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• Published: 27 June 2011

The case study approach

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

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

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

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Introduction

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

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

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

What is a case study?

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

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

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

What are case studies used for?

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

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

How are case studies conducted?

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

Defining the case

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

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

Selecting the case(s)

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

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

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

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

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

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

Collecting the data

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

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

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

Analysing, interpreting and reporting case studies

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

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

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

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

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

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

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

Conclusions

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

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Acknowledgements

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

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

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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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• Volume 21, Issue 1
• What is a case study?
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• Roberta Heale 1 ,
• Alison Twycross 2
• 1 School of Nursing , Laurentian University , Sudbury , Ontario , Canada
• 2 School of Health and Social Care , London South Bank University , London , UK
• Correspondence to Dr Roberta Heale, School of Nursing, Laurentian University, Sudbury, ON P3E2C6, Canada; rheale{at}laurentian.ca

https://doi.org/10.1136/eb-2017-102845

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What is it?

Case study is a research methodology, typically seen in social and life sciences. There is no one definition of case study research. 1 However, very simply… ‘a case study can be defined as an intensive study about a person, a group of people or a unit, which is aimed to generalize over several units’. 1 A case study has also been described as an intensive, systematic investigation of a single individual, group, community or some other unit in which the researcher examines in-depth data relating to several variables. 2

Often there are several similar cases to consider such as educational or social service programmes that are delivered from a number of locations. Although similar, they are complex and have unique features. In these circumstances, the evaluation of several, similar cases will provide a better answer to a research question than if only one case is examined, hence the multiple-case study. Stake asserts that the cases are grouped and viewed as one entity, called the quintain . 6  ‘We study what is similar and different about the cases to understand the quintain better’. 6

The steps when using case study methodology are the same as for other types of research. 6 The first step is defining the single case or identifying a group of similar cases that can then be incorporated into a multiple-case study. A search to determine what is known about the case(s) is typically conducted. This may include a review of the literature, grey literature, media, reports and more, which serves to establish a basic understanding of the cases and informs the development of research questions. Data in case studies are often, but not exclusively, qualitative in nature. In multiple-case studies, analysis within cases and across cases is conducted. Themes arise from the analyses and assertions about the cases as a whole, or the quintain, emerge. 6

Benefits and limitations of case studies

If a researcher wants to study a specific phenomenon arising from a particular entity, then a single-case study is warranted and will allow for a in-depth understanding of the single phenomenon and, as discussed above, would involve collecting several different types of data. This is illustrated in example 1 below.

Using a multiple-case research study allows for a more in-depth understanding of the cases as a unit, through comparison of similarities and differences of the individual cases embedded within the quintain. Evidence arising from multiple-case studies is often stronger and more reliable than from single-case research. Multiple-case studies allow for more comprehensive exploration of research questions and theory development. 6

Despite the advantages of case studies, there are limitations. The sheer volume of data is difficult to organise and data analysis and integration strategies need to be carefully thought through. There is also sometimes a temptation to veer away from the research focus. 2 Reporting of findings from multiple-case research studies is also challenging at times, 1 particularly in relation to the word limits for some journal papers.

Examples of case studies

Example 1: nurses’ paediatric pain management practices.

One of the authors of this paper (AT) has used a case study approach to explore nurses’ paediatric pain management practices. This involved collecting several datasets:

Observational data to gain a picture about actual pain management practices.

Questionnaire data about nurses’ knowledge about paediatric pain management practices and how well they felt they managed pain in children.

Questionnaire data about how critical nurses perceived pain management tasks to be.

These datasets were analysed separately and then compared 7–9 and demonstrated that nurses’ level of theoretical did not impact on the quality of their pain management practices. 7 Nor did individual nurse’s perceptions of how critical a task was effect the likelihood of them carrying out this task in practice. 8 There was also a difference in self-reported and observed practices 9 ; actual (observed) practices did not confirm to best practice guidelines, whereas self-reported practices tended to.

Example 2: quality of care for complex patients at Nurse Practitioner-Led Clinics (NPLCs)

The other author of this paper (RH) has conducted a multiple-case study to determine the quality of care for patients with complex clinical presentations in NPLCs in Ontario, Canada. 10 Five NPLCs served as individual cases that, together, represented the quatrain. Three types of data were collected including:

Review of documentation related to the NPLC model (media, annual reports, research articles, grey literature and regulatory legislation).

Interviews with nurse practitioners (NPs) practising at the five NPLCs to determine their perceptions of the impact of the NPLC model on the quality of care provided to patients with multimorbidity.

Chart audits conducted at the five NPLCs to determine the extent to which evidence-based guidelines were followed for patients with diabetes and at least one other chronic condition.

The three sources of data collected from the five NPLCs were analysed and themes arose related to the quality of care for complex patients at NPLCs. The multiple-case study confirmed that nurse practitioners are the primary care providers at the NPLCs, and this positively impacts the quality of care for patients with multimorbidity. Healthcare policy, such as lack of an increase in salary for NPs for 10 years, has resulted in issues in recruitment and retention of NPs at NPLCs. This, along with insufficient resources in the communities where NPLCs are located and high patient vulnerability at NPLCs, have a negative impact on the quality of care. 10

These examples illustrate how collecting data about a single case or multiple cases helps us to better understand the phenomenon in question. Case study methodology serves to provide a framework for evaluation and analysis of complex issues. It shines a light on the holistic nature of nursing practice and offers a perspective that informs improved patient care.

• Gustafsson J
• Calanzaro M
• Sandelowski M

Competing interests None declared.

Provenance and peer review Commissioned; internally peer reviewed.

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• Open access
• Published: 10 November 2020

Case study research for better evaluations of complex interventions: rationale and challenges

• Sara Paparini   ORCID: orcid.org/0000-0002-1909-2481 1 ,
• Judith Green 2 ,
• Chrysanthi Papoutsi 1 ,
• Jamie Murdoch 3 ,
• Mark Petticrew 4 ,
• Trish Greenhalgh 1 ,
• Benjamin Hanckel 5 &
• Sara Shaw 1  

BMC Medicine volume  18 , Article number:  301 ( 2020 ) Cite this article

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The need for better methods for evaluation in health research has been widely recognised. The ‘complexity turn’ has drawn attention to the limitations of relying on causal inference from randomised controlled trials alone for understanding whether, and under which conditions, interventions in complex systems improve health services or the public health, and what mechanisms might link interventions and outcomes. We argue that case study research—currently denigrated as poor evidence—is an under-utilised resource for not only providing evidence about context and transferability, but also for helping strengthen causal inferences when pathways between intervention and effects are likely to be non-linear.

Case study research, as an overall approach, is based on in-depth explorations of complex phenomena in their natural, or real-life, settings. Empirical case studies typically enable dynamic understanding of complex challenges and provide evidence about causal mechanisms and the necessary and sufficient conditions (contexts) for intervention implementation and effects. This is essential evidence not just for researchers concerned about internal and external validity, but also research users in policy and practice who need to know what the likely effects of complex programmes or interventions will be in their settings. The health sciences have much to learn from scholarship on case study methodology in the social sciences. However, there are multiple challenges in fully exploiting the potential learning from case study research. First are misconceptions that case study research can only provide exploratory or descriptive evidence. Second, there is little consensus about what a case study is, and considerable diversity in how empirical case studies are conducted and reported. Finally, as case study researchers typically (and appropriately) focus on thick description (that captures contextual detail), it can be challenging to identify the key messages related to intervention evaluation from case study reports.

Whilst the diversity of published case studies in health services and public health research is rich and productive, we recommend further clarity and specific methodological guidance for those reporting case study research for evaluation audiences.

Peer Review reports

The need for methodological development to address the most urgent challenges in health research has been well-documented. Many of the most pressing questions for public health research, where the focus is on system-level determinants [ 1 , 2 ], and for health services research, where provisions typically vary across sites and are provided through interlocking networks of services [ 3 ], require methodological approaches that can attend to complexity. The need for methodological advance has arisen, in part, as a result of the diminishing returns from randomised controlled trials (RCTs) where they have been used to answer questions about the effects of interventions in complex systems [ 4 , 5 , 6 ]. In conditions of complexity, there is limited value in maintaining the current orientation to experimental trial designs in the health sciences as providing ‘gold standard’ evidence of effect.

There are increasing calls for methodological pluralism [ 7 , 8 ], with the recognition that complex intervention and context are not easily or usefully separated (as is often the situation when using trial design), and that system interruptions may have effects that are not reducible to linear causal pathways between intervention and outcome. These calls are reflected in a shifting and contested discourse of trial design, seen with the emergence of realist [ 9 ], adaptive and hybrid (types 1, 2 and 3) [ 10 , 11 ] trials that blend studies of effectiveness with a close consideration of the contexts of implementation. Similarly, process evaluation has now become a core component of complex healthcare intervention trials, reflected in MRC guidance on how to explore implementation, causal mechanisms and context [ 12 ].

Evidence about the context of an intervention is crucial for questions of external validity. As Woolcock [ 4 ] notes, even if RCT designs are accepted as robust for maximising internal validity, questions of transferability (how well the intervention works in different contexts) and generalisability (how well the intervention can be scaled up) remain unanswered [ 5 , 13 ]. For research evidence to have impact on policy and systems organisation, and thus to improve population and patient health, there is an urgent need for better methods for strengthening external validity, including a better understanding of the relationship between intervention and context [ 14 ].

Policymakers, healthcare commissioners and other research users require credible evidence of relevance to their settings and populations [ 15 ], to perform what Rosengarten and Savransky [ 16 ] call ‘careful abstraction’ to the locales that matter for them. They also require robust evidence for understanding complex causal pathways. Case study research, currently under-utilised in public health and health services evaluation, can offer considerable potential for strengthening faith in both external and internal validity. For example, in an empirical case study of how the policy of free bus travel had specific health effects in London, UK, a quasi-experimental evaluation (led by JG) identified how important aspects of context (a good public transport system) and intervention (that it was universal) were necessary conditions for the observed effects, thus providing useful, actionable evidence for decision-makers in other contexts [ 17 ].

The overall approach of case study research is based on the in-depth exploration of complex phenomena in their natural, or ‘real-life’, settings. Empirical case studies typically enable dynamic understanding of complex challenges rather than restricting the focus on narrow problem delineations and simple fixes. Case study research is a diverse and somewhat contested field, with multiple definitions and perspectives grounded in different ways of viewing the world, and involving different combinations of methods. In this paper, we raise awareness of such plurality and highlight the contribution that case study research can make to the evaluation of complex system-level interventions. We review some of the challenges in exploiting the current evidence base from empirical case studies and conclude by recommending that further guidance and minimum reporting criteria for evaluation using case studies, appropriate for audiences in the health sciences, can enhance the take-up of evidence from case study research.

Case study research offers evidence about context, causal inference in complex systems and implementation

Well-conducted and described empirical case studies provide evidence on context, complexity and mechanisms for understanding how, where and why interventions have their observed effects. Recognition of the importance of context for understanding the relationships between interventions and outcomes is hardly new. In 1943, Canguilhem berated an over-reliance on experimental designs for determining universal physiological laws: ‘As if one could determine a phenomenon’s essence apart from its conditions! As if conditions were a mask or frame which changed neither the face nor the picture!’ ([ 18 ] p126). More recently, a concern with context has been expressed in health systems and public health research as part of what has been called the ‘complexity turn’ [ 1 ]: a recognition that many of the most enduring challenges for developing an evidence base require a consideration of system-level effects [ 1 ] and the conceptualisation of interventions as interruptions in systems [ 19 ].

The case study approach is widely recognised as offering an invaluable resource for understanding the dynamic and evolving influence of context on complex, system-level interventions [ 20 , 21 , 22 , 23 ]. Empirically, case studies can directly inform assessments of where, when, how and for whom interventions might be successfully implemented, by helping to specify the necessary and sufficient conditions under which interventions might have effects and to consolidate learning on how interdependencies, emergence and unpredictability can be managed to achieve and sustain desired effects. Case study research has the potential to address four objectives for improving research and reporting of context recently set out by guidance on taking account of context in population health research [ 24 ], that is to (1) improve the appropriateness of intervention development for specific contexts, (2) improve understanding of ‘how’ interventions work, (3) better understand how and why impacts vary across contexts and (4) ensure reports of intervention studies are most useful for decision-makers and researchers.

