case series study treatment

A case report is a detailed report of the diagnosis, treatment, response to treatment, and follow-up after treatment of an individual patient. A case series is group of case reports involving patients who were given similar treatment. Case reports and case series usually contain demographic information about the patient(s), for example, age, gender, ethnic origin.

When information on more than three patients is included, the case series is considered to be a systematic investigation designed to contribute to generalizable knowledge (i.e., research ), and therefore submission is required to the IRB.

For all case reports and case series, a signed HIPAA authorization should be obtained from the patients or their legally authorized representatives for the use and disclosure of their Protected Health Information. The only exception to the requirement for obtaining authorization is if the author of a case report or case series believes that the information is not identifiable; in this case, the author must consult with the Privacy Officer at Boston Medical Center ( [email protected] ) or the HIPAA Privacy Officer of Boston University ( [email protected] ) to seek an expert opinion about the magnitude of the risk of identifying an individual.

For case reports or case series containing more than three patients, the HIPAA authorization should be part of the consent form that is reviewed by the IRB.

For case reports or case series containing three or fewer patients, authors should prepare an authorization form using the following templates and arrange for review as indicated below. The red text in the template should be customized for the specific case report or case series. Please note that for deceased patients, authorization must be obtained from the personal representative, who is the administrator or executor of the patient’s estate.

• Boston Medical Center ( BMC Case Report HIPAA Authorization Template ) – review by the Privacy Officer at Boston Medical Center ( [email protected] ); a copy of the authorization must be filed in each patient’s medical record.
• Goldman School of Dental Medicine ( GSDM Case Report HIPAA Authorization Template ) – review by the HIPAA Privacy Officer of Boston University ( [email protected] )

Quantitative study designs: Case Studies/ Case Report/ Case Series

Quantitative study designs.

• Introduction
• Cohort Studies
• Randomised Controlled Trial
• Case Control
• Cross-Sectional Studies
• Study Designs Home

Case Study / Case Report / Case Series

Some famous examples of case studies are John Martin Marlow’s case study on Phineas Gage (the man who had a railway spike through his head) and Sigmund Freud’s case studies, Little Hans and The Rat Man. Case studies are widely used in psychology to provide insight into unusual conditions.

A case study, also known as a case report, is an in depth or intensive study of a single individual or specific group, while a case series is a grouping of similar case studies / case reports together.

A case study / case report can be used in the following instances:

• where there is atypical or abnormal behaviour or development
• an unexplained outcome to treatment
• an emerging disease or condition

The stages of a Case Study / Case Report / Case Series

Which clinical questions does Case Study / Case Report / Case Series best answer?

Emerging conditions, adverse reactions to treatments, atypical / abnormal behaviour, new programs or methods of treatment – all of these can be answered with case studies /case reports / case series. They are generally descriptive studies based on qualitative data e.g. observations, interviews, questionnaires, diaries, personal notes or clinical notes.

What are the advantages and disadvantages to consider when using Case Studies/ Case Reports and Case Series ?

What are the pitfalls to look for.

One pitfall that has occurred in some case studies is where two common conditions/treatments have been linked together with no comprehensive data backing up the conclusion. A hypothetical example could be where high rates of the common cold were associated with suicide when the cohort also suffered from depression.

Critical appraisal tools 

To assist with critically appraising Case studies / Case reports / Case series there are some tools / checklists you can use.

JBI Critical Appraisal Checklist for Case Series

JBI Critical Appraisal Checklist for Case Reports

Real World Examples

Some Psychology case study / case report / case series examples

Capp, G. (2015). Our community, our schools : A case study of program design for school-based mental health services. Children & Schools, 37(4), 241–248. A pilot program to improve school based mental health services was instigated in one elementary school and one middle / high school. The case study followed the program from development through to implementation, documenting each step of the process.

Cowdrey, F. A. & Walz, L. (2015). Exposure therapy for fear of spiders in an adult with learning disabilities: A case report. British Journal of Learning Disabilities, 43(1), 75–82. One person was studied who had completed a pre- intervention and post- intervention questionnaire. From the results of this data the exposure therapy intervention was found to be effective in reducing the phobia. This case report highlighted a therapy that could be used to assist people with learning disabilities who also suffered from phobias.

Li, H. X., He, L., Zhang, C. C., Eisinger, R., Pan, Y. X., Wang, T., . . . Li, D. Y. (2019). Deep brain stimulation in post‐traumatic dystonia: A case series study. CNS Neuroscience & Therapeutics. 1-8. Five patients were included in the case series, all with the same condition. They all received deep brain stimulation but not in the same area of the brain. Baseline and last follow up visit were assessed with the same rating scale.

