria. Any disagreements about the eligibility of studies were resolved by discussion or, if no consensus could be reached, by involving experienced researchers (MZ-S and RP).

Stages 4 and 5: Charting the Data and Collating, Summarizing, and Reporting the Results

The first reviewer (MCS) extracted data from the selected publications. For this purpose, an extraction tool developed by the authors was used. This tool comprised the following criteria: author(s), year of publication, country, research question, design, case definition, data sources, and methodologic and data-analysis triangulation. First, we extracted and summarized information about the case study design. Second, we narratively summarized the way in which the data and methodological triangulation were described. Finally, we summarized the information on within-case or cross-case analysis. This process was performed using Microsoft Excel. One reviewer (MCS) extracted data, whereas another reviewer (SA) cross-checked the data extraction, making suggestions for additions or edits. Any disagreements between the reviewers were resolved through discussion.

A total of 149 records were identified in 2 databases. We removed 20 duplicates and screened 129 reports by title and abstract. A total of 46 reports were assessed for eligibility. Through hand searches, we identified 117 additional records. Of these, we excluded 98 reports after title and abstract screening. A total of 17 reports were assessed for eligibility. From the 2 databases and the hand search, 63 reports were assessed for eligibility. Ultimately, we included 8 articles for data extraction. No further articles were included after the reference list screening of the included studies. A PRISMA flow diagram of the study selection and inclusion process is presented in Figure 1 . As shown in Tables 2 and ​ and3, 3 , the articles included in this scoping review were published between 2010 and 2022 in Canada (n = 3), the United States (n = 2), Australia (n = 2), and Scotland (n = 1).

PRISMA flow diagram.

Characteristics of Articles Included.

Overview of Within-Method, Between/Across-Method, and Data-Analysis Triangulation.

Research Question, Case Definition, and Case Study Design

The following sections describe the research question, case definition, and case study design. Case studies are most appropriate when asking “how” or “why” questions. 1 According to Yin, 1 how and why questions are explanatory and lead to the use of case studies, histories, and experiments as the preferred research methods. In 1 study from Canada, eg, the following research question was presented: “How and why did stakeholders participate in the system change process that led to the introduction of the first nurse practitioner-led Clinic in Ontario?” (p7) 19 Once the research question has been formulated, the case should be defined and, subsequently, the case study design chosen. 1 In typical case studies with mixed methods, the 2 types of data are gathered concurrently in a convergent design and the results merged to examine a case and/or compare multiple cases. 10

Research question

“How” or “why” questions were found in 4 studies. 16 , 17 , 19 , 22 Two studies additionally asked “what” questions. Three studies described an exploratory approach, and 1 study presented an explanatory approach. Of these 4 studies, 3 studies chose a qualitative approach 17 , 19 , 22 and 1 opted for mixed methods with a convergent design. 16

In the remaining studies, either the research questions were not clearly stated or no “how” or “why” questions were formulated. For example, “what” questions were found in 1 study. 21 No information was provided on exploratory, descriptive, and explanatory approaches. Schadewaldt et al 21 chose mixed methods with a convergent design.

Case definition and case study design

A total of 5 studies defined the case as an organizational unit. 17 , 18 - 20 , 22 Of the 8 articles, 4 reported multiple-case studies. 16 , 17 , 22 , 23 Another 2 publications involved single-case studies. 19 , 20 Moreover, 2 publications did not state the case study design explicitly.

Within-Method Triangulation

This section describes within-method triangulation, which involves employing at least 2 data-collection procedures within the same design approach. 6 , 7 This can also be called data source triangulation. 8 Next, we present the single data-collection procedures in detail. In 5 studies, information on within-method triangulation was found. 15 , 17 - 19 , 22 Studies describing a quantitative approach and the triangulation of 2 or more quantitative data-collection procedures could not be included in this scoping review.

Qualitative approach

Five studies used qualitative data-collection procedures. Two studies combined face-to-face interviews and documents. 15 , 19 One study mixed in-depth interviews with observations, 18 and 1 study combined face-to-face interviews and documentation. 22 One study contained face-to-face interviews, observations, and documentation. 17 The combination of different qualitative data-collection procedures was used to present the case context in an authentic and complex way, to elicit the perspectives of the participants, and to obtain a holistic description and explanation of the cases under study.

All 5 studies used qualitative interviews as the primary data-collection procedure. 15 , 17 - 19 , 22 Face-to-face, in-depth, and semi-structured interviews were conducted. The topics covered in the interviews included processes in the introduction of new care services and experiences of barriers and facilitators to collaborative work in general practices. Two studies did not specify the type of interviews conducted and did not report sample questions. 15 , 18

Observations

In 2 studies, qualitative observations were carried out. 17 , 18 During the observations, the physical design of the clinical patients’ rooms and office spaces was examined. 17 Hungerford et al 18 did not explain what information was collected during the observations. In both studies, the type of observation was not specified. Observations were generally recorded as field notes.

Public documents

In 3 studies, various qualitative public documents were studied. 15 , 19 , 22 These documents included role description, education curriculum, governance frameworks, websites, and newspapers with information about the implementation of the role and general practice. Only 1 study failed to specify the type of document and the collected data. 15

Electronic health records

In 1 study, qualitative documentation was investigated. 17 This included a review of dashboards (eg, provider productivity reports or provider quality dashboards in the electronic health record) and quality performance reports (eg, practice-wide or co-management team-wide performance reports).

Between/Across-Method Triangulation

This section describes the between/across methods, which involve employing both qualitative and quantitative data-collection procedures in the same study. 6 , 7 This procedure can also be denoted “methodologic triangulation.” 8 Subsequently, we present the individual data-collection procedures. In 3 studies, information on between/across triangulation was found. 16 , 20 , 21

Mixed methods

Three studies used qualitative and quantitative data-collection procedures. One study combined face-to-face interviews, documentation, and self-assessments. 16 One study employed semi-structured interviews, direct observation, documents, and service records, 20 and another study combined face-to-face interviews, non-participant observation, documents, and questionnaires. 23

All 3 studies used qualitative interviews as the primary data-collection procedure. 16 , 20 , 23 Face-to-face and semi-structured interviews were conducted. In the interviews, data were collected on the introduction of new care services and experiences of barriers to and facilitators of collaborative work in general practices.

Observation

In 2 studies, direct and non-participant qualitative observations were conducted. 20 , 23 During the observations, the interaction between health professionals or the organization and the clinical context was observed. Observations were generally recorded as field notes.

In 2 studies, various qualitative public documents were examined. 20 , 23 These documents included role description, newspapers, websites, and practice documents (eg, flyers). In the documents, information on the role implementation and role description of NPs was collected.

Individual journals

In 1 study, qualitative individual journals were studied. 16 These included reflective journals from NPs, who performed the role in primary health care.

Service records

Only 1 study involved quantitative service records. 20 These service records were obtained from the primary care practices and the respective health authorities. They were collected before and after the implementation of an NP role to identify changes in patients’ access to health care, the volume of patients served, and patients’ use of acute care services.

Questionnaires/Assessment

In 2 studies, quantitative questionnaires were used to gather information about the teams’ satisfaction with collaboration. 16 , 21 In 1 study, 3 validated scales were used. The scales measured experience, satisfaction, and belief in the benefits of collaboration. 21 Psychometric performance indicators of these scales were provided. However, the time points of data collection were not specified; similarly, whether the questionnaires were completed online or by hand was not mentioned. A competency self-assessment tool was used in another study. 16 The assessment comprised 70 items and included topics such as health promotion, protection, disease prevention and treatment, the NP-patient relationship, the teaching-coaching function, the professional role, managing and negotiating health care delivery systems, monitoring and ensuring the quality of health care practice, and cultural competence. Psychometric performance indicators were provided. The assessment was completed online with 2 measurement time points (pre self-assessment and post self-assessment).

Data-Analysis Triangulation

This section describes data-analysis triangulation, which involves the combination of 2 or more methods of analyzing data. 6 Subsequently, we present within-case analysis and cross-case analysis.

Mixed-methods analysis

Three studies combined qualitative and quantitative methods of analysis. 16 , 20 , 21 Two studies involved deductive and inductive qualitative analysis, and qualitative data were analyzed thematically. 20 , 21 One used deductive qualitative analysis. 16 The method of analysis was not specified in the studies. Quantitative data were analyzed using descriptive statistics in 3 studies. 16 , 20 , 23 The descriptive statistics comprised the calculation of the mean, median, and frequencies.