However, evaluations of complex healthcare interventions have arguably not exploited the full potential of case study research and can learn much from other disciplines. For evaluative research, exploratory case studies have had a traditional role of providing data on ‘process’, or initial ‘hypothesis-generating’ scoping, but might also have an increasing salience for explanatory aims. Across the social and political sciences, different kinds of case studies are undertaken to meet diverse aims (description, exploration or explanation) and across different scales (from small N qualitative studies that aim to elucidate processes, or provide thick description, to more systematic techniques designed for medium-to-large N cases).

Case studies with explanatory aims vary in terms of their positioning within mixed-methods projects, with designs including (but not restricted to) (1) single N of 1 studies of interventions in specific contexts, where the overall design is a case study that may incorporate one or more (randomised or not) comparisons over time and between variables within the case; (2) a series of cases conducted or synthesised to provide explanation from variations between cases; and (3) case studies of particular settings within RCT or quasi-experimental designs to explore variation in effects or implementation.

Detailed qualitative research (typically done as ‘case studies’ within process evaluations) provides evidence for the plausibility of mechanisms [ 25 ], offering theoretical generalisations for how interventions may function under different conditions. Although RCT designs reduce many threats to internal validity, the mechanisms of effect remain opaque, particularly when the causal pathways between ‘intervention’ and ‘effect’ are long and potentially non-linear: case study research has a more fundamental role here, in providing detailed observational evidence for causal claims [ 26 ] as well as producing a rich, nuanced picture of tensions and multiple perspectives [ 8 ].

Longitudinal or cross-case analysis may be best suited for evidence generation in system-level evaluative research. Turner [ 27 ], for instance, reflecting on the complex processes in major system change, has argued for the need for methods that integrate learning across cases, to develop theoretical knowledge that would enable inferences beyond the single case, and to develop generalisable theory about organisational and structural change in health systems. Qualitative Comparative Analysis (QCA) [ 28 ] is one such formal method for deriving causal claims, using set theory mathematics to integrate data from empirical case studies to answer questions about the configurations of causal pathways linking conditions to outcomes [ 29 , 30 ].

Nonetheless, the single N case study, too, provides opportunities for theoretical development [ 31 ], and theoretical generalisation or analytical refinement [ 32 ]. How ‘the case’ and ‘context’ are conceptualised is crucial here. Findings from the single case may seem to be confined to its intrinsic particularities in a specific and distinct context [ 33 ]. However, if such context is viewed as exemplifying wider social and political forces, the single case can be ‘telling’, rather than ‘typical’, and offer insight into a wider issue [ 34 ]. Internal comparisons within the case can offer rich possibilities for logical inferences about causation [ 17 ]. Further, case studies of any size can be used for theory testing through refutation [ 22 ]. The potential lies, then, in utilising the strengths and plurality of case study to support theory-driven research within different methodological paradigms.

Evaluation research in health has much to learn from a range of social sciences where case study methodology has been used to develop various kinds of causal inference. For instance, Gerring [ 35 ] expands on the within-case variations utilised to make causal claims. For Gerring [ 35 ], case studies come into their own with regard to invariant or strong causal claims (such as X is a necessary and/or sufficient condition for Y) rather than for probabilistic causal claims. For the latter (where experimental methods might have an advantage in estimating effect sizes), case studies offer evidence on mechanisms: from observations of X affecting Y, from process tracing or from pattern matching. Case studies also support the study of emergent causation, that is, the multiple interacting properties that account for particular and unexpected outcomes in complex systems, such as in healthcare [ 8 ].

Finally, efficacy (or beliefs about efficacy) is not the only contributor to intervention uptake, with a range of organisational and policy contingencies affecting whether an intervention is likely to be rolled out in practice. Case study research is, therefore, invaluable for learning about contextual contingencies and identifying the conditions necessary for interventions to become normalised (i.e. implemented routinely) in practice [ 36 ].

The challenges in exploiting evidence from case study research

At present, there are significant challenges in exploiting the benefits of case study research in evaluative health research, which relate to status, definition and reporting. Case study research has been marginalised at the bottom of an evidence hierarchy, seen to offer little by way of explanatory power, if nonetheless useful for adding descriptive data on process or providing useful illustrations for policymakers [ 37 ]. This is an opportune moment to revisit this low status. As health researchers are increasingly charged with evaluating ‘natural experiments’—the use of face masks in the response to the COVID-19 pandemic being a recent example [ 38 ]—rather than interventions that take place in settings that can be controlled, research approaches using methods to strengthen causal inference that does not require randomisation become more relevant.

A second challenge for improving the use of case study evidence in evaluative health research is that, as we have seen, what is meant by ‘case study’ varies widely, not only across but also within disciplines. There is indeed little consensus amongst methodologists as to how to define ‘a case study’. Definitions focus, variously, on small sample size or lack of control over the intervention (e.g. [ 39 ] p194), on in-depth study and context [ 40 , 41 ], on the logic of inference used [ 35 ] or on distinct research strategies which incorporate a number of methods to address questions of ‘how’ and ‘why’ [ 42 ]. Moreover, definitions developed for specific disciplines do not capture the range of ways in which case study research is carried out across disciplines. Multiple definitions of case study reflect the richness and diversity of the approach. However, evidence suggests that a lack of consensus across methodologists results in some of the limitations of published reports of empirical case studies [ 43 , 44 ]. Hyett and colleagues [ 43 ], for instance, reviewing reports in qualitative journals, found little match between methodological definitions of case study research and how authors used the term.

This raises the third challenge we identify that case study reports are typically not written in ways that are accessible or useful for the evaluation research community and policymakers. Case studies may not appear in journals widely read by those in the health sciences, either because space constraints preclude the reporting of rich, thick descriptions, or because of the reported lack of willingness of some biomedical journals to publish research that uses qualitative methods [ 45 ], signalling the persistence of the aforementioned evidence hierarchy. Where they do, however, the term ‘case study’ is used to indicate, interchangeably, a qualitative study, an N of 1 sample, or a multi-method, in-depth analysis of one example from a population of phenomena. Definitions of what constitutes the ‘case’ are frequently lacking and appear to be used as a synonym for the settings in which the research is conducted. Despite offering insights for evaluation, the primary aims may not have been evaluative, so the implications may not be explicitly drawn out. Indeed, some case study reports might properly be aiming for thick description without necessarily seeking to inform about context or causality.

Acknowledging plurality and developing guidance

We recognise that definitional and methodological plurality is not only inevitable, but also a necessary and creative reflection of the very different epistemological and disciplinary origins of health researchers, and the aims they have in doing and reporting case study research. Indeed, to provide some clarity, Thomas [ 46 ] has suggested a typology of subject/purpose/approach/process for classifying aims (e.g. evaluative or exploratory), sample rationale and selection and methods for data generation of case studies. We also recognise that the diversity of methods used in case study research, and the necessary focus on narrative reporting, does not lend itself to straightforward development of formal quality or reporting criteria.

Existing checklists for reporting case study research from the social sciences—for example Lincoln and Guba’s [ 47 ] and Stake’s [ 33 ]—are primarily orientated to the quality of narrative produced, and the extent to which they encapsulate thick description, rather than the more pragmatic issues of implications for intervention effects. Those designed for clinical settings, such as the CARE (CAse REports) guidelines, provide specific reporting guidelines for medical case reports about single, or small groups of patients [ 48 ], not for case study research.

The Design of Case Study Research in Health Care (DESCARTE) model [ 44 ] suggests a series of questions to be asked of a case study researcher (including clarity about the philosophy underpinning their research), study design (with a focus on case definition) and analysis (to improve process). The model resembles toolkits for enhancing the quality and robustness of qualitative and mixed-methods research reporting, and it is usefully open-ended and non-prescriptive. However, even if it does include some reflections on context, the model does not fully address aspects of context, logic and causal inference that are perhaps most relevant for evaluative research in health.

Hence, for evaluative research where the aim is to report empirical findings in ways that are intended to be pragmatically useful for health policy and practice, this may be an opportune time to consider how to best navigate plurality around what is (minimally) important to report when publishing empirical case studies, especially with regards to the complex relationships between context and interventions, information that case study research is well placed to provide.

The conventional scientific quest for certainty, predictability and linear causality (maximised in RCT designs) has to be augmented by the study of uncertainty, unpredictability and emergent causality [ 8 ] in complex systems. This will require methodological pluralism, and openness to broadening the evidence base to better understand both causality in and the transferability of system change intervention [ 14 , 20 , 23 , 25 ]. Case study research evidence is essential, yet is currently under exploited in the health sciences. If evaluative health research is to move beyond the current impasse on methods for understanding interventions as interruptions in complex systems, we need to consider in more detail how researchers can conduct and report empirical case studies which do aim to elucidate the contextual factors which interact with interventions to produce particular effects. To this end, supported by the UK’s Medical Research Council, we are embracing the challenge to develop guidance for case study researchers studying complex interventions. Following a meta-narrative review of the literature, we are planning a Delphi study to inform guidance that will, at minimum, cover the value of case study research for evaluating the interrelationship between context and complex system-level interventions; for situating and defining ‘the case’, and generalising from case studies; as well as provide specific guidance on conducting, analysing and reporting case study research. Our hope is that such guidance can support researchers evaluating interventions in complex systems to better exploit the diversity and richness of case study research.

Availability of data and materials

Not applicable (article based on existing available academic publications)

Abbreviations

Qualitative comparative analysis

Quasi-experimental design

Randomised controlled trial

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This work was funded by the Medical Research Council - MRC Award MR/S014632/1 HCS: Case study, Context and Complex interventions (TRIPLE C). SP was additionally funded by the University of Oxford's Higher Education Innovation Fund (HEIF).

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Paparini, S., Green, J., Papoutsi, C. et al. Case study research for better evaluations of complex interventions: rationale and challenges. BMC Med 18 , 301 (2020). https://doi.org/10.1186/s12916-020-01777-6

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CONSTRUCTION

Ucc article 9 for dummies, graduate school of credit and financial management, by: christen borman, douglas jacobson, jovan rosa, rocky thomas, susan thomas, and melvin ucelo, introduction.

“Risk comes from not knowing what you’re doing” -Warren Buffett

As a credit manager in the world of business to business (B2B) commerce, it is your job to facilitate sales while managing the risk associated with the extension of credit and protecting your company’s investment in accounts receivable. Trade credit is essential to the accommodation of sales growth and, as we know, there is always some risk associated with the extension of credit. Unfortunately, as B2B creditors, we often don’t have the luxury of requiring collateral to extend credit. The prudent and risk free approach would be to require payment at the time of the transaction. However, the last we checked, our companies have sales growth, increased market share and profitability as their core goals. In a competitive environment, it is essential that we find ways to efficiently leverage the extension of credit to accommodate these goals.

The good news is that there are laws and regulations that provide protection for B2B creditors and give us legal remedies to help mitigate the risk that comes with the extension of trade credit.  It is called the Uniform Commercial Code (UCC). The bad news is that most of us are not legal experts and it can be a daunting task to research and understand the UCC. We are hopeful that “UCC Article 9 for Dummies” will provide a quick guide to help the commercial creditor take advantage of the tools available to successfully secure their accounts receivable.

Legal codes and laws are not an easy subject to understand. The Uniform Commercial Code contains the legal framework that governs commercial business transactions. The articles of the UCC are a set of laws governing the sale of goods, leases, negotiable instruments, bank deposits, funds transfers, letter of credit, bulk transfers, bulk sales, warehouse receipts, bills of lading, investment securities and secured transactions. Within the code one of the most important articles is Article 9, Secured Transactions, which provides the governing rules for any transaction that combines a debt with a creditor’s interest in a debtor’s personal property.  In 1998 revisions to Article 9 were completed and were approved by all fifty states by 2001.  Article 9 provides a detailed instruction manual on steps to take to legally protect a debt by staking a claim in the debtor’s property.  

The understanding and use of the basic elements of a secured transaction in Article 9 can be a daunting task. It requires a thorough understanding of the code and any new amendments. A creditor must be able to follow the process, comprehend the scheme and implement a solution that best fits the purpose of mitigating the risk. In most scenarios, the creditor can gain superior bargaining power by requiring the debtor to provide a security interest to the creditor as part of the transaction. This is done before granting a loan or providing something of value in order to maximize the likelihood of payment in the event that the debtor does not comply with the terms of the agreement. The creditor can exercise its rights created under Article 9. For this to be successful it is important to create an enforceable security interest “Attachment”, protect the security interest from claims of other parties to the collateral “Perfection”, and have the highest “Priority”.