References and Further Reading  

Greenhalgh, T. (2014). How to read a paper: the basics of evidence-based medicine. (5th ed.). New York: Wiley.

Heale, R. & Twycross, A. (2018). What is a case study? Evidence Based Nursing, 21(1), 7-8.

Himmelfarb Health Sciences Library. (2019). Study design 101: case report. Retrieved from https://himmelfarb.gwu.edu/tutorials/studydesign101/casereports.cfm

Hoffmann T., Bennett S., Mar C. D. (2017). Evidence-based practice across the health professions. Chatswood, NSW: Elsevier.

Robinson, O. C., & McAdams, D. P. (2015). Four functional roles for case studies in emerging adulthood research. Emerging Adulthood, 3(6), 413-420.

• << Previous: Cross-Sectional Studies
• Next: Study Designs Home >>
• Last Updated: Aug 21, 2023 10:12 AM
• URL: https://deakin.libguides.com/quantitative-study-designs

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• Advanced Search
• Journal List
• Afr Health Sci
• v.12(4); 2012 Dec

Clinical “case series”: a concept analysis

To analyze the concept of “case series” in the medical literature compared with case reports.

A PubMed search for articles published during 2009 which had “case series” in their title was performed. A total number of 621 articles were retrieved. 586 papers were included in the analysis and 35 were excluded (18 were commentary letters, 5 were not in English, and twelve could not be retrieved by our Library). The number of patients and category of these articles were analyzed.

The median (range) of the number of cases of articles having “case series” in their title was 7 (1–6432) cases. 186/ 586 articles had less than 5 cases (31.7%, 95% CI (28.3–35.1%)). The median (range) of the number of cases of articles having “case report” as their publication type was 4 (1–178) cases. Out of the 219 articles categorized as case reports 114 (52.1%, 95% CI (45.6–58.6%)) had less than five cases.

Conclusions

The concept of “case series” is not well defined in the literature and does not reflect a specific research design. We suggest that a case series should have more than four patients while four paitents or less should be reported individually as case reports.

Introduction

There has been a recent trend in some journals to stop publishing case reports and publish more original articles instead. 1 , 2 This is possibly driven by the desire to get a higher impact factor, to properly utilize the limited space in the journals with economical gains, and to effectively use the time of the reviewers. This approach may have a negative impact on understanding the pathophysiology and management of rare diseases. Furthermore, group outcomes may not reflect exactly what happens in individual patients. 3 , 4 Reporting a study with a small number of patients may turn out to be very useful especially during an epidemic. Historically, reporting case series with small number of patients raised important concerns regarding serious conditions like the relationship between liver adenomas and contraceptive pills, Kaposi's sarcoma and AIDS, and the toxic effects of high concentrations of oxygen on the optic nerve in newborn infants. 5

Some journals have gone around that by accepting case series instead of case reports or alternatively establish a sister journal for case reports so as not to lose this important advantage. 1 An endeavor to launch indexed journals publishing only case reports was also attempted. 6 We have repeatedly noticed, during submitting articles to refereed journals, that the difference between a case series and a case report is not well defined. Both are seperate types of observational studies. 5 , 7 A case report is the smallest publishable unit in the medical literature while a case-series is an aggregation of several similar cases. 5 There is no defined limit for the smallest number of a case series. Some authors accepted even three cases to be a case series. 8 Furthermore, the style of reporting each of these types is different.

We were personally lost between the instruction of authors and the personal opinion of editors on defining a case series. Case series were some times rejected on the basis that they were considered by editors as case reports (personal expereince). We could not find a clear distinction between these two types in the medical literature and we aimed in this study to analyze the concept of “case series” as used recently in the medical literature and whether it is different from case reports.

A PubMed search was made through PubMed website 9 using the term “case series” between brackets. Search was limited to the title filed and the publication date between 1st of January 2009 to 31st of December 2009. The site was accessed on 18th of October 2010. Publications type was accessed on individual abstracts and tabbed. Some articles had more than one type which was vertically organized. The first line was considered as the first type, the second line as the second type, and the third line as the third type.

A total number of 621 articles were displayed. The abstracts of these articles were printed and reviewed manually. The number of cases in each paper was searched manually on the hard copy. 18 papers (letters to the Editor as commentaries on other published articles) and five non-English articles were excluded. 31 abstracts didn't have enough data regarding the number of studied cases. 19 full articles were retrieved through The National Medical Library of the Faculty of Medicine and Health Sciences, UAE University while the other 12 articles could not be retrieved and were excluded from the study. A total number of 586 papers were included in the analysis.

