Case-Control Clinical Study

A Case-Control Clinical Study is an observational clinical trial in which two existing experimental unit groups differing in observed outcome are identified and compared on the basis of some supposed causal attribute.

• AKA: Case-Referent Study, Retrospective Study.
• Context:
  • It can be designed to help determine if an exposure is associated with an outcome.
  • It divides subject into two groups: a case group and control group.
  • It can be a Case-Cohort Study.
  • It can be a Nested Case-Control Study.
  • Strengths/Advantages:
    • Inexpensive;
    • Timely;
    • Individualized data;
    • Ability to control for multiple confounders;
    • Good for rare diseases;
    • Can assess multiple exposures;
  • Weaknesses/Disadvantages:
    • Cannot calculate prevalence;
    • Can only assess one outcome;
    • Poor selection of controls can introduce bias;
    • May be difficult to identify enough cases
    • Prone to recall bias.
    • No demonstrated temporality
  • …
• Example(s):
  • Mammographic Density and the Risk of Tumor Recurrence in Asian Women: a Case-control Study,
  • Sleep Quality of Office Workers - A Case-Control Pilot Study (Boubekri et al., 2014),
  • …
• Counter-Example(s):
  • Case-Crossover Clinical Study,
  • Clinical Case Series,
  • Cross-Sectional Clinical Study,
  • Cohort Clinical Study,
  • Ecological Clinical Study,
  • Proportional Mortality Ratio (PMR) Clinical Study.
• See: Disease Exposure Measure, Health Outcome Measure, Descriptive Clinical Trial, Diagnostic Clinical Trial, Interventional Clinical Trial, Uncontrolled Clinical Intervention Study, Non-Randomized Experiment, Case Report, Clinical Trial, Treatment Group, Control Group, Subject-level Comparative Experiment.

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References

2022

• (ClinicalTrials.gov, 2022) ⇒ https://clinicaltrials.gov/ct2/about-studies/glossary Retrieved:2022-02-13.
  • QUOTE: Observational study model: The general design of the strategy for identifying and following up with participants during an observational study. Types of observational study models include cohort, case-control, case-only, case-cross-over, ecologic or community studies, family-based, and other.

2021a

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Case–control_study Retrieved:2021-11-21.
  • A case–control study (also known as case–referent study) is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case–control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have that condition/disease (the "cases") with patients who do not have the condition/disease but are otherwise similar (the "controls"). They require fewer resources but provide less evidence for causal inference than a randomized controlled trial. A case–control study produces only an odds ratio, which is an inferior measure of strength of association compared to relative risk.

2021b

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Glossary_of_clinical_research Retrieved:2021-11-21.
  • Case-control study
    • A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). Researchers study the medical and lifestyle histories of the people in each group to learn what factors may be associated with the disease or condition. For example, one group may have been exposed to a particular substance that the other was not. Also called a retrospective study. (NCI)

2021c

• (GW, 2021) ⇒ https://himmelfarb.gwu.edu/tutorials/studydesign101/casecontrols.cfm Retrieved:2021-11-21.
  • QUOTE: 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."

2021d

• (BMJ, 2021) ⇒ https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/8-case-control-and-cross-sectional Retrieved:2021-11-21.
  • QUOTE: As discussed in the previous chapter, one of the drawbacks of using a longitudinal approach to investigate the causes of disease with low incidence is that large and lengthy studies may be required to give adequate statistical power. An alternative which avoids this difficulty is the case-control or case-referent design. In a case-control study patients who have developed a disease are identified and their past exposure to suspected aetiological factors is compared with that of controls or referents who do not have the disease. This permits estimation of odds ratios (but not of attributable risks). Allowance is made for potential confounding factors by measuring them and making appropriate adjustments in the analysis. This statistical adjustment may be rendered more efficient by matching cases and controls for exposure to confounders, either on an individual basis (for example by pairing each case with a control of the same age and sex) or in groups (for example, choosing a control group with an overall age and sex distribution similar to that of the cases). Unlike in a cohort study, however, matching does not on its own eliminate confounding. Statistical adjustment is still required.

