Design and Methods.
Table 8.1 is derived from ‘Three Approaches to Case Study Methods in Education: Yin, Merriam, and Stake ‘ by Bedrettin Yazan, licensed under CC BY-NC-SA 4.0. 5
There are several forms of qualitative case studies. 1,2
Discovery-led case studies, which:
Theory-led case studies, which:
Single and collective case studies, where: 2, 9
In both intrinsic, instrumental and illustrative case studies, the exploration might take place within a single case. In contrast, a collective case study includes multiple individual cases, and the exploration occurs both within and between cases. Collective case studies may include comparative cases, whereby cases are sampled to provide points of comparison for either context or the phenomenon. Embedded case studies are increasingly common within multi-site, randomised controlled trials, where each of the study sites is considered a case.
Multiple forms of data collection and methods of analysis (e.g. thematic, content, framework and constant comparative analyses) can be employed, since case studies are characterised by the depth of knowledge they provide and their nuanced approaches to understanding phenomena within context. 2,5 This approach enables triangulation between data sources (interviews, focus groups, participant observations), researchers and theory. Refer to Chapter 19 for information about triangulation.
Advantages of using a case study approach include the ability to explore the subtleties and intricacies of complex social situations, and the use of multiple data collection methods and data from multiple sources within the case, which enables rigour through triangulation. Collective case studies enable comparison and contrasting within and across cases.
However, it can be challenging to define the boundaries of the case and to gain appropriate access to the case for the ‘deep dive’ form of analysis. Participant observation, which is a common form of data collection, can lead to observer bias. Data collection can take a long time and may require lengthy times, resources and funding to conduct the study. 9
Table 8.2 provides an example of a single case study and of a collective case study.
Title | ||
---|---|---|
Nayback-Beebe, 2012 | Clack, 2018 | |
‘The purpose of this phenomenological qualitative case study… was to gain a holistic understanding of the lived-experience of a male victim of intimate partner violence and the real-life context in which the violence emerged.’ | ‘in-depth investigation of the main barriers, facilitators and contextual factors relevant to successfully implementing these strategies in European acute care hospitals’ | |
‘What is the lived experience of living in and leaving an abusive intimate relationship for a white middle class male?’ | ‘(1) what are the main barriers and facilitators to successfully implementing CRBSI prevention procedures?; and (2) what role do contextual factors play?’ | |
A single, intrinsic qualitative research study. Following Yin’s case study approach, the authors wished to uncover the contextual conditions relevant to the phenomenon under study – living in and leaving an abusive intimate relationship as a white, middle-class male. The researchers wanted to understand and explore the contextual conditions related to female-to-male perpetrated intimate partner violence. | A qualitative comparative case study of 6 of the 14 hospitals participating in the Prevention of Hospital Infections by Intervention and Training (PROHIBIT) randomised controlled study on the prevention of catheter-related bloodstream infection prevention. The case study examined contextual factors that affect the implementation of an intervention, particularly across culturally, politically and economically diverse hospital settings in Europe. | |
United States of America, insights from a case study to provide nurses with an understanding that intimate partner violence occurs in the lives of men and women, and to be aware of this in the inpatient and outpatient settings. | European acute-care hospitals that were participating in the PROHIBIT randomised controlled trial. | |
Three in-depth interviews conducted for one month. The participant was a 44-year-old man who met the following inclusion criteria: • self-reported survivor of physical, emotional, verbal abuse, harassment and/or humiliation by a current or former partner • the violence occurred in the context of a heterosexual relationship • was in the process of leaving or had left the relationship | Data collection before and after the implementation of an intervention and included 129 interviews (133 hours) with hospital administration, IPC and ICU leadership and staff, telephone interviews with onsite investigators alongside 41 hours of direct observations | |
Existential phenomenology following Colaizzi’s method for data analysis. | Thematic analysis was inductive (first site visit) and deductive (second site visit), with cross-case analysis using a stacking technique; cases were grouped according to common characteristics and differences, and similarities were examined. | |
Theme 1. Living in the relationship – confrontation from within Theme 2. Living in the relationship – confrontation from without Theme 3. Leaving the relationship – realisation and relinquishment Overarching theme: Living with a knot in your stomach | Three meta themes were identified • implementation agendas • resourcing • boundary spanning |
Qualitative case studies provide a study design with diverse methods to examine the contextual factors relevant to understanding the why and how of a phenomenon within a case. The design incorporates single case studies and collective cases, which can also be embedded within randomised controlled trials as a form of process evaluation.
Qualitative Research – a practical guide for health and social care researchers and practitioners Copyright © 2023 by Darshini Ayton is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.
A discussion of qualitative & quantitative research design, case study research: an internal-external classification.
The following is a modified excerpt from Applied Qualitative Research Design: A Total Quality Framework Approach (Roller & Lavrakas, 2015, pp. 295-298).
Salmons mentions the work of Robert Yin and Robert Stake. The typologies of Yin (2014) and Stake (1995) are “two key approaches” in case study research that “ensure that the topic of interest is well explored, and that the essence of the phenomenon is revealed” (Baxter & Jack, 2008, p. 545). Yin (2014) outlines four fundamental types of case studies on the basis of the number of cases and units of analysis in the study design. Specifically, Yin’s typology consists of two types of single-case designs – a type with one unit of analysis (Type 1) and a type with multiple units of analysis (Type 2) – and two types of multiple-case designs – those with one unit of analysis (Type 3) and those with more than one (Type 4). Yin believes that theory development is “highly desired” in case study design and therefore selecting cases for a multiple-case design, for example, involves choosing cases that are expected to return results that support or challenge a theoretical proposition or construct.
Where Yin (2014) emphasizes theoretical development and the ability to say something beyond the specific cases studied, Stake (2006) asserts that “the power of case study is its attention to the local situation, not in how it represents other cases in general” (p. 8). Stake (1995) divides case studies into three types: intrinsic – a single case (an individual, group, organization, event, or other entity) that is important in its own right, not necessarily because of its potential predictive theoretical powers; instrumental – a single case where the focus is on going beyond the case to understand a broader phenomenon of interest; and collective – a multiple case version of instrumental where the focus is on learning about a phenomenon. Unlike Yin, Stake is not linking his case studies to the idea of testing preconceived theories but rather to the idea of using the peculiarities of any particular case to illuminate the phenomenon and magnify the understanding of the research topic.
An overarching differentiator in the Yin and Stake typologies is the extent to which case study outcomes are intended to tell the researcher something that is solely about the case itself – that is, the outcomes are “internalized” to the particular case – or the outcomes are intended to tell the researcher something beyond the case, either by facilitating theory development and/or enlightening the researcher’s understanding of a broader phenomenon – that is, the outcomes are “externalized” to situations outside the case.
This internal-external classification, and its relationship to the Yin and Stake typologies, is shown below.
In this internal-external classification, an intrinsic case study as defined by Stake, with its emphasis on what can be learned about the specific case itself, is classified as an internal type of design because the research findings will only be used to inform that specific case. An example of an internal case study is research that a healthcare organization might conduct to investigate its new patient-referral program to inform their need for new social media solutions.
Stake’s instrumental and collective case study types as well as Yin’s case study designs (i.e., types 1-4), with their emphasis on projecting case study results to something outside the case (i.e., a theory or phenomenon), are classified as external case study designs because the researcher’s primary focus is on extending the outcomes beyond the specific cases(s). For example, an external case study might be conducted with one or two state government department(s) to understand the impact of a newly-implemented, more restrictive sick-leave policy on all state employees.
The internal-external classification is one way to think broadly about case study design. Regardless of the design model, however, case study researchers would do well to clearly articulate, as Salmons states, the “methodological foundations” of their designs.
Baxter, P., & Jack, S. (2008). Qualitative case study methodology: Study design and implementation for novice researchers. The Qualitative Report , 13 (4), 544–559.
Roller, M. R., & Lavrakas, P. J. (2015). Applied qualitative research design: A total quality framework approach . New York: Guilford Press.
Stake, R. E. (1995). The art of case study research . Thousand Oaks, CA: Sage Publications.
Yin, R. K. (2014). Case study research: Design and methods (5th ed.). Thousand Oaks, CA: Sage Publications.
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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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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 ].
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 ].
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 ].
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.
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.
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.
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.
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 ].
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 ].
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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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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Division of Primary Care, The University of Nottingham, Nottingham, UK
Sarah Crowe & Anthony Avery
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Kathrin Cresswell, Ann Robertson & Aziz Sheikh
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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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Crowe, S., Cresswell, K., Robertson, A. et al. The case study approach. BMC Med Res Methodol 11 , 100 (2011). https://doi.org/10.1186/1471-2288-11-100
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Despite on-going debate about credibility, and reported limitations in comparison to other approaches, case study is an increasingly popular approach among qualitative researchers. We critically analysed the methodological descriptions of published case studies. Three high-impact qualitative methods journals were searched to locate case studies published in the past 5 years; 34 were selected for analysis. Articles were categorized as health and health services ( n= 12), social sciences and anthropology ( n= 7), or methods ( n= 15) case studies. The articles were reviewed using an adapted version of established criteria to determine whether adequate methodological justification was present, and if study aims, methods, and reported findings were consistent with a qualitative case study approach. Findings were grouped into five themes outlining key methodological issues: case study methodology or method, case of something particular and case selection, contextually bound case study, researcher and case interactions and triangulation, and study design inconsistent with methodology reported. Improved reporting of case studies by qualitative researchers will advance the methodology for the benefit of researchers and practitioners.
Case study research is an increasingly popular approach among qualitative researchers (Thomas, 2011 ). Several prominent authors have contributed to methodological developments, which has increased the popularity of case study approaches across disciplines (Creswell, 2013b ; Denzin & Lincoln, 2011b ; Merriam, 2009 ; Ragin & Becker, 1992 ; Stake, 1995 ; Yin, 2009 ). Current qualitative case study approaches are shaped by paradigm, study design, and selection of methods, and, as a result, case studies in the published literature vary. Differences between published case studies can make it difficult for researchers to define and understand case study as a methodology.
Experienced qualitative researchers have identified case study research as a stand-alone qualitative approach (Denzin & Lincoln, 2011b ). Case study research has a level of flexibility that is not readily offered by other qualitative approaches such as grounded theory or phenomenology. Case studies are designed to suit the case and research question and published case studies demonstrate wide diversity in study design. There are two popular case study approaches in qualitative research. The first, proposed by Stake ( 1995 ) and Merriam ( 2009 ), is situated in a social constructivist paradigm, whereas the second, by Yin ( 2012 ), Flyvbjerg ( 2011 ), and Eisenhardt ( 1989 ), approaches case study from a post-positivist viewpoint. Scholarship from both schools of inquiry has contributed to the popularity of case study and development of theoretical frameworks and principles that characterize the methodology.
The diversity of case studies reported in the published literature, and on-going debates about credibility and the use of case study in qualitative research practice, suggests that differences in perspectives on case study methodology may prevent researchers from developing a mutual understanding of practice and rigour. In addition, discussion about case study limitations has led some authors to query whether case study is indeed a methodology (Luck, Jackson, & Usher, 2006 ; Meyer, 2001 ; Thomas, 2010 ; Tight, 2010 ). Methodological discussion of qualitative case study research is timely, and a review is required to analyse and understand how this methodology is applied in the qualitative research literature. The aims of this study were to review methodological descriptions of published qualitative case studies, to review how the case study methodological approach was applied, and to identify issues that need to be addressed by researchers, editors, and reviewers. An outline of the current definitions of case study and an overview of the issues proposed in the qualitative methodological literature are provided to set the scene for the review.
Case study research is an investigation and analysis of a single or collective case, intended to capture the complexity of the object of study (Stake, 1995 ). Qualitative case study research, as described by Stake ( 1995 ), draws together “naturalistic, holistic, ethnographic, phenomenological, and biographic research methods” in a bricoleur design, or in his words, “a palette of methods” (Stake, 1995 , pp. xi–xii). Case study methodology maintains deep connections to core values and intentions and is “particularistic, descriptive and heuristic” (Merriam, 2009 , p. 46).
As a study design, case study is defined by interest in individual cases rather than the methods of inquiry used. The selection of methods is informed by researcher and case intuition and makes use of naturally occurring sources of knowledge, such as people or observations of interactions that occur in the physical space (Stake, 1998 ). Thomas ( 2011 ) suggested that “analytical eclecticism” is a defining factor (p. 512). Multiple data collection and analysis methods are adopted to further develop and understand the case, shaped by context and emergent data (Stake, 1995 ). This qualitative approach “explores a real-life, contemporary bounded system (a case ) or multiple bounded systems (cases) over time, through detailed, in-depth data collection involving multiple sources of information … and reports a case description and case themes ” (Creswell, 2013b , p. 97). Case study research has been defined by the unit of analysis, the process of study, and the outcome or end product, all essentially the case (Merriam, 2009 ).