The “publications type” was searched directly from the website as described above. This was available only on 352 out of 586 articles (60.1%).

An excel program was made to enter the “number of cases” and “the publication types” for each article. Data were analyzed with the PASW Statistics 18, SPSS Inc, USA. A standard formula to calculate the 95% confidence interval (95% CI) of proportions was used which is: 95% CI = p ± 1.96 x square root of (pq/n), where p is the studied portion and q is the alternate portion and n is the sample size. 10

The mean (SD) of the number of cases of articles having “case series” in their title was 57.2 (357.6) cases while the median range of the number of cases was 7 (1–6432) cases. Majority of these articles had 10 cases or less (63%) ( figure 1 ). 186 out of the studied 586 articles had less than 5 cases (31.7%, 95% CI (28.3–35.1%)). One paper had a single case reported as case series in a prestigious journal. 11 The largest number of patients was 6432 patients. 12 PubMed categories were available in 352 articles. 219 articles (62.2%, 95% CI (57.4–67%) were categorized as case report ( table 1 ). The mean (SD) of the number of cases of articles having “case report” as their publication type was 8.2 (15.4) cases while the median range of the number of cases was 4 (1–178) cases. 85% of those categorized as case reports had 10 patients or less ( figure 2 ). Out of the 219 articles categorized as case reports 114 (52.1%, 95% CI (45.6–58.6%)). had less than five cases compared with 105 (47.9%, 95% CI (41.4–54.4%)) having 5 or more cases. Only one study (0.5%) categorized as case report had one case. Other categories are shown in table 1 . This covered a wide range of research designs including randomized controlled trials in three articles and meta-analysis in one article.

Publication type, as defined by the U.S. National Library of Medicine, National Institutes of Health, of articles having “case series” in their title, published during 2009 and indexed by the PubMed website

Number of subjects studied in papers published during 2009 by the U.S. National Library of Medicine, National Institutes of Health “ PubMed” that have “case series” in their title. Total number of publications = 586 papers

Number of subjects of papers published during 2009 by the U.S. National Library of Medicine, National Institutes of Health “PubMed” that have “case series” in their title and categorized as “case report”. Total number of publications = 219 papers

An accurate observation may turn out to be the first step towards an important discovery in science. Similarly, many diseases were first observed at the bedside. A good descriptive study has a clear, specific, and measurrable definition of the studied disease. 5 Although it is possible to carry out large-scale randomized trials for rare conditions when resources are available, this may turn out to be extremely difficult and expensive. Furthermore, the design of observational studies and randomized trials answer different questions.

Both case reports and case series lack comparison groups, their data may be biased and incomplete. Despite that, they are useful for generating hypotheses for future studies. 13

Definitions

According to the latest version of the Dictionary of Epidemiology, a case series is defined as “a collection of patients with common characteristics used to describe some clinical, pathophysiological or operational aspects of a disease, treatment or diagnostic procedures”. 14 A case report is a “detailed description of a few patients or clinical cases with an unsual disease or complication, uncommon combinations of diseases, and unusual or misleading semiology, cause or outcome”. 14 Interestingly, The fourth version of the same dictionary which was published in 2001 did not have a defnition for a case series neither a case report indicating that epidemiologists have only recently tried to define these terms. 15 Even a standard Evidenced-based Medicine book did not differentiate between a case series and a case report. 16 The Centre for Evidence-Based Medicine, University of Oxford, UK has defined case-series as “a report on a series of patients with an outcome of interest” 17 .

Other definitions indicate that a case series has few patients. The Medical Research Council of South Africa defined it as “an uncontrolled observational study involving an intervention and outcome for more than one person ” 18 . The Centre for training and Research in Public Health, Italy defined case-series as a “report of a number of cases of disease” 19 . The National Cancer Institute of USA defined case series as “a group or series of case reports involving patients who were given similar treatment” 20 . Interestingly, the Mesh database site of PubMed does not have a definition for case series neither it was considered as a catgory when classifying the papers having “case series” in their title 21 . Some investigators do not include “case series” in the list of types of studies because they are generally not planned and do not involve a research hypothesis 22 .

