what is a case control study in research

Study Design 101: Case Control Study

• Case Report
• Case Control Study
• Cohort Study
• Randomized Controlled Trial
• Practice Guideline
• Systematic Review
• Meta-Analysis
• Helpful Formulas
• Finding Specific Study Types

A study that compares patients who have a disease or outcome of interest (cases) with patients who do not have the disease or outcome (controls), and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease.

Case control studies are observational because no intervention is attempted and no attempt is made to alter the course of the disease. The goal is to retrospectively determine the exposure to the risk factor of interest from each of the two groups of individuals: cases and controls. These studies are designed to estimate odds.

Case control studies are also known as "retrospective studies" and "case-referent studies."

• Good for studying rare conditions or diseases
• Less time needed to conduct the study because the condition or disease has already occurred
• Lets you simultaneously look at multiple risk factors
• Useful as initial studies to establish an association
• Can answer questions that could not be answered through other study designs

Disadvantages

• Retrospective studies have more problems with data quality because they rely on memory and people with a condition will be more motivated to recall risk factors (also called recall bias).
• Not good for evaluating diagnostic tests because it's already clear that the cases have the condition and the controls do not
• It can be difficult to find a suitable control group

Design pitfalls to look out for

Care should be taken to avoid confounding, which arises when an exposure and an outcome are both strongly associated with a third variable. Controls should be subjects who might have been cases in the study but are selected independent of the exposure. Cases and controls should also not be "over-matched."

Is the control group appropriate for the population? Does the study use matching or pairing appropriately to avoid the effects of a confounding variable? Does it use appropriate inclusion and exclusion criteria?

Fictitious Example

There is a suspicion that zinc oxide, the white non-absorbent sunscreen traditionally worn by lifeguards is more effective at preventing sunburns that lead to skin cancer than absorbent sunscreen lotions. A case-control study was conducted to investigate if exposure to zinc oxide is a more effective skin cancer prevention measure. The study involved comparing a group of former lifeguards that had developed cancer on their cheeks and noses (cases) to a group of lifeguards without this type of cancer (controls) and assess their prior exposure to zinc oxide or absorbent sunscreen lotions.

This study would be retrospective in that the former lifeguards would be asked to recall which type of sunscreen they used on their face and approximately how often. This could be either a matched or unmatched study, but efforts would need to be made to ensure that the former lifeguards are of the same average age, and lifeguarded for a similar number of seasons and amount of time per season.

Real-life Examples

Boubekri, M., Cheung, I., Reid, K., Wang, C., & Zee, P. (2014). Impact of windows and daylight exposure on overall health and sleep quality of office workers: a case-control pilot study. Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine, 10 (6), 603-611. https://doi.org/10.5664/jcsm.3780

This pilot study explored the impact of exposure to daylight on the health of office workers (measuring well-being and sleep quality subjectively, and light exposure, activity level and sleep-wake patterns via actigraphy). Individuals with windows in their workplaces had more light exposure, longer sleep duration, and more physical activity. They also reported a better scores in the areas of vitality and role limitations due to physical problems, better sleep quality and less sleep disturbances.

Togha, M., Razeghi Jahromi, S., Ghorbani, Z., Martami, F., & Seifishahpar, M. (2018). Serum Vitamin D Status in a Group of Migraine Patients Compared With Healthy Controls: A Case-Control Study. Headache, 58 (10), 1530-1540. https://doi.org/10.1111/head.13423

This case-control study compared serum vitamin D levels in individuals who experience migraine headaches with their matched controls. Studied over a period of thirty days, individuals with higher levels of serum Vitamin D was associated with lower odds of migraine headache.

Related Formulas

• Odds ratio in an unmatched study
• Odds ratio in a matched study

Related Terms

A patient with the disease or outcome of interest.

Confounding

When an exposure and an outcome are both strongly associated with a third variable.

A patient who does not have the disease or outcome.

Matched Design

Each case is matched individually with a control according to certain characteristics such as age and gender. It is important to remember that the concordant pairs (pairs in which the case and control are either both exposed or both not exposed) tell us nothing about the risk of exposure separately for cases or controls.

Observed Assignment

The method of assignment of individuals to study and control groups in observational studies when the investigator does not intervene to perform the assignment.

Unmatched Design

The controls are a sample from a suitable non-affected population.

Now test yourself!

1. Case Control Studies are prospective in that they follow the cases and controls over time and observe what occurs.

a) True b) False

2. Which of the following is an advantage of Case Control Studies?

a) They can simultaneously look at multiple risk factors. b) They are useful to initially establish an association between a risk factor and a disease or outcome. c) They take less time to complete because the condition or disease has already occurred. d) b and c only e) a, b, and c

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Quantitative study designs: Case Control

Quantitative study designs.

• Introduction
• Cohort Studies
• Randomised Controlled Trial

Case Control

• Cross-Sectional Studies
• Study Designs Home

In a Case-Control study there are two groups of people: one has a health issue (Case group), and this group is “matched” to a Control group without the health issue based on characteristics like age, gender, occupation. In this study type, we can look back in the patient’s histories to look for exposure to risk factors that are common to the Case group, but not the Control group. It was a case-control study that demonstrated a link between carcinoma of the lung and smoking tobacco . These studies estimate the odds between the exposure and the health outcome, however they cannot prove causality. Case-Control studies might also be referred to as retrospective or case-referent studies. 

Stages of a Case-Control study

This diagram represents taking both the case (disease) and the control (no disease) groups and looking back at their histories to determine their exposure to possible contributing factors.  The researchers then determine the likelihood of those factors contributing to the disease.

(FOR ACCESSIBILITY: A case control study is likely to show that most, but not all exposed people end up with the health issue, and some unexposed people may also develop the health issue)

Which Clinical Questions does Case-Control best answer?

Case-Control studies are best used for Prognosis questions.

For example: Do anticholinergic drugs increase the risk of dementia in later life? (See BMJ Case-Control study Anticholinergic drugs and risk of dementia: case-control study )

What are the advantages and disadvantages to consider when using Case-Control?

* Confounding occurs when the elements of the study design invalidate the result. It is usually unintentional. It is important to avoid confounding, which can happen in a few ways within Case-Control studies. This explains why it is lower in the hierarchy of evidence, superior only to Case Studies.

What does a strong Case-Control study look like?

A strong study will have:

• Well-matched controls, similar background without being so similar that they are likely to end up with the same health issue (this can be easier said than done since the risk factors are unknown). 
• Detailed medical histories are available, reducing the emphasis on a patient’s unreliable recall of their potential exposures. 

What are the pitfalls to look for?

• Poorly matched or over-matched controls.  Poorly matched means that not enough factors are similar between the Case and Control. E.g. age, gender, geography. Over-matched conversely means that so many things match (age, occupation, geography, health habits) that in all likelihood the Control group will also end up with the same health issue! Either of these situations could cause the study to become ineffective. 
• Selection bias: Selection of Controls is biased. E.g. All Controls are in the hospital, so they’re likely already sick, they’re not a true sample of the wider population. 
• Cases include persons showing early symptoms who never ended up having the illness. 