The case is an object to be studied for an identified reason that is peculiar or particular. Classification of the case and case selection procedures informs development of the study design and clarifies the research question. Stake ( 1995 ) proposed three types of cases and study design frameworks. These include the intrinsic case, the instrumental case, and the collective instrumental case. The intrinsic case is used to understand the particulars of a single case, rather than what it represents. An instrumental case study provides insight on an issue or is used to refine theory. The case is selected to advance understanding of the object of interest. A collective refers to an instrumental case which is studied as multiple, nested cases, observed in unison, parallel, or sequential order. More than one case can be simultaneously studied; however, each case study is a concentrated, single inquiry, studied holistically in its own entirety (Stake, 1995 , 1998 ).
Researchers who use case study are urged to seek out what is common and what is particular about the case. This involves careful and in-depth consideration of the nature of the case, historical background, physical setting, and other institutional and political contextual factors (Stake, 1998 ). An interpretive or social constructivist approach to qualitative case study research supports a transactional method of inquiry, where the researcher has a personal interaction with the case. The case is developed in a relationship between the researcher and informants, and presented to engage the reader, inviting them to join in this interaction and in case discovery (Stake, 1995 ). A postpositivist approach to case study involves developing a clear case study protocol with careful consideration of validity and potential bias, which might involve an exploratory or pilot phase, and ensures that all elements of the case are measured and adequately described (Yin, 2009 , 2012 ).
The future of qualitative research will be influenced and constructed by the way research is conducted, and by what is reviewed and published in academic journals (Morse, 2011 ). If case study research is to further develop as a principal qualitative methodological approach, and make a valued contribution to the field of qualitative inquiry, issues related to methodological credibility must be considered. Researchers are required to demonstrate rigour through adequate descriptions of methodological foundations. Case studies published without sufficient detail for the reader to understand the study design, and without rationale for key methodological decisions, may lead to research being interpreted as lacking in quality or credibility (Hallberg, 2013 ; Morse, 2011 ).
There is a level of artistic license that is embraced by qualitative researchers and distinguishes practice, which nurtures creativity, innovation, and reflexivity (Denzin & Lincoln, 2011b ; Morse, 2009 ). Qualitative research is “inherently multimethod” (Denzin & Lincoln, 2011a , p. 5); however, with this creative freedom, it is important for researchers to provide adequate description for methodological justification (Meyer, 2001 ). This includes paradigm and theoretical perspectives that have influenced study design. Without adequate description, study design might not be understood by the reader, and can appear to be dishonest or inaccurate. Reviewers and readers might be confused by the inconsistent or inappropriate terms used to describe case study research approach and methods, and be distracted from important study findings (Sandelowski, 2000 ). This issue extends beyond case study research, and others have noted inconsistencies in reporting of methodology and method by qualitative researchers. Sandelowski ( 2000 , 2010 ) argued for accurate identification of qualitative description as a research approach. She recommended that the selected methodology should be harmonious with the study design, and be reflected in methods and analysis techniques. Similarly, Webb and Kevern ( 2000 ) uncovered inconsistencies in qualitative nursing research with focus group methods, recommending that methodological procedures must cite seminal authors and be applied with respect to the selected theoretical framework. Incorrect labelling using case study might stem from the flexibility in case study design and non-directional character relative to other approaches (Rosenberg & Yates, 2007 ). Methodological integrity is required in design of qualitative studies, including case study, to ensure study rigour and to enhance credibility of the field (Morse, 2011 ).
Case study has been unnecessarily devalued by comparisons with statistical methods (Eisenhardt, 1989 ; Flyvbjerg, 2006 , 2011 ; Jensen & Rodgers, 2001 ; Piekkari, Welch, & Paavilainen, 2009 ; Tight, 2010 ; Yin, 1999 ). It is reputed to be the “the weak sibling” in comparison to other, more rigorous, approaches (Yin, 2009 , p. xiii). Case study is not an inherently comparative approach to research. The objective is not statistical research, and the aim is not to produce outcomes that are generalizable to all populations (Thomas, 2011 ). Comparisons between case study and statistical research do little to advance this qualitative approach, and fail to recognize its inherent value, which can be better understood from the interpretive or social constructionist viewpoint of other authors (Merriam, 2009 ; Stake, 1995 ). Building on discussions relating to “fuzzy” (Bassey, 2001 ), or naturalistic generalizations (Stake, 1978 ), or transference of concepts and theories (Ayres, Kavanaugh, & Knafl, 2003 ; Morse et al., 2011 ) would have more relevance.
Case study research has been used as a catch-all design to justify or add weight to fundamental qualitative descriptive studies that do not fit with other traditional frameworks (Merriam, 2009 ). A case study has been a “convenient label for our research—when we ‘can't think of anything ‘better”—in an attempt to give it [qualitative methodology] some added respectability” (Tight, 2010 , p. 337). Qualitative case study research is a pliable approach (Merriam, 2009 ; Meyer, 2001 ; Stake, 1995 ), and has been likened to a “curious methodological limbo” (Gerring, 2004 , p. 341) or “paradigmatic bridge” (Luck et al., 2006 , p. 104), that is on the borderline between postpositivist and constructionist interpretations. This has resulted in inconsistency in application, which indicates that flexibility comes with limitations (Meyer, 2001 ), and the open nature of case study research might be off-putting to novice researchers (Thomas, 2011 ). The development of a well-(in)formed theoretical framework to guide a case study should improve consistency, rigour, and trust in studies published in qualitative research journals (Meyer, 2001 ).
The purpose of this study was to analyse the methodological descriptions of case studies published in qualitative methods journals. To do this we needed to develop a suitable framework, which used existing, established criteria for appraising qualitative case study research rigour (Creswell, 2013b ; Merriam, 2009 ; Stake, 1995 ). A number of qualitative authors have developed concepts and criteria that are used to determine whether a study is rigorous (Denzin & Lincoln, 2011b ; Lincoln, 1995 ; Sandelowski & Barroso, 2002 ). The criteria proposed by Stake ( 1995 ) provide a framework for readers and reviewers to make judgements regarding case study quality, and identify key characteristics essential for good methodological rigour. Although each of the factors listed in Stake's criteria could enhance the quality of a qualitative research report, in Table I we present an adapted criteria used in this study, which integrates more recent work by Merriam ( 2009 ) and Creswell ( 2013b ). Stake's ( 1995 ) original criteria were separated into two categories. The first list of general criteria is “relevant for all qualitative research.” The second list, “high relevance to qualitative case study research,” was the criteria that we decided had higher relevance to case study research. This second list was the main criteria used to assess the methodological descriptions of the case studies reviewed. The complete table has been preserved so that the reader can determine how the original criteria were adapted.
Framework for assessing quality in qualitative case study research.
Checklist for assessing the quality of a case study report |
---|
Relevant for all qualitative research |
1. Is this report easy to read? |
2. Does it fit together, each sentence contributing to the whole? |
3. Does this report have a conceptual structure (i.e., themes or issues)? |
4. Are its issues developed in a series and scholarly way? |
5. Have quotations been used effectively? |
6. Has the writer made sound assertions, neither over- or under-interpreting? |
7. Are headings, figures, artefacts, appendices, indexes effectively used? |
8. Was it edited well, then again with a last minute polish? |
9. Were sufficient raw data presented? |
10. Is the nature of the intended audience apparent? |
11. Does it appear that individuals were put at risk? |
High relevance to qualitative case study research |
12. Is the case adequately defined? |
13. Is there a sense of story to the presentation? |
14. Is the reader provided some vicarious experience? |
15. Has adequate attention been paid to various contexts? |
16. Were data sources well-chosen and in sufficient number? |
17. Do observations and interpretations appear to have been triangulated? |
18. Is the role and point of view of the researcher nicely apparent? |
19. Is empathy shown for all sides? |
20. Are personal intentions examined? |
Added from Merriam ( ) |
21. Is the case study particular? |
22. Is the case study descriptive? |
23. Is the case study heuristic? |
Added from Creswell ( ) |
24. Was study design appropriate to methodology? |
Adapted from Stake ( 1995 , p. 131).
The critical review method described by Grant and Booth ( 2009 ) was used, which is appropriate for the assessment of research quality, and is used for literature analysis to inform research and practice. This type of review goes beyond the mapping and description of scoping or rapid reviews, to include “analysis and conceptual innovation” (Grant & Booth, 2009 , p. 93). A critical review is used to develop existing, or produce new, hypotheses or models. This is different to systematic reviews that answer clinical questions. It is used to evaluate existing research and competing ideas, to provide a “launch pad” for conceptual development and “subsequent testing” (Grant & Booth, 2009 , p. 93).
Qualitative methods journals were located by a search of the 2011 ISI Journal Citation Reports in Social Science, via the database Web of Knowledge (see m.webofknowledge.com). No “qualitative research methods” category existed in the citation reports; therefore, a search of all categories was performed using the term “qualitative.” In Table II , we present the qualitative methods journals located, ranked by impact factor. The highest ranked journals were selected for searching. We acknowledge that the impact factor ranking system might not be the best measure of journal quality (Cheek, Garnham, & Quan, 2006 ); however, this was the most appropriate and accessible method available.
International Journal of Qualitative Studies on Health and Well-being.
Journal title | 2011 impact factor | 5-year impact factor |
---|---|---|
2.188 | 2.432 | |
1.426 | N/A | |
0.839 | 1.850 | |
0.780 | N/A | |
0.612 | N/A |
In March 2013, searches of the journals, Qualitative Health Research , Qualitative Research , and Qualitative Inquiry were completed to retrieve studies with “case study” in the abstract field. The search was limited to the past 5 years (1 January 2008 to 1 March 2013). The objective was to locate published qualitative case studies suitable for assessment using the adapted criterion. Viewpoints, commentaries, and other article types were excluded from review. Title and abstracts of the 45 retrieved articles were read by the first author, who identified 34 empirical case studies for review. All authors reviewed the 34 studies to confirm selection and categorization. In Table III , we present the 34 case studies grouped by journal, and categorized by research topic, including health sciences, social sciences and anthropology, and methods research. There was a discrepancy in categorization of one article on pedagogy and a new teaching method published in Qualitative Inquiry (Jorrín-Abellán, Rubia-Avi, Anguita-Martínez, Gómez-Sánchez, & Martínez-Mones, 2008 ). Consensus was to allocate to the methods category.
Outcomes of search of qualitative methods journals.
Journal title | Date of search | Number of studies located | Number of full text studies extracted | Health sciences | Social sciences and anthropology | Methods |
---|---|---|---|---|---|---|
4 Mar 2013 | 18 | 16 | Barone ( ); Bronken et al. ( ); Colón-Emeric et al. ( ); Fourie and Theron ( ); Gallagher et al. ( ); Gillard et al. ( ); Hooghe et al. ( ); Jackson et al. ( ); Ledderer ( ); Mawn et al. ( ); Roscigno et al. ( ); Rytterström et al. ( ) | Nil | Austin, Park, and Goble ( ); Broyles, Rodriguez, Price, Bayliss, and Sevick ( ); De Haene et al. ( ); Fincham et al. ( ) | |
7 Mar 2013 | 11 | 7 | Nil | Adamson and Holloway ( ); Coltart and Henwood ( ) | Buckley and Waring ( ); Cunsolo Willox et al. ( ); Edwards and Weller ( ); Gratton and O'Donnell ( ); Sumsion ( ) | |
4 Mar 2013 | 16 | 11 | Nil | Buzzanell and D’Enbeau ( ); D'Enbeau et al. ( ); Nagar-Ron and Motzafi-Haller ( ); Snyder-Young ( ); Yeh ( ) | Ajodhia-Andrews and Berman ( ); Alexander et al. ( ); Jorrín-Abellán et al. ( ); Nairn and Panelli ( ); Nespor ( ); Wimpenny and Savin-Baden ( ) | |
Total | 45 | 34 | 12 | 7 | 15 |
In Table III , the number of studies located, and final numbers selected for review have been reported. Qualitative Health Research published the most empirical case studies ( n= 16). In the health category, there were 12 case studies of health conditions, health services, and health policy issues, all published in Qualitative Health Research . Seven case studies were categorized as social sciences and anthropology research, which combined case study with biography and ethnography methodologies. All three journals published case studies on methods research to illustrate a data collection or analysis technique, methodological procedure, or related issue.