It is very clear from these definitions that there is no clear distinction between a case report and a case series in the literature. The results of our paper reflect this finding. Some papers, even in prestigious journals, considered one case as a case series 11 and another labeled a group of more than 6000 cases as a case series 12 . We think that this misconception stemmed from clinicians who used the “case series” term linguistically as a series of patients collected over a period of time without considerations to the research design. This misconception was also carried out to the definition of a case report. Interestingly, the Mesh database site of PubMed 21 defined case reports as “Clinical presentations that may be followed by evaluative studies that eventually lead to a diagnosis” which is very similar to the definition of a case series. The National Cancer Institute of USA defined a case report as “a detailed report of the diagnosis, treatment, and follow-up of an individual patient containing some demographic information about the patient” 20 .

Statistical and study design considerations

The variance of the data, the difference between the means, and the power of a study will decide the sample size needed for a study. Finding a difference between two groups depends on the standard error of the mean of each of these groups.

It is obvious that if data of a group of subjects are to be summarized statistically, then a minimum number of subjects is needed to be valid. We have found from experience that, five is the minimum reasonable number of independent subjects in a group so as to combine their data 23 – 25 That is because, the standard error of the mean, which is used for comparisons, will be much larger for a number of subjects less than that. The standard error of the mean equals the standard deviation (a marker of variation in the data) divided by the square root of the sample size. 10 This opinion agrees with Patterson et al who suggested that five cases is the lowest advised number of a case series. 7

Nevertheless, it is important to stress that the number of patients per se will not indicate the required research design. Clincial trials were performed even in a single patient using himself/herself as his/her own control. 26 Using this approcah, randomized controlled trials in a specific patients (N=1 clinical trial) were used to define the best treatment for that patient. 26

The style of a case report and a case series

A useful definition of a case report that we have found in the literature was “a description of clincial events of one or several patients in a narrative form”. 27 This, by surface validity, is similar to the patient's medical report. Each patient will have his/her own medical report which is written in a seperate section. Case series will contain individual patients' data like demography, diagnosis, and management. Data of a small case series can be presented as a table and pooled together if needed without the need for individual detailed desription 28 . This may occasionally alert clinicians to unnoticed serious clincial events. 28 , 29 This approach also enabled auhtors to develop unique new management algorithms for treating rare serious conditions 30 , 31 . Furhtermore, a case series may have been collected over a specific period of time which should be mentioned in the paper. A case series can be consecutive if all eligible patients were identified by the researchers during the study period. Alternatively, it can be nonconsecutive if it includes some, but not all, of the eligible patients. 32 , 33

We think that the distinction between a case report and a case series should be clear in the instruction of authors of different journals. This will save the time of the authors and editors and enhance the review process of medical journals. Some journals will accept only a case series design but not a case report. We suggest that patients less than 5 to be reported individually as case reports and those above 4 to be presented as a case series. Our study has shown that more than 30% of the papers having “case series” in their title have less than 5 cases and more than 50% of those “case series” labeled as a case report have less than 5 cases. The upper limit of a case series could not be defined by us but we suggest ten as an upper limit, similar to what was suggested by the European Urology 34 . This journal has clear instructions to authors that a “case series” should report on no more than 10 patients. An observational study of more patients based on rates is a different category and should be possibly labeled as a rate-based descriptive study. 7

In summary we have shown that the concept of “case series” is not well defined in the recent literature. We tried to analyze this concept and came with a suggestion that a case series should have more than four patients while four paitents or less should be reported individually as case reports. We hope that our suggestion will be accepted by the scientific community.

School of Health Sciences

Narration audio (MP4)

Narration audio (OGG)

Toggle Navigation

• Case series
• Cross-sectional studies
• Cross-sectional surveys
• Potential biases
• Analysis of cross-sectional studies
• Strengths and Weaknesses

Case series (also known as clinical series)

Case series typically involve a much smaller number of patients than the more powerful case-control study or Randomised controlled trial (RCT). In this design patients with a known exposure to a treatment are tracked prospectively to identify new forms of disease or adverse effects. Case series can also be retrospective - here medical records are examined to identify a link between exposure and disease.

You can see how case series designs may be confounded by selection bias because physicians choose to study patients from their hospital or clinic who they suspect have an illness that may be linked to an exposure.

Case series can be consecutive or non-consecutive. The results of case series can generate hypotheses that are useful in designing further studies including RCTs. No causal inferences should be made from case series regarding the efficacy of an investigated treatment. Case series have no control group, so they have no statistical validity. The benefit of case series is that they are easy to understand and can be written up in a very short period of time.

A case series is simply a series of cases of disease which can raise awareness initially of a new disease or disease variant. Acquired immunodeficiency disease syndrome (AIDS) and bovine spongiform encephalopathy (BSE), were initially described from the excess occurrence of cases of related rare diseases, which eventually led to new disease definitions.