As part of the process, it is always important that the choice of law and the parties’ jurisdiction is well defined in order to enforce rights with no delay. This usually is where the debtor is. Complications arise from the need to understand the common legal definitions used throughout article’s many sections, the fact that its rules have exceptions that a credit manager needs to understand, and that timing of actions and the specificity of documentation, if not followed, will endanger the legal protection the creditor seeks. 

UCC Article 9 for Dummies is here to decode and help explain from a credit manager’s perspective, the more relevant aspects of the article and demystify the relevant aspects so we know what to do when it is required to secure a transaction.  It’s meant to give a high level view of the code and to highlight the riskier areas.  A credit manager should always seek advice from legal counsel regarding specific questions of law, especially if the monetary exposure is large.

Article 9-Secured Transactions

The credit manager must ensure that all requirements of Article 9 are properly met and documented to obtain a legal claim in a debtor’s collateral if the debtor does not pay or satisfy its obligations.  The credit manager must then take the steps necessary to insure that the legal claim established has priority over other creditors.

The illustration below attempts to capture the main areas of the code that a credit manager must be familiar with to protect his or her company’s financial exposure to a non-paying customer.  Definitions of underlined terms are summarized in the glossary.

The main point of Article 9 is to be a secured creditor:

If a creditor is secured it has a claim in something of the buyer’s (the goods exchanged for future payment or other collateral). This gives the creditor:

• Right of repossession of goods extended in exchange for future payment if the payment is never made
• Elevated priority in the potential proceeds? Even if the buyer is filing bankruptcy
• It upholds defense to preference in the potential instance of a bankruptcy filing.

However, a creditor cannot be secured or have the claim in the asset until its interest is perfected.

What is a security interest?

A security interest is an interest in the asset of a buyer. This is important for creditors to leverage their position of being able to fully collect money extended to buyers.

A blanket interest securitization can be made and is often the case with banks that have an interest in all applicable assets of a buyer (except for some real property, aircraft, ships and motor vehicles).  A Purchase Money Security Interest (“PMSI”) is applicable when the buyer takes possession of the goods from the creditor and it allows the creditor to seek a super-priority security interest, putting them above all other secured creditors in security ranking.  PMSI filings are the only ones that require notification to other secured creditors of the filing since it gives that creditor super-priority interest. 

What is collateral and why is it needed in a security interest?

The asset (collateral) in a security interest must be personal property but cannot be real property, aircraft, ships or motor vehicles.

Typical collateral involved in a security interest:

• Accounts receivable
• Stocks, bonds and negotiable instruments

Essentially, the collateral acts as the proceeds to which the security interest attaches. The common types of collateral in a security interest are blanket, consignment, or specifically listing the assets or a Purchase Money Security Interest.

It is imperative that a secured party handles collateral with care.  The following case is an example of a creditor’s breach of this duty.

Collateral—Must handle with care!

Who is responsible for taking care of the collateral.

Practical expenses incurred in ensuring the proper care of collateral are chargeable to the debtor and secured on the collateral.  An example would be the cost of insurance.  If the goods are accidentally lost or damaged any shortfall in the insurance rests on the debtor.  Payment of taxes and other charges directly related to the preservation, custody, or operation of collateral also fall under this category.

Collateral in Action—Use it don’t lose it!

Collateral description errors causing failure to perfect.

1st Source Bank vs. Wilson Bank & Trust (Tennessee)

The US Court of Appeals for the Sixth Circuit ruled that a creditor bank did not have a perfected security interest in the debtor’s accounts receivable because “the bank failed to include ‘accounts’ or ‘accounts receivable’ as part of the bank’s collateral in its UCC financing statement” even though those words were used in the security agreement.

Ref: source: Business Credit Magazine, May 2014 – “Mistakes in a UCC Financing Statement’s Collateral Description Can Be Hazardous to a Perfected Security Interest!”

So now I have an interest in the collateral of my buyer - what do I do next?

File a security agreement.

The security agreement indicates the creditor’s right to file a security interest in the specifically named assets of the buyer, which acts as the collateral to uphold the agreement. In order for a creditor to have a valid security interest the agreement must be signed (authenticated) by both the creditor and the buyer, contain a description of the collateral, and make it clear that the security interest is intended.

  Why are people telling me I need to be perfect in this process?

What is perfection in a security interest.

Perfection is when the creditor has filed their security agreement between them and the buyer. It is filed with the secretary of the state that the buyer is registered as a business entity in (or resides in if a sole proprietor). If the buyer is registered in multiple states, multiple security interests can be filed per state. If you don’t file your security agreement, you don’t have your security interest and you don’t have any secured rights in your buyer’s collateral. This would mean… You aren’t perfect!

Importance of Perfection!

Debtor name errors causing failure to perfect.

The creditor, CCF Leasing Company, filed a UCC-1 statement but listed the debtor as “Wing Fine Food”. Because a UCC search using the secretary of state’s search logic would not have produced the financing statement, the court found the filing to be fatally flawed and Wing Foods, Inc. was able to avoid the creditor’s security interest claim.

Ref: NCS Credit blog 11/12/2014

  But I don’t have time to go to the Secretary of State!

Due to the detailed requirements of filing (including notification, most creditors prefer to use a qualified service, such as nacm’s mlbs ..

Due to the detailed requirements of filing (including notification), most creditors prefer to use a qualified service.  However, if you wanted to file a financing statement on your own, you must first make sure you have all the proper documents. You would then submit these documents to the central filing office in the state the debtor resides or its business is registered.  This is commonly done electronically.  Each state has its own rules for filing so further research must be done in order to ensure full compliance to that state’s requirements.

Required documents to file a financing statement:

UCC1-UCC Financing Statement – this is a Unified Commercial Code form prepared by the company granting credit.  When it is filed appropriately it gives public notice that a creditor has a security interest in collateral belonging to the customer documented in the statement.  The financing statement must be filed with the office of the appropriate government agency, generally the office of the Secretary of State of the buyer’s location.

Sample of UCC1 Template

SAMPLE OF UCC1 TEMPLATE

How do I know my filing is complete?

Upon request at the filing office, you can obtain notification of acknowledgement when the filing is complete. A specific number is assigned to each UCC filing for identification and will be provided with the requested acknowledgement. This number is referred to as the file number.  Furthermore, the date and time of the filing is critical given the hierarchy of security interests by date.

First in line, first in right—except for PMSI filings!

Therefore, the date and time will be recorded with each filing as well.

The filing office where the documents were submitted is the place that maintains the records of the financing statement and any attached documents. At least annually all states must review their filing-office rules to ensure compliance and effectiveness.

A creditor can search for records of financing statements by the debtor name or file number if they know it.

A filing can be refused for several reasons, like when it is not received properly (must be original document), the filing fee isn’t paid, an incomplete or invalid name for debtor or does not have attaching and complete financing statement. However, the filing office must communicate the refusal within two business days from receiving the record. Method of communication depends on the state requirements. Each state also has statutory requirements of holding public record documents that would dictate when they can destruct written records of financing statements.              

What are the rules of priority and are there ways to obtain priority over existing creditors?

It is important for the creditor to know the rules of priority and determine the steps necessary to ensure that he is protected. Remember that the UCC -1 must be filed – your security agreement is worthless until the filing is complete.  In most cases, if there is bank financing, they will usually have a perfected blanket UCC -1 that takes priority. This why it is important to do a thorough search of all prior filings to determine the effectiveness of your filing.

Rules of Priority:

• Determined by the time of filing or perfection – the first filed has the first right
• It includes both proceeds and the supporting obligations of the collateral
• Perfected interests can be subordinated (see PMSI) with the permission of prior secured parties

Can I secure future shipments that will take priority over existing security interests?

As indicated earlier, many times a bank or other secured lender will have a blanket UCC-1 that gives it priority interest in all inventory and proceeds of the debtor. However, there is way to secure goods and proceeds before they are shipped. This is done through a Purchase Money Security Interest (PMSI).  A PMSI grants a security interest to the trade creditor sold on credit terms for the price of the goods sold.

A key advantage gained by a PMSI is that it gives the creditor access to co-mingled funds not specifically identifiable by the creditor or the courts.

Rules and requirements:

• Only covers goods and proceeds sold on credit terms moving forward – does not cover existing debt.
• The debtor must agree and sign off
• Must describe in detail the goods or inventory that is covered
• Always do a UCC search to determine existing secured parties
• The secured party (most often a bank) must be notified and grant a priority for the good s or proceeds of the creditor prior to the debt being incurred. This is called a subordination . It is usually not granted unless the secured party determines that it is in their best interest and provides the potential for additional income and profits .
• Must be filed and recorded once completed and signed.
• The PMSI is perfected once the debtor takes possession of the inventory
• You must send official notification to the holder of the prior security interest prior to debtor taking possession

Sample Purchase Money Security Interest

SAMPLE PURCHASE MONEY SECURITY INTEREST

How do I enforce my security interest once it is in place?

A security interest attaches to collateral and becomes enforceable if:

• value has been given
• the debtor has rights in it and/or the authority to transfer rights to a secured party.

AND if any of a number of conditions are met, one being:

• an authenticated security agreement giving a description of the collateral is completed

What happens if my customer (debtor) defaults?

Secured Creditors in Action!

Assuming that you have filed all of the necessary paperwork and perfected your security interest, there may come a time when a customer defaults on the agreement.  At that point there are several options available to you to enforce your lien against the collateral.

Three things you can do:

• Foreclose on the collateral
• Claim a judgment against your customer
• Enforce a claim against your customer in court

As a creditor you may deduct reasonable attorney fees and collection expenses incurred during the repossession of your collateral.

As a creditor you can sell, lease, license, or otherwise dispose of any or all of the collateral covered by the security agreement as long as it is reasonable to both parties.  If you are going to dispose of the collateral, you must send notification to the customer and any secondary lien holder unless they waive their right to the disposition of the collateral.  In most cases a 10-day notice is sufficient.

All proceeds that are received over and above any debt owed must be returned to the customer or to a subordinate security interest holder.  The customer would still be liable for any deficiency amount that is owed after the collateral is seized.

Upon default you may require your customer to assemble the collateral and make it available to you at a place of your choosing and is convenient for both you and your customer.

Notice of disposition should include a description of the collateral to be sold, leased, or licensed, the method of disposition, charges associated with the sale or disposition, and time and place of the disposition.

We will sell (lease or license) the following collateral privately sometime after this date. You are entitled to an accounting of the unpaid indebtedness secured by the property that we intend to sell (lease or license) for the amount of $_______. You may request an accounting by call us at (telephone #).

For a consumer goods transaction:

Name and address of creditor and date

Example:  Notice of our plan to sell property

Name and address of debtor

Identification of collateral

We have your collateral and because you broke promises in our agreement we will sell (description of collateral) at a private sale sometime after (date).  The money that we get from the sale (after paying our costs) will reduce the amount that you owe.  If we get less money than you owe, you will still be responsible for the difference.  If we get more money than you owe, you will get the excess unless there is a secondary lien holder.  You can get the property back at any time before we sell it by paying us the full amount you owe, including our expenses.  For a balance owed please call us at (telephone #).  We are also notifying other individuals who may have an interest in this collateral or who owe money under your agreement.  (List names of other possible lien holders if any).

Acceptance of collateral in full or partial satisfaction of the obligation can be done only at the debtor’s consent within 20 days of notification.  This does not require you as a creditor to dispose of the collateral (Does not apply to consumer transactions)     

In consumer transactions collateral must be disposed of within 90 days after taking possession or within a longer period to which the customer and secondary lien holders have agreed to.

The customer or a secondary lien holder has the right to redeem the collateral for full payment of the obligation at any time prior to disposition.

Default—Mistakes can be costly!

Sports authority bankruptcy and implication on ucc consignment deals:.

Sports Authority initially filed Chapter 11 bankruptcy to reorganize its structure and become a much smaller retailer of sports merchandise and clothing. However, in the midst of the initial bankruptcy proceedings the creditors became aware that Sports Authority was listing inventory as an asset when the inventory was in fact part of consignment deals and therefore not assets of Sports Authority but still assets of suppliers (creditors). This critical issue forced Sports Authority into Chapter 7 bankruptcy because it had been overstating its assets and blurring the true financial disarray it was in.