The methodological descriptions of 34 case studies were critically reviewed using the adapted criteria. All articles reviewed contained a description of study methods; however, the length, amount of detail, and position of the description in the article varied. Few studies provided an accurate description and rationale for using a qualitative case study approach. In the 34 case studies reviewed, three described a theoretical framework informed by Stake ( 1995 ), two by Yin ( 2009 ), and three provided a mixed framework informed by various authors, which might have included both Yin and Stake. Few studies described their case study design, or included a rationale that explained why they excluded or added further procedures, and whether this was to enhance the study design, or to better suit the research question. In 26 of the studies no reference was provided to principal case study authors. From reviewing the description of methods, few authors provided a description or justification of case study methodology that demonstrated how their study was informed by the methodological literature that exists on this approach.
The methodological descriptions of each study were reviewed using the adapted criteria, and the following issues were identified: case study methodology or method; case of something particular and case selection; contextually bound case study; researcher and case interactions and triangulation; and, study design inconsistent with methodology. An outline of how the issues were developed from the critical review is provided, followed by a discussion of how these relate to the current methodological literature.
A third of the case studies reviewed appeared to use a case report method, not case study methodology as described by principal authors (Creswell, 2013b ; Merriam, 2009 ; Stake, 1995 ; Yin, 2009 ). Case studies were identified as a case report because of missing methodological detail and by review of the study aims and purpose. These reports presented data for small samples of no more than three people, places or phenomenon. Four studies, or “case reports” were single cases selected retrospectively from larger studies (Bronken, Kirkevold, Martinsen, & Kvigne, 2012 ; Coltart & Henwood, 2012 ; Hooghe, Neimeyer, & Rober, 2012 ; Roscigno et al., 2012 ). Case reports were not a case of something, instead were a case demonstration or an example presented in a report. These reports presented outcomes, and reported on how the case could be generalized. Descriptions focussed on the phenomena, rather than the case itself, and did not appear to study the case in its entirety.
Case reports had minimal in-text references to case study methodology, and were informed by other qualitative traditions or secondary sources (Adamson & Holloway, 2012 ; Buzzanell & D'Enbeau, 2009 ; Nagar-Ron & Motzafi-Haller, 2011 ). This does not suggest that case study methodology cannot be multimethod, however, methodology should be consistent in design, be clearly described (Meyer, 2001 ; Stake, 1995 ), and maintain focus on the case (Creswell, 2013b ).
To demonstrate how case reports were identified, three examples are provided. The first, Yeh ( 2013 ) described their study as, “the examination of the emergence of vegetarianism in Victorian England serves as a case study to reveal the relationships between boundaries and entities” (p. 306). The findings were a historical case report, which resulted from an ethnographic study of vegetarianism. Cunsolo Willox, Harper, Edge, ‘My Word’: Storytelling and Digital Media Lab, and Rigolet Inuit Community Government (2013) used “a case study that illustrates the usage of digital storytelling within an Inuit community” (p. 130). This case study reported how digital storytelling can be used with indigenous communities as a participatory method to illuminate the benefits of this method for other studies. This “case study was conducted in the Inuit community” but did not include the Inuit community in case analysis (Cunsolo Willox et al., 2013 , p. 130). Bronken et al. ( 2012 ) provided a single case report to demonstrate issues observed in a larger clinical study of aphasia and stroke, without adequate case description or analysis.
Case selection is a precursor to case analysis, which needs to be presented as a convincing argument (Merriam, 2009 ). Descriptions of the case were often not adequate to ascertain why the case was selected, or whether it was a particular exemplar or outlier (Thomas, 2011 ). In a number of case studies in the health and social science categories, it was not explicit whether the case was of something particular, or peculiar to their discipline or field (Adamson & Holloway, 2012 ; Bronken et al., 2012 ; Colón-Emeric et al., 2010 ; Jackson, Botelho, Welch, Joseph, & Tennstedt, 2012 ; Mawn et al., 2010 ; Snyder-Young, 2011 ). There were exceptions in the methods category ( Table III ), where cases were selected by researchers to report on a new or innovative method. The cases emerged through heuristic study, and were reported to be particular, relative to the existing methods literature (Ajodhia-Andrews & Berman, 2009 ; Buckley & Waring, 2013 ; Cunsolo Willox et al., 2013 ; De Haene, Grietens, & Verschueren, 2010 ; Gratton & O'Donnell, 2011 ; Sumsion, 2013 ; Wimpenny & Savin-Baden, 2012 ).
Case selection processes were sometimes insufficient to understand why the case was selected from the global population of cases, or what study of this case would contribute to knowledge as compared with other possible cases (Adamson & Holloway, 2012 ; Bronken et al., 2012 ; Colón-Emeric et al., 2010 ; Jackson et al., 2012 ; Mawn et al., 2010 ). In two studies, local cases were selected (Barone, 2010 ; Fourie & Theron, 2012 ) because the researcher was familiar with and had access to the case. Possible limitations of a convenience sample were not acknowledged. Purposeful sampling was used to recruit participants within the case of one study, but not of the case itself (Gallagher et al., 2013 ). Random sampling was completed for case selection in two studies (Colón-Emeric et al., 2010 ; Jackson et al., 2012 ), which has limited meaning in interpretive qualitative research.
To demonstrate how researchers provided a good justification for the selection of case study approaches, four examples are provided. The first, cases of residential care homes, were selected because of reported occurrences of mistreatment, which included residents being locked in rooms at night (Rytterström, Unosson, & Arman, 2013 ). Roscigno et al. ( 2012 ) selected cases of parents who were admitted for early hospitalization in neonatal intensive care with a threatened preterm delivery before 26 weeks. Hooghe et al. ( 2012 ) used random sampling to select 20 couples that had experienced the death of a child; however, the case study was of one couple and a particular metaphor described only by them. The final example, Coltart and Henwood ( 2012 ), provided a detailed account of how they selected two cases from a sample of 46 fathers based on personal characteristics and beliefs. They described how the analysis of the two cases would contribute to their larger study on first time fathers and parenting.
The limits or boundaries of the case are a defining factor of case study methodology (Merriam, 2009 ; Ragin & Becker, 1992 ; Stake, 1995 ; Yin, 2009 ). Adequate contextual description is required to understand the setting or context in which the case is revealed. In the health category, case studies were used to illustrate a clinical phenomenon or issue such as compliance and health behaviour (Colón-Emeric et al., 2010 ; D'Enbeau, Buzzanell, & Duckworth, 2010 ; Gallagher et al., 2013 ; Hooghe et al., 2012 ; Jackson et al., 2012 ; Roscigno et al., 2012 ). In these case studies, contextual boundaries, such as physical and institutional descriptions, were not sufficient to understand the case as a holistic system, for example, the general practitioner (GP) clinic in Gallagher et al. ( 2013 ), or the nursing home in Colón-Emeric et al. ( 2010 ). Similarly, in the social science and methods categories, attention was paid to some components of the case context, but not others, missing important information required to understand the case as a holistic system (Alexander, Moreira, & Kumar, 2012 ; Buzzanell & D'Enbeau, 2009 ; Nairn & Panelli, 2009 ; Wimpenny & Savin-Baden, 2012 ).
In two studies, vicarious experience or vignettes (Nairn & Panelli, 2009 ) and images (Jorrín-Abellán et al., 2008 ) were effective to support description of context, and might have been a useful addition for other case studies. Missing contextual boundaries suggests that the case might not be adequately defined. Additional information, such as the physical, institutional, political, and community context, would improve understanding of the case (Stake, 1998 ). In Boxes 1 and 2 , we present brief synopses of two studies that were reviewed, which demonstrated a well bounded case. In Box 1 , Ledderer ( 2011 ) used a qualitative case study design informed by Stake's tradition. In Box 2 , Gillard, Witt, and Watts ( 2011 ) were informed by Yin's tradition. By providing a brief outline of the case studies in Boxes 1 and 2 , we demonstrate how effective case boundaries can be constructed and reported, which may be of particular interest to prospective case study researchers.
Ledderer ( 2011 ) used a qualitative case study research design, informed by modern ethnography. The study is bounded to 10 general practice clinics in Denmark, who had received federal funding to implement preventative care services based on a Motivational Interviewing intervention. The researcher question focussed on “why is it so difficult to create change in medical practice?” (Ledderer, 2011 , p. 27). The study context was adequately described, providing detail on the general practitioner (GP) clinics and relevant political and economic influences. Methodological decisions are described in first person narrative, providing insight on researcher perspectives and interaction with the case. Forty-four interviews were conducted, which focussed on how GPs conducted consultations, and the form, nature and content, rather than asking their opinion or experience (Ledderer, 2011 , p. 30). The duration and intensity of researcher immersion in the case enhanced depth of description and trustworthiness of study findings. Analysis was consistent with Stake's tradition, and the researcher provided examples of inquiry techniques used to challenge assumptions about emerging themes. Several other seminal qualitative works were cited. The themes and typology constructed are rich in narrative data and storytelling by clinic staff, demonstrating individual clinic experiences as well as shared meanings and understandings about changing from a biomedical to psychological approach to preventative health intervention. Conclusions make note of social and cultural meanings and lessons learned, which might not have been uncovered using a different methodology.
Gillard et al. ( 2011 ) study of camps for adolescents living with HIV/AIDs provided a good example of Yin's interpretive case study approach. The context of the case is bounded by the three summer camps of which the researchers had prior professional involvement. A case study protocol was developed that used multiple methods to gather information at three data collection points coinciding with three youth camps (Teen Forum, Discover Camp, and Camp Strong). Gillard and colleagues followed Yin's ( 2009 ) principles, using a consistent data protocol that enhanced cross-case analysis. Data described the young people, the camp physical environment, camp schedule, objectives and outcomes, and the staff of three youth camps. The findings provided a detailed description of the context, with less detail of individual participants, including insight into researcher's interpretations and methodological decisions throughout the data collection and analysis process. Findings provided the reader with a sense of “being there,” and are discovered through constant comparison of the case with the research issues; the case is the unit of analysis. There is evidence of researcher immersion in the case, and Gillard reports spending significant time in the field in a naturalistic and integrated youth mentor role.
This case study is not intended to have a significant impact on broader health policy, although does have implications for health professionals working with adolescents. Study conclusions will inform future camps for young people with chronic disease, and practitioners are able to compare similarities between this case and their own practice (for knowledge translation). No limitations of this article were reported. Limitations related to publication of this case study were that it was 20 pages long and used three tables to provide sufficient description of the camp and program components, and relationships with the research issue.
Researcher and case interactions and transactions are a defining feature of case study methodology (Stake, 1995 ). Narrative stories, vignettes, and thick description are used to provoke vicarious experience and a sense of being there with the researcher in their interaction with the case. Few of the case studies reviewed provided details of the researcher's relationship with the case, researcher–case interactions, and how these influenced the development of the case study (Buzzanell & D'Enbeau, 2009 ; D'Enbeau et al., 2010 ; Gallagher et al., 2013 ; Gillard et al., 2011 ; Ledderer, 2011 ; Nagar-Ron & Motzafi-Haller, 2011 ). The role and position of the researcher needed to be self-examined and understood by readers, to understand how this influenced interactions with participants, and to determine what triangulation is needed (Merriam, 2009 ; Stake, 1995 ).
Gillard et al. ( 2011 ) provided a good example of triangulation, comparing data sources in a table (p. 1513). Triangulation of sources was used to reveal as much depth as possible in the study by Nagar-Ron and Motzafi-Haller ( 2011 ), while also enhancing confirmation validity. There were several case studies that would have benefited from improved range and use of data sources, and descriptions of researcher–case interactions (Ajodhia-Andrews & Berman, 2009 ; Bronken et al., 2012 ; Fincham, Scourfield, & Langer, 2008 ; Fourie & Theron, 2012 ; Hooghe et al., 2012 ; Snyder-Young, 2011 ; Yeh, 2013 ).
Good, rigorous case studies require a strong methodological justification (Meyer, 2001 ) and a logical and coherent argument that defines paradigm, methodological position, and selection of study methods (Denzin & Lincoln, 2011b ). Methodological justification was insufficient in several of the studies reviewed (Barone, 2010 ; Bronken et al., 2012 ; Hooghe et al., 2012 ; Mawn et al., 2010 ; Roscigno et al., 2012 ; Yeh, 2013 ). This was judged by the absence, or inadequate or inconsistent reference to case study methodology in-text.