Your browser does not support video playback

• Download the staff opinions video (MP4)
• Download the staff opinions video (WEBM)

What is Case Series?

• Asploro Journal of Biomedical and Clinical Case Reports
• ISSN : 2582-0370
• Article Type : Editorial
• Asp Biomed Clin Case Rep. 2018 Aug 17;1(1):10-15

El-Gilany AH 1* 1 Professor of Public Health, Faculty of Medicine,  Mansoura University , Egypt

Corresponding Author:  Abdel-Hady El-Gilany MD  ORCID ID Address:  Professor of Public Health & Preventive Medicine, Faculty of Medicine,  Mansoura University  Egypt. Received date : 06 August 2018;  Accepted date : 16 August 2018;  Published date : 17 August 2018

Citation:  El-Gilany AH. What is case series?. Asp Biomed Clin Case Rep. 2018 Aug 17;1(1):10-15.

Copyright  © 2018 El-Gilany AH. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords:  Case Series, Exposure Series, Definition, Types, Importance, Limitations

This is the second part of a series on case reports and case series studies. It will help junior researchers to comprehend what is the case series/exposure series as a type of research. It highlights the definition, types, importance, limitations, and differences between case series and exposure series. Examples of important historical case series that were instrumental in the early identification of health problems will be mentioned. A special editorial will be devoted to consecutive controlled case series (CCCS)/ self-controlled case series (SCCS) as an important research method.

Introduction

Case series (also known as clinical series) represents one of the most basic types of study designs, in which researchers describe the experience of a small group of people. It presents a detailed account of the clinical experience of individual study subjects and can evaluate large numbers of individuals and summarize the data using descriptive statistical measures [1]. A case series is a variation of a single case report in which the author describes several cases and their relation to one another and to the existing body of literature.

The Dictionary of Epidemiology defined a case series as – a collection of patients with common characteristics used to describe some clinical, pathophysiological or operational aspects of a disease, treatment or diagnostic procedures [2]. Case series is an observational, descriptive research design. It is most useful for describing the potential effectiveness of new interventions, for describing the effectiveness of interventions on unusual diagnoses, and for describing unusual responses (either good or bad) to interventions. Case series can be conducted retrospectively or prospectively. The primary distinction between case reports/series and the single-subject experiment is that the researcher does not manipulate the intervention in a case report/series but merely describes/documents what happened during the normal course of the intervention. Despite limitations, case series can often have a significant impact on the current practice of medicine and they are often used to put together case definitions of new diseases and to define future areas of clinical study [3]. However, no causal inferences should be made from case series regarding the efficacy of the investigated treatment [4]. A case series samples patients with both a specific outcome and a specific exposure, or samples patients with a specific outcome and includes patients regardless of whether they have specific exposures [5].

Types of Case Series

There are many classifications for case series.

Informal vs. Formal Case Series : [6,7]

• Informal case series : Cases are selected for specific reasons: best case, worse case, significant variations. The format of this kind of case series is: introduction; case 1, case 2, case 3, etc. (each case is presented as a short case description); discussion (cases will be compared to one another, related cases to the current literature, implications of the findings, teaching points and what changes in clinical practice this might engender).
• Formal case series : Include all cases of a specific type, or with specific selection criteria, presented more like a cohort study than a single case report and its format is introduction methods, results, and discussion/conclusions.

Consecutive vs. Non-Consecutive Case Series : [5,8]

• Consecutive case series : Includes all eligible patients identified by the researchers during the study period. The patients are treated in the order in which they are identified. Consecutiveness increases the quality of the case series.
• Non-consecutive case series : Includes some, but not all, of the eligible patients identified by the researchers during the study period.

Exposure or Outcome-Based Sampling : [5,9]

• Exposure-based sampling : Include all patients treated and have specific outcomes or adverse events. Sampling is based on both a specific outcome and presence of a specific exposure.
• Outcome-based  sampling: Includes patients with the specific outcome regardless of exposure. Thus neither absolute risk nor relative risk can be calculated. Selection is based only on a specific outcome, and data are collected on previous exposures.

Clinical vs. Population-Based Series : [10-12]

• Clinical case series : Usually a coherent and consecutive set of cases of a disease recruited from one or more center by one or more researcher. It is a clinic-based register of cases that are analyzed together to learn about the disease. They are of value in epidemiology for studying symptoms and signs, creating case definitions as well as clinical education, audit, and research.
• Population-based case series : When a clinical case-series is limited and complete for a defined geographical area for which the population is known, it is a population-based case-series consisting of a population register of cases. It is usually compiled for administrative and legal reasons.