Critical appraisal tools 

To assist with critically appraising case control studies there are some tools / checklists you can use.

CASP - Case Control Checklist

JBI – Critical appraisal checklist for case control studies

CEBMA – Centre for Evidence Based Management  – Critical appraisal questions (focus on leadership and management)

STROBE - Observational Studies checklists includes Case control

SIGN - Case-Control Studies Checklist

Real World Examples

Smoking and carcinoma of the lung; preliminary report

• Doll, R., & Hill, A. B. (1950). Smoking and carcinoma of the lung; preliminary report.  British Medical Journal ,  2 (4682), 739–748. Retrieved from  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2038856/
• Key Case-Control study linking tobacco smoking with lung cancer
• Notes a marked increase in incidence of Lung Cancer disproportionate to population growth.
• 20 London Hospitals contributed current Cases of lung, stomach, colon and rectum cancer via admissions, house-physician and radiotherapy diagnosis, non-cancer Controls were selected at each hospital of the same-sex and within 5 year age group of each.
• 1732 Cases and 743 Controls were interviewed for social class, gender, age, exposure to urban pollution, occupation and smoking habits.
• It was found that continued smoking from a younger age and smoking a greater number of cigarettes correlated with incidence of lung cancer.

Anticholinergic drugs and risk of dementia: case-control study

• Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., . . . Savva, G. M. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ , 361, k1315. Retrieved from  http://www.bmj.com/content/361/bmj.k1315.abstract .
• A recent study linking the duration and level of exposure to Anticholinergic drugs and subsequent onset of dementia.
• Anticholinergic Cognitive Burden (ACB) was estimated in various drugs, the higher the exposure (measured as the ACB score) the greater likeliness of onset of dementia later in life.
• Antidepressant, urological, and antiparkinson drugs with an ACB score of 3 increased the risk of dementia. Gastrointestinal drugs with an ACB score of 3 were not strongly linked with onset of dementia.
• Tricyclic antidepressants such as Amitriptyline have an ACB score of 3 and are an example of a common area of concern.

Omega-3 deficiency associated with perinatal depression: Case-Control study 

• Rees, A.-M., Austin, M.-P., Owen, C., & Parker, G. (2009). Omega-3 deficiency associated with perinatal depression: Case control study. Psychiatry Research , 166(2), 254-259. Retrieved from  http://www.sciencedirect.com/science/article/pii/S0165178107004398 .
• During pregnancy women lose Omega-3 polyunsaturated fatty acids to the developing foetus.
• There is a known link between Omgea-3 depletion and depression
• Sixteen depressed and 22 non-depressed women were recruited during their third trimester
• High levels of Omega-3 were associated with significantly lower levels of depression.
• Women with low levels of Omega-3 were six times more likely to be depressed during pregnancy.

References and Further Reading

Doll, R., & Hill, A. B. (1950). Smoking and carcinoma of the lung; preliminary report. British Medical Journal, 2(4682), 739–748. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2038856/

Greenhalgh, Trisha. How to Read a Paper: the Basics of Evidence-Based Medicine, John Wiley & Sons, Incorporated, 2014. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/deakin/detail.action?docID=1642418 .

Himmelfarb Health Sciences Library. (2019). Study Design 101: Case-Control Study. Retrieved from https://himmelfarb.gwu.edu/tutorials/studydesign101/casecontrols.cfm   

Hoffmann, T., Bennett, S., & Del Mar, C. (2017). Evidence-Based Practice Across the Health Professions (Third edition. ed.): Elsevier. 

Lewallen, S., & Courtright, P. (1998). Epidemiology in practice: case-control studies. Community Eye Health, 11(28), 57.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1706071/  

Pelham, B. W. a., & Blanton, H. (2013). Conducting research in psychology : measuring the weight of smoke /Brett W. Pelham, Hart Blanton (Fourth edition. ed.): Wadsworth Cengage Learning. 

Rees, A.-M., Austin, M.-P., Owen, C., & Parker, G. (2009). Omega-3 deficiency associated with perinatal depression: Case control study. Psychiatry Research, 166(2), 254-259. Retrieved from http://www.sciencedirect.com/science/article/pii/S0165178107004398

Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., … Savva, G. M. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ, 361, k1315. Retrieved from http://www.bmj.com/content/361/bmj.k1315.abstract

Statistics How To. (2019). Case-Control Study: Definition, Real Life Examples. Retrieved from https://www.statisticshowto.com/case-control-study/  

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What is a Case-Control Study?

Affiliations.

• 1 Department of Neurosurgery, University of Alabama at Birmingham.
• 2 Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
• 3 Department of Neurosurgery, Mobile Infirmary Medical Center, Mobile, Alabama.
• PMID: 30535401
• DOI: 10.1093/neuros/nyy590

Case-control (case-control, case-controlled) studies are beginning to appear more frequently in the neurosurgical literature. They can be more robust, if well designed, than the typical case series or even cohort study to determine or refine treatment algorithms. The purpose of this review is to define and explore the differences between case-control studies and other so-called nonexperimental, quasiexperimental, or observational studies in determining preferred treatments for neurosurgical patients.

Keywords: Case–control; Observational study; Study design.

Copyright © 2018 by the Congress of Neurological Surgeons.

• Biomedical Research
• Case-Control Studies*
• Research Design

Case Study Research Method in Psychology

Saul Mcleod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul Mcleod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

Learn about our Editorial Process

Olivia Guy-Evans, MSc

Associate Editor for Simply Psychology

BSc (Hons) Psychology, MSc Psychology of Education

Olivia Guy-Evans is a writer and associate editor for Simply Psychology. She has previously worked in healthcare and educational sectors.

On This Page:

Case studies are in-depth investigations of a person, group, event, or community. Typically, data is gathered from various sources using several methods (e.g., observations & interviews).

The case study research method originated in clinical medicine (the case history, i.e., the patient’s personal history). In psychology, case studies are often confined to the study of a particular individual.

The information is mainly biographical and relates to events in the individual’s past (i.e., retrospective), as well as to significant events that are currently occurring in his or her everyday life.

The case study is not a research method, but researchers select methods of data collection and analysis that will generate material suitable for case studies.

Freud (1909a, 1909b) conducted very detailed investigations into the private lives of his patients in an attempt to both understand and help them overcome their illnesses.

This makes it clear that the case study is a method that should only be used by a psychologist, therapist, or psychiatrist, i.e., someone with a professional qualification.

There is an ethical issue of competence. Only someone qualified to diagnose and treat a person can conduct a formal case study relating to atypical (i.e., abnormal) behavior or atypical development.