In six studies, the methodological justification provided did not relate to case study. There were common issues identified. Secondary sources were used as primary methodological references indicating that study design might not have been theoretically sound (Colón-Emeric et al., 2010 ; Coltart & Henwood, 2012 ; Roscigno et al., 2012 ; Snyder-Young, 2011 ). Authors and sources cited in methodological descriptions were inconsistent with the actual study design and practices used (Fourie & Theron, 2012 ; Hooghe et al., 2012 ; Jorrín-Abellán et al., 2008 ; Mawn et al., 2010 ; Rytterström et al., 2013 ; Wimpenny & Savin-Baden, 2012 ). This occurred when researchers cited Stake or Yin, or both (Mawn et al., 2010 ; Rytterström et al., 2013 ), although did not follow their paradigmatic or methodological approach. In 26 studies there were no citations for a case study methodological approach.
The findings of this study have highlighted a number of issues for researchers. A considerable number of case studies reviewed were missing key elements that define qualitative case study methodology and the tradition cited. A significant number of studies did not provide a clear methodological description or justification relevant to case study. Case studies in health and social sciences did not provide sufficient information for the reader to understand case selection, and why this case was chosen above others. The context of the cases were not described in adequate detail to understand all relevant elements of the case context, which indicated that cases may have not been contextually bounded. There were inconsistencies between reported methodology, study design, and paradigmatic approach in case studies reviewed, which made it difficult to understand the study methodology and theoretical foundations. These issues have implications for methodological integrity and honesty when reporting study design, which are values of the qualitative research tradition and are ethical requirements (Wager & Kleinert, 2010a ). Poorly described methodological descriptions may lead the reader to misinterpret or discredit study findings, which limits the impact of the study, and, as a collective, hinders advancements in the broader qualitative research field.
The issues highlighted in our review build on current debates in the case study literature, and queries about the value of this methodology. Case study research can be situated within different paradigms or designed with an array of methods. In order to maintain the creativity and flexibility that is valued in this methodology, clearer descriptions of paradigm and theoretical position and methods should be provided so that study findings are not undervalued or discredited. Case study research is an interdisciplinary practice, which means that clear methodological descriptions might be more important for this approach than other methodologies that are predominantly driven by fewer disciplines (Creswell, 2013b ).
Authors frequently omit elements of methodologies and include others to strengthen study design, and we do not propose a rigid or purist ideology in this paper. On the contrary, we encourage new ideas about using case study, together with adequate reporting, which will advance the value and practice of case study. The implications of unclear methodological descriptions in the studies reviewed were that study design appeared to be inconsistent with reported methodology, and key elements required for making judgements of rigour were missing. It was not clear whether the deviations from methodological tradition were made by researchers to strengthen the study design, or because of misinterpretations. Morse ( 2011 ) recommended that innovations and deviations from practice are best made by experienced researchers, and that a novice might be unaware of the issues involved with making these changes. To perpetuate the tradition of case study research, applications in the published literature should have consistencies with traditional methodological constructions, and deviations should be described with a rationale that is inherent in study conduct and findings. Providing methodological descriptions that demonstrate a strong theoretical foundation and coherent study design will add credibility to the study, while ensuring the intrinsic meaning of case study is maintained.
The value of this review is that it contributes to discussion of whether case study is a methodology or method. We propose possible reasons why researchers might make this misinterpretation. Researchers may interchange the terms methods and methodology, and conduct research without adequate attention to epistemology and historical tradition (Carter & Little, 2007 ; Sandelowski, 2010 ). If the rich meaning that naming a qualitative methodology brings to the study is not recognized, a case study might appear to be inconsistent with the traditional approaches described by principal authors (Creswell, 2013a ; Merriam, 2009 ; Stake, 1995 ; Yin, 2009 ). If case studies are not methodologically and theoretically situated, then they might appear to be a case report.
Case reports are promoted by university and medical journals as a method of reporting on medical or scientific cases; guidelines for case reports are publicly available on websites ( http://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/guidelines/case_report.html ). The various case report guidelines provide a general criteria for case reports, which describes that this form of report does not meet the criteria of research, is used for retrospective analysis of up to three clinical cases, and is primarily illustrative and for educational purposes. Case reports can be published in academic journals, but do not require approval from a human research ethics committee. Traditionally, case reports describe a single case, to explain how and what occurred in a selected setting, for example, to illustrate a new phenomenon that has emerged from a larger study. A case report is not necessarily particular or the study of a case in its entirety, and the larger study would usually be guided by a different research methodology.
This description of a case report is similar to what was provided in some studies reviewed. This form of report lacks methodological grounding and qualities of research rigour. The case report has publication value in demonstrating an example and for dissemination of knowledge (Flanagan, 1999 ). However, case reports have different meaning and purpose to case study, which needs to be distinguished. Findings of our review suggest that the medical understanding of a case report has been confused with qualitative case study approaches.
In this review, a number of case studies did not have methodological descriptions that included key characteristics of case study listed in the adapted criteria, and several issues have been discussed. There have been calls for improvements in publication quality of qualitative research (Morse, 2011 ), and for improvements in peer review of submitted manuscripts (Carter & Little, 2007 ; Jasper, Vaismoradi, Bondas, & Turunen, 2013 ). The challenging nature of editor and reviewers responsibilities are acknowledged in the literature (Hames, 2013 ; Wager & Kleinert, 2010b ); however, review of case study methodology should be prioritized because of disputes on methodological value.
Authors using case study approaches are recommended to describe their theoretical framework and methods clearly, and to seek and follow specialist methodological advice when needed (Wager & Kleinert, 2010a ). Adequate page space for case study description would contribute to better publications (Gillard et al., 2011 ). Capitalizing on the ability to publish complementary resources should be considered.
There is a level of subjectivity involved in this type of review and this should be considered when interpreting study findings. Qualitative methods journals were selected because the aims and scope of these journals are to publish studies that contribute to methodological discussion and development of qualitative research. Generalist health and social science journals were excluded that might have contained good quality case studies. Journals in business or education were also excluded, although a review of case studies in international business journals has been published elsewhere (Piekkari et al., 2009 ).
The criteria used to assess the quality of the case studies were a set of qualitative indicators. A numerical or ranking system might have resulted in different results. Stake's ( 1995 ) criteria have been referenced elsewhere, and was deemed the best available (Creswell, 2013b ; Crowe et al., 2011 ). Not all qualitative studies are reported in a consistent way and some authors choose to report findings in a narrative form in comparison to a typical biomedical report style (Sandelowski & Barroso, 2002 ), if misinterpretations were made this may have affected the review.
Case study research is an increasingly popular approach among qualitative researchers, which provides methodological flexibility through the incorporation of different paradigmatic positions, study designs, and methods. However, whereas flexibility can be an advantage, a myriad of different interpretations has resulted in critics questioning the use of case study as a methodology. Using an adaptation of established criteria, we aimed to identify and assess the methodological descriptions of case studies in high impact, qualitative methods journals. Few articles were identified that applied qualitative case study approaches as described by experts in case study design. There were inconsistencies in methodology and study design, which indicated that researchers were confused whether case study was a methodology or a method. Commonly, there appeared to be confusion between case studies and case reports. Without clear understanding and application of the principles and key elements of case study methodology, there is a risk that the flexibility of the approach will result in haphazard reporting, and will limit its global application as a valuable, theoretically supported methodology that can be rigorously applied across disciplines and fields.
The authors have not received any funding or benefits from industry or elsewhere to conduct this study.
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Blog Beginner Guides 6 Types of Case Studies to Inspire Your Research and Analysis
Written by: Ronita Mohan Sep 20, 2021
Case studies have become powerful business tools. But what is a case study? What are the benefits of creating one? Are there limitations to the format?
If you’ve asked yourself these questions, our helpful guide will clear things up. Learn how to use a case study for business. Find out how cases analysis works in psychology and research.
We’ve also got examples of case studies to inspire you.
Haven’t made a case study before? You can easily create a case study with Venngage’s customizable case study templates .
Click to jump ahead:
6 types of case studies, what is a business case study, what is a case study in research, what is a case study in psychology, what is the case study method, benefits of case studies, limitations of case studies, faqs about case studies.
A case study is a research process aimed at learning about a subject, an event or an organization. Case studies are use in business, the social sciences and healthcare.
A case study may focus on one observation or many. It can also examine a series of events or a single case. An effective case study tells a story and provides a conclusion.
Healthcare industries write reports on patients and diagnoses. Marketing case study examples , like the one below, highlight the benefits of a business product.
Now that you know what a case study is, let’s look at the six different types of case studies next.
There are six common types of case reports. Depending on your industry, you might use one of these types.
Explanatory case studies, exploratory case reports, intrinsic case studies, instrumental case studies, collective case reports.
We go into more detail about each type of study in the guide below.
Related: 15+ Professional Case Study Examples [Design Tips + Templates]
When you have an existing hypothesis, you can design a descriptive study. This type of report starts with a description. The aim is to find connections between the subject being studied and a theory.
Once these connections are found, the study can conclude. The results of this type of study will usually suggest how to develop a theory further.
A study like the one below has concrete results. A descriptive report would use the quantitative data as a suggestion for researching the subject deeply.
When an incident occurs in a field, an explanation is required. An explanatory report investigates the cause of the event. It will include explanations for that cause.
The study will also share details about the impact of the event. In most cases, this report will use evidence to predict future occurrences. The results of explanatory reports are definitive.
Note that there is no room for interpretation here. The results are absolute.
The study below is a good example. It explains how one brand used the services of another. It concludes by showing definitive proof that the collaboration was successful.
Another example of this study would be in the automotive industry. If a vehicle fails a test, an explanatory study will examine why. The results could show that the failure was because of a particular part.
Related: How to Write a Case Study [+ Design Tips]
An explanatory report is a self-contained document. An exploratory one is only the beginning of an investigation.
Exploratory cases act as the starting point of studies. This is usually conducted as a precursor to large-scale investigations. The research is used to suggest why further investigations are needed.
An exploratory study can also be used to suggest methods for further examination.
For example, the below analysis could have found inconclusive results. In that situation, it would be the basis for an in-depth study.
Intrinsic studies are more common in the field of psychology. These reports can also be conducted in healthcare or social work.
These types of studies focus on a unique subject, such as a patient. They can sometimes study groups close to the researcher.
The aim of such studies is to understand the subject better. This requires learning their history. The researcher will also examine how they interact with their environment.
For instance, if the case study below was about a unique brand, it could be an intrinsic study.
Once the study is complete, the researcher will have developed a better understanding of a phenomenon. This phenomenon will likely not have been studied or theorized about before.
Examples of intrinsic case analysis can be found across psychology. For example, Jean Piaget’s theories on cognitive development. He established the theory from intrinsic studies into his own children.
Related: What Disney Villains Can Tell Us About Color Psychology [Infographic]
This is another type of study seen in medical and psychology fields. Instrumental reports are created to examine more than just the primary subject.
When research is conducted for an instrumental study, it is to provide the basis for a larger phenomenon. The subject matter is usually the best example of the phenomenon. This is why it is being studied.
Take the example of the fictional brand below.
Assume it’s examining lead generation strategies. It may want to show that visual marketing is the definitive lead generation tool. The brand can conduct an instrumental case study to examine this phenomenon.
Collective studies are based on instrumental case reports. These types of studies examine multiple reports.
There are a number of reasons why collective reports are created:
A researcher could use multiple reports, like the one below, to build a collective case report.
Related: 10+ Case Study Infographic Templates That Convert
A business or marketing case study aims at showcasing a successful partnership. This can be between a brand and a client. Or the case study can examine a brand’s project.
There is a perception that case studies are used to advertise a brand. But effective reports, like the one below, can show clients how a brand can support them.
Hubspot created a case study on a customer that successfully scaled its business. The report outlines the various Hubspot tools used to achieve these results.
Hubspot also added a video with testimonials from the client company’s employees.
So, what is the purpose of a case study for businesses? There is a lot of competition in the corporate world. Companies are run by people. They can be on the fence about which brand to work with.
Business reports stand out aesthetically, as well. They use brand colors and brand fonts . Usually, a combination of the client’s and the brand’s.
With the Venngage My Brand Kit feature, businesses can automatically apply their brand to designs.
A business case study, like the one below, acts as social proof. This helps customers decide between your brand and your competitors.
Don’t know how to design a report? You can learn how to write a case study with Venngage’s guide. We also share design tips and examples that will help you convert.
Related: 55+ Annual Report Design Templates, Inspirational Examples & Tips [Updated]
Research is a necessary part of every case study. But specific research fields are required to create studies. These fields include user research, healthcare, education, or social work.
For example, this UX Design report examined the public perception of a client. The brand researched and implemented new visuals to improve it. The study breaks down this research through lessons learned.