Qualitative methods of analysis

Two studies combined deductive and inductive qualitative analysis, 19 , 22 and 2 studies only used deductive qualitative analysis. 15 , 18 Qualitative data were analyzed thematically in 1 study, 22 and data were treated with content analysis in the other. 19 The method of analysis was not specified in the 2 studies.

Within-case analysis

In 7 studies, a within-case analysis was performed. 15 - 20 , 22 Six studies used qualitative data for the within-case analysis, and 1 study employed qualitative and quantitative data. Data were analyzed separately, consecutively, or in parallel. The themes generated from qualitative data were compared and then summarized. The individual cases were presented mostly as a narrative description. Quantitative data were integrated into the qualitative description with tables and graphs. Qualitative and quantitative data were also presented as a narrative description.

Cross-case analyses

Of the multiple-case studies, 5 carried out cross-case analyses. 15 - 17 , 20 , 22 Three studies described the cross-case analysis using qualitative data. Two studies reported a combination of qualitative and quantitative data for the cross-case analysis. In each multiple-case study, the individual cases were contrasted to identify the differences and similarities between the cases. One study did not specify whether a within-case or a cross-case analysis was conducted. 23

Confirmation or contradiction of data

This section describes confirmation or contradiction through qualitative and quantitative data. 1 , 4 Qualitative and quantitative data were reported separately, with little connection between them. As a result, the conclusions on neither the comparisons nor the contradictions could be clearly determined.

Confirmation or contradiction among qualitative data

In 3 studies, the consistency of the results of different types of qualitative data was highlighted. 16 , 19 , 21 In particular, documentation and interviews or interviews and observations were contrasted:

• Confirmation between interviews and documentation: The data from these sources corroborated the existence of a common vision for an NP-led clinic. 19
• Confirmation among interviews and observation: NPs experienced pressure to find and maintain their position within the existing system. Nurse practitioners and general practitioners performed complete episodes of care, each without collaborative interaction. 21
• Contradiction among interviews and documentation: For example, interviewees mentioned that differentiating the scope of practice between NPs and physicians is difficult as there are too many areas of overlap. However, a clear description of the scope of practice for the 2 roles was provided. 21

Confirmation through a combination of qualitative and quantitative data

Both types of data showed that NPs and general practitioners wanted to have more time in common to discuss patient cases and engage in personal exchanges. 21 In addition, the qualitative and quantitative data confirmed the individual progression of NPs from less competent to more competent. 16 One study pointed out that qualitative and quantitative data obtained similar results for the cases. 20 For example, integrating NPs improved patient access by increasing appointment availability.

Contradiction through a combination of qualitative and quantitative data

Although questionnaire results indicated that NPs and general practitioners experienced high levels of collaboration and satisfaction with the collaborative relationship, the qualitative results drew a more ambivalent picture of NPs’ and general practitioners’ experiences with collaboration. 21

Research Question and Design

The studies included in this scoping review evidenced various research questions. The recommended formats (ie, how or why questions) were not applied consistently. Therefore, no case study design should be applied because the research question is the major guide for determining the research design. 2 Furthermore, case definitions and designs were applied variably. The lack of standardization is reflected in differences in the reporting of these case studies. Generally, case study research is viewed as allowing much more freedom and flexibility. 5 , 24 However, this flexibility and the lack of uniform specifications lead to confusion.

Methodologic Triangulation

Methodologic triangulation, as described in the literature, can be somewhat confusing as it can refer to either data-collection methods or research designs. 6 , 8 For example, methodologic triangulation can allude to qualitative and quantitative methods, indicating a paradigmatic connection. Methodologic triangulation can also point to qualitative and quantitative data-collection methods, analysis, and interpretation without specific philosophical stances. 6 , 8 Regarding “data-collection methods with no philosophical stances,” we would recommend using the wording “data source triangulation” instead. Thus, the demarcation between the method and the data-collection procedures will be clearer.

Within-Method and Between/Across-Method Triangulation

Yin 1 advocated the use of multiple sources of evidence so that a case or cases can be investigated more comprehensively and accurately. Most studies included multiple data-collection procedures. Five studies employed a variety of qualitative data-collection procedures, and 3 studies used qualitative and quantitative data-collection procedures (mixed methods). In contrast, no study contained 2 or more quantitative data-collection procedures. In particular, quantitative data-collection procedures—such as validated, reliable questionnaires, scales, or assessments—were not used exhaustively. The prerequisites for using multiple data-collection procedures are availability, the knowledge and skill of the researcher, and sufficient financial funds. 1 To meet these prerequisites, research teams consisting of members with different levels of training and experience are necessary. Multidisciplinary research teams need to be aware of the strengths and weaknesses of different data sources and collection procedures. 1

Qualitative methods of analysis and results

When using multiple data sources and analysis methods, it is necessary to present the results in a coherent manner. Although the importance of multiple data sources and analysis has been emphasized, 1 , 5 the description of triangulation has tended to be brief. Thus, traceability of the research process is not always ensured. The sparse description of the data-analysis triangulation procedure may be due to the limited number of words in publications or the complexity involved in merging the different data sources.

Only a few concrete recommendations regarding the operationalization of the data-analysis triangulation with the qualitative data process were found. 25 A total of 3 approaches have been proposed 25 : (1) the intuitive approach, in which researchers intuitively connect information from different data sources; (2) the procedural approach, in which each comparative or contrasting step in triangulation is documented to ensure transparency and replicability; and (3) the intersubjective approach, which necessitates a group of researchers agreeing on the steps in the triangulation process. For each case study, one of these 3 approaches needs to be selected, carefully carried out, and documented. Thus, in-depth examination of the data can take place. Farmer et al 25 concluded that most researchers take the intuitive approach; therefore, triangulation is not clearly articulated. This trend is also evident in our scoping review.

Mixed-methods analysis and results

Few studies in this scoping review used a combination of qualitative and quantitative analysis. However, creating a comprehensive stand-alone picture of a case from both qualitative and quantitative methods is challenging. Findings derived from different data types may not automatically coalesce into a coherent whole. 4 O’Cathain et al 26 described 3 techniques for combining the results of qualitative and quantitative methods: (1) developing a triangulation protocol; (2) following a thread by selecting a theme from 1 component and following it across the other components; and (3) developing a mixed-methods matrix.

The most detailed description of the conducting of triangulation is the triangulation protocol. The triangulation protocol takes place at the interpretation stage of the research process. 26 This protocol was developed for multiple qualitative data but can also be applied to a combination of qualitative and quantitative data. 25 , 26 It is possible to determine agreement, partial agreement, “silence,” or dissonance between the results of qualitative and quantitative data. The protocol is intended to bring together the various themes from the qualitative and quantitative results and identify overarching meta-themes. 25 , 26

The “following a thread” technique is used in the analysis stage of the research process. To begin, each data source is analyzed to identify the most important themes that need further investigation. Subsequently, the research team selects 1 theme from 1 data source and follows it up in the other data source, thereby creating a thread. The individual steps of this technique are not specified. 26 , 27

A mixed-methods matrix is used at the end of the analysis. 26 All the data collected on a defined case are examined together in 1 large matrix, paying attention to cases rather than variables or themes. In a mixed-methods matrix (eg, a table), the rows represent the cases for which both qualitative and quantitative data exist. The columns show the findings for each case. This technique allows the research team to look for congruency, surprises, and paradoxes among the findings as well as patterns across multiple cases. In our review, we identified only one of these 3 approaches in the study by Roots and MacDonald. 20 These authors mentioned that a causal network analysis was performed using a matrix. However, no further details were given, and reference was made to a later publication. We could not find this publication.