 Famous Case Studies

• Anna O – One of the most famous case studies, documenting psychoanalyst Josef Breuer’s treatment of “Anna O” (real name Bertha Pappenheim) for hysteria in the late 1800s using early psychoanalytic theory.
• Little Hans – A child psychoanalysis case study published by Sigmund Freud in 1909 analyzing his five-year-old patient Herbert Graf’s house phobia as related to the Oedipus complex.
• Bruce/Brenda – Gender identity case of the boy (Bruce) whose botched circumcision led psychologist John Money to advise gender reassignment and raise him as a girl (Brenda) in the 1960s.
• Genie Wiley – Linguistics/psychological development case of the victim of extreme isolation abuse who was studied in 1970s California for effects of early language deprivation on acquiring speech later in life.
• Phineas Gage – One of the most famous neuropsychology case studies analyzes personality changes in railroad worker Phineas Gage after an 1848 brain injury involving a tamping iron piercing his skull.

Clinical Case Studies

• Studying the effectiveness of psychotherapy approaches with an individual patient
• Assessing and treating mental illnesses like depression, anxiety disorders, PTSD
• Neuropsychological cases investigating brain injuries or disorders

Child Psychology Case Studies

• Studying psychological development from birth through adolescence
• Cases of learning disabilities, autism spectrum disorders, ADHD
• Effects of trauma, abuse, deprivation on development

Types of Case Studies

• Explanatory case studies : Used to explore causation in order to find underlying principles. Helpful for doing qualitative analysis to explain presumed causal links.
• Exploratory case studies : Used to explore situations where an intervention being evaluated has no clear set of outcomes. It helps define questions and hypotheses for future research.
• Descriptive case studies : Describe an intervention or phenomenon and the real-life context in which it occurred. It is helpful for illustrating certain topics within an evaluation.
• Multiple-case studies : Used to explore differences between cases and replicate findings across cases. Helpful for comparing and contrasting specific cases.
• Intrinsic : Used to gain a better understanding of a particular case. Helpful for capturing the complexity of a single case.
• Collective : Used to explore a general phenomenon using multiple case studies. Helpful for jointly studying a group of cases in order to inquire into the phenomenon.

Where Do You Find Data for a Case Study?

There are several places to find data for a case study. The key is to gather data from multiple sources to get a complete picture of the case and corroborate facts or findings through triangulation of evidence. Most of this information is likely qualitative (i.e., verbal description rather than measurement), but the psychologist might also collect numerical data.

1. Primary sources

• Interviews – Interviewing key people related to the case to get their perspectives and insights. The interview is an extremely effective procedure for obtaining information about an individual, and it may be used to collect comments from the person’s friends, parents, employer, workmates, and others who have a good knowledge of the person, as well as to obtain facts from the person him or herself.
• Observations – Observing behaviors, interactions, processes, etc., related to the case as they unfold in real-time.
• Documents & Records – Reviewing private documents, diaries, public records, correspondence, meeting minutes, etc., relevant to the case.

2. Secondary sources

• News/Media – News coverage of events related to the case study.
• Academic articles – Journal articles, dissertations etc. that discuss the case.
• Government reports – Official data and records related to the case context.
• Books/films – Books, documentaries or films discussing the case.

3. Archival records

Searching historical archives, museum collections and databases to find relevant documents, visual/audio records related to the case history and context.

Public archives like newspapers, organizational records, photographic collections could all include potentially relevant pieces of information to shed light on attitudes, cultural perspectives, common practices and historical contexts related to psychology.

4. Organizational records

Organizational records offer the advantage of often having large datasets collected over time that can reveal or confirm psychological insights.

Of course, privacy and ethical concerns regarding confidential data must be navigated carefully.

However, with proper protocols, organizational records can provide invaluable context and empirical depth to qualitative case studies exploring the intersection of psychology and organizations.

• Organizational/industrial psychology research : Organizational records like employee surveys, turnover/retention data, policies, incident reports etc. may provide insight into topics like job satisfaction, workplace culture and dynamics, leadership issues, employee behaviors etc.
• Clinical psychology : Therapists/hospitals may grant access to anonymized medical records to study aspects like assessments, diagnoses, treatment plans etc. This could shed light on clinical practices.
• School psychology : Studies could utilize anonymized student records like test scores, grades, disciplinary issues, and counseling referrals to study child development, learning barriers, effectiveness of support programs, and more.

How do I Write a Case Study in Psychology?

Follow specified case study guidelines provided by a journal or your psychology tutor. General components of clinical case studies include: background, symptoms, assessments, diagnosis, treatment, and outcomes. Interpreting the information means the researcher decides what to include or leave out. A good case study should always clarify which information is the factual description and which is an inference or the researcher’s opinion.

1. Introduction

• Provide background on the case context and why it is of interest, presenting background information like demographics, relevant history, and presenting problem.
• Compare briefly to similar published cases if applicable. Clearly state the focus/importance of the case.

2. Case Presentation

• Describe the presenting problem in detail, including symptoms, duration,and impact on daily life.
• Include client demographics like age and gender, information about social relationships, and mental health history.
• Describe all physical, emotional, and/or sensory symptoms reported by the client.
• Use patient quotes to describe the initial complaint verbatim. Follow with full-sentence summaries of relevant history details gathered, including key components that led to a working diagnosis.
• Summarize clinical exam results, namely orthopedic/neurological tests, imaging, lab tests, etc. Note actual results rather than subjective conclusions. Provide images if clearly reproducible/anonymized.
• Clearly state the working diagnosis or clinical impression before transitioning to management.

3. Management and Outcome

• Indicate the total duration of care and number of treatments given over what timeframe. Use specific names/descriptions for any therapies/interventions applied.
• Present the results of the intervention,including any quantitative or qualitative data collected.
• For outcomes, utilize visual analog scales for pain, medication usage logs, etc., if possible. Include patient self-reports of improvement/worsening of symptoms. Note the reason for discharge/end of care.

4. Discussion

• Analyze the case, exploring contributing factors, limitations of the study, and connections to existing research.
• Analyze the effectiveness of the intervention,considering factors like participant adherence, limitations of the study, and potential alternative explanations for the results.
• Identify any questions raised in the case analysis and relate insights to established theories and current research if applicable. Avoid definitive claims about physiological explanations.
• Offer clinical implications, and suggest future research directions.

5. Additional Items

• Thank specific assistants for writing support only. No patient acknowledgments.
• References should directly support any key claims or quotes included.
• Use tables/figures/images only if substantially informative. Include permissions and legends/explanatory notes.
• Provides detailed (rich qualitative) information.
• Provides insight for further research.
• Permitting investigation of otherwise impractical (or unethical) situations.

Case studies allow a researcher to investigate a topic in far more detail than might be possible if they were trying to deal with a large number of research participants (nomothetic approach) with the aim of ‘averaging’.