By knowing the past history of these patients, including examination of past medical records, and by continuing to observe them to death, health professionals can build up a picture of the natural history of a disease in clinical case series. Population case-series is a systematic extension of this series but which includes additional cases, e.g. those dying without being seen by the clinicians. It adds breadth to the understanding of the spectrum and natural history of the disease. Information on the population permits calculation of rates, understanding the distribution of disease in populations and to the study of variations over time, between places and by population characteristics. Epidemiologically the most important case-series are registers of serious diseases or deaths, and of health service utilization, e.g. hospital admissions.

Design of Case Series

Case series research is a descriptive study to present patients in their natural clinical setting. The case series can be retrospective or prospective and may be consecutive or nonconsecutive depending on whether all cases presenting to the reporting authors over a period were included, or only a selection [13].

The study question should be focused and appropriate. The question should not be whether the investigated treatment is more effective or safer than another treatment. It should list the study population, the intervention and the primary outcome [4].

The setting : Select a suitable observation period and identify cases with events in this period. It may be tempting to include patients seen over a large period of time to increase sample size. However, the use of a short inclusion period minimizes known and unknown changes over time in co-interventions, prognosis, and even in the intervention under study [4,14].

Number of cases : there is no thumb rule or a magic number. The general number of cases reported in a case series range from 20 to 50, but may vary from as few as 2 or 3 to as many as more than 100 [10] or even thousands [6].

N.B. Case-only analyses are sometimes performed in genetic epidemiology to investigate the association between an exposure and a genotype [15].

What to look for : Look at when the events arose in relation to the exposures. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment [4,16,17].

• What : The diagnosis or case definition should be clear and applied equally to all individuals in the series. The case definition should mention the inclusion and exclusion criteria, which should be based on widely used validated definitions. If authors use their own criteria, definition and justification are necessary to enable readers to compare the studied population with their own patients.
• When : The date when the disease or death occurred (time).
• Where : The place where the person lived, worked etc (place).
• Who : The characteristics of the population (person). Noting the socio-demographic characteristics of a series of cases, as well as the temporal and spatial distributions can sometimes provide a clue to risk factors and hence help generate a hypothesis. This can be tested subsequently with more elaborate analytic studies.
• The opportunity to collect additional data from medical records (possibly by electronic Data linkage) or the person directly.

A detailed description of the intervention and the co-intervention should be stated. This will ensure repeatability of the study by other investigators. It is very important to thoroughly describe co-interventions. Additionally, indications for the studied treatment should be explained. This will primarily determine the consistency of the patient group [4].

The blinding of outcome assessors is ideal in every kind of research design and can be implemented quite usefully in case-series studies (e.g., by having some investigators collect data only on an outcome and others collect data only on patient characteristics). This prevents the investigators’ measurements from being influenced (intentionally or unintentionally) by their personal treatment preference [4].

The method of data acquisition (telephone interview, clinical measurement, or chart review) should be addressed in the study report for the sake of repeatability and the appraisal of measurement bias [4].

Analysis : As the design of a case series is descriptive, only descriptive statistics should be used. Case-series data are analyzed using rates. In three circumstances (spatial clustering, stable population and when there is no suitable denominator) use proportional ratios, not rates.

Findings can be presented as proportions (%) of the study populations with the outcome, confidence intervals; means, standard deviations for continuous variables and consider subgroups that need data presented separately [18]. No comparative tests yielding p values should be done. By describing summary statistics, the author errs on the conservative side of speculation and avoids misleading with fancy probability statistics [19].

Reporting:  A statement of the external validity of the obtained data should be given. This includes (1) patient characteristics and (2) completeness of follow-up. The presence of chance and the presence, direction, and magnitude of bias should be acknowledged [4].

Patients may differ according to prognostic variables, such as age, etiology, and disease severity among geographical regions. This may complicate comparisons with other reports or explain discrepancies.

The follow-up rates and reasons for loss to follow-up should be stated. Completeness of follow-up varies considerably among similar case series, making it difficult for readers to compare them. Therefore, authors should be cautious when interpreting their own results in relation to results of apparently similar case series [20].

No absolute conclusions on the studied treatment should be stated, the lack of a comparison group prohibits any hypothesis from being tested. Valid conclusions basically repeat the descriptive study findings e.g. our patients treated by treatment X showed good outcome Y after Z months of follow-up [21].