Case Studies in Nursing Research and Recommendations

Because it focused on the implementation of NPs in primary health care, the setting of this scoping review was narrow. However, triangulation is essential for research in this area. This type of research was found to provide a good basis for understanding methodologic and data-analysis triangulation. Despite the lack of traceability in the description of the data and methodological triangulation, we believe that case studies are an appropriate design for exploring new nursing roles in existing health care systems. This is evidenced by the fact that case study research is widely used in many social science disciplines as well as in professional practice. 1 To strengthen this research method and increase the traceability in the research process, we recommend using the reporting guideline and reporting checklist by Rodgers et al. 9 This reporting checklist needs to be complemented with methodologic and data-analysis triangulation. A procedural approach needs to be followed in which each comparative step of the triangulation is documented. 25 A triangulation protocol or a mixed-methods matrix can be used for this purpose. 26 If there is a word limit in a publication, the triangulation protocol or mixed-methods matrix needs to be identified. A schematic representation of methodologic and data-analysis triangulation in case studies can be found in Figure 2 .

Schematic representation of methodologic and data-analysis triangulation in case studies (own work).

Limitations

This study suffered from several limitations that must be acknowledged. Given the nature of scoping reviews, we did not analyze the evidence reported in the studies. However, 2 reviewers independently reviewed all the full-text reports with respect to the inclusion criteria. The focus on the primary care setting with NPs (master’s degree) was very narrow, and only a few studies qualified. Thus, possible important methodological aspects that would have contributed to answering the questions were omitted. Studies describing the triangulation of 2 or more quantitative data-collection procedures could not be included in this scoping review due to the inclusion and exclusion criteria.

Conclusions

Given the various processes described for methodologic and data-analysis triangulation, we can conclude that triangulation in case studies is poorly standardized. Consequently, the traceability of the research process is not always given. Triangulation is complicated by the confusion of terminology. To advance case study research in nursing, we encourage authors to reflect critically on methodologic and data-analysis triangulation and use existing tools, such as the triangulation protocol or mixed-methods matrix and the reporting guideline checklist by Rodgers et al, 9 to ensure more transparent reporting.

Supplemental Material

Acknowledgments.

The authors thank Simona Aeschlimann for her support during the screening process.

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Supplemental Material: Supplemental material for this article is available online.

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Traffic Analysis Toolbox Volume V: Traffic Analysis Toolbox Case Studies — Benefits and Applications: Reliability Analysis Guidance Addendum

• By Morris, Paul ; Semeja, Nick
• Creators: Morris, Paul ; Semeja, Nick Morris, Paul ; Semeja, Nick Less -
• Corporate Creators: Leidos
• Contributors: Spiller, Neil
• Corporate Contributors: United States. Department of Transportation. Federal Highway Administration. Office of Operations
• Subject/TRT Terms: [+] Case Studies Reliability Software Transportation Planning
• Publication/ Report Number: FHWA-HOP-20-T014
• Resource Type: Tech Report
• Right Statement: Public Domain
• Geographical Coverage: United States
• Contracting Officer: Spiller, Neil
• Corporate Publisher: United States. Department of Transportation. Federal Highway Administration. Office of Operations
• Abstract: This document is an addendum to the Traffic Analysis Toolbox Volume V: Traffic Analysis Toolbox Case Studies— Benefits and Applications (Federal Highway Administration Report No. FHWA-HOP-06-005) and reflects up-to date guidance on incorporating travel time reliability (TTR) in the Traffic Analysis Toolbox. "Traffic analysis tools" is a collective term used to describe a variety of software-based analytical procedures and methodologies that support different aspects of traffic and transportation analyses. Traffic analysis tools include methodologies such as sketch planning, travel demand modeling, traffic signal optimization, and traffic simulation. The purpose of this addendum is to give the reader a summary of real-world case studies that demonstrate the benefits of using traffic analysis tools for the project. More ▼ -->
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Comparative case study on NAMs: towards enhancing specific target organ toxicity analysis

• Regulatory Toxicology
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• Published: 29 August 2024

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• Kristina Jochum 1 ,
• Andrea Miccoli 1 , 2 , 5 ,
• Cornelia Sommersdorf 3 ,
• Oliver Poetz 3 , 4 ,
• Albert Braeuning 5 ,
• Tewes Tralau 1 &
• Philip Marx-Stoelting   ORCID: orcid.org/0000-0002-6487-2153 1  

Traditional risk assessment methodologies in toxicology have relied upon animal testing, despite concerns regarding interspecies consistency, reproducibility, costs, and ethics. New Approach Methodologies (NAMs), including cell culture and multi-level omics analyses, hold promise by providing mechanistic information rather than assessing organ pathology. However, NAMs face limitations, like lacking a whole organism and restricted toxicokinetic interactions. This is an inherent challenge when it comes to the use of omics data from in vitro studies for the prediction of organ toxicity in vivo. One solution in this context are comparative in vitro–in vivo studies as they allow for a more detailed assessment of the transferability of the respective NAM data. Hence, hepatotoxic and nephrotoxic pesticide active substances were tested in human cell lines and the results subsequently related to the biology underlying established effects in vivo. To this end, substances were tested in HepaRG and RPTEC/tERT1 cells at non-cytotoxic concentrations and analyzed for effects on the transcriptome and parts of the proteome using quantitative real-time PCR arrays and multiplexed microsphere-based sandwich immunoassays, respectively. Transcriptomics data were analyzed using three bioinformatics tools. Where possible, in vitro endpoints were connected to in vivo observations. Targeted protein analysis revealed various affected pathways, with generally fewer effects present in RPTEC/tERT1. The strongest transcriptional impact was observed for Chlorotoluron in HepaRG cells (increased CYP1A1 and CYP1A2 expression). A comprehensive comparison of early cellular responses with data from in vivo studies revealed that transcriptomics outperformed targeted protein analysis, correctly predicting up to 50% of in vivo effects.

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Comparison of base-line and chemical-induced transcriptomic responses in heparg and rptec/tert1 cells using tempo-seq.

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Introduction

Given the at times heated discussions about regulatory toxicology in the political and public domain, the quite remarkable track record of toxicological health protection sometimes tends to go unnoticed. Not only are chemical scares such as the chemically induced massive acute health impacts in the 1950ies, 60ies and 70ies a thing of the past (Herzler et al. 2021 ), but in many parts of the world, there are now regulatory frameworks in place which aim at the early identification of potential health risks from chemicals. Within Europe, the most notable in terms of impact are probably REACH (EC 2006 ) and the regulations on pesticides (EC 2009 ) both of which still overwhelmingly rely on animal data for their risk assessments. This has manifold reasons, one being the historical reliability of animal-based systems for the prediction of adversity in humans. However, there are a number of challenges to this traditional approach. These comprise capacity issues when it comes to the testing of thousands of new or hitherto untested substances, the testing of mixtures, the ever-daunting question of species specificity or the limitation of current in vivo studies regarding less accessible endpoints such as for example immunotoxicity or developmental neurotoxicity.

Over recent years, so-called New Approach Methodologies (NAMs) have thus attracted increased attention and importance for regulatory toxicology. The United States Environmental Protection Agency (US EPA 2018 ) defines NAM as ‘…a broadly descriptive reference to any technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment that avoids the use of intact animals… ’. One instance of an attempt to replace an animal test with an in vitro test system is the embryonic stem cell test in the area of developmental toxicology (Buesen et al. 2004 ; Seiler et al. 2006 ). This stand-alone test was first evaluated for assessing the embryotoxic potential of chemicals as early on as 2004 (Genschow et al. 2004 ). While its establishment as a regulatory prediction model took several more years, one major outcome was the realization that the use of NAMs in general is greatly improved when used as part of a biologically and toxicologically meaningful testing battery (Marx-Stoelting et al. 2009 ; Schenk et al. 2010 ). It should be noted that despite all the potential of such testing batteries a tentative one to one replacement of animal studies is neither practical nor straight forward. The reason is not only the complexity of the endpoints in question but also practical constraints. This was recently exemplified by Landsiedel et al. who pointed out that with the number of different organs and tissues tested during one sub-chronic rodent study, and assuming that 5 NAMs are needed to address the adverse outcomes in any of those organs, it would take decades just to replace this one study. Any regulatory use of NAMs should hence preferably rely on their direct use (Landsiedel et al. 2022 ).

An example from the field of hepatotoxicity testing is the in vitro toolbox for steatosis that was developed by Luckert et al. ( 2018 ) based on the adverse outcome pathway (AOP) concept by Vinken ( 2015 ). The authors employed five assays covering relevant key events from the AOP in HepaRG cells after incubation with the test substance Cyproconazole. Concomitantly, transcript and protein marker patterns for the identification of steatotic compounds were established in HepaRG cells (Lichtenstein et al. 2020 ). The findings were subsequently brought together in a proposed protocol for AOP-based analysis of liver steatosis in vitro (Karaca et al. 2023a ).