Because of their in-depth, multi-sided approach, case studies often shed light on aspects of human thinking and behavior that would be unethical or impractical to study in other ways.

Research that only looks into the measurable aspects of human behavior is not likely to give us insights into the subjective dimension of experience, which is important to psychoanalytic and humanistic psychologists.

Case studies are often used in exploratory research. They can help us generate new ideas (that might be tested by other methods). They are an important way of illustrating theories and can help show how different aspects of a person’s life are related to each other.

The method is, therefore, important for psychologists who adopt a holistic point of view (i.e., humanistic psychologists ).

Limitations

• Lacking scientific rigor and providing little basis for generalization of results to the wider population.
• Researchers’ own subjective feelings may influence the case study (researcher bias).
• Difficult to replicate.
• Time-consuming and expensive.
• The volume of data, together with the time restrictions in place, impacted the depth of analysis that was possible within the available resources.

Because a case study deals with only one person/event/group, we can never be sure if the case study investigated is representative of the wider body of “similar” instances. This means the conclusions drawn from a particular case may not be transferable to other settings.

Because case studies are based on the analysis of qualitative (i.e., descriptive) data , a lot depends on the psychologist’s interpretation of the information she has acquired.

This means that there is a lot of scope for Anna O , and it could be that the subjective opinions of the psychologist intrude in the assessment of what the data means.

For example, Freud has been criticized for producing case studies in which the information was sometimes distorted to fit particular behavioral theories (e.g., Little Hans ).

This is also true of Money’s interpretation of the Bruce/Brenda case study (Diamond, 1997) when he ignored evidence that went against his theory.

Breuer, J., & Freud, S. (1895).  Studies on hysteria . Standard Edition 2: London.

Curtiss, S. (1981). Genie: The case of a modern wild child .

Diamond, M., & Sigmundson, K. (1997). Sex Reassignment at Birth: Long-term Review and Clinical Implications. Archives of Pediatrics & Adolescent Medicine , 151(3), 298-304

Freud, S. (1909a). Analysis of a phobia of a five year old boy. In The Pelican Freud Library (1977), Vol 8, Case Histories 1, pages 169-306

Freud, S. (1909b). Bemerkungen über einen Fall von Zwangsneurose (Der “Rattenmann”). Jb. psychoanal. psychopathol. Forsch ., I, p. 357-421; GW, VII, p. 379-463; Notes upon a case of obsessional neurosis, SE , 10: 151-318.

Harlow J. M. (1848). Passage of an iron rod through the head.  Boston Medical and Surgical Journal, 39 , 389–393.

Harlow, J. M. (1868).  Recovery from the Passage of an Iron Bar through the Head .  Publications of the Massachusetts Medical Society. 2  (3), 327-347.

Money, J., & Ehrhardt, A. A. (1972).  Man & Woman, Boy & Girl : The Differentiation and Dimorphism of Gender Identity from Conception to Maturity. Baltimore, Maryland: Johns Hopkins University Press.

Money, J., & Tucker, P. (1975). Sexual signatures: On being a man or a woman.

Further Information

• Case Study Approach
• Case Study Method
• Enhancing the Quality of Case Studies in Health Services Research
• “We do things together” A case study of “couplehood” in dementia
• Using mixed methods for evaluating an integrative approach to cancer care: a case study

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Rosacea and autoimmune disease: a case-control study in the all of us database

• Research Letter
• Published: 25 May 2024
• Volume 316 , article number  252 , ( 2024 )

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• Austin J. Piontkowski 1 ,
• Daniela Mikhaylov 1 ,
• Omar Alani 1 ,
• Jeremy Orloff 1 ,
• Camille Powers 1 ,
• Nicholas Gulati 1 &
• Benjamin Ungar 1  

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Egeberg A, Hansen RP, Gislason HG, Thyssen PJ (2016) Clustering of autoimmune diseases in patients with rosacea. J Am Acad Dermatol 74(4):667–72e1

Article   PubMed   Google Scholar  

Rainer MB, Kang S, Chien LA (2017) Rosacea: Epidemiology, pathogenesis, and treatment. Dermato-Endocrinology 9(1):e1361574

Article   PubMed   PubMed Central   Google Scholar  

Damsky W, King AB (2017) JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol 76(4):736–744

Article   CAS   PubMed   PubMed Central   Google Scholar  

Ren M, Yang X, Teng Y, Lu W, Ding Y, Tao X (2023) Successful Treatment of Granulomatous Rosacea by JAK Inhibitor Abrocitinib: A Case Report. Clinical, Cosmetic and Investigational Dermatology 16:3369-74

Sun YH, Man XY, Xuan XY, Huang CZ, Shen Y, Lao LM (2022) Tofacitinib for the treatment of erythematotelangiectatic and papulopustular rosacea: a retrospective case series. Dermatol Ther 35(11)

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Acknowledgements

The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.

The authors have not received any funding for this project.

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Department of Dermatology, Icahn School of Medicine at Mount Sinai, 5 East 98th St, 5th Floor, New York, NY, 10029, USA

Austin J. Piontkowski, Daniela Mikhaylov, Omar Alani, Jeremy Orloff, Camille Powers, Nicholas Gulati & Benjamin Ungar

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Contributions

AP contributed to conceptualization, data curation, formal analysis, investigation, methodology, and writing – original draft. DM and OA contributed to writing – original draft. JO and CP contributed to writing – review & editing. NG contributed to writing – review & editing and supervision. BU contributed to conceptualization, project administration, methodology, supervision, and writing – review & editing. All authors reviewed the manuscript.

Corresponding author

Correspondence to Benjamin Ungar .

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BU is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Incyte, Rapt Therapeutics, and Pfizer. He is also a consultant for Arcutis Biotherapeutics, Bristol Myers Squibb, Castle Biosciences, Fresenius Kabi, Galderma, Janssen, Lilly, Pfizer, Primus Pharmaceuticals, Sanofi, and UCB. The other authors have no conflicts of interest.

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Piontkowski, A.J., Mikhaylov, D., Alani, O. et al. Rosacea and autoimmune disease: a case-control study in the all of us database. Arch Dermatol Res 316 , 252 (2024). https://doi.org/10.1007/s00403-024-02993-3

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Factors Associated With Chronic Arthropathy And Rheumatological Diseases After Chikungunya Infection in Colombia: A Case-Control Study

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Objective To identify the factors associated with the development of chronic arthropathy and rheumatological conditions in individuals who presented with clinical chikungunya infection.

Methods A case-control study was carried out among individuals with a clinical diagnosis of chikungunya treated at a Colombian Health Provider Institution between 2014 and 2015. Two logistic regression models were constructed: one excluding the variables with more than 50% of the missing data, and another with all the variables but with the imputed data.