Clinical reports are a necessity in the medical field. These documents are used to share knowledge with other professionals. They also help examine new or unusual diseases or symptoms.
The pandemic has led to a significant increase in research. For example, Spectrum Health studied the value of health systems in the pandemic. They created the study by examining community outreach.
The pandemic has significantly impacted the field of education. This has led to numerous examinations on remote studying. There have also been studies on how students react to decreased peer communication.
Social work case reports often have a community focus. They can also examine public health responses. In certain regions, social workers study disaster responses.
You now know what case studies in various fields are. In the next step of our guide, we explain the case study method.
In the field of psychology, case studies focus on a particular subject. Psychology case histories also examine human behaviors.
Case reports search for commonalities between humans. They are also used to prescribe further research. Or these studies can elaborate on a solution for a behavioral ailment.
The American Psychology Association has a number of case studies on real-life clients. Note how the reports are more text-heavy than a business case study.
Famous psychologists such as Sigmund Freud and Anna O popularised the use of case studies in the field. They did so by regularly interviewing subjects. Their detailed observations build the field of psychology.
It is important to note that psychological studies must be conducted by professionals. Psychologists, psychiatrists and therapists should be the researchers in these cases.
Related: What Netflix’s Top 50 Shows Can Teach Us About Font Psychology [Infographic]
The case study method, or case method, is a learning technique where you’re presented with a real-world business challenge and asked how you’d solve it.
After working through it independently and with peers, you learn how the actual scenario unfolded. This approach helps develop problem-solving skills and practical knowledge.
This method often uses various data sources like interviews, observations, and documents to provide comprehensive insights. The below example would have been created after numerous interviews.
Case studies are largely qualitative. They analyze and describe phenomena. While some data is included, a case analysis is not quantitative.
There are a few steps in the case method. You have to start by identifying the subject of your study. Then determine what kind of research is required.
In natural sciences, case studies can take years to complete. Business reports, like this one, don’t take that long. A few weeks of interviews should be enough.
The case method will vary depending on the industry. Reports will also look different once produced.
As you will have seen, business reports are more colorful. The design is also more accessible . Healthcare and psychology reports are more text-heavy.
Designing case reports takes time and energy. So, is it worth taking the time to write them? Here are the benefits of creating case studies.
For example, the business study below creates a story around a brand partnership. It makes for engaging reading. The study also shows evidence backing up the information.
We’ve shared the benefits of why studies are needed. We will also look at the limitations of creating them.
Related: How to Present a Case Study like a Pro (With Examples)
There are a few disadvantages to conducting a case analysis. The limitations will vary according to the industry.
These are some of the common weaknesses of creating case reports. If you’re on the fence, look at the competition in your industry.
Other brands or professionals are building reports, like this example. In that case, you may want to do the same.
A case study has a very particular research methodology. They are an in-depth study of a person or a group of individuals. They can also study a community or an organization. Case reports examine real-world phenomena within a set context.
The length of studies depends on the industry. It also depends on the story you’re telling. Most case studies should be at least 500-1500 words long. But you can increase the length if you have more details to share.
The one thing you shouldn’t ask is ‘yes’ or ‘no’ questions. Case studies are qualitative. These questions won’t give you the information you need.
Ask your client about the problems they faced. Ask them about solutions they found. Or what they think is the ideal solution. Leave room to ask them follow-up questions. This will help build out the study.
When you’re ready to present a case study, begin by providing a summary of the problem or challenge you were addressing. Follow this with an outline of the solution you implemented, and support this with the results you achieved, backed by relevant data. Incorporate visual aids like slides, graphs, and images to make your case study presentation more engaging and impactful.
Now you know what a case study means, you can begin creating one. These reports are a great tool for analyzing brands. They are also useful in a variety of other fields.
Use a visual communication platform like Venngage to design case studies. With Venngage’s templates, you can design easily. Create branded, engaging reports, all without design experience.
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Hood, M. (2009). Case Study. In: Heigham, J., Croker, R.A. (eds) Qualitative Research in Applied Linguistics. Palgrave Macmillan, London. https://doi.org/10.1057/9780230239517_4
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The challenge of transforming organized DNA structures into their metallized counterparts persists in the scientific field. In this context, utilizing DNA molecules modified with 7-deazapurine, provides a transformative solution. In this study, we present the solution structure of a DNA duplex that can be transformed into its metallized equivalent while retaining the natural base pairing arrangement through the creation of silver-modified Watson-Crick base pairs. Unlike previously documented X-ray structures, our research demonstrates the feasibility of preserving the intrinsic DNA self-assembly while incorporating Ag I into the double helix, illustrating that the binding of silver does not disrupt the canonical base-pairing organization. Moreover, in our case, the uninterrupted Ag I chain deviates from forming conventional straight linear chains; instead, it adheres to a helical arrangement dictated by the underlying DNA structure. This research challenges conventional assumptions and opens the door to precisely design structures based on the organization of highly stable Ag-DNA assemblies.
DNA, considered the essential molecule of life, has evolved into a versatile tool for cutting-edge science through the concept of DNA nanotechnology pioneered by Seeman 1 . In this context, DNA functions as the molecular equivalent of LEGO blocks, with single-stranded DNA (ss-DNA) serving as basic building units. Researchers can ingeniously program these units to self-assemble into intricate, customized structures on the nanoscale 2 , 3 , such as polyhedra 4 , lattices 5 , cages, nanomachines 6 , or origami 7 while adhering to Watson–Crick (W-C) base pairing rules. This versatile methodology continues to captivate scientists across various disciplines, presenting them with the ambitious challenge of enhancing DNA assemblies with properties that go beyond the inherent characteristics of nucleic acids, while preserving their designed shapes. Towards this purpose, the metallization of DNA molecules has been widely explored due to the unique intrinsic properties metals can provide 8 , 9 . However, metallizing DNA for control at the nanoscale is a significant goal. The challenge lies in the non-specific binding of metal ions, leading to unpredictable complex metallic DNA assemblies. To address this, metal-mediated or -modified base pairs 10 offer a solution, enabling precise control over metal positioning and stoichiometry 11 , 12 . Although researchers have successfully created metal-DNA systems with individual metal ions in double helix structures, fully metallized DNA structures remain limited 13 , 14 , 15 , 16 , 17 , 18 , and predicting their structure has been a challenge.
In this context, we have developed a method to introduce Ag I ions into oligonucleotides at each base pair. Our findings strongly indicate that this approach maintains the integrity of the canonical base pairing arrangement through W-C metal-modified base pairs 15 , 16 . This is achieved using 7-deazaadenine (X) and 7-deazaguanine (Y) analogs in place of A and G bases, forming hydrogen-bonded X-T and Y-C base pairs 19 , 20 . Upon introducing Ag I ions, these transform into silver-modified X-Ag I -T and Y-Ag I -C base pairs that can maintain the original W-C structure. This methodology allows for the creation of 7d DNA molecules and their conversion into silver- 7d DNA equivalent, where Ag I ions replace hydrogen bonds. Unlike previous research, which lacked the preservation of the W-C arrangement, our method provides improved predictability and design control for metal-DNA duplex structures.
This work elucidated the solution-state structure of a silver- 7d DNA double helix containing entire silver-modified Watson–Crick base pairs. Our results demonstrated that 7d DNA molecules can create predictable silver- 7d DNA-based assemblies by following canonical base pairing rules. We have employed a variety of different techniques, including circular dichroism (CD), mass spectrometry (ESI-HRMS), nuclear magnetic resonance (NMR) and UV-Vis spectroscopy, and small-angle x-ray scattering (SAXS) to reveal the interaction of Ag I within the interior positions of a 7d DNA molecule. Notably, the structural features of the resulting silver- 7d DNA system were determined using high-resolution NMR spectroscopy and density functional (DFT) calculations.
In our investigation, we employed the self-complementary oligonucleotide sequence 5′-d(YYX CTC YXY TCC)−3′ (ODN1, forms duplex I ), akin to the one utilized in previous research that reported the consecutive formation of silver-metallized base pairs within the DNA double helix 14 . However, in this particular study, we introduced a modification by replacing the canonical A and G bases with 7-deazaadenine (X) and 7-deazaguanine (Y) bases, respectively. Additionally, we substituted the C base in the ninth position with the Y base to create a self-complementary C-Y base pair, in contrast to the C-C mismatch pair in the previous research. To facilitate a comparison with results obtained using ODN1, we employed the equivalent canonical sequence 5′-d(GGA CTC GAG TCC)−3′ as a reference (ODN2, forms duplex II ).
We conducted initial CD titration experiments to investigate conformational changes in duplexes I and II upon interaction with Ag I ions. Both free duplexes displayed distinct CD features, with a maximum 280 nm and a minimum at 245 nm (Fig. 1 ). For duplex I , the addition of Ag I resulted in a gradual reduction in ellipticity and flattening of the 280 nm band, with changes stabilizing upon adding 1 equivalent of Ag I per base pair (Ag/bp), thus indicating a saturation point (Fig. 1a ). In contrast, duplex II showed a decrease in ellipticity and a complete inversion of the entire CD spectrum, manifesting a pronounced descending band at 280 nm, also stabilizing soon after adding 1Ag/bp (Fig. 1b ). The results indicate that both duplexes interact with Ag I ions but leading to different conformational changes. A comparative analysis of the CD spectra for duplex I and duplex I-Ag at 1Ag/bp suggests that these structures may share structural similarities. This conclusion arises from the observation that the CD profile of duplex I-Ag exhibits reduced ellipticity while maintaining a very similar profile to that of duplex I , with both spectra exhibiting a decline around 245 nm and an ascent around 280 nm, indicating closely superimposable profiles (Fig. 1c ). These similarities highlight the close conformational relationship between duplex I and I-Ag . This assertion gains further support when examining the differences between canonical duplex II and II-Ag at the same point. In this case, the CD curves exhibited complete inversion with respect to each other, resembling mirror images (Fig. 1d ), indicating that the II-Ag adopted a completely new organization. According to previous studies on canonical sequences, this new organization arises through the formation of non-canonical metallated base pairs, where Ag-binding to purine N7-positions plays a key role 13 , 21 , 22 . However, duplex I-Ag cannot form metallated base pairs involving the purines N7-atom, implying that its metalation process must involve the formation of alternative silver-metallized base pairs.
a , b CD curves registered for duplex I and II , respectively, upon adding a controlled amount of Ag I . c , d Ellipticity variation at the bands centered at 250 and 280 nm for duplex I and II , respectively. Conditions: 2 µM duplex, 5 mM MOPS pH 8.5, 100 mM NaClO 4 , Ag I equivalent (equiv.) per base pair (bp) indicated in the inset.
UV-variable temperature measurements were conducted to investigate the denaturation behavior of duplexes I and II in the presence and absence of Ag I ions. In the absence of Ag I ions, both duplex I and II exhibited sigmoidal melting curves with a melting temperature of 42 and 51 °C, respectively (Supplementary Fig. 1 ). The variation between them is attributable to the weaker hydrogen bonds formed by 7-deazapurine nucleobases in duplex I . The addition of Ag I ions caused a gradual flattening of the melting curves during the titration experiment until they disappeared in the presence of 1Ag/bp. The primary conclusion derived from these findings is the formation of metallated species, where metal ions replace canonical hydrogen bonds, increasing the duplexes’ thermal stability. This enhanced stability surpasses the experimental measurement range in the presence of 1Ag/bp. It is important to exercise caution if attempting to draw conclusions from the melting curves recorded before reaching the saturation point at 1Ag/bp. Before saturation and throughout the titration experiment, fully metallized duplexes coexist with mixed-partially or non-metallized duplexes (see NMR data discussion below), complicating the interpretation of the data. Therefore, we did not attempt to calculate the melting temperature variations, and our subsequent studies will be conducted at the saturation point to ensure more precise and reliable results.
To gain deeper insights into the denaturing process, we conducted CD-melting experiments for duplex I and II in the absence and presence of 1.1 equivalent of Ag I per base pair, slightly exceeding the saturation point. In the absence of metal ions, the CD curves displayed a reversible behavior during the melting and alignment process, aligning with a denaturing reversible process (Supplementary Fig. 2 ). The ellipticity intensity variances of the CD curves at 20 °C before and after heating is attributed to condensation events occurring on the cuvette’s surface, slightly altering the concentration without affecting CD curves shape. A plot of the CD variation with temperature showed the expected enhanced thermal stability for duplex II compared to duplex I , mirroring the results of the UV-melting experiment (Supplementary Fig. 2d , 2d ’). However, in the presence of 1 equiv. of Ag I ions, different outcomes were observed for each duplex. Duplex I-Ag experienced reversible changes during the heating-cooling process, whereas duplex II-Ag underwent a non-reversible conformational change. This difference is particularly evident when comparing the CD curves at 90 and 20 °C (after cooling), as I-Ag displayed markedly different CD profiles at the two temperatures, whereas II-Ag displayed similar curves (Supplementary Fig. 3d , 3d ’). The CD and UV experiments clearly demonstrated that the binding of Ag I to duplex I and II leads to more stable species. However, the resulting conformational changes were markedly different for each duplex. Since it is well-known that the purine N7-position plays a crucial role in stabilizing silver-metallized canonical duplexes, the absence of 7-deazapurines in duplex II could promote the formation of silver-modified Watson–Crick base pairs.