Advantages [4,14,22-26]

• High external validity: the study results are closer to those obtained in routine clinical practice and may, therefore, be considered more relevant.
• It could be useful when a randomized controlled trial is not appropriate or possible.
• No interference in the treatment decision process
• A wide range of patients
• Study conduct takes little time
• Easy to write and can be useful in new observations or disease.
• Useful for hypothesis generation, but conclusions about etiology cannot be made.
• Informative for very rare disease with few established risk factors.
• Informs patients and physicians about natural history and prognostic factors.
• Easy and inexpensive to do in hospital settings.
• Can help identify potential health problems such as the acute outbreaks of the severe acute respiratory syndrome (SARS).
• Stimulate interest in an area, leading to more detailed studies, and advancing knowledge.
• An important link between clinical medicine and epidemiology
• One of the first steps in the outbreak investigation
• Can provide the key to sound case-control and cohort studies and trials. Many case series are followed by clinical trials.
• Provides ―anecdotal‖ evidence about a treatment or adverse reaction.
• The case series method is self-matched: estimation is within-individuals.
• As a result, all fixed confounders are automatically controlled: for example,  socioeconomic level, genetic factors, location, diet, state of health.
• Only uses information on cases: no controls are required.
• Studying predictive symptoms, signs, and tests.
• Creating case definitions
• Clinical education, audit, and research
• Health services research
• Establishing safety profiles

Disadvantages [ 1,4,10,16,20,22,26-28 ]

• Lack of a control (or comparison) group this raises the question ―compared to what?
• Data collection often incomplete.
• Generally short-term
• Lack of a denominator to calculate rates of disease.
• Strong publication bias favoring positive results.
• Cannot study cause and effect relationships.
• Cannot assess disease frequency
• Lacks external validity because cases may not be representative.
• An outcome may be a chance finding, not characteristic of the disease.
• Cannot easily examine disease etiology
• Not planned before and lacks hypothesis and are often not considered by many authorities to be research studies.
• Selection bias (investigators self-select): The selective nature and the limited amount of information provide little evidence of causality and cannot say much about patterns of disease occurs due to the seasonal nature of some diseases. A series of patients with a certain illness and/or a suspected linked exposure draw their patients from a particular population (such as a hospital or clinic) which may not appropriately represent the wider population.
• Very low internal validity due to the lack of a comparator group exposed to the same array of intervening variables. The effects seen may be wholly or partly due to intervening effects such as the placebo effect, Hawthorne effect, time effects, practice effects or the natural history effect.
• Information bias:  Cases can be retrieved retrospectively or collected prospectively. Information on cases retrieved retrospectively is generally more objective, as it is collected routinely in relevant medical records. Missing or incomplete information could be an issue. For prospectively collected information, it is desirable to have standard protocols and forms to collect the necessary information, to avoid missing data for some patients. In a purely descriptive case series, confounding is not a concern, as the association between a certain factor and an outcome is not being studied.
• Sampling variation : A precise estimate of the rate of a disease, independent from chance, can be obtained only by increasing the number of diseased subjects.

Case Series that was Instrumental in the Early Identification of Health Problems

– Congenital Rubella Syndrome : The classic description of a series of infants born with congenital cataracts, some with additional cardiac abnormalities, in Australia in 1941. This led Gregg in Sydney to postulate a causal link between a severe epidemic of rubella that had occurred six to nine months before the children were born and the subsequent abnormalities. It is now well known that if a woman develops rubella during pregnancy it may affect her unborn baby.

– A case report published in the UK in 1961 described the development of a pulmonary embolism in a 40-year-old pre-menopausal woman, five weeks after she had started using an oral contraceptive (OC) to treat endometriosis. Because pulmonary embolism is rare in women of that age, the author suggested that it might have been caused by the OC, particularly since it was a novel exposure at that time. More detailed studies have consistently shown that there is an association between the use of OCs and the risk of pulmonary embolism.

– A report of a series of five cases of Pneumocystis carinii pneumonia that occurred in young, previously healthy, homosexual men in three Los Angeles hospitals in a six-month period during 1980–81. Until then, this disease had been seen almost exclusively in immunosuppressed e.g. the elderly, the severely malnourished and those on anti-cancer chemotherapy. This cluster of cases in young men suggested that the men were suffering from a previously unknown disease, possibly related to sexual behavior which was proved to be HIV/AIDS.

[1].  Kestenbaum B, “An introduction to clinical research”.  Epidemiology and biostatistics : 25, 2009.

[2].  Porta M (ed). A dictionary of epidemiology /edited for the International Epidemiological Association, 5th edition.  Oxford University Press , UK: pp: 33, 2008 .