Results In total 133 cases and 216 controls were obtained (349 individuals). In both models, female gender was a risk factor (OR: 2.27, CI95: 1.03 - 4.97, p = 0.04, and OR: 2.37, CI95: 1.09 - 5.17, p = 0.029, respectively), while acute involvement of the wrists was a protective factor (OR: 0.44, CI95: 0.20 - 0.95, p < 0.037; and OR: 0.29, CI95: 0.13 - 0.65, p = 0.003 respectively). Arthralgia duration was a risk factor in the imputed data model (OR: 1.03, CI95: 1.00 - 1.06, p = 0.02).

Conclusion Female gender and the duration of joint symptoms in the acute phase were the main risk factors for the development of chronic chikungunya arthropathy or rheumatological pathology. Wrist involvement was a protective factor. Only rheumatoid arthritis was found to be a rheumatological disease associated with chikungunya infections. Finally, this study suggests that the interaction between usual cardiovascular factors could enhance the probability of developing chronic symptoms.

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The study was approved by the Ethics Committee of the Faculty of Health of the Universidad del Valle Colombia. CIREH and the Ethics Committee of the HPI from which the study subjects came (approved record 007-93 020).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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• About Adverse Childhood Experiences
• Risk and Protective Factors
• Program: Essentials for Childhood: Preventing Adverse Childhood Experiences through Data to Action
• Adverse childhood experiences can have long-term impacts on health, opportunity and well-being.
• Adverse childhood experiences are common and some groups experience them more than others.

What are adverse childhood experiences?

Adverse childhood experiences, or ACEs, are potentially traumatic events that occur in childhood (0-17 years). Examples include: 1

• Experiencing violence, abuse, or neglect.
• Witnessing violence in the home or community.
• Having a family member attempt or die by suicide.

Also included are aspects of the child’s environment that can undermine their sense of safety, stability, and bonding. Examples can include growing up in a household with: 1

• Substance use problems.
• Mental health problems.
• Instability due to parental separation.
• Instability due to household members being in jail or prison.

The examples above are not a complete list of adverse experiences. Many other traumatic experiences could impact health and well-being. This can include not having enough food to eat, experiencing homelessness or unstable housing, or experiencing discrimination. 2 3 4 5 6

Quick facts and stats

ACEs are common. About 64% of adults in the United States reported they had experienced at least one type of ACE before age 18. Nearly one in six (17.3%) adults reported they had experienced four or more types of ACEs. 7

Preventing ACEs could potentially reduce many health conditions. Estimates show up to 1.9 million heart disease cases and 21 million depression cases potentially could have been avoided by preventing ACEs. 1

Some people are at greater risk of experiencing one or more ACEs than others. While all children are at risk of ACEs, numerous studies show inequities in such experiences. These inequalities are linked to the historical, social, and economic environments in which some families live. 5 6 ACEs were highest among females, non-Hispanic American Indian or Alaska Native adults, and adults who are unemployed or unable to work. 7

ACEs are costly. ACEs-related health consequences cost an estimated economic burden of $748 billion annually in Bermuda, Canada, and the United States. 8

ACEs can have lasting effects on health and well-being in childhood and life opportunities well into adulthood. 9 Life opportunities include things like education and job potential. These experiences can increase the risks of injury, sexually transmitted infections, and involvement in sex trafficking. They can also increase risks for maternal and child health problems including teen pregnancy, pregnancy complications, and fetal death. Also included are a range of chronic diseases and leading causes of death, such as cancer, diabetes, heart disease, and suicide. 1 10 11 12 13 14 15 16 17

ACEs and associated social determinants of health, such as living in under-resourced or racially segregated neighborhoods, can cause toxic stress. Toxic stress, or extended or prolonged stress, from ACEs can negatively affect children’s brain development, immune systems, and stress-response systems. These changes can affect children’s attention, decision-making, and learning. 18

Children growing up with toxic stress may have difficulty forming healthy and stable relationships. They may also have unstable work histories as adults and struggle with finances, jobs, and depression throughout life. 18 These effects can also be passed on to their own children. 19 20 21 Some children may face further exposure to toxic stress from historical and ongoing traumas. These historical and ongoing traumas refer to experiences of racial discrimination or the impacts of poverty resulting from limited educational and economic opportunities. 1 6

Adverse childhood experiences can be prevented. Certain factors may increase or decrease the risk of experiencing adverse childhood experiences.

Preventing adverse childhood experiences requires understanding and addressing the factors that put people at risk for or protect them from violence.

Creating safe, stable, nurturing relationships and environments for all children can prevent ACEs and help all children reach their full potential. We all have a role to play.