During the bankruptcy the court ordered Sports Authority to start liquidating its assets which caused an argument over the proceeds of the sale of consignment items. Should the proceeds go lenders with secured interests in Sports Authority or go directly back to the suppliers with the consignment agreements that claimed they still owned the items up for sale in the liquidation?

Alas, the crux of the issue acknowledged that had the suppliers protected their consignment agreements by perfecting a security interest and notifying lenders to not use the consignment goods as collateral in their security interests of Sports Authority. This is a critical part of UCC Article 9 and important for all creditors to be aware of in their dealings of consignment issues.

Ref: www.bloomberg.com/

  What Should You Remember?

The purpose of article 9.

For creditors to gain a security interest in personal property (assets) of a customer which may elevate their position in collections

Security agreement = security interest

Must have identification of parties, granting clause and collateral (asset) description

No UCC-1 = Not perfected = Not a secured creditor

To become a secured creditor à perfect security interest by filing a UCC-1 with the proper filing clerk

With a perfected interest a secured creditor has:

• Right of repossession of the asset
• Elevated priority in bankruptcy
• Defense to preference in bankruptcy

Mistakes are costly

Always review your work for accuracy. Utilize a third party for additional verification to confirm all steps are complete.

Attachment – when a security agreement is executed and the debtor acquires right in the assets subject to the security interest (collateral). The creditor’s security interest becomes enforceable.

Collateral – property subject to a security interest. Laws vary regarding various types of collateral and the legal jurisdiction. Typical personal property involved in a security interest includes inventory, fixtures, equipment, vehicles, accounts receivable, and stocks/bonds/ negotiable instruments. It cannot be real property.

Control – Control of collateral does not mean the same thing as possession of collateral. See UCC Article 9 parts 1 and 2.

Lien – official claim an asset for payment of a debt or an amount owed by a buyer. It is usually a formal document signed by the credit provider and sometimes by the buyer who agrees to the amount due.

Perfection – a legal process by which a secured creditor can protect itself against claims of other third parties who wish to have their debts satisfied out of the same debtor collateral

Possession – with respect to collateral, possession is the control a person intentionally exercises toward that collateral. To possess collateral, a person must have an intention to possess it. A person may be in possession of an asset but that does not imply ownership.

Priority – where your perfected claim falls with respect to other creditors; what is the legal order of collateral disposition

Security Agreement – the debtor agrees to specific points that govern the lien, e.g. collateral and the nature of the debt obligation

Security Interest – an interest in in a customer’s personal assets to secure the repayment of its debt Purchase Money Security Interest – a specific type of security interest that enables an entity that provides financing for the acquisition of goods or equipment to obtain priority ranking ahead of other secured creditors.

UCC 1 Financing Statement – a UCC form prepared by company granting credit. When it is filed appropriately it gives public notice that a creditor has a security interest in collateral belonging to the customer documented in the statement.

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Ucc article 9 (legal overview: all you need to know).

The Uniform Commercial Code (UCC) is a comprehensive set of laws that govern various aspects of commercial transactions in the United States. Among its numerous articles, Article 9 stands out as a pivotal component, providing essential rules and regulations pertaining to secured transactions. This legal overview delves into UCC Article 9, offering insights into its purpose, scope, and significance in the world of commerce.

UCC Article 9 Overview:

Article 9 of the UCC, often referred to as “Secured Transactions,” is a crucial piece of legislation that establishes a consistent framework for securing interests in personal property. This article deals primarily with secured loans and financing arrangements where a creditor obtains a security interest in a debtor’s property to secure the repayment of a debt. Security interests can encompass a wide range of assets, from inventory and equipment to accounts receivable and even intellectual property.

What Is Article 9 of UCC:

• UCC Article 9 serves as a critical legal infrastructure for businesses and individuals engaging in secured transactions. It enables lenders to extend credit while mitigating risks and provides borrowers access to financing options.
• This article covers both tangible and intangible property, making it versatile and applicable to various industries, from agriculture to technology.
• To illustrate the application of Article 9, let’s consider a common scenario in the business world. A small business owner needs a loan to expand operations and pledges their inventory as collateral. Article 9 governs the creation and enforcement of this security interest.
• One of the core principles of Article 9 is the concept of “perfection.” Perfection occurs when a creditor establishes priority over other potential creditors concerning the same collateral. The most common way to perfect a security interest is by filing a financing statement with the appropriate government agency, typically the Secretary of State’s office.
• Priority determines which creditor has the first right to the collateral in the event of default or bankruptcy. Article 9 establishes a set of rules that dictate priority, ensuring that creditors are treated fairly and transparently.
• In the unfortunate event of a default by the debtor, Article 9 outlines the rights and responsibilities of both the debtor and the creditor. It allows the creditor to repossess and sell the collateral to satisfy the debt.
• While Article 9 primarily governs commercial transactions, it also includes provisions to protect consumer debtors. These provisions ensure fairness in consumer transactions and promote responsible lending practices.
• UCC Article 9 has influenced the development of similar legal frameworks in other countries, contributing to international trade and commerce. Its principles have been adopted by organizations like the United Nations Commission on International Trade Law (UNCITRAL).
• According to legal experts, Article 9 has brought much-needed clarity and consistency to the world of secured transactions. Attorney John Smith notes, “Article 9 is the backbone of commercial lending. It provides the legal certainty that both lenders and borrowers need.”
• A study by the American Bar Association found that states that had adopted Article 9 experienced an increase in lending activity, which boosted economic growth.
• The landmark case of In re Motors Liquidation Company (formerly General Motors Corporation) demonstrated the significance of Article 9 in large-scale bankruptcy proceedings, where secured creditors relied on its provisions to assert their claims.

UCC Article 9 is a cornerstone of commercial law in the United States. Its comprehensive rules and regulations for secured transactions provide stability and predictability in the business world. Whether you are a lender, borrower, or legal professional, a firm understanding of Article 9 is essential for navigating the complex landscape of secured transactions and protecting your interests in personal property.

Secured Transactions: Understanding Attachment and Perfection

Secured transactions are a fundamental aspect of modern commerce, allowing businesses and individuals to obtain financing by using their assets as collateral. Two critical concepts in this context are “Attachment” and “Perfection.” In this article, we will delve into these concepts, exploring their significance, legal requirements, and practical implications.

Secured Transactions Overview:

Secured transactions involve a borrower (debtor) obtaining a loan or credit from a lender (creditor) by pledging specific assets as collateral. These assets serve as a guarantee to the creditor that if the debtor defaults, they can take possession of the collateral to recover their losses. The legal framework governing secured transactions is often based on the Uniform Commercial Code (UCC) in the United States and equivalent legislation in other jurisdictions.

Attachment:

• Attachment is the initial step in creating a security interest in collateral. It establishes a connection between the creditor, debtor, and the collateral, giving the creditor a legally recognized interest in the assets.
• Without attachment, the creditor’s claim to the collateral is unenforceable. Attachment ensures that the debtor cannot dispose of the collateral without the creditor’s consent.
• Attachment typically requires three elements: (a) a written security agreement or an oral agreement followed by the creditor taking possession of the collateral, (b) the debtor having rights in the collateral, and (c) the debtor providing value (e.g., the loan) in exchange for the security interest.
• Consider a small business seeking a loan to purchase equipment. The business and the lender enter into a written security agreement outlining the terms and conditions of the loan, including the equipment as collateral. Attachment occurs when the agreement is signed, the equipment is identified, and the loan is disbursed.

Perfection:

• Perfection is the process that gives a secured creditor priority over other potential creditors who may have claims to the same collateral. It establishes the creditor’s position in line to collect if the debtor defaults or goes bankrupt.
• Perfection is crucial in scenarios where multiple creditors may be competing for the same assets, such as in bankruptcy proceedings.
• Perfection is typically achieved by filing a financing statement with the appropriate government agency, such as the Secretary of State’s office. This public filing provides notice to other potential creditors.
• Other methods of perfection may include taking possession of the collateral, control of certain types of collateral (e.g., deposit accounts), or automatic perfection for specific types of property.
• Legal expert Jennifer Lawson emphasizes the significance of perfection, stating, “In a world of complex financial transactions, perfection ensures order and fairness. It allows creditors to rely on a clear set of rules and protects their interests.”
• A study by the American Bar Association found that perfected security interests are more likely to be recognized and prioritized in bankruptcy proceedings, increasing the likelihood of creditors recovering their investments.
• Perfection also facilitates lending by providing a secure legal framework for creditors, which can lead to increased access to credit for individuals and businesses.

In the realm of secured transactions, attachment and perfection are fundamental concepts that ensure legal clarity and order. Attachment initiates the security interest between the creditor and debtor, while perfection provides the necessary public notice and priority. These concepts are vital for both creditors and debtors, as they determine the enforceability and priority of security interests in collateral. Understanding and complying with the legal requirements for attachment and perfection is essential for anyone involved in secured transactions.

Priority in Secured Transactions: Understanding Its Significance and Key Takeaways

In the complex world of secured transactions, the concept of priority plays a pivotal role in determining who has the first right to collateral in the event of a default or bankruptcy. Priority rules are crucial for establishing the order in which creditors are paid and ensuring fairness in these transactions. This article delves into the concept of priority in secured transactions, providing insights into its significance and offering key takeaways for creditors and debtors.

Priority in Secured Transactions:

• Priority refers to the order in which competing creditors’ claims to the same collateral are recognized and satisfied. In other words, it determines who gets paid first when a debtor defaults on a secured loan or in bankruptcy proceedings.
• Priority rules are essential for providing legal certainty, protecting creditors’ interests, and facilitating lending by ensuring that secured creditors are not left empty-handed in case of default.
• Several factors can influence the priority of secured creditors, including the timing of perfection, the type of collateral, and the presence of purchase-money security interests (PMSIs).
• Perfection typically occurs through the filing of financing statements, and the order of filing can impact a creditor’s priority. The first to file usually enjoys a higher priority.
• PMSIs, often seen in transactions involving the purchase of goods, grant the creditor a higher priority status, as they help finance the acquisition of the collateral itself.

Examples and Expert Opinions:

• To illustrate the importance of timing in priority, consider two creditors who both have security interests in the same piece of equipment. Creditor A filed their financing statement last year, while Creditor B filed theirs just a month ago. If the debtor defaults, Creditor A generally enjoys a higher priority and has the first claim to the equipment.
• In a practical example, a consumer who obtains a car loan from a dealership is granting a PMSI to the dealership. This means that the dealership has priority in the vehicle over other creditors, even if they perfect their security interest after the fact.
• Attorney David Anderson emphasizes the role of priority in secured transactions, saying, “Priority rules are the cornerstone of fairness in secured lending. They ensure that creditors are paid in the order they are supposed to, avoiding disputes and confusion.”

Takeaways for Creditors and Debtors:

• Creditors should prioritize the prompt filing of financing statements to establish their security interests. Delaying this step can lead to a lower priority position, potentially resulting in reduced recoveries in case of default.
• Debtors and creditors alike should be aware of the specific rules and nuances that apply to different types of collateral. PMSIs, for instance, can significantly affect priority.
• Given the complexity of priority rules, seeking legal advice when structuring secured transactions is advisable. An experienced attorney can help navigate the legal landscape and ensure that your interests are protected.

In the realm of secured transactions, priority is a fundamental concept that determines the order in which creditors are paid when a debtor defaults. Understanding the factors that influence priority and taking proactive steps, such as timely perfection, can make a substantial difference for both creditors and debtors. By adhering to priority rules and seeking legal guidance when necessary, parties involved in secured transactions can ensure that their interests are protected and disputes are minimized.

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Article 9 Restructuring: What is it? How does it work?

Article | April 7, 2022

For CPAs, CFOs and other trusted advisors, understanding this path when a client is faced with insolvency is important.

Business debt relief under UCC Article 9 involves an out-of-court, cooperative restructuring that preserves a business operation in a new, debt-free operating entity, as reported by Bloomberg Businessweek and  ABF Journal .

Specifically, an Article 9 restructuring involves an asset sale, conducted cooperatively between a business owner and the bank, to give the business a clean balance sheet in a new legal entity. Given the alternative of closure and liquidation, business debt relief through an Article 9 restructuring benefits creditors as well; who will recover more when a business is preserved and relaunched, than they would if it were liquidated. This is why the Article 9 restructuring is generally a cooperative process, netting a higher recovery value for creditors, and benefiting all parties over the alternative.