The electrospray ionization mass spectrometry (ESI-MS) experiment unequivocally provided evidence for the formation of I - Ag complex (Supplementary Fig. 4 ). The deconvoluted mass spectrum for the reaction between duplex I and Ag I ions showed the peaks for duplex I (7281.0 g/mol) with 7-12 Ag I ions (106.9 a.u) bound, demonstrating the formation of I-Ag complexes, including the saturated system with twelve metal ions (Supplementary Table 1 ).
Small-angle X-ray scattering (SAXS) and anomalous small-angle X-ray scattering (ASAXS) provided structural information about duplexes I and II in the absence and presence of Ag I ions. The scattering data for duplex I (at 0.7 mM) is consistent with the formation of a double helix structure, exhibiting an excellent match with the simulated scattering, up to q value of 0.2 Å −1 (Supplementary Fig. 5 ). Above this q value, the experimental curve starts to incorporate solvent scattering, primarily due to the relatively weak scattering of the low-concentration and light-atom species. Nonetheless, the match is convincing within the entire Guinier region ( q ~0.01 to 0.2 Å −1 ), confirming the expected size and shape of the double helix (vide infra). Adding 1.1 equiv. Ag I per base pair to duplex I leads to only small changes in the scattering data, suggesting the incorporation of Ag I does not lead to significant conformal changes. We performed a PDDF (pair distance distribution function) analysis of the scattering data, which revealed the differences and similarities of the scattering, with and without Ag I ions (Fig. 2 and Supplementary Figs. 6 , 7 ). The PDDF is a probability distribution of scattering vectors through the dissolved species, obtained by a Fourier transform of the reciprocal space scattering data. The maximum diameter (r) where probability goes to 0 describes the maximum diameter of the scattering species; 37.4 Å for duplex I and 36.1 Å for I-Ag , precisely equivalent to the length of the duplex I . A slightly smaller R g (radius of gyration, a shape independent, root mean square average of the distance of the electrons from the center of the particle) is reported for I-Ag than for duplex I (Supplementary Figs. 6 , 7 ). This is consistent with the incorporation of the Ag I ions in the center of the helix, more thoroughly evaluated with ASAXS, discussed below. The addition of Ag I also increases the P(r), also due to the presence of heavy atoms in the center, and a low shoulder to the right appears (Fig. 2 ). The low shoulder indicates a bimodal electron density, with lower scattering intensity from the shell (the DNA surrounding the Ag-chain).
a scattering plot and b pair distance distribution function (PDDF) analysis.
To determine the precise location of Ag I within both the I-Ag and II-Ag complexes, we conducted ASAXS measurements at a synchrotron source. This involved collecting SAXS data using X-rays at 20 different energy levels, each situated just 1 keV below the silver K-edge at 25.514 keV (Supplementary Figs. 8 – 24 , Supplementary Tables 2, 3 for I-Ag , and Table 4 for II-Ag ). For this investigation, we performed detailed modeling of various scattering components based on the solid cylinder model for these complexes (Fig. 3a ). A comparative analysis of the data revealed that both duplexes contained Ag I within the cylindrical region, meaning the double helices encapsulate them. However, I-Ag saturates at approximately 1 equivalent and II-Ag does not reach saturation within our experimental range of 3 equivalents (Fig. 3b ). The length of I-Ag structure remained relatively consistent at around 40 Å. In contrast, II-Ag structure substantially increased, indicative of polymerization events (Fig. 3c and Supplementary Table 4 ). Overall, the modeling data indicated that Ag I interacts with the interior regions of the double helices in both I-Ag and II-Ag complexes but yielding different structural outcomes, as also revealed by the herein described CD experiments.
a Solid cylinder model of the Ag-DNA complexes. The Ag I ions can bind the base pairs or be free within the cylindrical regions. Metrical information derived from the Ag-DNA complexes modeling, namely: b the number of Ag I per base pairs of the complex (Ag/bp); c the lengths (H). The data were represented using red symbols with error bars for I-Ag complexes and blue symbols with error bars for II-Ag complexes, along with auxiliary lines to highlight the trend of the points.
NMR spectroscopy measurements were employed to further study the interaction of Ag I ions with duplex I and II . For this, a solution of duplex I was titrated with Ag I in the range between 0 and 2.5Ag/bp. 1 H NMR spectra were recorded at various points during the titration to monitor the interaction (Fig. 4a ). Based on signals corresponding to hydrogen-bonded imino (δ 12–15 ppm) and amino (δ 8–9 ppm) protons, the spectra indicate a double-stranded structure for the oligonucleotide at the start of titration. After adding Ag I ions, the signals characteristic for the starting duplex structure began to decrease. Then, several new signals appeared in the spectra, indicating an interaction between duplex I and Ag I ions. Finally, at about 1.5 equivalents, the signals converged into a single set, which stayed unchanged until the endpoint of the titration (Fig. 4 a, b ). The presence of four signals originating from amino protons indicates the formation of hydrogen bonds within the final structure. The number of non-exchangeable signals suits a symmetric antiparallel double-stranded structure similar to the one adopted natively by duplex I . Notably, the imino proton signals are absent in line with the expected position of the coordinated Ag I ions in place of T-H3 and Y-H1 protons in the modified base pairs. The double-stranded nature of the final structure was further confirmed by DOSY NMR measurements, which gave similar translational diffusion coefficients (D T ) of 1.15 and 1.16 · 10 −10 m 2 s −1 for the Ag I free and bound structures, respectively, under comparable conditions. This is also similar to the D T measured for the canonical duplex II analog at 1.21 · 10 −10 m 2 s −1 , indicating a comparable hydrodynamic radius for all three structures.
a Imino, aromatic, and methyl regions of 1 H NMR spectra of the titration, Ag I concentration presented in equivalents per base pair. b Normalized signal intensities of T10 H7 proton (methyl group) in I and I-Ag structures in 1 H NMR spectra of the titration. c Aromatic-anomeric region of NOESY spectrum of I-Ag at 25 °C showing the characteristic sequence walk. d H1-H2’/H2” DQF-COSY spectra of I and I-Ag showing patterns characteristic of S sugar puckers.
The appearance of additional signals in 1 H NMR spectra during the titration with Ag I indicates that the incorporation of silver proceeds through several partially metallated intermediates with silver ions bound at various positions within the duplex. The presence of these intermediates is consistent with minor structural rearrangements associated with the incorporation of silver ions that permit the coexistence of silver-mediated and canonical base pairs. On the other hand, it has been observed previously that single-step transitions are typical where larger structure rearrangements, like base bulging or strand slipping, are required 13 , 14 .
The entire process described for duplex I is in marked contrast to titration of the standard analog duplex II , where the number of signals in 1 H NMR spectra increased throughout the course of titration and did not converge to a single well-defined structure by ten equivalents Ag I ions per base pair (Supplementary Fig. 28 ). These results are consistent with previous observations that Ag I ions tend to promote the formation of non-canonical base pairs in DNA, such as C-Ag I -C, T-Ag I -T, or G-Ag I -G homodimers, while the standard metallized Watson–Crick A-T and G-C are disfavored, leading to loss of base pairing pattern, emergence of an ensemble of structures with degenerate folding energies, and ultimately the aggregation of the refolded oligonucleotides 13 , 14 , 21 . This is reflected by the progressive line broadening and signal loss in 1 H NMR spectra with increasing concentrations of silver ions in the solution.
A NOESY walk was completed in the aromatic-anomeric and the aromatic-H2’/H2” region for the entire length of the I-Ag complex (Fig. 4b ), which is consistent with a right-handed double-helical structure with all χ torsion angles in anti -orientation. Cross peaks involving protons of the Y7 residue were weaker than expected, indicating a possible distortion, or increased structural flexibility in the I-Ag complex at the C6-Y7 step.
H1’-H2’ and H1’-H2” cross-peak patterns in DQF-COSY spectra indicate South sugar pucker for most residues, except for C4, T10, C11, and C12, where higher 3 J H1’H2” values indicate a significant fraction of North sugar pucker for the respective ribose moieties. The same observation is true for duplex I and I-Ag and is a known feature of pyrimidine residues in general (Fig. 4b, c ).
31 P NMR chemical shifts for duplex I are similar to the canonical analog II in the absence of Ag I ions. After the formation of the complex, the chemical shift of X3P, X8P and Y9P shift upfield by 0.5 to 1.1 ppm (Supplementary Fig. 29 ). This observation indicates a backbone rearrangement from the canonical BI type toward BII type. On the other hand, patterns in HP-COSY spectra mainly indicate similar H3’ and H5’/H5” J coupling values, which imply similar γ and β torsion angles for duplex I in the presence and absence of Ag I ions, except for the C6-Y7 step, where the C6H3’ to Y7P cross-peak is changed upon addition of the silver ions. This could be due to a backbone distortion at this step or due to the signal broadening observed for the Y7 residue.
We applied NMR restraints derived from NOESY and DQF-COSY spectra to construct structural models of the I and I-Ag duplexes in AMBER. The silver-modified model was constructed by replacing imino protons within Watson–Crick base pairs with silver ions. The appropriate parameters for the metal ion binding terms were determined based on DFT calculations in Gaussian software, and parameters for the metal-mediated base pairs were obtained with the help of MCPB software 23 . A total of 250 NOE-derived distance restraints were applied for the native structure of duplex I and 320 for the silver-mediated duplex I-Ag structure. Additionally, sugar pucker was restrained to 140–180° range for residues 1-3 and 5-9 in both structures and backbone torsions were restrained in duplex I based on 31 P NMR chemical shifts and HP-COSY cross-peaks.
The NMR structure shows duplex I-Ag forms a right-handed helical structure resembling the B-type DNA helix (Fig. 5a ), with an average twist of 34° and an average rise of 3.3 Å (compared to 33° and 3.3 Å in the structure of duplex I , Supplementary Table 5 ). The main difference compared to the canonical structure is the reorientation of the bases required to accommodate the silver ions within the base pairs (Fig. 5b ). The average base opening parameter for the silver-modified duplex is −35°, compared to values in the structure of duplex I without the silver ions (the latter is also the same as in a model B-type duplex). The propeller twist of the base pairs is also increased to an average value of −20°, compared to −8° in the model of duplex I or −11° for B-DNA type structures in general (Fig. 5c ). The change in base pair geometry forces the breaking of one of the hydrogen bonds in the C-Y base pair, leaving the base pair connected with one hydrogen bond and the silver coordination bond in place of the original three hydrogen bonds. Our model suggests that the 2-amino groups of Y residues, which are released from hydrogen bonding in C-Y base pairs, tend to form inter-base pair hydrogen bonds when a purine residue precedes the residue. Four such pairs are observed in our model: Y2-C12*, T5-Y9*, Y9-T5*, and C12-Y2* (asterisks denote complementary strand residues). Inter-planar hydrogen bonding has been observed in silver ion-mediated DNA structures before and has been proposed as an important factor for structure stabilization 14 . The differences observed between C-Y and T-X base pairs, and between different base steps, could have implications for the stability of various sequences of the 7d DNA system. Likewise, this structural detail could factor into the reasons why A-T base pairs have not been observed in native sequence contexts to date, while G-C pairs have.
a Side and top views of the lowest energy structure following NMR restrained MD. b Selected structural parameters for I and I-Ag . While most structural parameters remain similar, the base pairs are perturbed, as reflected in the propeller twist and base pair opening. Typical values for B-DNA and A-DNA type structures are indicated in the graphs, where applicable. c Base pair geometry for the metal-modified base pairs in I-Ag complex and duplex I .