One promising use for such cell-based systems is their combination with multi-level omics. In conjunction with sufficient biological and mechanistic knowledge, the wealth of information provided by multi-omics data should potentially allow some prediction of substance-induced adversity. That said any such prediction can of course only be reliable within the established limits of such systems such as the lack of a whole organism and incomplete toxicokinetics and restrictions on adequately capturing the effects of long-term exposure (Schmeisser et al. 2023 ). Regulatory use and trust in cell-based systems will, therefore, strongly rely on how they compare to the outcome of studies based on systemic data (Schmeisser et al. 2023 ).

Pesticide active substances are a group of compounds with profound in vivo data. Some examples for active substances commonly used in PPPs are the fungicides Cyproconazole, Fluxapyroxad, Azoxystrobin and Thiabendazole, as well as the herbicide Chlorotoluron and the multi-purpose substance 2-Phenylphenol. For these compounds, several short- and long-term studies in rodents have been conducted and multiple adverse effects in target organs like liver or kidneys were observed (see Table  1 ). Liver steatosis, as one potential adverse health outcome, has been associated with triazole fungicides, such as Cyproconazole, but other active substances such as Azoxystrobin are suspected to interfere with the lipid metabolism as well (Gao et al. 2014 ; Luckert et al. 2018 ). Potential modes of action for adverse effects include the activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which has been shown for Cyproconazole and Fluxapyroxad (Marx-Stoelting et al. 2017 ; Tamura et al. 2013 ; Zahn et al. 2018 ). Notably, even when an active substance is considered to be of low acute toxicity, e.g. Chlorotoluron, Thiabendazole and 2-Phenylphenol (EC 2015 ; US EPA 2002 ; WHO 1996 ), they might still exhibit adverse chronic effects (Mizutani et al. 1990 ; WHO 1996 ). This is the reason why pesticide active substances and plant protection products (PPP) are assessed extensively before their placing on the market (EC 2009 ).

The target organs most frequently affected by pesticide active ingredients are the liver and kidneys (Nielsen et al. 2012 ). Hence, an in vitro test system aimed at the prediction of pesticide organ toxicity should be able to model effects on these two target organs. One of the best options currently available for hepatotoxicity studies in vitro is the cell line HepaRG (Ashraf et al. 2018 ). Before their use in toxicological assays, the cells undergo a differentiation process resulting in CYP-dependent activities close to the levels in primary human hepatocytes (Andersson et al. 2012 ; Hart et al. 2010 ). They also feature the capability to induce or inhibit a variety of CYP enzymes (Antherieu et al. 2010 ; Hartman et al. 2020 ) and the expression of phase II enzymes, membrane transporters and transcription factors (Aninat et al. 2006 ). Antherieu et al. ( 2012 ) demonstrated that HepaRG cells can sustain various types of chemically induced hepatotoxicity following acute and repeated exposure. Hence, HepaRG cells have the potential to replace the use of primary human hepatocytes in the study of acute and chronic effects of xenobiotics in the liver. In 2012, the European Commission Joint Research Centre’s European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) coordinated a validation study finding differentiated HepaRG cells as a reliable and relevant tool for CYP enzyme activity studies (EURL ECVAM 2012 ). This led to the proposal of a respective draft test guideline by the OECD in 2019 (OECD 2019 ). Additionally, as part of the US EPA Tox21 project, HepaRG cells were used for an assay assessing toxicogenomics (Franzosa et al. 2021 ).

A promising test system for investigations of nephrotoxicity is the tERT1 immortalized renal proximal tubular epithelial cell line RPTEC/tERT1 (further referred to as RPTEC). These non-cancerous cells have been found to closely resemble primary counterparts showing typical morphology and functionality (Shah et al. 2017 ; Wieser et al. 2008 ). Aschauer et al. ( 2015 ) demonstrated the applicability of RPTEC for investigation of repeated-dose nephrotoxicity using a transcriptomic-based approach. Simon et al. ( 2014 ) showed similar toxicological responses of RPTEC and the target tissue to exposure to benzo[ a ]pyrene and cadmium. Conclusively, RPTEC can be a useful tool for toxicological studies.

In the present study, six pesticide active substances were analyzed in two cell lines, namely the liver cell line HepaRG and the kidney cell line RPTEC. Assays were performed following exposure to the highest non-cytotoxic concentration and comprised targeted protein and transcriptomics analysis. Triggered pathways were identified and compared with established results from in vivo experiments.

Materials and methods

All test substances were purchased in analytical grade (purity ≥ 98.0%) from Sigma-Aldrich, Pestanal® (Taufkirchen, Germany): Cyproconazole, CAS no. 94361–06-5, catalog no. 46068, batch no. BCCD4066; Fluxapyroxad, CAS no. 907204–31-3, catalog no. 37047, batch no. BCCF6749; Azoxystrobin, CAS no. 131860–33-8, catalog no. 31697, batch no. BCCF6593; Chlorotoluron, CAS no. 15545–48-9, catalog no. 45400, batch no. BCBW1414; Thiabendazole, CAS no. 148–79-8, catalog no. 45684, batch no. BCBV5436; 2-Phenylphenol, CAS no. 90–43-7, catalog no. 45529, batch no. BCCF1784. William’s E medium, fetal calf serum (FCS) good forte (catalog no. P40-47500, batch no. P131102), recombinant human insulin and l -glutamine were acquired from PAN-Biotech GmbH (Aidenbach, Germany), FCS superior (catalog no. S0615, batch no. 0001659021) from Bio&Sell (Feucht bei Nürnberg, Germany). Dimethyl sulfoxide (DMSO, purity ≥ 99.8%), hydrocortisone-hemisuccinate (HC/HS), hydrocortisone, epidermal growth factor (EGF) and neutral red (NR) were purchased from Sigma-Aldrich (Taufkirchen, Germany). Dulbecco’s modified eagle medium (DMEM) and Ham’s F Nutrition mix were obtained from Gibco® Life Technologies (Karlsruhe, Germany), trypsin–EDTA, Penicillin–Streptomycin and insulin-transferrin-selenium from Capricorn Scientific GmbH (Ebsdorfergrund, Germany).

Cell culture

HepaRG cells were obtained from Biopredic International (Sant Grégoire, France) and kept in 75 cm 2 flasks under humid conditions at 37 °C and 5% CO 2 . Cells were grown in proliferation medium consisting of William’s E medium with 2 mM l -glutamine, supplemented with 10% FCS good forte, 100 U mL −1 penicillin, 100 µg mL −1 streptomycin, 0.05% human insulin and 50 µM HC/HS for 2 weeks. Then, HepaRG cells were passaged using trypsin–EDTA solution and seeded in 75 cm 2 flasks, 6-well, 12-well and 96-well plates at a density of 20 000 cells per cm 2 . Cells in cell culture dishes were maintained in proliferation medium for another 2 weeks before the medium was changed to differentiation medium (i.e., proliferation medium supplemented by 1.7% DMSO) and cells were cultured for another 2 weeks. Thereafter, cells were used in experiments within 4 weeks, while media was changed to treatment media (i.e., proliferation media supplemented by 0.5% DMSO and 2% FCS) 2 days prior to the experiments.

The RPTEC cell line was obtained from Evercyte GmbH (Vienna, Austria) and cultivated as previously described (Aschauer et al. 2013 ; Wieser et al. 2008 ). Cells were grown in a 1:1 mixture of DMEM and Ham’s F-12 Nutrient Mix, supplemented with 2.5% FCS superior, 100 U mL −1 penicillin, 100 µg mL −1 streptomycin, 2 mM l -glutamine, 36 ng mL −1 hydrocortisone, 10 ng mL −1 EGF, 5 µg mL −1 insulin, 5 µg mL −1 transferrin and 5 ng mL −1 selenium. RPTEC were cultivated in 75 cm 2 flasks until they reached near confluence. Then, cells were passaged using trypsin–EDTA and seeded at 30% density in 75 cm 2 flasks for further sub-cultivation and 6-well, 12-well and 96-well plates for experiments. To obtain complete differentiation, cells in cell culture dishes were maintained for 14 days before they were used in experiments.