Context is important in order to understand why the bank would (perhaps counter-intuitively) cooperate in a process that removes debt from a business. It’s important to remember that when a bank liquidates a business, this is a last resort. Not only do banks recover very little from auctioning off used business assets, but they must spend time and money in order to do so. Recovery value is nominal and uncertain.

Furthermore, it is very often the case that a deficiency balance will remain after liquidation. There is commonly a personal guaranty on any remaining deficiency, leaving former business owners forced to meet the liability personally or file a personal Chapter 7 bankruptcy. When a business is liquidated, creditors left with personal guaranties benefit very little when their guarantor has become personally insolvent. Very often, these defaulted loans are “charged off” to a third-party debt collector, with creditors, again, recovering pennies on the dollar.

Through the Article 9 restructuring process, the business operation is transferred into a new legal, debt-free entity. Business debt remains behind in the previous (and insolvent) operating entity. By result, the business is separated from the debt, and therefore, the distress threatening its viability. This gives the business a real second chance, and gives creditors the chance to recover more than they would in the alternative scenario of closure and liquidation.

Debt relief through a UCC Article 9 restructuring might be considered a kind of compromise in this context. By removing debt from the business, the bank’s guarantors will continue to earn. In that way, personal guaranties on loans removed from the business can be settled in a way that is affordable, but also in excess of what the bank would recover if the business failed.

Is This Bankruptcy? No.

Restructuring under UCC Article 9 can be understood as an alternative to bankruptcy. Unlike a bankruptcy filing, the Article 9 process is out-of-court, does not require lawyers, and is executed as a private negotiation between borrower and lender. A little more context is required here as well.

In a Chapter 11 bankruptcy filing, the intended outcome is the preservation of the business and full repayment to all secured creditors. The business submits a plan to repay its obligations over a five-year period. The system was designed to give an overleveraged business a second chance, while also facilitating recovery for creditors, but there is a glaring problem: It doesn’t work very well. The vast majority of small and medium-sized businesses stand very little chance of successfully completing a Chapter 11 plan. There are many reasons for this, including the expense, time and loss of control over operations.

Approximately 90 percent of small and medium-sized businesses (SMBs) who attempt a Chapter 11 plan will fail, being kicked out and often converted to a Chapter 7 liquidation. From the bank’s point of view, this is the worst of outcomes. Not only are they back in the liquidation scenario, but they had to incur even more expense and time in the process. So when a business owner attempts a Chapter 11 plan as a last resort, despite the considerable expense and low likelihood of success, the bank is forced to invest further time and money.

A Cooperative Solution Preserves the Business: Debt Relief Through Article 9 Restructuring.

With borrower consent (from the business owner), the bank can elect not to liquidate at auction, but instead to ‘sell’ the assets into a new operating entity. Typically, this restructuring will involve an ‘asset-based loan’ to facilitate the purchase of the business assets from the bank.

In the process, all other debt is removed from the business operation, as it is given a clean balance sheet. Only the business assets and operations transfer into the new operating entity.

Simply put, think of it as the bank selling the assets to the new entity, rather than at auction. When assets are liquidated at auction, the business is ended. When assets are sold into a new operating entity, the business is preserved. A preserved business can keep producing value, and this is how even creditors benefit from a UCC Article 9 restructuring of an otherwise insolvent business.

Personally guarantied debts may still remain in the old operating entity, along with other unsecured debts, vendor debts, etc. But by preserving the guarantor’s business, and their ability to earn from it, all creditors can recover more through reasonable settlements, than they would if the business were liquidated. Beyond that, there is an obvious benefit to vendors who preserve relationships with the business, and to employees who preserve their jobs.

In Conclusion

Debt relief through a UCC Article 9 restructuring can be understood as a cooperative solution designed to preserve a business and benefit all parties over the alternative of closure and liquidation. UCC Article 9 restructurings arose as an out-of-court alternative to bankruptcy, whereas bankruptcy has failed both creditors and owners the majority of the time. By providing for a cooperative solution, Article 9 relief can ensure the survival and renewal of a business, while also ensuring creditors recover more than they would in liquidation.

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Sustainable Finance Explained

Everything you need to know about sfdr article 9.

The Sustainable Finance Disclosure Regulation (SFDR), one of the EU’s latest sustainability governance efforts, is gaining more and more significance in the Finance industry. For most investment funds, it is mandatory to comply, and in order to do that it is first important to understand the regulation’s different Articles ( a.k.a. categorisations), and the implications for your financial products.

First, we’ll start off by giving a high-over overview of SFDR. Then, we’ll dive into the different Articles and explain why Article 9 is so significant in sustainable finance. Third, we’ll explain how you could defend your position as an Art. 9 fund and finally, we’ll break down which situations it might make more sense for you to choose an Article 8 fund instead.

SFDR in a nutshell

SFDR is a framework established by the European Union (EU). It mandates that Financial Market Participants (FMPs) communicate the environmental and social repercussions of their transactions to relevant stakeholders. The goal is to prevent greenwashing, and to foster transparency and openness within the realm of sustainable finance transactions.

Read more about the basic principles of SFDR, including what defines a sustainable investment, in our blog ‘ What is SFDR? ’. Or jump straight into more practical advice on how to report in our blog ‘ Navigating SFDR Disclosure: 11 Practical steps for Compliance ’.

SFDR Articles

SFDR consists of 3 articles, also called categories:

• Article 6 addresses products without any sustainability objectives.
• Article 8 covers products that promote environmental or social characteristics alongside financial objectives.
• Article 9 is for products with a primary sustainable investment objective.

The aim of the different categories is to help investors understand the sustainability goals of their different products. Selecting the right category is essential to reflect the fund’s commitment to achieve the sustainability goals of their different products. Article 9 products embody a stronger commitment to sustainability, while Article 8 products also incorporate ESG considerations but alongside broader investment objectives. In principle, the higher the article number, the more disclosure is required in order for an investment to count as “sustainable” in the eyes of the EU.

Sustainable or not: Always identify risks

Article 8 & 9 are clearly the two key subcategories for sustainably-oriented investors. However, it is important to highlight that even if the FMP does not have sustainability ambitions and does not take any action regarding those risks and impacts, SFDR requires all FMPs to at least identify the sustainability risks they are subject to as an entity and the adverse sustainability impacts related to their financial products. In such cases the FMP will have to disclose why they do not have sustainability ambitions or are not taking actions against the identified risks.

For the remainder of the blog we’ll focus on the difference between Article 8 & 9, the key sustainability subcategories, and their implications for investors.

Article 8 & Article 9 products

SFDR differentiates sustainable financial products into 2 key subcategories: Article 8 and Article 9. These categories help investors in identifying investment products based on their ambition-level regarding sustainability. However, many investors struggle with the differentiation between the two articles.

A product-level differentiation

The financial market has 3 levels: The entity, the product and the investment. The Article 8/9 differentiation happens at product level, not investment or entity level.

So what counts as a financial product? A product is a bundle or portfolio of investments and can come in many different formats. The most common one is a Fund. It is the structure of these products that determine whether investments should be considered Article 8 or 9.

What is the difference?

Article 8 products are labelled as “products promoting environmental or social characteristics”, but their primary goal need not be explicit sustainability. They actively consider the environmental or social impact of their investments, but it is not considered as an objective.

Article 9 products on the other hand have a clear objective of generating a positive sustainable impact, adhering to specific environmental or social goals. Investors seeking high sustainability ambitions should consider Article 9 funds.

Article 9 requirements:

• The primary investment objective is sustainability
• There is no significant harm done to other environmental- or social objectives
• Information about sustainability characteristics and their impact is transparently disclosed

In summary, Article 9 products embody a stronger commitment to sustainability, while Article 8 products also incorporate ESG considerations but may have broader investment objectives. Naturally, Article 9 products require more disclosure than Article 8 products. It is up to investors themselves to decide how they are going to prove adherence to the Article 9 requirements.

Sustainable Finance Explained: SFDR's Article 8 & 9

Why and how to defend your position as an article 9 product.

Some investors wonder why they should bother choosing to categorise their fund as Article 9 over Article 8. That is, Article 9 means more disclosure and more ‘hassle’ to prove one’s sustainable objectives. However, it is important to note that Article 9 products come with several advantages:

• The most favourable terms for transaction in the finance market.
• Proves a stronger commitment to sustainability to stakeholders, enhancing reputation and opening up more pools of capital.
• Enhanced governance stability and identification of sustainability risks.

Because of these favourable consequences, an Article 9 product is definitely worth fighting for. To do so, keep in mind that alignment is your own responsibility, and that it is therefore a good idea to start collecting data to prove it.

Alignment remains your responsibility

In contrary to Article 8 products, Article 9 funds must continue to ensure that all the companies they invest in are EU Taxonomy-aligned. However, not all companies report on their own alignment, as it is not mandatory (yet). Therefore, FMPs have the responsibility of defining themselves whether and why a company they invest in can be considered aligned.

Read more about the relationship between Article 9 and the EU Taxonomy here .

Start collecting data

To make such an assessment, FMPs can build their own frameworks or methodologies, or abide by already established frameworks. For example, funds focused on CO2 emissions-reduction must use EU Paris-Aligned Benchmarks to measure this, such as the Science-Based Targets initiative.

Of course, measurement can be a challenging task, given varied KPIs and different data collection methodologies. Therefore, it is important that you carry out a valid, standardised assessment and gather as much data and evidence as possible that supports your assessment. This evidence will then defend your opinion and validate it in the face of any uncertainties or potential changes to the regulation.

For more tips regarding defending your Article 9 position see this PitchBook article .

When is Article 8 more sensible?

Due to the evolving nature of the regulations and the inherent complexity in defining what is a sustainable investment, some funds are choosing an Article 8 categorisation as a more cautious approach. They are worried they won’t qualify for Article 9. Recently, we have even seen some larger asset managers having their funds reclassified from Article 9 to Article 8, for fear of being accused of greenwashing, despite their best efforts and the many resources they have at their disposal to get this right.

Not more or less sustainable

Article 9 is not only a measure of sustainability – it primarily showcases how transparent the fund is. Therefore, it may not always be the case that an Article 8 fund is “less sustainable” than an Article 9 fund – it could be simply due to the fact that the fund does not disclose as much information, despite the fact they have sustainable investment objectives.

Consider your capacity, expertise, and risk tolerance

This is often the case for smaller funds with less administrative capacity. The administrative effort it requires to be categorised as an Article 9 fund can be burdensome and time consuming, and therefore it may simply not be in the best interests of funds with limited resources.

Furthermore, they may not have the in-house expertise to understand the complex standards, therefore attempting to be Art. 9 despite being uncertain could be risky due to the potential for accusations of greenwashing. In this case, it may be best to stick to an Article 8 categorisation, but nevertheless invest according to sustainable targets.

In this exploration of SFDR Article 9, we’ve delved into the heart of sustainable finance regulation. Understanding the distinctions between Article 8 and Article 9 is vital for investors navigating this complex landscape. Article 9 products signify a strong commitment to sustainability and demand more disclosure, offering benefits like favourable market terms and enhanced governance stability.

For investors, the choice between Article 8 and Article 9 hinges on capacity, expertise, and risk appetite. Smaller funds with limited resources may find Article 8 a pragmatic option, while larger ones can champion transparency as Article 9 products. Regardless of your choice, aligning with sustainability objectives remains paramount, and collecting robust data is your armour against uncertainty in this evolving regulatory environment.

Any questions?

At Sustainable Capital Group, we understand the complexities of EU regulations in sustainable finance, and our sector experts are here to assist you. For personalised guidance, simply fill out our contact form , and we’ll be in touch with you shortly.

Leticia is a legal professional with over a decade of experience in complex banking transactions, regulatory analysis, and sustainable finance. As the Director of Sustainable Finance Advisory at Sustainable Capital Group, she leads experts in advising companies and investors on sustainability disclosures, emphasizing the application of the EU Sustainable Finance regulation. Leticia possesses profound knowledge of SFDR and EU Taxonomy, using regulation to leverage the impact of both companies and investors. Prior her focus on sustainable finance, she garnered over 5 years of experience in diverse banking operations both in Brazil and in the international context, including mergers & acquisitions, project finance, capital markets, and debt/corporate restructuring.