[3].  Suresh K, Suresh G, Thomas SV, “Design and data analysis 1 study design”.  Ann Indian Acad Neurol , vol.15, no.2: 76–80, 2012 .

[4].  Kooistra B, Dijkman B, Einhorn TA, et al., “How to design a good case series”.  J Bone Joint Surg Am , vol.91, (Suppl 3): 21 -26, 2009.

[5].  Dekkers OM, Egger M, Altman DG, et al., “Distinguishing case series from cohort studies”.  Ann Intern Med,  vol.156, (1 Pt 1): 37-40, 2012.

[6].  Carey TS, Boden SD, “A Critical Guide to Case Series Reports”.  Spine , vol.28, no.15: 1631–34, 2003 .

[7]. Lutheran HealthCare, “Guidelines for Writing Case Reports & Case Series”. Accessed: August 1, 2018

[8].  National Cancer Institute Dictionary of Cancer Terms. Accessed: August 12, 2018

[9].  Crandall M, Eastman A, Violano P, et al., “Prevention of firearm-related injuries with restrictive licensing and concealed carry laws: an eastern Association for the Surgery of trauma systematic review”.  J Trauma Acute Care Surg,  vol.81, no.5: 952–60, 2016.

[10].  Omair A, “Selecting the appropriate study design for your research: Descriptive study designs”.  J Health Spec , vol.3, no.3: 153-56, 2015.

[11].  Mandil A, “Study Designs in Epidemiology. Lecture presented at High Institute of Public Health University of Alexandria”.  Accessed: August 6, 2018

[12].  Study design Bhopal R, Bruce and Usher J Professor of Public Health, Public Health Sciences Section, Division of Community Health Sciences, University of Edinburgh, Edinburgh EH89AG. Accessed: August 6, 2018

[13].  Esene IN, Ngu J, El Zoghby M, et al., “Case series and descriptive cohort studies in neurosurgery: the confusion and solution”.  Childs Nerv Syst,  vol.30, no.8: 1321–32, 2014 .

[14].  Whitaker H. Case series studies:  rationale, design and analysis. Open University, UK. Accessed: August 11, 2018

[15].  Khoury MJ, Flanders WD, “Nontraditional epidemiologic approaches in the analysis of gene-environment interaction: case-control studies with no controls”. Am J Epidemiol, vol.144, no.3: 207–13, 1996.

[16].  Yu I, Tse S, “Workshop 3 — Sources of bias in case series, patient cohorts, and randomized controlled trials”.  Hong Kong Med J,  vol.17, no.6: 478-79, 2011.

[17].  Howick J. Introduction to study design. Accessed August 13, 2018

[18].  Ford DE, introduction to clinical research, study design, case series and cross-sectional.  July 14, 2010. Accessed: August 13, 2018

[19].  Griffin D, Audige L, “Common statistical methods in orthopaedic clinical studies”.  Clin Orthop Relat Res,  vol.413: 70-79, 2003 .

[20].  Dalziel K, Round A, Stein K, et al., “Do the findings of case series studies vary significantly according to methodological characteristics?”,  Health Technol Assess,  vol.9, no.2: iii-iv, 1-146, 2005.

[21].  von Elm E, Altman DG, Egger M, et al., “The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies”.  Lancet , vol.370, no. 9596: 1453-57, 2007 .

[22].  Cummings P, Weiss NS, “Case series and exposure series: the role of studies without controls in providing information about the etiology of injury or disease”.  Inj Prev , vol.4, no.1: 54–57, 1998 .

[23].  Hartz A, Marsh JL, “Methodologic issues in observational studies”.  Clin Orthop Relat Res , vol.413: 33-42, 2003.

[24].   Audigé L, Hanson B, Kopjar B, “Issues in the planning and conduct of nonrandomized studies”.  Injury,  vol.37, no.4: 340-48, 2006.

[25].  Degu G, Yigzaw T, “Lecture notes. For health science students. Research methodology”.  Ethiopia Public Health Training Initiative:  P.25, 2006.

[26]. Webb P, Bain C, “Essential epidemiology. An introduction for students and health professionals. Second Edition”: P.72, 2011.

[27].  Cole P, “Introduction. In: Breslow NE, Day NE, editors. Statistical Methods in Cancer Research: The Analysis of Case-control Studies. IARC Publication No. 32. Vol. 1. Lyon: International Agency for Research on Cancer; 1980”. Accessed: August 13, 2018

[28].  Polgar S, Thomas SA, “Introduction to research in the health Sciences”.  Churchill Livingstone . 2013

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to share on Tumblr (Opens in new window)
• Click to share on Pinterest (Opens in new window)