Test concentrations

All substances were dissolved in DMSO and diluted in the respective medium to a final DMSO concentration of 0.5% before incubation. HepaRG treatment medium and 0.5% DMSO in RPTEC medium served as solvent controls for HepaRG cells and RPTEC, respectively. At least 3 biological replicates, i.e., independent experiments, were performed for each assay.

Cell viability

Cell viability was investigated with the WST-1 assay (Immunservice, Hamburg, Germany), according to the manufacturer’s protocol and subsequent NR uptake assay according to Repetto et al. ( 2008 ). HepaRG cells and RPTEC were seeded in 96-well plates and incubated with the test substances for 72 h. Triton X-100 (0.01%, Thermo Fisher Scientific, Darmstadt, Germany) was used as positive control for reduced cell viability. At the end of the incubation period, 10 µL WST-1 solution was added to each well and incubated for 30 min at 37 °C. The tetrazolium salt WST-1 is metabolized by cellular mitochondrial dehydrogenases of living cells to a formazan derivative, the absorbance of which was measured at 450 nm with an Infinite M200 PRO plate reader (Tecan, Maennedorf, Switzerland). The reading of each well was related to the absorbance value at the reference wavelength of 620 nm, and blank values were subtracted before the relation to the solvent control.

Afterwards the NR uptake assay was performed, where incorporation of NR into lysosomes of viable cells is measured. One day prior to the assay, NR medium was prepared by diluting a 4 mg mL −1 NR stock solution in PBS 1:100 with the respective cell culture medium for HepaRG cells and RPTEC, and incubated at 37 °C over night. After the WST-1 measurement, the incubation medium was removed and cells were washed twice with PBS. Subsequently, 100 µL NR medium, previously centrifuged for 10 min at 600 ×  g , was added and incubated for 2 h. Afterwards, cells were washed twice with PBS, and 100 µL destaining solution (49.5:49.5:1 ethanol absolute, distilled water, glacial acetic acid) per well was added. Plates were shaken at 500 rotations min −1 for 10 min and fluorescence of NR was measured with an Infinite M200 PRO plate reader (Tecan, Maennedorf, Switzerland) at 530 nm excitation and 645 nm emission. Each reading was subtracted by the blank value and normalized to the solvent control.

Multiplexed microsphere-based sandwich immunoassays

Marker proteins and protein modifications were analyzed by Signatope GmbH (Tübingen, Germany) with a multiplexed microsphere-based sandwich immunoassay. Cells were seeded in 6-well plates and incubated with the test substances for 36 and 72 h. Protein extraction was performed by adding 250 µL pre-cooled extraction buffer, supplied by the company, to the cells in each well and subsequent incubation for 30 min at 4 °C. Cell lysates were transferred to 1.5 mL reaction tubes and centrifuged for 30 min at 4 °C and 15 000 ×  g . The supernatant was aliquoted in 60 µL batches and stored at -80 °C until shipment. After thawing, aliquots were directly used and not frozen again. Samples were analyzed for 8 proteins and protein modifications, each representing a marker for a certain form of toxicity (Table  2 ).

Quantitative real-time PCR and PCR profiler arrays

RT-qPCR was conducted to ensure well performing RNA for subsequent PCR profiler arrays. Cells were seeded in 12-well plates and incubated with the test substances for 36 h. RNA extraction was performed with the RNA easy Mini Kit (Qiagen, Venlo, Netherlands) according to the manufacturer’s manual. Yield RNA concentration and purity were analyzed with a Nanodrop spectrometer (NanoDrop 2000, Thermo Fischer Scientific, Darmstadt, Germany) and RNA samples were stored at -80 °C until further use. Reverse transcription to cDNA was conducted using the High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Waltham, MA, USA) according to the manufacturer’s protocol with a GeneAmp ® PCR System 9700 (Applied Biosystems, Darmstadt, Germany) and cDNA samples were stored at – 20 °C. RT-qPCR was performed with Maxima SYBR Green/ROX Master Mix (Thermo Fisher Scientific, Darmstadt, Germany) according to manufacturer’s protocol. In brief, 9 µL master mix, consisting of 5 µL Maxima SYBR Green/ROX qPCR Master Mix, 0.6 µL each of forward and reverse primers (2.5 µM) and 2.8 µL nuclease-free water, was added to each well of a 384-well plate. Primer sequences are shown in Online Resource 1. Subsequently, 20 ng cDNA was added to each well to a final volume of 10 µL and RT-qPCR was performed with an ABI 7900HT Fast Real-Time PCR system instrument (Applied Biosystems, Darmstadt, Germany). In brief, activation took place at 95 °C for 15 min, followed by 40 cycles of 15 s at 95 °C and 60 s at 60 °C, followed by 15 min at 60 °C and default melting curve analysis. Data were processed using 7900 software v241 and Microsoft Excel 2021. Threshold cycle (C T ) was set to 0.5, melting curve was checked and manual baseline correction was performed for each gene individually. Yield C T -values were extracted to Microsoft Excel 2021 and relative gene expression was obtained with the 2 −ΔΔCt method according to Livak and Schmittgen ( 2001 ). GUSB and HPRT1 served as endogenous control genes for HepaRG cells, GUSB and GAPDH were used for RPTEC. Primer efficiency was tested beforehand according to Schmittgen and Livak ( 2008 ). Only RNA samples showing amplification in RT-qPCR were used for further analysis with PCR profiler arrays. For quality control purposes, yield 2 −ΔΔCt values from RT-qPCR and PCR profiler arrays were compared and had to be within the same range (Online Resource 1).

For performing the PCR profiler array, cDNA was synthesized from 1 µg RNA using the RT 2 First Strand Kit (Qiagen, Venlo, Netherlands) according to the manufacturer’s protocol with a GeneAmp® PCR System 9700 (Applied Biosystems, Darmstadt, Germany). Subsequently, the RT 2 Profiler™ PCR Array Human Molecular Toxicology Pathway Finder or Nephrotoxicity (Qiagen, Venlo, Netherlands) was conducted with RT 2 SYBR ® Green ROX qPCR Mastermix (Qiagen, Venlo, Netherlands) according to the manufacturer’s protocol. RT-qPCR was performed with an ABI 7900HT Fast Real-Time PCR system instrument (Applied Biosystems, Darmstadt, Germany), where activation of polymerase took place for 10 min at 95 °C, followed by 40 cycles of 15 s at 95 °C and 60 s at 60 °C and default melting curve analysis. Data were analyzed using 7900 software v241 and Excel 2021. C T was set to 0.2, melting curve was checked and manual baseline correction was performed. Yield C T -values were extracted and further analyzed.

• Pathway analysis

Further evaluation of PCR array data was performed with functional class scoring methods such as Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as with the bioinformatics analysis and search tool Ingenuity Pathway Analysis Software (IPA). Following the manufacturer’s instructions, yield C T -values were uploaded to the Qiagen Gene Globe Webportal Footnote 1 and analyzed using the standard ΔΔC T method referring to an untreated control. A cut-off C T was set to 35, all 5 built-in housekeeping genes were manually selected as reference genes and their arithmetic mean used for normalization. Means of fold regulation and p-values were calculated and further evaluated with the bioinformatics tools following the protocol provided in Online Resource 2. The processed results from HepaRG cells and RPTEC were used as input data individually, as well as combined. For the combined analysis, duplicate genes that were present on both arrays were removed.

To generate a first overview, the percentage of differentially expressed genes (DEG) per pathway was determined as previously published (Heise et al. 2018 ). Genes were assorted to pathways as suggested on the manufacturer’s web page. Footnote 2 The percentage of DEG was calculated as number of genes whose expression significantly differed by a fold change of 2, as determined by Student’s t- test (p < 0.05), related to the total number of genes in the pathway.

GO enrichment and KEGG analysis

The freely available web tools GOrilla Footnote 3 and ShinyGO 0.80 Footnote 4 were used for GO enrichment and KEGG analysis, respectively (Eden et al. 2007 , 2009 ; Ge et al. 2020 ). Detailed protocols are provided in Online Resource 2 together with the R code for determining DEG and background genes (see Data availability), which was adapted from Feiertag et al. ( 2023 ).