• Merrick MT, Ford DC, Ports KA, et al. Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention — 25 States, 2015–2017. MMWR Morb Mortal Wkly Rep 2019;68:999-1005. DOI: http://dx.doi.org/10.15585/mmwr.mm6844e1 .
• Cain KS, Meyer SC, Cummer E, Patel KK, Casacchia NJ, Montez K, Palakshappa D, Brown CL. Association of Food Insecurity with Mental Health Outcomes in Parents and Children. Science Direct. 2022; 22:7; 1105-1114. DOI: https://doi.org/10.1016/j.acap.2022.04.010 .
• Smith-Grant J, Kilmer G, Brener N, Robin L, Underwood M. Risk Behaviors and Experiences Among Youth Experiencing Homelessness—Youth Risk Behavior Survey, 23 U.S. States and 11 Local School Districts. Journal of Community Health. 2022; 47: 324-333.
• Experiencing discrimination: Early Childhood Adversity, Toxic Stress, and the Impacts of Racism on the Foundations of Health | Annual Review of Public Health https://doi.org/10.1146/annurev-publhealth-090419-101940 .
• Sedlak A, Mettenburg J, Basena M, et al. Fourth national incidence study of child abuse and neglect (NIS-4): Report to Congress. Executive Summary. Washington, DC: U.S. Department of Health an Human Services, Administration for Children and Families.; 2010.
• Font S, Maguire-Jack K. Pathways from childhood abuse and other adversities to adult health risks: The role of adult socioeconomic conditions. Child Abuse Negl. 2016;51:390-399.
• Swedo EA, Aslam MV, Dahlberg LL, et al. Prevalence of Adverse Childhood Experiences Among U.S. Adults — Behavioral Risk Factor Surveillance System, 2011–2020. MMWR Morb Mortal Wkly Rep 2023;72:707–715. DOI: http://dx.doi.org/10.15585/mmwr.mm7226a2 .
• Bellis, MA, et al. Life Course Health Consequences and Associated Annual Costs of Adverse Childhood Experiences Across Europe and North America: A Systematic Review and Meta-Analysis. Lancet Public Health 2019.
• Adverse Childhood Experiences During the COVID-19 Pandemic and Associations with Poor Mental Health and Suicidal Behaviors Among High School Students — Adolescent Behaviors and Experiences Survey, United States, January–June 2021 | MMWR
• Hillis SD, Anda RF, Dube SR, Felitti VJ, Marchbanks PA, Marks JS. The association between adverse childhood experiences and adolescent pregnancy, long-term psychosocial consequences, and fetal death. Pediatrics. 2004 Feb;113(2):320-7.
• Miller ES, Fleming O, Ekpe EE, Grobman WA, Heard-Garris N. Association Between Adverse Childhood Experiences and Adverse Pregnancy Outcomes. Obstetrics & Gynecology . 2021;138(5):770-776. https://doi.org/10.1097/AOG.0000000000004570 .
• Sulaiman S, Premji SS, Tavangar F, et al. Total Adverse Childhood Experiences and Preterm Birth: A Systematic Review. Matern Child Health J . 2021;25(10):1581-1594. https://doi.org/10.1007/s10995-021-03176-6 .
• Ciciolla L, Shreffler KM, Tiemeyer S. Maternal Childhood Adversity as a Risk for Perinatal Complications and NICU Hospitalization. Journal of Pediatric Psychology . 2021;46(7):801-813. https://doi.org/10.1093/jpepsy/jsab027 .
• Mersky JP, Lee CP. Adverse childhood experiences and poor birth outcomes in a diverse, low-income sample. BMC pregnancy and childbirth. 2019;19(1). https://doi.org/10.1186/s12884-019-2560-8 .
• Reid JA, Baglivio MT, Piquero AR, Greenwald MA, Epps N. No youth left behind to human trafficking: Exploring profiles of risk. American journal of orthopsychiatry. 2019;89(6):704.
• Diamond-Welch B, Kosloski AE. Adverse childhood experiences and propensity to participate in the commercialized sex market. Child Abuse & Neglect. 2020 Jun 1;104:104468.
• Shonkoff, J. P., Garner, A. S., Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care, & Section on Developmental and Behavioral Pediatrics (2012). The lifelong effects of early childhood adversity and toxic stress. Pediatrics, 129(1), e232–e246. https://doi.org/10.1542/peds.2011-2663
• Narayan AJ, Kalstabakken AW, Labella MH, Nerenberg LS, Monn AR, Masten AS. Intergenerational continuity of adverse childhood experiences in homeless families: unpacking exposure to maltreatment versus family dysfunction. Am J Orthopsych. 2017;87(1):3. https://doi.org/10.1037/ort0000133 .
• Schofield TJ, Donnellan MB, Merrick MT, Ports KA, Klevens J, Leeb R. Intergenerational continuity in adverse childhood experiences and rural community environments. Am J Public Health. 2018;108(9):1148-1152. https://doi.org/10.2105/AJPH.2018.304598 .
• Schofield TJ, Lee RD, Merrick MT. Safe, stable, nurturing relationships as a moderator of intergenerational continuity of child maltreatment: a meta-analysis. J Adolesc Health. 2013;53(4 Suppl):S32-38. https://doi.org/10.1016/j.jadohealth.2013.05.004 .

Adverse Childhood Experiences (ACEs)

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Observational Studies: Cohort and Case-Control Studies

Jae w. song.

1 Research Fellow, Section of Plastic Surgery, Department of Surgery The University of Michigan Health System; Ann Arbor, MI

Kevin C. Chung

2 Professor of Surgery, Section of Plastic Surgery, Department of Surgery The University of Michigan Health System; Ann Arbor, MI

Observational studies are an important category of study designs. To address some investigative questions in plastic surgery, randomized controlled trials are not always indicated or ethical to conduct. Instead, observational studies may be the next best method to address these types of questions. Well-designed observational studies have been shown to provide results similar to randomized controlled trials, challenging the belief that observational studies are second-rate. Cohort studies and case-control studies are two primary types of observational studies that aid in evaluating associations between diseases and exposures. In this review article, we describe these study designs, methodological issues, and provide examples from the plastic surgery literature.

Because of the innovative nature of the specialty, plastic surgeons are frequently confronted with a spectrum of clinical questions by patients who inquire about “best practices.” It is thus essential that plastic surgeons know how to critically appraise the literature to understand and practice evidence-based medicine (EBM) and also contribute to the effort by carrying out high-quality investigations. 1 Well-designed randomized controlled trials (RCTs) have held the pre-eminent position in the hierarchy of EBM as level I evidence ( Table 1 ). However, RCT methodology, which was first developed for drug trials, can be difficult to conduct for surgical investigations. 3 Instead, well-designed observational studies, recognized as level II or III evidence, can play an important role in deriving evidence for plastic surgery. Results from observational studies are often criticized for being vulnerable to influences by unpredictable confounding factors. However, recent work has challenged this notion, showing comparable results between observational studies and RCTs. 4 , 5 Observational studies can also complement RCTs in hypothesis generation, establishing questions for future RCTs, and defining clinical conditions.

Levels of Evidence Based Medicine

From REF 1 .

Observational studies fall under the category of analytic study designs and are further sub-classified as observational or experimental study designs ( Figure 1 ). The goal of analytic studies is to identify and evaluate causes or risk factors of diseases or health-related events. The differentiating characteristic between observational and experimental study designs is that in the latter, the presence or absence of undergoing an intervention defines the groups. By contrast, in an observational study, the investigator does not intervene and rather simply “observes” and assesses the strength of the relationship between an exposure and disease variable. 6 Three types of observational studies include cohort studies, case-control studies, and cross-sectional studies ( Figure 1 ). Case-control and cohort studies offer specific advantages by measuring disease occurrence and its association with an exposure by offering a temporal dimension (i.e. prospective or retrospective study design). Cross-sectional studies, also known as prevalence studies, examine the data on disease and exposure at one particular time point ( Figure 2 ). 6 Because the temporal relationship between disease occurrence and exposure cannot be established, cross-sectional studies cannot assess the cause and effect relationship. In this review, we will primarily discuss cohort and case-control study designs and related methodologic issues.

Analytic Study Designs. Adapted with permission from Joseph Eisenberg, Ph.D.

Temporal Design of Observational Studies: Cross-sectional studies are known as prevalence studies and do not have an inherent temporal dimension. These studies evaluate subjects at one point in time, the present time. By contrast, cohort studies can be either retrospective (latin derived prefix, “retro” meaning “back, behind”) or prospective (greek derived prefix, “pro” meaning “before, in front of”). Retrospective studies “look back” in time contrasting with prospective studies, which “look ahead” to examine causal associations. Case-control study designs are also retrospective and assess the history of the subject for the presence or absence of an exposure.