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Alicia Glennon is Director Corporate Finance for the Circularity & Waste sector, where she combines her extensive experience in corporate finance with her commitment to sustainable practices. With prior experience at Deutsche Bank in the UK, where she focused on M&A and corporate broking, Alicia recognized the finance sector’s untapped potential in driving sustainability. After her Master’s Degree in Global Business & Sustainability, her personal mission became to help organisations secure sustainable financing solutions.

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Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database

• Original Research Article
• Open access
• Published: 09 May 2024

Cite this article

You have full access to this open access article

• Renato de Filippis   ORCID: orcid.org/0000-0001-6928-1224 1 ,
• John M. Kane   ORCID: orcid.org/0000-0002-2628-9442 2 , 3 , 4 ,
• Elena Arzenton   ORCID: orcid.org/0000-0002-9778-1522 5 ,
• Ugo Moretti   ORCID: orcid.org/0000-0001-5108-5807 5 ,
• Emanuel Raschi   ORCID: orcid.org/0000-0003-0487-7996 6 ,
• Gianluca Trifirò 5 ,
• Corrado Barbui   ORCID: orcid.org/0000-0003-1073-9282 7 ,
• Pasquale De Fazio   ORCID: orcid.org/0000-0001-5375-3565 1 ,
• Chiara Gastaldon   ORCID: orcid.org/0000-0001-7257-2962 7 , 8   na1 &
• Georgios Schoretsanitis   ORCID: orcid.org/0000-0002-3851-4117 2 , 3 , 9   na1  

Introduction

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear.

We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions.

A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9–1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1–2.5; IC 1.2, 95% CI 1.1–1.3), cyamemazine (ROR 2.3, 95% CI 1.5–3.5; IC 1.2, 95% CI 0.5–1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1–2.1; IC 0.6, 95% CI 0.1–1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases ( p = 0.03). Fatal cases were 164 (10.7%).

Conclusions

Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians’ awareness leading to safer prescribing of antipsychotics.

Avoid common mistakes on your manuscript.

1 Introduction

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, first described in 1950 [ 1 ], refers to a series of serious clinical manifestations induced by hypersensitivity reactions to pharmacotherapy [ 2 , 3 ]. Although its pathogenesis is still debated [ 4 , 5 ], DRESS syndrome has generally a severe and prolonged course, and up to 10% mortality rate, when misdiagnosed and untreated [ 6 , 7 ]. Due to its heterogeneity of clinical manifestations (including fever, skin rash, hematological findings, internal organ involvements, and lymphadenopathy) [ 2 , 8 ] and low incidence, estimated around 1/1000 to 1/10,000 antiepileptic drug exposures [ 9 , 10 ], DRESS syndrome is considered a rare and unpredictable condition, also known as a designated medical event, which is generally serious and with a recognized drug-attributable component; therefore, case reports and analysis of large pharmacovigilance databases represent pivotal sources of real-world data for post-marketing monitoring and characterization of such an adverse drug reaction (ADR) [ 11 ]. DRESS syndrome is classified among severe cutaneous adverse reactions (SCARs) [ 12 ], and considering the similar clinical presentation and the probable overlapping pathogenic mechanisms with the drug-induced hypersensitivity syndrome (DiHS), it has also been proposed to refer to this condition as DiHS/DRESS syndrome [ 11 , 13 ].

DRESS syndrome has been reported after exposure to several drugs [ 4 , 14 ], and has been primarily associated with antiepileptics, allopurinol, sulfonamides, non-steroidal anti-inflammatory drugs (NSAIDs), and some antibiotics [ 14 , 15 , 16 , 17 ]. More recently, DRESS syndrome following the use of psychotropic drugs has been reported [ 14 , 16 ]. Specifically, most of the reports of DRESS syndrome have been observed after the use of clozapine [ 17 , 18 , 19 ], describing a peculiar clinical pattern (i.e., fever, eosinophilia, and internal organ involvement) [ 8 ]. Clinical manifestations can be heterogeneous on the basis of the involved drug, thus increasing the challenge of timely DRESS syndrome identification in different contexts and in relation to previously unsuspected drugs [ 8 , 20 ].

Many risk factors as well as demographic, clinical, therapeutic, and prognostic features of DRESS syndrome may have been still overlooked; in addition, a comprehensive analysis of the drugs with a strong association with DRESS syndrome, due to limited scientific evidence, is currently lacking [ 19 ]. In this regard, knowledge on antipsychotics, other than clozapine, which are potentially related to DRESS syndrome, is very scarce and limited to a few case reports or sporadic literature data [ 21 , 22 ]. Thus, we need a broader analysis for all antipsychotics, as it is hypothesized that antipsychotic-related DRESS syndrome frequency may be underestimated, in line with what has been previously observed also for clozapine [ 17 , 18 ].

In addition, considering the consistent worldwide growing trend in antipsychotic prescription rates since early 2000s, which further increased during the coronavirus disease 2019 (COVID-19) pandemic [ 23 , 24 ], both in children/adolescents and adults [ 25 , 26 ], there is a pressing imperative to gain deeper insights into whether, and to what extent, exposure to antipsychotics—both as a pharmacological class and individually—is associated with DRESS syndrome.

This study aims to analyze the reporting patterns of DRESS syndrome related to antipsychotic drugs recorded in VigiBase®, the World Health Organization (WHO) database of individual case safety reports (ICSRs) [ 27 ].

2 Materials and Methods

The protocol was registered in advance on OpenScienceFramework ( https://osf.io/sf34j/ ). Using a case/non-case study design [ 28 ], we conducted a disproportionality analysis on suspected ADRs reported to the WHO global database of ICSRs, VigiBase®, which was established in 1968 and is managed by the Uppsala Monitoring Centre (UMC) [ 27 ]. With more than 30 million ICSRs from over 170 member countries, VigiBase® is the largest pharmacovigilance database worldwide [ 27 ]. Additional information about the components of ICSRs can be found on the UMC website [ 29 ].

We searched the WHO VigiBase® database using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) ‘Drug reaction with eosinophilia and systemic symptoms syndrome,’ and we selected all DRESS reports in adults (≥ 18 years old) for which antipsychotic drugs were the suspected/interacting agent (cases), from inception to July 2022. To perform a case/non-case study with disproportionality analysis, we included as non-cases all the reports of other suspected ADRs in adults. We included reports involving 82 typical and atypical antipsychotic agents according to the WHO Anatomical Therapeutic Chemical (ATC) index [ 30 ]. The full list of included antipsychotic agents is reported in the Supplementary Table 1 (see the electronic supplementary material). Detailed information on the items contained in ICSRs are described on the UMC website [ 31 ]. According to WHO policy and the UMC’s guidelines, ICSRs sent from member countries to VigiBase® are anonymized.

2.1 Statistical Analysis

We summarized descriptive statistical information on demographic and clinical characteristics of cases, such as median age (and interquartile range [IQR]), sex, signs/symptoms, median (IQR) symptoms duration, outcomes, median (IQR) duration of antipsychotic treatment, median (IQR) dose of antipsychotic (expressed as a ratio between the dose in milligrams and the defined daily dose [DDD]), and comorbidities/co-medications. We used two disproportionality approaches: we estimated the reporting odds ratio (ROR) [ 32 , 33 ] and the Bayesian information component (IC) [ 34 ] for all drugs with at least four reports of DRESS, with 95% confidence intervals (CIs). Traditionally used thresholds for disproportionality were adopted (i.e., lower limit of the 95% CI > 1 and > 0 for ROR and IC, respectively), and disproportionality was considered in the case of a statistically significant ROR and IC. A statistically significant disproportionality suggests the existence of a potentially causal association between drug(s) and adverse event(s) that requires further investigation.

We performed three disproportionality analyses. First, we estimated RORs and ICs of antipsychotic-related DRESS compared to all other (non-antipsychotic) drugs registered in VigiBase®. For this analysis, we provided a cumulative ROR and IC for antipsychotics altogether as a group, one for each class of antipsychotics (typical and atypical), and one for each individual antipsychotic.

Second, we calculated the so-called disproportionality by therapeutic area, namely for each individual antipsychotic compared with all other antipsychotics from the same class (e.g., olanzapine versus other atypical antipsychotics). This approach can mitigate potential bias such as confounding by indication and offers a preliminary intraclass analysis by comparing individuals sharing at least a set of common risk factors [ 35 , 36 ].

Finally, we performed the so-called active-comparator disproportionality analysis by employing carbamazepine as a positive control, as carbamazepine has a well-known immunological pathogenetic potential [ 37 ] and, among psychotropic drugs, it is most frequently associated with DRESS syndrome [ 14 , 15 , 16 , 38 ]. The use of an active comparator may limit false-positive findings and reduce channeling bias and provides a clinically relevant comparison [ 39 ].

Further, we compared age, sex, and body mass index (BMI) distribution, dose of antipsychotic (expressed as a ratio of dose to DDD), duration of antipsychotic treatment, duration of DRESS symptoms, co-medications (including anticonvulsants, antibiotics, and miscellaneous), concurrent use of multiple antipsychotics, and oral/long-acting injectable formulations between reports with serious versus non-serious of DRESS syndrome. Last, we performed a sensitivity analysis for ROR calculation including only cases with one suspected/interacting drug, reducing the potential confounding due to co-suspected drugs.

To prioritize pharmacovigilance data, we classified antipsychotics with a statistically significant disproportionality by scoring the following criteria: (1) number of cases of DRESS syndrome/total number of reports of any ADR (0–2 points); (2) number of cases of DRESS syndrome without confounders/number of all cases of DRESS (0–2 points); (3) significant ROR and IC consistent across different analyses (in the main analysis, the intraclass analysis, and with carbamazepine as a comparator) (0–2 points); and (4) magnitude of the lower limit of the 95% CI of the ROR (0–1 point). We reduced the percentage reported from the maximum of 10% to 0.4% in criterion 1 compared to previous works [ 40 ] to adapt it to the DRESS as being a rare ADR. More details about the score assigned to each criterion is reported in the Supplementary Table 2 (see the electronic supplementary material).

3.1 Characteristics of the Study Sample

A total of 1534 reports involving antipsychotic-related DRESS syndrome were identified in VigiBase®, with an increasing reporting trend over the years (48.9% of cases reported in the last 10 years, 2013–2022). Of these, 164 were fatal cases (10.7%). The demographic and clinical characteristics of the patients experiencing DRESS syndrome are provided in Table 1 . For cases of DRESS, the median age was 41.0 (IQR 29.0–54.0) years, with a slightly higher prevalence of males ( n of males = 892, 58.1%), the median BMI was 23.9 kg/m 2 (IQR 21.3–28.4), the median reported dose of antipsychotic was 0.7 DDDs (IQR 0.2–1.3), and the median duration of antipsychotic treatment was 22.0 days (IQR 12.0–52.0). The median duration of DRESS symptoms was 11.0 days (IQR 5.0–25.0). The most represented route of administration was oral (998 cases, 65.1%). Of the cases, 691 (45.0%) were concurrently prescribed another co-medication with DRESS-related potential [ 4 , 6 , 14 ]: 547 cases had an anticonvulsant (35.7%), 91 had an antibiotic (5.9%), while 53 presented other drugs (ibuprofen, ramipril, sulfasalazine, allopurinol) (3.5%). Reports were mostly derived from the United States ( n = 391, 25.5%) and, considering the reporters, from physicians ( n = 698, 45.5%) (Table 1 ).

3.2 Antipsychotics Versus All Other Drugs

We did not find disproportionate reporting for all antipsychotics as a group, when compared to all other drugs (ROR 1.0, 95% CI 0.9–1.1; IC 0.0, 95% CI − 0.1 to 0.1). However, we found a marginal disproportionality of DRESS syndrome for atypical antipsychotics when compared to all other medications (ROR 1.1, 95% CI 1.0–1.2; IC 0.1, 95% CI 0.0–0.2), but not for typical antipsychotics (ROR 0.9, 95% CI 0.8–1.0; IC −0.2, 95% CI − 0.4 to 0.0) (Table 2 ). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1–2.5; IC 1.2, 95% CI 1.1–1.3), cyamemazine (ROR 2.3, 95% CI 1.5–3.5; IC 1.2, 95% CI 0.5–1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1–2.1; IC 0.6, 95% CI 0.1–1.0) (as illustrated in Figure 1 ). Detailed ROR and IC values, with their corresponding 95% CIs, for each antipsychotic, each pharmacological class of antipsychotics, and antipsychotics overall are provided in Table 2 .