Ingenuity pathway analysis

In addition to GO enrichment and KEGG analysis, further evaluation of PCR array data was performed with the bioinformatics analysis and search tool IPA (Qiagen, Hilden, Germany, analysis date: Nov. 2023) as previously published (Karaca et al. 2023b ). IPA is a commercial bioinformatics tool for analyzing RNA data, predicting pathway activation and functional interrelations using a curated pathway database. Using Fisher’s exact test, IPA identifies overrepresented pathways by measuring significant overlaps between user-provided gene lists and predefined gene sets. Means of fold regulation and p -values were uploaded to IPA following the protocol provided in Online Resource 2. Cut-off was set to – 1.5 and + 1.5 for fold regulation and 0.05 for the p -value. Fold regulation represents fold change results in a biologically meaningful way. In case the fold change is greater than 1, the fold regulation is equal to the fold change. For fold change values less than 1, the fold regulation is the negative inverse of the fold change. No further filtering was applied and an IPA core analysis was run. One Excel spread sheet per substance was obtained including all predicted diseases or functions annotations, the associated categories, the p-value of overlap as well as the number and names of the DEG found in the respective annotation (Online Resource 3). Predicted effects on other organs than the liver or the kidneys, such as heart or lungs, were discarded. For further comparison with in vivo data only the categories were used, combined with the p-value of the annotation, which was the highest.

Comparison with animal studies

The data obtained from targeted protein and transcriptomics analyses were compared with known in vivo observations from Draft Assessment Reports (DARs) of the pesticide active substances required for pesticide legislation. To facilitate the comparison of the data, the in vitro data was transformed into a more comprehensible form by applying evaluation matrices as shown in Table  3 .

The in vivo effects attributed to the pesticide active substances were taken from the publication by Nielsen et al. ( 2012 ). Additionally, the DARs of the two substances not reported in Nielsen et al . were analyzed and assigned accordingly. All in vivo effects identified by the authors for liver and kidneys can be found in Online Resource 1. Based on expert knowledge, descriptions of in vitro outcomes were combined with in vivo observations (see Tables  4 and 5 ).

Based on the combination of the in vitro and the in vivo data, it was possible to draw conclusions on the concordance of the predictions. In order to establish optimized thresholds for regarding an effect as in vitro positive, the analyses were performed by considering at least medium effects, strong and very strong effects, or very strong effects only (see Table  3 ) and comparing these to the corresponding in vivo effect. In case multiple in vitro predictors were connected to the same in vivo observation, a positive prediction from one was sufficient to be considered in vitro positive. For protein analyses, the comparison was performed for the data from HepaRG cells and RPTEC individually, as well as combined, where a positive prediction from one of the cell lines was considered sufficient and compared to hepatotoxic and nephrotoxic in vivo effects. For the gene transcription analysis, the categories obtained by IPA were compared to in vivo observations from DARs. A further evaluation integrating protein and transcriptional data was conducted, wherein a positive result from either data type was sufficient to classify a sample as in vitro positive. Online Resource 1 shows the combination of the results in detail. The percentage of concordance between in vitro prediction and in vivo observation was calculated. Indicative concordance was defined as percentage of in vivo positive observations that were predicted to be positive by the in vitro test system.

Statistical analysis

Statistical analysis was performed using R 4.2.1 and RStudio 2023.09.1 + 494. Data evaluation was done with Microsoft Excel 2021.

All experiments were performed in at least three independent biological replicates. Technical replicates, when applicable, were averaged and subsequently mean and standard deviation values were calculated from biological replicates. For targeted protein analysis, statistical significance was calculated with bootstrap technique using R package boot (Canty and Ripley 2016 ; Davidson and Hinkley 1997 ) to account for the high variability that results when the protein expression is affected. Data visualization was done using ggplot2 package (Wickham 2016 ). Calculation of statistical significance of altered gene transcription was performed using Student’s t -test, and R package ComplexHeatmaps was used for data visualization (Gu 2022 ). All R scripts can be found using the link provided in the Data availability section.

Impairment of cell viability

Each substance was tested for its effect on the viability of HepaRG cells and RPTEC. Based on these results, the highest non-cytotoxic concentration was determined and employed in further experiments together with a second concentration (i.e., 0.33 × highest non-cytotoxic concentration). For HepaRG cells, published data were used as a starting point for cytotoxicity testing and confirmed with WST-1 and NR uptake assays. The highest non-cytotoxic concentration, defined as the concentration determining a cell viability greater than 80%, is shown in Table  6 .

For RPTEC, a relatively new cell line, little data was available. At least 3 biological replicates were performed in technical triplicates to determine the highest non-cytotoxic concentrations (Table  6 ). The bar graphs in Online Resource 4 depict the concentration-dependent course of all tested concentrations per substance limited by solubility. Online Resource 1 provides a table with calculated approximations of substance concentrations in the target organ at LOAEL or NOEAL level based on in vivo toxicokinetic results from DARs. These approximations can be compared with the selected in vitro concentrations based on cytotoxicity experiments.

Effects on marker proteins

The result from multiplex microsphere-based sandwich immunoassays of treated HepaRG cells and RPTEC are shown in Figs.  1 and 2 , respectively. In HepaRG cells, incubation with the highest non-cytotoxic concentrations of Azoxystrobin, Chlorotoluron and Thiabendazole increased the expression of total LC3B, an indicator of autophagy, after 36 h (all three compounds) and 72 h (Chlorotoluron and Thiabendazole). Strong effects were observed on cleaved PARP, an indicator of apoptosis, after 36 h of incubation with 120 µM Cyproconazole (247 ± 147%) and 300 µM Thiabendazole (359 ± 204%). However, after 72 h incubation with 120 µM Cyproconazole, the level of cleaved PARP was strongly reduced. Expression of HIF 1-alpha, an indicator of hypoxia, was significantly increased after 36 h incubation with 45 µM Azoxystrobin (214 ± 24%). Fluxapyroxad and 2-Phenylphenol did not significantly increase the expression of any of the protein analytes.

Effects on protein abundance and protein modification of key proteins observed in HepaRG cells after 36 and 72 h of incubation with the test substances using a multiplexed microsphere-based sandwich immunoassay panel. Results are shown as means of 3 independent experiments, normalized to solvent controls. Statistical differences to the solvent control were calculated with bootstrapping (* p  < 0.05)

Effects on protein abundance and protein modification of key proteins in RPTEC after 36 and 72 h of incubation with the test substances using a multiplexed microsphere-based sandwich immunoassay panel. Results are shown as means of 3 independent experiments, normalized to solvent controls. Statistical differences to the solvent control were calculated with bootstrapping (* p  < 0.05)

In RPTEC, the abundance of p-elF4B, involved in eukaryotic translation initiation, was increased after 36 and 72 h incubation with 300 µM Cyproconazole (165 ± 45% and 201 ± 51%, respectively), all conditions of Fluxapyroxad, incubation with 3 µM Azoxystrobin for 36 h (166 ± 56%) and incubation with 900 µM Chlorotoluron for 36 and 72 h (238 ± 59% and 170 ± 44%, respectively). Thiabendazole exposure for 36 h resulted in an increase of cleaved PARP at both tested concentrations. Due to the high standard deviation, these results were not statistically significant.

Comparing the results from HepaRG cells and RPTEC, fewer effects were observed in RPTEC than in HepaRG cells. Effects of Azoxystrobin and Chlorotoluron on p-elF4B were observed in both cell lines, as well as increased levels of cleaved PARP after Thiabendazole exposure; yet these results were only significant in HepaRG cells. 2-Phenylphenol did not increase the expression of any of the tested proteins in either cell line, while Fluxapyroxad only affected p-elF4B in RPTEC.

A graphical representation of all data points from HepaRG and RPTEC including means and standard deviations can be found in Online Resource 4.

Changes at the gene transcription level

Changes at the protein level are often preceded by changes at the gene expression level. These were analyzed by RT 2 Profiler™ PCR arrays. Figures  3 and 4 show the results from HepaRG cells and RPTEC, respectively. The genes included in the array were assigned to certain pathways according to the information provided on the manufacturer’s web page. For data interpretation, the percentage of DEG was calculated. In HepaRG cells, most DEG were observed following the exposure to Chlorotoluron. Overall, genes categorized as CYPs and phase I were predominantly affected. Cyproconazole and Chlorotoluron exerted effects on genes associated with fatty acid metabolism (10 and 55%, respectively). Of all steatosis-associated genes, 47% were altered by Chlorotoluron. With regards to individual genes, the strongest increase was observed for CYP1A1 and CYP1A2 , both in the group of CYPs and phase I, after exposure to Chlorotoluron (479-fold and 57-fold, respectively) and Thiabendazole (330-fold and 215-fold, respectively).