COHORT STUDY

The term “cohort” is derived from the Latin word cohors . Roman legions were composed of ten cohorts. During battle each cohort, or military unit, consisting of a specific number of warriors and commanding centurions, were traceable. The word “cohort” has been adopted into epidemiology to define a set of people followed over a period of time. W.H. Frost, an epidemiologist from the early 1900s, was the first to use the word “cohort” in his 1935 publication assessing age-specific mortality rates and tuberculosis. 7 The modern epidemiological definition of the word now means a “group of people with defined characteristics who are followed up to determine incidence of, or mortality from, some specific disease, all causes of death, or some other outcome.” 7

Study Design

A well-designed cohort study can provide powerful results. In a cohort study, an outcome or disease-free study population is first identified by the exposure or event of interest and followed in time until the disease or outcome of interest occurs ( Figure 3A ). Because exposure is identified before the outcome, cohort studies have a temporal framework to assess causality and thus have the potential to provide the strongest scientific evidence. 8 Advantages and disadvantages of a cohort study are listed in Table 2 . 2 , 9 Cohort studies are particularly advantageous for examining rare exposures because subjects are selected by their exposure status. Additionally, the investigator can examine multiple outcomes simultaneously. Disadvantages include the need for a large sample size and the potentially long follow-up duration of the study design resulting in a costly endeavor.

Cohort and Case-Control Study Designs

Advantages and Disadvantages of the Cohort Study

Cohort studies can be prospective or retrospective ( Figure 2 ). Prospective studies are carried out from the present time into the future. Because prospective studies are designed with specific data collection methods, it has the advantage of being tailored to collect specific exposure data and may be more complete. The disadvantage of a prospective cohort study may be the long follow-up period while waiting for events or diseases to occur. Thus, this study design is inefficient for investigating diseases with long latency periods and is vulnerable to a high loss to follow-up rate. Although prospective cohort studies are invaluable as exemplified by the landmark Framingham Heart Study, started in 1948 and still ongoing, 10 in the plastic surgery literature this study design is generally seen to be inefficient and impractical. Instead, retrospective cohort studies are better indicated given the timeliness and inexpensive nature of the study design.

Retrospective cohort studies, also known as historical cohort studies, are carried out at the present time and look to the past to examine medical events or outcomes. In other words, a cohort of subjects selected based on exposure status is chosen at the present time, and outcome data (i.e. disease status, event status), which was measured in the past, are reconstructed for analysis. The primary disadvantage of this study design is the limited control the investigator has over data collection. The existing data may be incomplete, inaccurate, or inconsistently measured between subjects. 2 However, because of the immediate availability of the data, this study design is comparatively less costly and shorter than prospective cohort studies. For example, Spear and colleagues examined the effect of obesity and complication rates after undergoing the pedicled TRAM flap reconstruction by retrospectively reviewing 224 pedicled TRAM flaps in 200 patients over a 10-year period. 11 In this example, subjects who underwent the pedicled TRAM flap reconstruction were selected and categorized into cohorts by their exposure status: normal/underweight, overweight, or obese. The outcomes of interest were various flap and donor site complications. The findings revealed that obese patients had a significantly higher incidence of donor site complications, multiple flap complications, and partial flap necrosis than normal or overweight patients. An advantage of the retrospective study design analysis is the immediate access to the data. A disadvantage is the limited control over the data collection because data was gathered retrospectively over 10-years; for example, a limitation reported by the authors is that mastectomy flap necrosis was not uniformly recorded for all subjects. 11

An important distinction lies between cohort studies and case-series. The distinguishing feature between these two types of studies is the presence of a control, or unexposed, group. Contrasting with epidemiological cohort studies, case-series are descriptive studies following one small group of subjects. In essence, they are extensions of case reports. Usually the cases are obtained from the authors' experiences, generally involve a small number of patients, and more importantly, lack a control group. 12 There is often confusion in designating studies as “cohort studies” when only one group of subjects is examined. Yet, unless a second comparative group serving as a control is present, these studies are defined as case-series. The next step in strengthening an observation from a case-series is selecting appropriate control groups to conduct a cohort or case-control study, the latter which is discussed in the following section about case-control studies. 9

Methodological Issues

Selection of subjects in cohort studies.

The hallmark of a cohort study is defining the selected group of subjects by exposure status at the start of the investigation. A critical characteristic of subject selection is to have both the exposed and unexposed groups be selected from the same source population ( Figure 4 ). 9 Subjects who are not at risk for developing the outcome should be excluded from the study. The source population is determined by practical considerations, such as sampling. Subjects may be effectively sampled from the hospital, be members of a community, or from a doctor's individual practice. A subset of these subjects will be eligible for the study.

Levels of Subject Selection. Adapted from Ref 9 .

Attrition Bias (Loss to follow-up)

Because prospective cohort studies may require long follow-up periods, it is important to minimize loss to follow-up. Loss to follow-up is a situation in which the investigator loses contact with the subject, resulting in missing data. If too many subjects are loss to follow-up, the internal validity of the study is reduced. A general rule of thumb requires that the loss to follow-up rate not exceed 20% of the sample. 6 Any systematic differences related to the outcome or exposure of risk factors between those who drop out and those who stay in the study must be examined, if possible, by comparing individuals who remain in the study and those who were loss to follow-up or dropped out. It is therefore important to select subjects who can be followed for the entire duration of the cohort study. Methods to minimize loss to follow-up are listed in Table 3 .

Methods to Minimize Loss to Follow-Up

Adapted from REF 2 .

CASE-CONTROL STUDIES

Case-control studies were historically borne out of interest in disease etiology. The conceptual basis of the case-control study is similar to taking a history and physical; the diseased patient is questioned and examined, and elements from this history taking are knitted together to reveal characteristics or factors that predisposed the patient to the disease. In fact, the practice of interviewing patients about behaviors and conditions preceding illness dates back to the Hippocratic writings of the 4 th century B.C. 7

Reasons of practicality and feasibility inherent in the study design typically dictate whether a cohort study or case-control study is appropriate. This study design was first recognized in Janet Lane-Claypon's study of breast cancer in 1926, revealing the finding that low fertility rate raises the risk of breast cancer. 13 , 14 In the ensuing decades, case-control study methodology crystallized with the landmark publication linking smoking and lung cancer in the 1950s. 15 Since that time, retrospective case-control studies have become more prominent in the biomedical literature with more rigorous methodological advances in design, execution, and analysis.