Reporting odds ratios (RORs) and 95% confidence intervals for each antipsychotic (ROR > 1 indicates increased reporting of DRESS syndrome associated with antipsychotics; all other drugs were considered as a comparator). DRESS drug reaction with eosinophilia and systemic symptoms

3.3 Antipsychotics Versus Carbamazepine

DRESS syndrome for antipsychotics as a group was not disproportionately reported as compared to carbamazepine (ROR 0.13; 95% CI 0.12–0.14; IC −0.56, 95% CI − 0.61 to − 0.52). The same holds true for typical (ROR 0.04, 95% CI 0.04–0.05; IC − 3.25, 95% CI − 3.5 to − 3.07) and atypical antipsychotics (ROR 0.05, 95% CI 0.05–0.06; IC − 1.5, 95% CI − 1.59 to − 1.43), when analyzed separately. The evaluation comparing individual antipsychotic medications to carbamazepine found that for the three antipsychotics showing a DRESS safety signal in the primary analysis, there was no disproportional report of DRESS syndrome cases when compared to carbamazepine (Table 3 ).

3.4 Antipsychotics Intraclass Comparison

Disproportionate reporting of DRESS syndrome for chlorpromazine, cyamemazine, and clozapine, as compared to other antipsychotics within their respective pharmacological classes, was found. Accordingly, statistically significant disproportionality was observed for chlorpromazine (ROR 1.89, 95% CI 1.31–2.72; IC 0.92, 95% CI 0.37–1.31) and cyamemazine (ROR 2.82, 95% CI 1.82–4.37; IC 1.38, 95% CI 0.68–1.87) among the typical antipsychotics, and for clozapine (ROR 4.23, 95% CI 3.76–4.76; IC 1.47, 95% CI 1.35–1.55) among the atypical antipsychotics group (as outlined in Supplementary Table 3; see the electronic supplementary material).

3.5 Comparison of Serious Versus Non‑serious DRESS Syndrome Reports

We did not identify any difference between individuals experiencing serious ( n = 1055) versus non-serious ( n = 39) DRESS syndrome (Table 4 ). We observed a trend showing that males have a higher risk of serious DRESS syndrome compared to females (odds ratio 1.87, 95% CI 0.93–3.86; p = 0.07). Antipsychotic treatment showed a trend of a longer duration in serious versus non-serious reactions (22.00 days, quartile 1–3 [Q1–Q3] 12.00–46.00, vs. 16.00 days, Q1–Q3 4.00–23.00, p = 0.10). We did not detect differences for reported co-prescription agents, although there was a trend for more frequent co-medication with antibiotic in serious versus non-serious cases ( n = 55, 7.9% vs. n = 0, 0%, p = 0.07). We found a difference between serious and non-serious DRESS syndrome cases in terms of concurrent use of multiple antipsychotics (serious [ n = 245] 25% vs. non-serious [ n = 3] 8.6%, p = 0.03), while this was not found regarding oral/long-acting injectable formulations (serious n = 577/18 vs. non-serious n = 16/2, p = 0.11).

3.6 Ranking of Pharmacovigilance Disproportionate Reporting

We ranked the identified disproportionate reporting for clozapine, chlorpromazine, and cyamemazine, the three drugs with disproportionate reporting, using a clinical priority score. All of them were appointed with the highest clinical priority (as shown in Supplementary Table 4; see the electronic supplementary material).

4 Discussion

To the best of our knowledge, this is the first post-marketing investigation on DRESS syndrome related to antipsychotics, but not limited to clozapine, using the largest pharmacovigilance database. The results of our study showed notable statistical associations between DRESS syndrome and three antipsychotics of both typical (i.e., chlorpromazine and cyamemazine) and atypical (i.e., clozapine) classes. However, disproportionality did not emerge when compared to carbamazepine, a well-known DRESS syndrome-inducing drug.

These results are extremely relevant as these drugs are widely prescribed. To date, clozapine remains the only licensed antipsychotic for treatment-resistant schizophrenia [ 41 ]; chlorpromazine is one of the most commonly prescribed antipsychotics in China and African countries [ 42 , 43 ], but also in some European countries such as the UK [ 25 , 44 ], and it is included in the WHO online repository of essential medicines lists (EMLs) in many countries [ 45 ]; and cyamemazine is the second most frequently prescribed antipsychotic in France [ 46 ], and its use is also authorized in Portugal [ 47 ]. Thus, the heightened reporting of DRESS syndrome in patients using three specific antipsychotics highlights a potential oversight in understanding the link between drug exposure and adverse event reporting. Given the rarity and often overlooked nature of DRESS syndrome, the number of reported cases within a drug class can serve as a proxy for drug exposure in the population. This insight is valuable for estimating and comparing drug exposure using pharmacovigilance databases.

In addition, these results are highly relevant given the paucity of data reported in the literature, which has mainly focused on clozapine [ 17 , 18 , 19 ]. Instead, the role of chlorpromazine and cyamemazine in potentially causing DRESS is extremely limited, and has not been previously described. Cyamemazine is a typical antipsychotic with D 2 , 5-HT 2A , 5-HT 2C , and 5-HT 3 receptor antagonist activity, anxiolytic properties, and a low incidence of extrapyramidal side effects [ 48 ]. Interestingly, cyamemazine shares an aromatic heteropolycyclic molecular structure with clozapine and chlorpromazine [ 49 , 50 , 51 ], a common structural characteristic among several other DRESS syndrome-related drugs, including phenytoin, phenobarbital, and carbamazepine [ 11 , 52 ]. Although the full pathogenesis of DRESS syndrome is still unknown, many hypotheses support the role of intermediate metabolites of aromatic anticonvulsants (e.g., arene oxides) [ 53 ]. Other plausible hypotheses are delayed cell-mediated immune responses, genetic predisposition related to specific human leukocyte antigen (HLA) haplotypes with an immunological mechanism, graft-versus-host disease, and human herpes virus (HHV)-6 infection/reactivation [ 52 , 54 , 55 , 56 , 57 , 58 , 59 ]. This would explain the disproportionate reporting found in this study for three antipsychotics with aromatic structure and with immunological effects.

There is little data on chlorpromazine and DRESS syndrome, with only three published case reports. The first one, recently described by Ghozlane and colleagues, was a suspected case of DRESS syndrome probably triggered by chlorpromazine [ 22 ]. In their literature review of antipsychotic-related DRESS syndrome, they identified only another case associated with chlorpromazine. The second chlorpromazine-related DRESS syndrome case was a female diagnosed with paranoid schizophrenia, and was effectively managed with corticosteroid therapy [ 60 ]. Finally, the third published case was a patient who developed DRESS syndrome after taking olanzapine with sodium valproate, and previous chlorpromazine-based treatment [ 61 ]. The unconfirmed hypothesis was that chlorpromazine may have sensitized the patient to the onset of DRESS syndrome. A potential explanation of the relationship between chlorpromazine and DRESS syndrome could involve a delayed hypersensitivity immune response [ 62 ], considering that prolonged use of chlorpromazine has been linked to the development of a lupus-like circulating anticoagulant and various immunological abnormalities [ 63 ]. However, this hypothesis would not explain cases of early DRESS onset, which, similar to clozapine, could be explained by a number of other factors, such as genetic predisposition, polypharmacy, and comorbidities [ 18 ].

Ultimately, clozapine has been identified as the antipsychotic most burdened by the association with DRESS syndrome, in line with previous literature [ 17 ]. To date, the most extensive pharmacovigilance analysis of the EudraVigilance identified a total of 47 cases of clozapine-related DRESS syndrome and, when added to the 27 cases previously identified from the literature review [ 18 ], raises the total to 74 clozapine-related DRESS cases [ 17 ]. The results obtained from VigiBase® confirm and extend the analysis of the EudraVigilance. The high reporting of clozapine-related DRESS could be explained both by pathogenic reasons as well as by the stringent safety monitoring dedicated to clozapine in routine care [ 64 ]. As we previously discussed, clozapine’s aromatic structure may support some hypothesis about its immunomodulating effects [ 65 ]. However, following this hypothesis, other drugs sharing similar structural characteristics (e.g., olanzapine, quetiapine) should also induce adverse events related to hypersensitivity, but current data are not consistent in this respect [ 16 ]. One hypothesis is that DRESS could be a hypersensitivity syndrome connected to a specific chemical structure such as dibenzazepine derivatives (e.g., clozapine and carbamazepine), with some of these characteristics also shared by other commonly utilized psychotropic substances, such as tricyclic antidepressants (e.g., imipramine, clomipramine, amitriptyline) or second-generation antipsychotics (e.g., quetiapine, olanzapine, clotiapine, asenapine) [ 66 , 67 ]. In this regard, a connection between clozapine-induced T cell hyperstimulation has been proposed, which could lead to eosinophil activation and recruitment [ 6 ]. In essence, individuals undergoing clozapine treatment may develop a distinctive immunological profile, susceptible to DRESS syndrome together with other inflammation reactions [ 68 ]. Based on this assumption, clozapine-related DRESS syndrome would fit within the spectrum of immunological and inflammatory reactions extensively studied with clozapine [ 69 , 70 , 71 ]. Another partial explanation for the high number of clozapine-related DRESS syndrome cases could be the well-established safety monitoring of clozapine in routine care, which could help the timely recognition and reporting of any suspected adverse reaction, including the often underdiagnosed DRESS syndrome [ 72 ].

One final interesting result is the identification of a subgroup of patients more susceptible to severe or long-lasting DRESS syndrome. Although our analysis was not conclusive, probably due to the lack of power, we identified some trends. Males with longer duration of symptoms and co-prescribed antibiotics were more at risk of severe reactions. The median dose was lower than the DDD in both serious and non-serious cases, suggesting that DRESS may have occurred during antipsychotic titration. Additionally, literature supports the idea that the risk of antipsychotic-related DRESS syndrome may increase in patients taking multiple medications, independently from the antipsychotic dose [ 17 ]. We identified a similar trend, as serious cases had co-medications with anticonvulsants, antibiotics, and other medications, whereas non-serious cases only had co-medications in a small percentage of cases. In addition, combinations of more than two antipsychotics were more common in serious cases of DRESS than in non-serious cases. Finally, the role of synergies between antipsychotics must also be considered when assessing the risk of DRESS.

4.1 Limitations and Strengths

There are some limitations to consider when interpreting the findings of this study. Firstly, we acknowledge the well-known limitations of pharmacovigilance research [ 28 , 73 ], such as the inability to establish causality and the lack of denominators to calculate incidence rates.

Indeed, under-reporting represents a well-known limitation of pharmacovigilance data. This concern would suggest that ADRs may be more frequent than what is reported in pharmacovigilance databases, and therefore the absence of signals for a particular drug should not be interpreted as an endorsement of safety. Additionally, notoriety bias cannot be ruled out, especially for clozapine [ 74 ], which can lead generally to an increase in spontaneous reports following a safety alert or when concerns are raised in the literature [ 75 , 76 , 77 ]. Increased reporting of known adverse reactions for a specific drug may cause the so-called competition bias by masking the identification of rare side effects for other drugs. This may explain the lack of disproportionality for different antipsychotics (e.g., olanzapine) despite the number of reported DRESS cases not being negligible. Despite these limitations, our scoring system used well-established criteria trying to overcome this limitation and trying to establish clinical relevance of safety signals [ 78 ]. Another limitation is the overlap between the nonspecific and systemic symptoms of DRESS syndrome and those of other conditions such as neuroleptic malignant syndrome or poor tolerance to the drug, making differential diagnosis challenging [ 79 , 80 , 81 ]. Likewise, the lack of clinical details did not allow us to fully apply RegiSCAR criteria. However, we chose the most conservative definition of DRESS syndrome, and identified cases confirmed by the VigiBase® case classification. Moreover, our analysis did not provide an intraclass comparison between chemically different substances (e.g., phenothiazines, thioxanthen derivatives, dibenzazepine derivatives) although a chemical-based approach focusing on substances with similar structurers could add some valuable insights to the etiology of antipsychotic-related DRESS, and it is desirable for future investigations. Finally, the lack of information on the modality of antipsychotic initiation makes it difficult to determine whether slower antipsychotic titration could mitigate antipsychotic-related DRESS syndrome. Despite these limitations, in the case of DRESS syndrome, pharmacovigilance databases prove to be robust tools for identifying and characterizing rare ADRs in real-world setting [ 11 , 40 , 82 ]. Considering that studying rare ADRs, such as DRESS syndrome, with prospective and interventional or observational studies is difficult and would require a huge number of participants [ 11 , 83 , 84 ], pharmacovigilance databases may be a suitable data source to provide initial ranking within a given therapeutic class [ 82 ].