Relative quantities of mRNA transcript levels observed after 36 h exposure of HepaRG cells to non-cytotoxic concentrations of the test substances using the Human Molecular Toxicology Pathway Finder RT 2 Profiler™ PCR Array. Data evaluation was performed using the 2 −∆∆ Ct method, according to Livak and Schmittgen ( 2001 ). All target genes were normalized to 5 housekeeping genes. Results are shown as mean of 3 biological replicates and statistical analysis was performed by one sample Student’s t -test (* p  < 0.05)

Relative quantities of mRNA transcript levels observed after 36 h exposure of RPTEC to non-cytotoxic concentrations of the test substances using the Human Nephrotoxicity RT 2 Profiler™ PCR Array. Data evaluation was performed using the 2 −∆∆ Ct method, according to Livak and Schmittgen ( 2001 ). All target genes were normalized to 5 housekeeping genes. Results are shown as mean of 3 biological replicates and statistical analysis was performed by one sample Student’s t -test (* p  < 0.05)

In RPTEC, the cluster encompassing most of the DEG was that associated with regulation of the cell cycle. Here, Cyproconazole, Fluxapyroxad, Azoxystrobin, and Chlorotoluron affected the expression of over 40% of the associated genes. Genes associated with apoptosis were altered following the exposure to all substances, particularly Cyproconazole and Chlorotoluron (47 and 37%, respectively). Cyproconazole additionally showed pronounced effects on genes encoding for extracellular matrix and tissue remodeling molecules (27 and 40%, respectively). All substances affected about 20% of all genes contained in the group of genes related to cell proliferation. Cyproconazole, Chlorotoluron and 2-Phenylphenol affected 25% of all oxidative stress-associated genes. In comparison to HepaRG cells, where CYPs and phase I was the most impacted group, in RPTEC only one of the DEG established for any of the substances belonged to the group of xenobiotic metabolism. At the level of individual genes, HMOX1, a nephrotoxicity marker, was induced over twofold after incubation with all substances, but highest for Cyproconazole (eightfold). Of all genes, the strongest induction was observed for IGFBP1 , a member of the insulin-like growth factor-binding protein family, which was increased 53-fold by incubation with Cyproconazole and over 52-fold after incubation with Chlorotoluron.

A graphical representation of all data points including means and standard deviations can be found in Online Resource 4 for HepaRG and RPTEC results.

Data analysis with GO enrichment and KEGG analysis

Gene expression results were analyzed with GO enrichment and KEGG analysis. All effects obtained in the analyses can be found in Online Resource 3.

The GO enrichment analysis of HepaRG DEG from the incubation with Cyproconazole pointed at changes in secondary and xenobiotic metabolic processes , and the combined analysis additionally resulted in significant enrichment of response to estrogen . DEG modulated by the exposure to Chlorotoluron were involved in 16 ontologies including metabolic, biosynthetic, and catabolic processes , with lipid metabolic process and organic hydroxyl compound metabolic process being the most statistically supported (i.e., p-value: 9.2 × 10 –8 and 7.7 × 10 –7 , respectively). In RPTEC, nucleic acid metabolic process was the only significantly enriched GO term for Chlorotoluron, while the combined analysis revealed a total of 23. Analysis of DEG from incubation with Thiabendazole resulted, among others, in hits for xenobiotic, terpenoid, and isoprenoid metabolic process in HepaRG and combined results. Although analysis of DEG from incubation with 2-Phenylphenol did not result in significantly enriched GO terms from the HepaRG or the RPTEC data; the combined data set showed 5 enriched terms with NADP metabolic process and myeloid leukocyte migration having the lowest p-values (6.9 × 10 –4 , both).

For KEGG analysis, the HepaRG data set for Fluxapyroxad and Chlorotoluron showed enrichment of drug metabolism-cytochrome P450 , as well as taurine and hypotaurine metabolism (Fluxapyroxad) and metabolic pathways (Chlorotoluron). Thiabendazole data revealed enrichment of steroid hormone biosynthesis , metabolism of xenobiotics by cytochrome P450 and chemical carcinogenesis-DNA adducts . RPTEC data set for Azoxystrobin and Chlorotoluron showed multiple cancer-related pathways. The combined data set only resulted in few pathways: hepatocellular carcinoma for Azoxystrobin, metabolic pathways for Chlorotoluron and mineral absorption for 2-Phenylphenol. All other analyses did not result in any significant enrichment.

Data analysis with ingenuity pathway analysis software

Gene expression data were further analyzed with the IPA software. In total 32 different categories of diseases or functions were predicted. Figure  5 shows the ten most frequently resulting categories. Liver Hyperplasia/Hyperproliferation is the only common category across all cell lines and substances. The statistical confidence of the pathway analysis was strongest for Chlorotoluron, which also induced most DEG. Comparing the three methodologies of input data, lower p-values were observed for HepaRG and combined analysis and most categories of diseases or functions were predicted by the combined analysis. Evidently, effects on the kidney were predicted from the input data from liver cells and vice versa.

Results obtained by analysis of transcriptomics data with Qiagen Ingenuity Pathway Analysis. The 10 categories most affected are represented. The x-axis shows the -log 10 value of the p-value obtained for the respective effect

In a final step, the data acquired from targeted protein and transcriptomics analyses were compared with known in vivo observations. Given that the comparison focused on aligning the responses from human cell lines with whole animal data, the analysis focused on the extent to which the omics-responses were indicative of the respective biological response in vivo (indicative concordance). To establish an optimized threshold for the evaluation of in vitro predictions, the in vitro data were transformed by applying evaluation matrices as shown in Table  3 . Based on that, activated key proteins and thus cellular functions were identified for each substance from targeted protein analyses. For the evaluation of gene transcripts, the p-values for the categories obtained by IPA were considered. Indicative concordance with known in vivo results is shown in Table  7 .

For the protein analysis, the indicative concordance ranged from 18 to 47% for the single cell lines and their combination, respectively. In contrast to the results from targeted protein analyses, the indicative concordance for the transcriptomic response was much stronger with greatest values of 55, 63 and 76% for the single cell lines and their combination, respectively. Likewise, for those cases where no effect was seen in vivo, no adverse indications were seen in vitro in 80, 91 and 78% of cases, respectively. For protein analysis, this value ranged from 78 to 86% and was 50% for the combined analysis of protein and transcriptional data. It should be noted, however, that these values decreased when the evaluation criteria were less strict (medium or strong instead of very strong).

In the present study, the pathways triggered by non-cytotoxic concentrations of six pesticide active substances were examined, employing targeted protein and transcriptomics analyses in the liver cell line HepaRG and the kidney cell line RPTEC. Utilizing evaluation matrices and prediction software tools, the observed cellular responses were interpreted and compared with outcomes from established in vivo experiments, in order to assess the relevance of our in vitro model systems in predicting the impact of pesticide exposure on human hepatic and renal cellular function. The primary emphasis of this investigation did not lie in delineating discrete effects attributable to individual substances; rather, it centered on discerning the predictive capacity of the system and serving as a case study to highlight the current challenges in the regulatory adoption of NAMs.

When targeted protein data were used to predict in vivo impacts in rodents, the best result was achieved by the combined analysis and setting the evaluation criteria to medium effects (47%). Regarding the indicative concordance based on transcriptional data, medium effects in HepaRG cells seemed the most promising resulting in a 55% match. This is notable given the systemic as well as species differences between the corresponding test systems. It also highlights that the “gold standard”, i.e., the reference standard used for comparison, is in fact not necessarily indisputable (Trevethan 2017 ). Various studies pointed at the shortcomings of traditional animal studies, such as interspecies concordance, poor reproducibility and unsatisfactory extrapolation to humans (Goodman 2018 ; Karmaus et al. 2022 ; Luijten et al. 2020 ; Ly Pham et al. 2020; Smirnova et al. 2018 ; Wang and Gray 2015 ). One example illustrating the difficulties in extrapolating data from rodents to humans is the question whether Cyproconazole causes neoplasms in the liver. Here, animal studies with CD-1 mice showed statistically significant positive trends for hepatocellular adenomas and combined tumors in male mice (EFSA 2010 ; Hester et al. 2012 ). Ensuing studies identified CAR activation by Cyproconazole as the underlying Mode of Action (MoA) (Peffer et al. 2007 ). Marx-Stoelting et al. ( 2017 ) investigated effects of Cyproconazole in mice with humanized CAR and PXR and demonstrated increased sensitivity of rodents to CAR agonist-induced effects, compared to humanized mice. In line with these observations the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) concluded that Cyproconazole is unlikely to pose a carcinogenic risk to humans (JMPR 2010 ). Likewise, Cyproconazole was not considered to cause neoplasms in the liver when analyzed for this study. However, such detailed analysis of a substance’s MoA is scarce.