The silver ions within duplex I-Ag form a helical arrangement mirroring the pattern of base pairs. The overall helix retains a narrow central cavity similar to the native B-type helix, and the silver ions thread among the DNA bases, appearing obscured by the nucleobases when viewed from the top (Fig. 5a ). The average distance between consecutive Ag I ions along the structure is 3.8 ± 0.3 Å, exceeding the sum of the ionic radii (3.44 Å), suggesting a general absence of argentophilic interactions 24 . However, the distances between silver ions (Ag-Ag) vary depending on the sequence, reducing to 3.27 Å at steps 3 and 9. This proximity seems primarily influenced by base pair shift, slide and atom distance within the base pairs and reflects the leading role of interactions between the DNA nucleotides in determining the position of silver ions. This observation suggests the possibility of directing potential electronic properties of the assemblies throughout DNA sequence. Notably, the Ag I arrangement differs from that seen in previously published X-ray structures of silver-mediated structures of canonical DNA 13 , 14 . This could reflect differences in the relative contribution of argentophilic interactions to the structures due to differences in nucleotide chemistry of applied conditions. A previously published solution structure of a DNA duplex with three consecutive silver-mediated base pairs did not show significant argentophilic interactions, similar to our findings here 25 .
To study the positioning of the Ag I ions more precisely, we performed DFT-based (PBEh-3c) calculations on the I-Ag complex in the presence of sodium counterions and water molecules. To our knowledge, no comprehensive DFT study has been conducted on an entire metal-DNA system with twelve consecutive metal-modified base pairs. Previous theoretical DFT (M06-2X) investigations in this area have been limited to fragments of up to six units in size 21 .
Notably, the DFT-optimized geometry of the I-Ag complex closely resembles the structure derived from the NMR data (Fig. 6 and Supplementary Table 5 ). These structures align in several critical aspects, suggesting a robust agreement between the two structure determination methods. While subtle differences in specific parameters exist, these distinctions do not reduce the broader concordance between the NMR and DFT-optimized structure. For instance, the twist angle is approximately 34° in the NMR and DFT structures, showcasing a high level of agreement. Furthermore, parameters like the minor groove width, slide, rise, and tilt exhibit noteworthy alignment.
Structures for I-Ag complex obtained by different methodologies: a NMR spectroscopy and b DFT calculations. c Superposition of the NMR (blue) and DFT (orange) structures.
In addition, the parameters of buckle, opening, and major groove width appear to show minor variations considering the standard errors. However, the propeller angle (−8 ° ± 9) appears to be more distinct from that revealed in the NMR (−21 ° ± 4). It is essential to recognize that these differences are subtle and fall well within the range of experimental computational approximations. Thus, they do not detract from the overarching consensus on the core helical NMR structure of I-Ag .
Similar to the NMR-derived model, the Watson–Crick pairing is preserved, with silver ions substituting a hydrogen bond with a linear coordination bond. These ions align according to the helix turn dictated by the base pairs, with an average Ag···Ag distance of 3.6 ± 0.3 Å, slightly smaller than observed in the NMR model (Supplementary Table 6 ). This situation excludes the formation of contiguous argentophilic interactions, confining them to specific regions throughout the sequence, particularly at steps 2, 3, and 9, in close accordance with the NMR data. This stands in contrast to the observations made in crystal structures of Ag-DNA systems featuring non-canonical base pairings, where a continuous array of argentophilic interactions occurs 13 , 14 . However, in some sections of the double strand, certain silver ions are observed with distances less than 3.44 Å, suggesting the potential existence of argentophilic interactions.
The findings outlined in this study illustrate the potential of utilizing 7d DNA molecules for constructing double helices made of silver-modified Watson–Crick pairing, as illustrated by the NMR solution structure of duplex I-Ag . A significant breakthrough emerges from the fact that I-Ag retains the original conformation of duplex I , initially formed by canonical Waton-Crick base pairs. Importantly, our study also revealed that the structural framework of duplex I dictate the helical organization of silver ions along the central axis, in contrast to prior X-ray diffraction findings. These exciting findings open the door for precisely engineering silver patterns at the nanoscale by strategically designing 7d DNA molecules, and offering enhanced stability to programmed DNA-based nanostructures, leveraging canonical DNA assembly capabilities.
The oligonucleotide ODN1 was synthesized with a K&A Laborgeraete GbR DNA/RNA synthesizer following manufacturer protocols. The non-canonical 7-deazaadenine and 7-deazaguanine phosphoramidites nucleosides were purchased from ChemBiotech (Münster, Germany) and Glen Research (Maravai LifeSciences, USA). The purification was performed by RP-HPLC using an Azura preparative 2.1 L HPLC system (Knauer, Berlin, Germany) with a C18 column (Kromasyl EternityXT-5-C18), and acetonitrile/tetraethylammonium acetate buffer mobile phases. DMT groups were removed by reaction in 80% acetic acid for 30 min. Samples were then transferred to a pure water phase by ethyl ether extraction and desalted on a Sephadex G25 column using FPLC (ÄKTApurifier 10, GE HealthCare, Chicago, Illinois, USA). Desalted samples were lyophilized for further use and analyzed by HPLC (Supplementary Fig. 30 ). The oligonucleotide ODN2 was purchased from Sigma-Aldrich with HPLC purification grade. ESI-MS spectrometry (negative mode): Calcd for ODN1 [(C 122 H 153 N 40 O 70 P 11 )-H] - : 3639.4496 Da, found: 3639.2654 Da (Supplementary Fig. 31 ). Calcd for ODN2 [C 116 H 147 N 46 O 70 P 11 )-H] - : 3645.3773 Da, found: 3645.5057 Da (Supplementary Fig. 32 ).
UV-vis spectra were recorded on an Agilent Technologies Cary 100 Spectrophotometer in association with a Temperature Controller. UV-melting curves were registered at 265 nm with a heating rate of 0.5 °C·min −1 and data interval of 1 °C. The melting curve graphs were prepared using normalized Absorbance (A norm = (A-A min )/(A max -A min ) at 265 nm.
CD spectra were recorded on a Jasco J-815 instrument equipped with a Peltier temperature controller. The duplex I and II titration experiments upon adding controlled amounts of Ag I ions were recorded by keeping the corresponding duplex concentration constant at 2 µM in water containing 100 mM NaClO 4 and 5 mM MOPS buffer at pH 8.5. The aliquots from a stock solution of AgClO 4 (1000 µM) were added to this solution, along with identical aliquots from an oligonucleotide stock solution (4 µM DNA, 200 mM NaClO 4, 10 mM MOPS buffer) to keep the DNA and buffer concentration constant.
Molecular mass determination for I-Ag complexes was performed by ESI-MS using a Micro Tof-Q Instrument (Bruker Daltonics GmbH, Bremen, Germany) equipped with a time-of-flight analyzer (ESI-TOF MS), with ESI-L Low-Concentration Tuning Mix (Agilent Technologies, USA), interfaced with an Agilent Technologies Series 1100 HPLC pump and equipped with an autosampler, both controlled by the Compass Software. The interaction of duplex I (0.2 mM) with Ag I ions was analyzed in negative mode. For each experiment, 10–20 μL of the sample was injected at 30–55 μL・min −1 ; the capillary counter electrode voltage was 4.5 kV; desolvation temperature at 85 °C; dry gas at 6 L・min −1 . Spectra were collected throughout an m/z range from 500 to 2500. The liquid carrier was a 90:10 mixture of 25 mM ammonium acetate and acetonitrile, pH 7.5. Molecular mass determination for ODN1 and ODN2 were registered for 50 μM sample in Tris buffer, using a High-Resolution QTOF Mass Spectrometer (Bruker, Compact model) (Acquisition parameters shown in Supplementary Figs. 31 , 32 ).
For these experiments, the duplexes were prepared at different concentrations. The concentrated samples (0.7 mM duplex) provided sufficient signal-to-noise dispersion data on the benchtop instrument (Anton Paar SAXSpace). On the other hand, more diluted samples (0.2 mM duplex) were employed to register scattering and anomalous scattering (ASAXS) data in a synchrotron source (Advanced Photon Source, APS).
X-ray scattering data were collected on an Anton Paar SAXSpace instrument equipped with a Cu-Kα radiation source (1.54 Å) with line collimation, a Dectris Mythen 1 K detector and a temperature-controlled sample stage (TCS150) with a capillary holder. Data was collected with the maximum sample-detector distance in high-intensity mode resulting in a q = 0.01−0.78 Å −1 range. Samples were prepared in 1.5 mm borosilicate capillaries and sealed with paraffin wax. The sample temperature was lowered to 10 ˚C and held at this temperature for 5 min prior to data collection. Sample stability was monitored by collecting 3 × 15 min frames using Anton Paar’s SAXS data software. If stable, these frames were averaged and processed using SAXSanalysis software (normalization, primary beam removal, background subtraction, and desmearing). All analyses and curve-fitting were carried out utilizing IRENA macros with IgorPro 6.3 (Wavemetrics) software 26 . To simulate scattering data from the crystal structure, we used SolX software 27 .
ASAXS data were collected for duplexes I and II at 0.2 mM concentration, with and without added Ag I , over twenty energies from the Ag K-edge (25.5140 keV) to below the K-edge (24.5140 keV) at the NSF’s ChemMatCARS (15-ID-D) beamline of Advanced Photon Source (APS). By utilizing the energy-dependent SAXS data, we extracted various scattering components, specifically the SAXS-terms, Cross-terms, and Resonant-terms (Supplementary Figs. 25 , 26 ). The Resonant-terms of the scattered intensity provided valuable insight into the distribution of the Ag I within the samples. However, due to the overall low-electron density contrast between the oligonucleotides and water, scattering from water dominated beyond 0.35 Å −1 . This dominance limited the resolution for locating ions within the complexes and therefore it was only feasible to model the complexes assuming a solid cylinder. The energy-dependent SAXS data were analyzed using a solid cylinder model to obtain information about the structure of the Ag-DNA complexes. The analysis details are available in the Supplementary Information in the AXSAX Analysis section.
NMR spectra were acquired on Bruker AVANCE NEO 600 and 800 MHz spectrometers equipped with QCI and TCI cryogenic probes at 25 °C, if not stated differently. NMR samples were prepared from DNA stock solutions at final 0.8 mM DNA oligonucleotide concentrations in 90%/10% H 2 O/ 2 H 2 O or 100% 2 H 2 O, 100 mM NaClO 4 , 100 mM Tris/HNO 3 (pH 8.6). Water suppression in 1 H and 2D 1 H− 1 H NOESY (τ m = 100 ms) experiments was achieved by using excitation sculpting method. 2D 1 H- 1 H TOCSY (τm = 80 ms) and DQF-COSY spectra were acquired in 100% 2 H 2 O. Sixteen different gradient strengths (1−51 G·cm -1 ) were used in DOSY experiments. 1 H NMR chemical shifts were referenced with respect to the signal at δ 0.0 ppm for external standard DSS. NMR spectra were processed and analyzed by using TopSpin (Bruker) and Sparky (UCSF) software.
Distance restraints were obtained by integration of signals in NOE spectra. For non-exchangable signals, cytosine H5-H6 signals were used as a reference for distance (2.34 Å). For well-resolved and well-formed peaks, restraints were set as d ± 20%, while for partially overlapped, weak or malformed peaks, qualitative restraints were set based on binning to strong (1.8–3.6 Å), medium (2.6–5.0 Å) or weak (3.5–6.5 Å) classes. Hydrogen bonding restraints were set as upper bounds based on the standard Sanger geometries for duplex I . Hydrogen bond restraints for the silver-modified duplex I-Ag were set at 2.4 Å for the remaining hydrogen bond pairs (X H2 – T O2 and C H4 – Y O6) to account for the weaker or absent signals observed in the NMR spectra. Torsion restraints were included, which were set according to cross-peak patterns in DQF-COSY and HP-COSY spectra. Backbone torsions were restrained to a standard B-DNA type for duplex I based on 31 P NMR chemical shifts and cross-peaks in 1 H- 31 P HP-COSY spectra (the following restraints were used: α−70° to −45°, β 130° to 230°, γ 40° to 50°, ε −170° to 20°, ζ −75° to −105°). Backbone torsions were left unrestrained for the metal-modified duplex I-Ag to allow the model freedom to explore possible alternative backbone conformations indicated by chemical shift changes in the 31 P NMR spectrum.
The X and Y building blocks were constructed using the RED server 28 . To make fragments compatible with the standard library nucleotides, the Gaussian calculated electrostatic potentials output from the server were inputted again to the resp program (AmberTools 19) and the partial charges corresponding to the caps were kept constrained at the appropriate values.
MCPB.py was used to parametrize the metal-coordinated structures 23 . The B3LYP functional with the DGDZVP basis set was used for the DFT calculations. Partial charges for the final fragments were refitted in Amber Tools using resp for compatibility.