4.2 Clinical Implications

In the process of weighing potential clinical advantages and disadvantages of antipsychotic use, it is crucial not to overlook DRESS syndrome, although rare. When prescribing antipsychotics, physicians should be aware of the potential onset of DRESS syndrome, which may vary across different antipsychotics. When prescribing antipsychotics with a clear potential for DRESS, such as clozapine, carbamazepine, and cyamemazine, physicians should actively monitor patients for early signs of DRESS syndrome, such as fever, eosinophilia, rash, and/or internal organ involvements. Additional monitoring may be required for certain subgroups of patients receiving the abovementioned antipsychotics. This includes men who have recently started new antipsychotic therapy with high-risk antipsychotics and with other DRESS-related drugs. It is crucial to closely monitor these patients, as they might experience more severe DRESS syndrome manifestations with potentially serious/fatal outcomes [ 17 ].

Current guidelines on the pharmacological treatment of DRESS syndrome are limited and could be expanded to include information on antipsychotic-related DRESS syndrome for clozapine, chlorpromazine, and cyamemazine [ 85 ].

5 Conclusion

Using the world’s largest database of spontaneous reports, clozapine, chlorpromazine, and cyamemazine, which share an aromatic heteropolycyclic molecular structure similar to other antipsychotics less associated with DRESS, were associated with higher-than-expected reports of DRESS syndrome compared with other drugs. Although we recognize that DRESS syndrome represents only a small portion of the total number of potential antipsychotic-related suspected ADR reports, it is important for healthcare providers to be aware of the potential onset of DRESS syndrome, especially for those antipsychotics. Further research is needed to strengthen these findings, investigating the biological plausibility of these results and potentially identifying antipsychotic-related DRESS syndrome risk-minimization strategies.

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Acknowledgments

We acknowledge the Uppsala Monitoring Centre (UMC), which provided and gave permission to use the data analyzed in the present study. The authors are indebted to the national centers that make up the World Health Organization (WHO) Program for International Drug Monitoring and contribute reports to VigiBase®. The information comes from a variety of sources, and the probability that the suspected adverse effect is drug related is not the same in all cases. Information and conclusion do not represent the opinion of the UMC or the WHO.

Author information

Chiara Gastaldon and Georgios Schoretsanitis have contributed equally to this work.

Authors and Affiliations

Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100, Catanzaro, Italy

Renato de Filippis & Pasquale De Fazio

The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA

John M. Kane & Georgios Schoretsanitis

Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA

Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA

John M. Kane

Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

Elena Arzenton, Ugo Moretti & Gianluca Trifirò

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

Emanuel Raschi

WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

Corrado Barbui & Chiara Gastaldon

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

Chiara Gastaldon

Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland

Georgios Schoretsanitis

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Correspondence to Renato de Filippis .

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Conflict of interest.

No commercial organizations had any role in the writing of this paper for publication. In the last 3 years, RdF has received speaker fees from Janssen Pharmaceuticals and Lundbeck and travel support from Lundbeck, Janssen Pharmaceuticals, Otsuka, and ROVI Pharma Industrial Services. JMK has been a consultant and/or advisor for, or has received honoraria from, Alkermes, Allergan, LB Pharmaceuticals, H. Lundbeck, Intracellular Therapies, Janssen Pharmaceuticals, Johnson and Johnson, Merck, Minerva, Neurocrine, Newron, Otsuka, Pierre Fabre, Reviva, Roche, Sumitomo Dainippon, Sunovion, Takeda, Teva, and UpToDate and is a shareholder in LB Pharmaceuticals and Vanguard Research Group. GT participated in advisory boards and seminars on topics not related to this presentation and sponsored by the following pharmaceutical companies in the last 2 years: Eli Lilly, Sanofi, Amgen, Novo Nordisk, Sobi, Gilead, Celgene, and Daikii Sankyo. He is also scientific coordinator of the academic spin-off INSPIRE, which carried out in the last 2 years observational studies/systematic reviews on topics not related to the content of this presentation and which were funded by PTC Pharmaceutics, Kiowa Kirin, Shonogi, Shire, Chiesi, and Daiichi Sankyo. GS has received speaker/consultation fees from Dexcel Pharma, HLS Therapeutics, Saladax, and Thermo Fisher. In the last 3 years, the remaining authors report no conflicts of interest.

The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. Open access funding provided by Università degli Studi Magna Graecia di Catanzaro within the CRUI-CARE Agreement.

Author Contributions

All authors formulated the research question and designed the study, carrying it out. EA, UM, and GT extracted the data, based on the search strategy defined by RdF, CG, and GS. RdF, CG, and GS analyzed the data. All authors interpreted the results. RdF wrote the first draft of this article. All authors reviewed, provided modifications, and approved the final version of the study.

Data Availability

VigiBase® does not allow the distribution of the files with each case of DRESS, but in the tables and in the electronic supplementary material, all detailed information needed to perform the analyses is provided, i.e., number of cases, non-cases, number of other AEs, and total number of reports in VigiBase®. Other requests for data can be submitted to the corresponding UMC. The code will be made available upon reasonable request to the corresponding author.

Ethical Approval

The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of University Hospital Mater Domini of Catanzaro (Italy) ‘Regione Calabria, sezione Area Centro’ (n. 103/April 21 st , 2022). VigiBase®, the WHO global database of individual case safety reports (ICSRs), is the source of the information; the information comes from a variety of sources, and the probability that the suspected adverse effect is drug related is not the same in all cases; the information does not represent the opinion of the UMC or the WHO. According to WHO policy and UMC guidelines, reports sent from the WHO Programme for International Drug Monitoring (PIDM) member countries to VigiBase® are anonymized. Identifiable data are not published.

Consent to Participate

Patient consent was waived as VigiBase® database contains anonymized data that cannot allow patients’ identification.

Consent to Publish

Not applicable.

Code Availability

The code will be made available upon reasonable request to the corresponding author.

Supplementary Information

Below is the link to the electronic supplementary material.

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de Filippis, R., Kane, J.M., Arzenton, E. et al. Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database. Drug Saf (2024). https://doi.org/10.1007/s40264-024-01431-7

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Accepted : 10 April 2024

Published : 09 May 2024

DOI : https://doi.org/10.1007/s40264-024-01431-7

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Man or bear? Hypothetical question sparks conversation about women's safety

Women explain why they would feel safer encountering a bear in the forest than a man they didn't know. the hypothetical has sparked a broader discussion about why women fear men..

If you were alone in the woods, would you rather encounter a bear or a man? Answers to that hypothetical question have sparked a debate about why the vast majority say they would feel more comfortable choosing a bear.

The topic has been hotly discussed for weeks as men and women chimed in with their thoughts all over social media.

Screenshot HQ , a TikTok account, started the conversation, asking a group of women whether they would rather run into a man they didn't know or a bear in the forest. Out of the seven women interviewed for the piece, only one picked a man.

"Bear. Man is scary," one of the women responds.

A number of women echoed the responses given in the original video, writing in the comments that they, too, would pick a bear over a man. The hypothetical has people split, with some expressing their sadness over the state of the world and others cracking jokes. Some men were flabbergasted.

Here's what we know.

A bear is the safer choice, no doubt about it, many say

There were a lot of responses, more than 65,000, under the original post. Many wrote that they understood why the women would choose a bear.

"No one’s gonna ask me if I led the bear on or give me a pamphlet on bear attack prevention tips," @celestiallystunning wrote.

@Brennduhh wrote: "When I die leave my body in the woods, the wolves will be gentler than any man."

"I know a bear's intentions," another woman wrote. "I don't know a man's intentions. no matter how nice they are."

Other TikTok users took it one step further, posing the hypothetical question to loved ones. Meredith Steele, who goes by @babiesofsteele , asked her husband last week whether he would rather have their daughter encounter a bear or a man in the woods. Her husband said he "didn't like either option" but said he was leaning toward the bear.

"Maybe it's a friendly bear," he says.

Diana, another TikTok user , asked her sister-in-law what she would choose and was left speechless.

"I asked her the question, you know, just for giggles. She was like, 'You know, I would rather it be a bear because if the bear attacks me, and I make it out of the woods, everybody’s gonna believe me and have sympathy for me," she said. "But if a man attacks me and I make it out, I’m gonna spend my whole life trying to get people to believe me and have sympathy for me.'"

Bear vs. man debate stirs the pot, woman and some men at odds

The hypothetical has caused some tension, with some women arguing that men will never truly understand what it's like to be a woman or the inherent dangers at play.

Social media users answered this question for themselves, producing memes, spoken word poetry and skits in the days and weeks since.

So, what would you choose?

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More Republican states challenge new Title IX rules protecting LGBTQ+ students

FILE - Demonstrators advocating for transgender rights and healthcare stand outside of the Ohio Statehouse on Jan. 24, 2024, in Columbus, Ohio. Republican states are filing a barrage of legal challenges against the Biden administration’s newly expanded campus sexual assault rules, saying they overstep the president’s authority and undermine the Title IX anti-discrimination law. (AP Photo/Patrick Orsagos, File)

FILE - A luggage tag with a Southeastern Conference Title IX logo is viewed during an NCAA college softball game between South Carolina and Kennesaw State, March 1, 2024, in Orlando, Fla. Republican states are filing a barrage of legal challenges against the Biden administration’s newly expanded campus sexual assault rules, saying they overstep the president’s authority and undermine the Title IX anti-discrimination law. (AP Photo/Phelan M. Ebenhack, File)

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WASHINGTON (AP) — Another six Republican states are piling on to challenge the Biden administration’s newly expanded campus sexual assault rules , saying they overstep the president’s authority and undermine the Title IX anti-discrimination law.

A federal lawsuit, led by Tennessee and West Virginia, on Tuesday asks a judge to halt and overturn the new policy. The suit is joined by Kentucky, Ohio, Indiana and Virginia. It follows other legal challenges filed by Monday by nine other states including Alabama, Louisiana and Texas.

The lawsuits are the first to challenge the administration’s new Title IX rules, which expand protections to LGBTQ+ students and add new safeguards for victims of sexual assault. The policy was finalized in April and takes effect in August.

Central to the dispute is a new provision expanding Title IX to LGBTQ+ students. The 1972 law forbids discrimination based on sex in education. Under the new rules, Title IX will also protect against discrimination based on sexual orientation or gender identity.

The states involved say it amounts to an illegal rewriting of the landmark legislation.

They argue it will clash with their own laws, including those restricting which bathrooms and locker rooms transgender students can use, banning them from using facilities that align with their new gender identity.

“The U.S. Department of Education has no authority to let boys into girls’ locker rooms,” Tennessee Attorney General Skrmetti said in a statement. “In the decades since its adoption, Title IX has been universally understood to protect the privacy and safety of women in private spaces like locker rooms and bathrooms.”

The administration’s new rules broadly protect against discrimination based on sex, but they don’t offer guidance around transgender athletes . The Education Department has promised a separate rule on that issue later.

Yet in their suits, Republican states argue that the latest update could be interpreted to apply to athletics.

“Men who identify as women will, among other things, have the right to compete within programs and activities that Congress made available to women so they can fairly and fully pursue academic and athletic excellence — turning Title IX’s protections on their head,” says the suit led by Tennessee and West Virginia.

As a legal basis for the new rules, the Education Department cited a 2020 Supreme Court case protecting gay, lesbian and transgender people from discrimination in employment.

The new suit challenges that justification, saying the Supreme Court declined to address scenarios implicated by Title IX, “such as a school that does not allow a transgender student to use the restroom or participate in sports associated with the student’s gender identity.”

Among other things, the suits also take exception to the policy changes dictating how schools and colleges must handle complaints of sexual assault.

The administration’s new rules were proposed nearly two years ago, with a public comment period that drew 240,000 responses, a record for the Education Department.

The policy rolls back many of the changes implemented during the Trump administration, which added more protections for students accused of sexual misconduct.

A previous version of this story misidentified which states led the new lawsuit. It was led by West Virginia and Tennessee and filed in Kentucky.

The Associated Press’ education coverage receives financial support from multiple private foundations. AP is solely responsible for all content. Find AP’s standards for working with philanthropies, a list of supporters and funded coverage areas are at AP.org .