Another important factor impeding the comparison of in vitro and in vivo data are the different ontologies. The need for harmonized ontologies and reporting formats of in vivo data has been expressed by many researchers in the field of in silico toxicology and has been addressed in multiple projects (Hardy et al. 2012 ; Sanz et al. 2017 ). For example, uncertainty arises as to the reason if and why an effect for a particular organ is possibly not reported. Depending on the case and study in question, this might be because absent effects were simply not explicitly reported as negative, or because other organ toxicities occurred at lower doses and hence data for the remaining organs were omitted or not assessed, or because the focus of the study was another organ (Smirnova et al. 2018 ). While this does not pose a problem for when such studies are used for risk assessment, it does affect the comparison with in vitro results. Another major obstacle is the retrospective conclusive combination of large and comprehensive sets of mechanistic data in vitro with systemic and histopathological observations in vivo. This issue has recently been picked up by on-going European ONTOX project Footnote 5 (“ontology-driven and artificial intelligence-based repeated dose toxicity testing of chemicals for next generation risk assessment “) and has led the consortium to reverse the strategy and build NAMs to predict systemic repeated dose toxicity effects to enable human risk assessment when combined with exposure assessment (Vinken et al. 2021 ). A recent publication by Jiang et al. ( 2023 ) as part of the ONTOX project identified transcriptomic signatures of drug-induced intrahepatic cholestasis with potential future use as prediction model. However, not all pathologies have been analyzed so far, and those that have were often only studied for a limited number of chemicals, limiting their transferability. Hence, this study relied on the use of computational tools such as IPA, GO enrichment and KEGG analysis, to draw functional conclusions from transcriptomics data. While IPA results in categorized diseases or functions annotations, KEGG and GO analyses display enriched ontologies. Therefore, while KEGG and GO results were too ambiguous to be related to distinct in vivo observations, it was feasible to combine IPA results with in vivo observations. It is noteworthy that even though GO enrichment and KEGG analysis seem fairly similar, the results varied widely between the predictions from the various software tools. Soh et al. ( 2010 ) analyzed consistency, comprehensiveness, and compatibility of pathway databases and made several crucial findings such as the inconsistency of associated genes across different databases pertaining to the same biological pathway. Furthermore, common biological pathways shared across different databases were frequently labeled with names that provided limited indication of their interrelationships. Chen et al. ( 2023 ) demonstrated that using the same gene list with different analysis methods may result in non-concordant overrepresented, enriched or perturbed pathways. Taken together, these considerations may explain the divergent findings from the different transcriptomics analyses in the present study. Additionally, these findings underscore the challenges associated with integrating pathway data from diverse sources and emphasize the need for standardized and cohesive representation of biological pathways in databases.

Compared to the transcriptomic data, protein analyses from HepaRG cells and RPTEC cells resulted in a comparatively low indicative concordance. This challenges the notion that protein analysis may be superior in prediction (Wu et al. 2023 ). One likely explanation is that proteins often reflect molecular functions and adverse effects more accurately, and diseases frequently involve dysregulated post-translational modifications, which are challenging to detect and may be poorly correlated with mRNA levels (Kannaiyan and Mahadevan 2018 ; Kelly et al. 2010 ; Zhao et al. 2020 ). However, due to the relatively low number of protein markers as compared to the number of mRNA markers, the targeted transcriptomics analysis is associated with a higher likelihood of finding a match. In the gene transcription analysis with ensuing IPA evaluation, 370 genes were analysed for HepaRG. In contrast, the protein analysis conducted in this study focussed on 8 proteins or modifications, each indicative of a particular cellular function, that were analysed at two time points after incubation of cells with two concentrations of the test substances. Consequently, a cellular response to a stressor over time can be observed, such as the different levels of cleaved PARP after 36 h and 72 h of incubation with Cyproconazole in HepaRG cells. While elevated levels of this apoptosis indicator were noted after 36 h, reduced levels were observed after 72 h. Possible explanations for this include a cellular feedback mechanism or an advanced stage of apoptosis.

Another central observation is that combination of cell lines and methods significantly increases indicative concordance (up to 88%). In the case of targeted protein analysis, combination of results led to an overall value of 47%, compared to approximately 20% for each cell line. Similar trends were observed for transcriptomic data with 76% indicative concordance for combined results, albeit decreasing the cases where an in vivo negative effect corresponded to no adverse indication seen in vitro , as the total number of positive in vitro effects was increased. Nonetheless, the idea that including omics data in regulatory process will unreasonably increase positive findings and lead to overprotectiveness can be challenged as strengthening the evaluation criteria lead to a reversion of this trend. The shortcomings of stand-alone in vitro tests to replace animal experiments have long been known. For example, single tests do not cover all possible outcomes of interest or all modes of action possibly causing a toxicological effect (Hartung et al. 2013 ; Rovida et al. 2015 ). In the present study, reported in vivo effects such as lesions of biliary epithelium or inflammation of the liver may not be fully represented by a single hepatic cell line. Hence, regulatory toxicologists strive to implement so-called integrated testing strategies (ITS) (Caloni et al. 2022 ). Results from projects in the fields of embryonic, developmental and reproductive, or acute oral toxicity have shown that test batteries increase the predictive value over individual assays (Piersma et al. 2013 ; Prieto et al. 2013 ; Sogorb et al. 2014 ). To share these novel methodologies in ITS for safety evaluations in the regulatory context, the OECD Integrated Approaches for Testing and Assessment (IATA) Case Studies Project offers a platform where comprehensive information on case studies, such as consideration documents capturing learnings and lessons from the review experience, can be found. Footnote 6

While this publication’s scope did not extend to establishing a conclusive ITS for liver and kidney toxicity, it serves as a valuable starting point for future analyses in this direction and offers ongoing assistance and insights. Moving forward, it could prove beneficial when exploring testing protocols that integrate protein and transcriptomics analyses, enhancing the comprehensiveness of safety evaluations in this domain.

Data availability

The data sets generated during the current study are available in the Jochum-et-al-2024 GitHub repository, https://github.com/KristinaJochum/Jochum-et-al-2024 .

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Kristina Jochum, Andrea Miccoli, Tewes Tralau & Philip Marx-Stoelting

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Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany

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Conceptualization: Oliver Poetz, Albert Braeuning, Philip Marx-Stoelting, Tewes Tralau; methodology: Kristina Jochum, Philip Marx-Stoelting, Oliver Poetz; formal analysis and investigation: Kristina Jochum, Andrea Miccoli, Cornelia Sommersdorf; writing—original draft preparation: Kristina Jochum, Philip Marx-Stoelting; writing—review and editing: Andrea Miccoli, Cornelia Sommersdorf, Oliver Poetz, Albert Braeuning, Tewes Tralau, Philip Marx-Stoelting; funding acquisition: Tewes Tralau, Philip Marx-Stoelting; resources: Tewes Tralau, Philip Marx-Stoelting, Oliver Poetz.

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Oliver Poetz is a shareholder of SIGNATOPE GmbH. Cornelia Sommersdorf is an employee at SIGNATOPE GmbH. SIGNATOPE offers assay development and service using immunoassay technology.

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Jochum, K., Miccoli, A., Sommersdorf, C. et al. Comparative case study on NAMs: towards enhancing specific target organ toxicity analysis. Arch Toxicol (2024). https://doi.org/10.1007/s00204-024-03839-7

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Received : 03 July 2024

Accepted : 08 August 2024

Published : 29 August 2024

DOI : https://doi.org/10.1007/s00204-024-03839-7

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