Case-control studies identify subjects by outcome status at the outset of the investigation. Outcomes of interest may be whether the subject has undergone a specific type of surgery, experienced a complication, or is diagnosed with a disease ( Figure 3B ). Once outcome status is identified and subjects are categorized as cases, controls (subjects without the outcome but from the same source population) are selected. Data about exposure to a risk factor or several risk factors are then collected retrospectively, typically by interview, abstraction from records, or survey. Case-control studies are well suited to investigate rare outcomes or outcomes with a long latency period because subjects are selected from the outset by their outcome status. Thus in comparison to cohort studies, case-control studies are quick, relatively inexpensive to implement, require comparatively fewer subjects, and allow for multiple exposures or risk factors to be assessed for one outcome ( Table 4 ). 2 , 9

Advantages and Disadvantages of the Case-Control Study

An example of a case-control investigation is by Zhang and colleagues who examined the association of environmental and genetic factors associated with rare congenital microtia, 16 which has an estimated prevalence of 0.83 to 17.4 in 10,000. 17 They selected 121 congenital microtia cases based on clinical phenotype, and 152 unaffected controls, matched by age and sex in the same hospital and same period. Controls were of Hans Chinese origin from Jiangsu, China, the same area from where the cases were selected. This allowed both the controls and cases to have the same genetic background, important to note given the investigated association between genetic factors and congenital microtia. To examine environmental factors, a questionnaire was administered to the mothers of both cases and controls. The authors concluded that adverse maternal health was among the main risk factors for congenital microtia, specifically maternal disease during pregnancy (OR 5.89, 95% CI 2.36-14.72), maternal toxicity exposure during pregnancy (OR 4.76, 95% CI 1.66-13.68), and resident area, such as living near industries associated with air pollution (OR 7.00, 95% CI 2.09-23.47). 16 A case-control study design is most efficient for this investigation, given the rarity of the disease outcome. Because congenital microtia is thought to have multifactorial causes, an additional advantage of the case-control study design in this example is the ability to examine multiple exposures and risk factors.

Selection of Cases

Sampling in a case-control study design begins with selecting the cases. In a case-control study, it is imperative that the investigator has explicitly defined inclusion and exclusion criteria prior to the selection of cases. For example, if the outcome is having a disease, specific diagnostic criteria, disease subtype, stage of disease, or degree of severity should be defined. Such criteria ensure that all the cases are homogenous. Second, cases may be selected from a variety of sources, including hospital patients, clinic patients, or community subjects. Many communities maintain registries of patients with certain diseases and can serve as a valuable source of cases. However, despite the methodologic convenience of this method, validity issues may arise. For example, if cases are selected from one hospital, identified risk factors may be unique to that single hospital. This methodological choice may weaken the generalizability of the study findings. Another example is choosing cases from the hospital versus the community; most likely cases from the hospital sample will represent a more severe form of the disease than those in the community. 2 Finally, it is also important to select cases that are representative of cases in the target population to strengthen the study's external validity ( Figure 4 ). Potential reasons why cases from the original target population eventually filter through and are available as cases (study participants) for a case-control study are illustrated in Figure 5 .

Levels of Case Selection. Adapted from Ref 2 .

Selection of Controls

Selecting the appropriate group of controls can be one of the most demanding aspects of a case-control study. An important principle is that the distribution of exposure should be the same among cases and controls; in other words, both cases and controls should stem from the same source population. The investigator may also consider the control group to be an at-risk population, with the potential to develop the outcome. Because the validity of the study depends upon the comparability of these two groups, cases and controls should otherwise meet the same inclusion criteria in the study.

A case-control study design that exemplifies this methodological feature is by Chung and colleagues, who examined maternal cigarette smoking during pregnancy and the risk of newborns developing cleft lip/palate. 18 A salient feature of this study is the use of the 1996 U.S. Natality database, a population database, from which both cases and controls were selected. This database provides a large sample size to assess newborn development of cleft lip/palate (outcome), which has a reported incidence of 1 in 1000 live births, 19 and also enabled the investigators to choose controls (i.e., healthy newborns) that were generalizable to the general population to strengthen the study's external validity. A significant relationship with maternal cigarette smoking and cleft lip/palate in the newborn was reported in this study (adjusted OR 1.34, 95% CI 1.36-1.76). 18

Matching is a method used in an attempt to ensure comparability between cases and controls and reduces variability and systematic differences due to background variables that are not of interest to the investigator. 8 Each case is typically individually paired with a control subject with respect to the background variables. The exposure to the risk factor of interest is then compared between the cases and the controls. This matching strategy is called individual matching. Age, sex, and race are often used to match cases and controls because they are typically strong confounders of disease. 20 Confounders are variables associated with the risk factor and may potentially be a cause of the outcome. 8 Table 5 lists several advantages and disadvantages with a matching design.

Advantages and Disadvantages for Using a Matching Strategy

Multiple Controls

Investigations examining rare outcomes may have a limited number of cases to select from, whereas the source population from which controls can be selected is much larger. In such scenarios, the study may be able to provide more information if multiple controls per case are selected. This method increases the “statistical power” of the investigation by increasing the sample size. The precision of the findings may improve by having up to about three or four controls per case. 21 - 23

Bias in Case-Control Studies

Evaluating exposure status can be the Achilles heel of case-control studies. Because information about exposure is typically collected by self-report, interview, or from recorded information, it is susceptible to recall bias, interviewer bias, or will rely on the completeness or accuracy of recorded information, respectively. These biases decrease the internal validity of the investigation and should be carefully addressed and reduced in the study design. Recall bias occurs when a differential response between cases and controls occurs. The common scenario is when a subject with disease (case) will unconsciously recall and report an exposure with better clarity due to the disease experience. Interviewer bias occurs when the interviewer asks leading questions or has an inconsistent interview approach between cases and controls. A good study design will implement a standardized interview in a non-judgemental atmosphere with well-trained interviewers to reduce interviewer bias. 9

The STROBE Statement: The Strengthening the Reporting of Observational Studies in Epidemiology Statement

In 2004, the first meeting of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) group took place in Bristol, UK. 24 The aim of the group was to establish guidelines on reporting observational research to improve the transparency of the methods, thereby facilitating the critical appraisal of a study's findings. A well-designed but poorly reported study is disadvantaged in contributing to the literature because the results and generalizability of the findings may be difficult to assess. Thus a 22-item checklist was generated to enhance the reporting of observational studies across disciplines. 25 , 26 This checklist is also located at the following website: www.strobe-statement.org . This statement is applicable to cohort studies, case-control studies, and cross-sectional studies. In fact, 18 of the checklist items are common to all three types of observational studies, and 4 items are specific to each of the 3 specific study designs. In an effort to provide specific guidance to go along with this checklist, an “explanation and elaboration” article was published for users to better appreciate each item on the checklist. 27 Plastic surgery investigators should peruse this checklist prior to designing their study and when they are writing up the report for publication. In fact, some journals now require authors to follow the STROBE Statement. A list of participating journals can be found on this website: http://www.strobe-statement.org./index.php?id=strobe-endorsement .

Due to the limitations in carrying out RCTs in surgical investigations, observational studies are becoming more popular to investigate the relationship between exposures, such as risk factors or surgical interventions, and outcomes, such as disease states or complications. Recognizing that well-designed observational studies can provide valid results is important among the plastic surgery community, so that investigators can both critically appraise and appropriately design observational studies to address important clinical research questions. The investigator planning an observational study can certainly use the STROBE statement as a tool to outline key features of a study as well as coming back to it again at the end to enhance transparency in methodology reporting.

Acknowledgments

Supported in part by a Midcareer Investigator Award in Patient-Oriented Research (K24 AR053120) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to Dr. Kevin C. Chung).

None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.

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