Starting structures were obtained through the fiber module of the NAB software, creating A-type and B-type Arnott DNA fibers. For duplexes I and I-Ag the standard nucleotides were appropriately substituted, and silver ions were inserted in place of the guanine H1 or thymine H3 protons to construct the starting silver-modified models.
Molecular dynamics simulations were performed with AMBER 20 software 29 . The starting structures were subjected to a short minimization followed by a molecular dynamics run for a total duration of 60 ps (300,000 steps with a time step of 0.002 ns), during which the structures were heated to 400 K over 6 ps, kept at that temperature for 34 ps, then cooled to 0 K over the final 20 ps. Structures were checked for convergence. The ten lowest energy structures were selected for final analysis. DNA structure parameters were obtained from the web 3DNA server 30 .
Theoretical model was built using the Avogadro software 31 , 32 . Sodium counterions were added to the phosphate groups, thus resulting in neutral model systems. Moreover, the solvent effect was included by the so-called explicit solvent model, in which 50 water molecules were placed around the molecule (base pairs, phosphates, counterions). After a partial geometry optimization of this model system, using semiempirical methods (PM3) within the ORCA 5.0.2 computational program 33 , 34 , a suitable geometry was obtained for further complete optimization by quantum mechanics ab initio calculations using the PBEh-3c method 35 . The latter method is a highly effective electronic structure technique that excels in optimizing geometries and calculating interaction energies of non-covalent complexes. This approach utilizes a global hybrid version of the Perdew–Burke–Ernzerhof (PBE) functional, which includes a significant proportion of non-local Fock-exchange (42%), and a valence-double-zeta Gaussian AO basis set (def2-mSVP) and Def2-ECP for silver 36 . To correct for basis set superposition errors (BSSE) and London dispersion effects, the gCP and D3 schemes are employed, respectively 37 , 38 .
Structure coordinates are deposited at the Protein Data Bank under accession code 9GDM ( https://www.wwpdb.org/ ), and data derived from NMR spectroscopy at the BioMagResBankn under accession code 34942 ( https://bmrb.io/ ). The coordinates of the DFT-optimized structure generated in this study are provided in the Source Data file with this paper. All data were available from the corresponding authors upon request. Source data are provided with this paper.
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Financial support from Spanish MINECO (project PID2020-120186RB-I00), Spanish MICIU (Salvador Madariaga Program, Ref. PRX19/00290), Junta de Andalucia (project P20_00702). We also thank the “Centro de Servicios de Informática y Redes de Comunicaciones” (CSIRC) (UGRGrid), Universidad de Granada, for providing computing time on the Alhambra supercomputer . U.J. and J.P. acknowledge the financial support of the Slovenian Research Agency (grants P1-0242 and J1-1704). O.P. acknowledges the financial support provided by the Spanish Ministerio de Ciencia e Innovación (PID2022-138479NB-I00). O.P. is member of the “Grup de Recerca de la Generalitat de Catalunya” (Ref. 2021 SGR 00668). We thank Matthew Cranswick, from the Advanced Technology Manufacturing Institute at Oregon State University, for his support and assistance in conducting benchtop SAXS experiments (Anton Paar SAXSpace). The authors acknowledge the CERIC-ERIC Consortium for the access to experimental facilities and financial support (project 20172040 and 20222132). This research used the Advanced Photon Source (APS) resources, a US Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory (ANL) under Contract No. DE-AC02-06CH11357. NSF’s ChemMatCARS, Sector 15 at the APS, ANL, is supported by the Divisions of Chemistry (CHE) and Materials Research (DMR), National Science Foundation, under grant number NSF/CHE-1834750.
These authors contributed equally: Uroš Javornik, Antonio Pérez-Romero.
Slovenian NMR Center, National Institute of Chemistry, SI-1000, Ljubljana, Slovenia
Uroš Javornik & Janez Plavec
Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000, Ljubljana, Slovenia
Departamento de Química Inorgánica, Universidad de Granada, 18001, Granada, Spain
Antonio Pérez-Romero, Carmen López-Chamorro & Miguel A. Galindo
Department of Chemistry, Oregon State University, Corvallis, OR, 97331-4003, USA
Rachelle M. Smith & May Nyman
Departamento de Química Orgánica, Universidad de Granada, 18001, Granada, Spain
José A. Dobado
Departament de Química, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Barcelona, Spain
Oscar Palacios
NSF’s ChemMatCARS, Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA
Mrinal K. Bera
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U.J. conducted and interpreted NMR experiments. A.P.-R contributed to experimental planning, and, together with C.L.-C, designed thermal-UV and CD experiments, executed and analyzed them. R.M.S. registered SAXS data. J.A.D. conceived, performed, and analyzed DFT calculations. O.P. recorded and analyzed MS experiments. M.N. and M.K.B. conceptualized SAXS and ASAXS experiments and analyzed the results. M.K.B. registered ASAXS data. J.P. conceived, designed the NMR experiments, and took the lead in solving the duplexes solution-state structures. M.A.G. recorded benchtop SAXS data, conceived the research idea, directed the research, and led manuscript writing. All authors provided essential input, shaping the research, analysis, and manuscript.
Correspondence to May Nyman , Janez Plavec or Miguel A. Galindo .
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The authors declare no competing interests.
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Javornik, U., Pérez-Romero, A., López-Chamorro, C. et al. Unveiling the solution structure of a DNA duplex with continuous silver-modified Watson-Crick base pairs. Nat Commun 15 , 7763 (2024). https://doi.org/10.1038/s41467-024-51876-8
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The kinematic and electromyographic analysis of roller skating at different speeds on a treadmill: a case study.
2. materials and methods, 2.1. participant, 2.2. electromyographic and inertial measurement unit recordings, 2.3. experimental procedures, 2.4. data analysis, 2.4.1. skating cycle definition, 2.4.2. semg, 4. discussion, 5. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.
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Bongiorno, G.; Sisti, G.; Dal Mas, F.; Biancuzzi, H.; Varrecchia, T.; Chini, G.; Ranavolo, A.; Pellegrini, B.; Bortolan, L.; Miceli, L. The Kinematic and Electromyographic Analysis of Roller Skating at Different Speeds on a Treadmill: A Case Study. Sensors 2024 , 24 , 5738. https://doi.org/10.3390/s24175738
Bongiorno G, Sisti G, Dal Mas F, Biancuzzi H, Varrecchia T, Chini G, Ranavolo A, Pellegrini B, Bortolan L, Miceli L. The Kinematic and Electromyographic Analysis of Roller Skating at Different Speeds on a Treadmill: A Case Study. Sensors . 2024; 24(17):5738. https://doi.org/10.3390/s24175738
Bongiorno, Giulia, Giulio Sisti, Francesca Dal Mas, Helena Biancuzzi, Tiwana Varrecchia, Giorgia Chini, Alberto Ranavolo, Barbara Pellegrini, Lorenzo Bortolan, and Luca Miceli. 2024. "The Kinematic and Electromyographic Analysis of Roller Skating at Different Speeds on a Treadmill: A Case Study" Sensors 24, no. 17: 5738. https://doi.org/10.3390/s24175738
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IMAGES
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COMMENTS
A case study is an enquiry into one specific instance among many. Sometimes the case is selected because it is the specific case we wish to know about. There is something special about that case that makes it worth investigating. Such cases are described as intrinsic cases. "The case is given…we need to learn about that particular case" Stake ...
Whether it is psychology, business or the arts, the type of case study can apply to any field. Explanatory. The explanatory case study focuses on an explanation for a question or a phenomenon. Basically put, an explanatory case study is 1 + 1 = 2. The results are not up for interpretation.
The three main case study types often used are intrinsic, instrumental, and collective. Intrinsic case studies are useful for learning about unique cases. Instrumental case studies help look at an individual to learn more about a broader issue. A collective case study can be useful for looking at several cases simultaneously.
An intrinsic case study is conducted when a researcher has an inherent interest in the case itself. Instrumental case studies are employed when the case is used to provide insight into a particular issue or phenomenon. A collective case study, on the other hand, involves studying multiple cases simultaneously to investigate some general ...
Intrinsic case studies focus on gaining a better understanding of the case. These are often undertaken when the researcher has an interest in a specific case. Instrumental case study is used when the case itself is not of the utmost importance, and the issue or phenomenon (ie, the research question) ...
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. An intrinsic case study is typically undertaken to learn about a unique phenomenon. The researcher should define the uniqueness of the ...
For this project, we used an intrinsic exploratory case study approach (Baxter & Jack, 2008; Stake, 2002;Yin, 2002). Case studies are "aimed at description and exploration of complex and entangled ...
A Case study is: An in-depth research design that primarily uses a qualitative methodology but sometimes includes quantitative methodology. Used to examine an identifiable problem confirmed through research. Used to investigate an individual, group of people, organization, or event. Used to mostly answer "how" and "why" questions.
Intrinsic case studies will enhance the understanding by researcher and reader concerning new phenomena. The "No Theory First" case study research design is a classic and often cited candidate for building theory. As the phenomenon is new and in the absence of a theory, qualitative data are inspected for aggregation and interpretation. ...
The Intrinsic Case. The final type of case study design is an intrinsic case study, in which the focus is on the case itself. Issues to be considered for an intrinsic case study may be related to evaluating a program or may range as far afield as studying a student having difficulty with a particular aspect of his or her schooling (Stake, 2005 ...
Why a qualitative case study was conducted: A single, intrinsic qualitative research study. Following Yin's case study approach, the authors wished to uncover the contextual conditions relevant to the phenomenon under study - living in and leaving an abusive intimate relationship as a white, middle-class male. The researchers wanted to ...
A case study is one of the most commonly used methodologies of social research. This article attempts to look into the various dimensions of a case study research strategy, the different epistemological strands which determine the particular case study type and approach adopted in the field, discusses the factors which can enhance the effectiveness of a case study research, and the debate ...
The guide for the case study report is often omitted from case study plans because investigators view the reporting phase as being far in the future. Yin (1994) proposed that the report is planned at the start. Case studies do not have a widely accepted reporting format - hence the experience of the investigator is a key factor (Tellis, 1997).
This descriptive, intrinsic case study explored a transformative leadership professional development opportunity designed for school counselors in a large, urban school district. Interviews with 19 participating school counselors provided increased understanding of school counselors' beliefs, skills, and agency regarding leadership and ...
Stake (1995) divides case studies into three types: intrinsic - a single case (an individual, group, organization, event, or other entity) that is important in its own right, not necessarily because of its potential predictive theoretical powers; instrumental - a single case where the focus is on going beyond the case to understand a ...
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[].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.
The definitions of case study evolved over a period of time. Case study is defined as "a systematic inquiry into an event or a set of related events which aims to describe and explain the phenomenon of interest" (Bromley, 1990).Stoecker defined a case study as an "intensive research in which interpretations are given based on observable concrete interconnections between actual properties ...
These include the intrinsic case, the instrumental case, and the collective instrumental case. The intrinsic case is used to understand the particulars of a single case, rather than what it represents. An instrumental case study provides insight on an issue or is used to refine theory. ... while ensuring the intrinsic meaning of case study is ...
A business or marketing case study aims at showcasing a successful partnership. This can be between a brand and a client. Or the case study can examine a brand's project. There is a perception that case studies are used to advertise a brand. But effective reports, like the one below, can show clients how a brand can support them.
case studies are not sharp, and a case study may fit under more than one type. Stake (1995), one of the leading case study researchers, defines three broad types of case study. First, he describes the intrinsic case study, in which interest lies purely in one particular case itself. There is no attempt
First, method, source, and data triangulation were conducted concurrently to overcome differences in data collection methods from two qualitative intrinsic case studies. Second, code and meaning saturation were used in ATLAS.ti to identify similar meanings and interpretations despite different data collection methods.
an interesting candidate for an intrinsic case study. This paper presents a distinctive way of handling an interfering and disruptive student in an academic course at the university. The description of the case takes the reader on a narrative journey and demonstrates a solution for the inappropriate behavior. The lecturer's persistent
In this study, we present the solution structure of a DNA duplex that can be transformed into its metallized equivalent while retaining the natural base pairing arrangement through the creation of ...
This study employed a descriptive, intrinsic case study design in which the case under investigation (Creswell & Poth, 2018) was school counselors and school counseling administrators participating in a transformative leadership professional development program to support district-wide implementation of comprehensive school counseling programs ...
Elite athletes in speed roller skates perceive skating to be a more demanding exercise for the groin when compared to other cyclic disciplines, increasing their risk of injury. The objective of this study was to monitor the kinematic and electromyographic parameters of roller speed skaters, linearly, on a treadmill, and to compare different skating speeds, one at 20 km/h and one at 32 km/h, at ...