2016

• (Grant, 2016) ⇒ William B. Grant (2016). "The role of geographical ecological studies in identifying diseases linked to UVB exposure and/or vitamin D". In: Dermato Endocrinology 8(1):e1137400. DOI:10.1080/19381980.2015.1137400.
  • QUOTE: Observational studies come in several forms:
    • Case–control. Risk-modifying factors measured at the time of disease diagnosis.
    • Cohort and nested case–control. Subjects are enrolled in a study, risk-modifying factors are assessed, and then the cohort is monitored (for up to many years). Those who develop diseases are compared with like individuals who did not.
    • Cross-sectional. An entire population is sampled, with health status and health parameters and risk-modifying factors measured.

2014

• (Thiese, 2014) ⇒ Matthew S. Thiese. (2014). “Observational and Interventional Study Design Types; An Overview.” In: Biochemia Medica (Zagreb). Journal, 24(2).
  • QUOTE: Case-control studies were traditionally referred to as retrospective studies, due to the nature of the study design and execution (...). In this study design, researchers identify study participants based on their case status, i.e. diseased or not diseased. Quantification of the number of individuals among the cases and the controls who are exposed allow for statistical associations between exposure and outcomes to be established (...). An example of a case control study is analysing the relationship between obesity and knee replacement surgery. Cases are participants who have had knee surgery, and controls are a random sampling of those who have not, and the comparison is the relative odds of being obese if you have knee surgery as compared to those that do not. Matching on one or more potential confounders allows for minimization of those factors as potential confounders in the exposure-outcome relationship (...). Additionally, case-control studies are at increased risk for bias, particularly recall bias, due to the known case status of study participants (...). Other points of consideration that have specific weight in case-control studies include the appropriate selection of controls that balance generalizability and minimize bias, the minimization of survivor bias, and the potential for length time bias (...). The largest strength of case-control studies is that this study design is the most efficient study design for rare diseases. Additional strengths include low cost, relatively fast execution compared to cohort studies, the ability to collect individual participant specific data, the ability to control for multiple confounders, and the ability to assess multiple exposures of interest. The measure of risk that is calculated in case-control studies is the odds ratio, which are the odds of having the exposure if you have the disease. Other measures of risk are not applicable to case-control studies. Any measure of prevalence and associated measures, such as prevalence odds ratio, in a case-control study is artificial because the researcher arbitrarily sets the proportion of cases to non-cases in this study design. Temporality can be suggested, however, it is rarely definitively demonstrated because it is unknown if the development of the disease truly preceded the exposure. It should be noted that for certain outcomes, particularly death, the criteria for demonstrating temporality in that specific exposure-outcome relationship are met and the use of relative risk as a measure of risk may be justified.

2011

• (Young & Karr, 2011) ⇒ S Stanley Young, and Alan Karr. (2011). “Deming, Data and Observational Studies." Wiley Online Library.
  • QUOTE: “Any claim coming from an observational study is most likely to be wrong.” Startling, but true. … As long ago as 1988 (1,2) it was noted that there are contradicted results for case-control studies in 56 different topic areas,

2002

• (Grimes & Schulz, 2002) ⇒ David A Grimes, and Kenneth F Schulz. (2002). “Bias and Causal Associations in Observational Research." The Lancet, The Lancet, 359(9302). doi:10.1016/S0140-6736(02)07451-2

1998

• (Lewallen & Courtright, 1998) ⇒ Susan Lewallen, and Paul Courtright (1998). "Epidemiology in Practice: Case-Control Studies". In: Community Eye Health Journal, 11(28).
  • QUOTE: A case-control study is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest). In theory, the case-control study can be described simply. First, identify the cases (a group known to have the outcome) and the controls (a group known to be free of the outcome). Then, look back in time to learn which subjects in each group had the exposure(s), comparing the frequency of the exposure in the case group to the control group.

    By definition, a case-control study is always retrospective because it starts with an outcome then traces back to investigate exposures. When the subjects are enrolled in their respective groups, the outcome of each subject is already known by the investigator. This, and not the fact that the investigator usually makes use of previously collected data, is what makes case-control studies "retrospective".

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