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Presented at a Webinar on Research Methodology in Health Sciences at Northern Area Armed Forces Hospital (NAAFH) on 5th September 2022. By Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard) Professor of Epidemiology and Bioethics
LEARNING OBJECTIVES
- Definition and types of case-control studies.
- Design, strengths, and weaknesses of case-control studies.
- Selection of cases and controls.
KEYWORDS AND TERMS
- Case: selection, incident, prevalent
- Case-base
- Case-cohort
- Case-control
- Case-only
- Control, community control. Dead, friend, hospital, neighbor, relative
- Exposure odds ratio
- Matching, 1:1
- Matching, 1: many
- Matching, overmatch
- Population base
BASICS OF THE CASE-CONTROL STUDY
- Popular because of its low cost, rapid results, and flexibility.
- Uses a small number of subjects.
- Is used for disease (rare and non-rare) as well as non-disease situations.
- Can be exploratory or definitive.
- Is retrospective information on exposure (cause of disease).
VARIANTS OF THE CASE-CONTROL DESIGN
- Case-base,
- Case-cohort,
- Case-only, crossover designs.
CASE-BASE DESIGN
- Cases are all diseased individuals in the
population.
- Controls are a random sample of disease-free individuals in the same base population.
CASE-COHORT
DESIGN (NESTED)
- Sampling from a cohort (closed or open).
- Cases and controls are selected from the same
cohort.
- Blood and other biological specimens collected from the cohort at the start can be analyzed for exposure information when cases of disease appear.
CASE-ONLY
DESIGN
- Used in genetic studies in which the control exposure distribution can be worked out theoretically.
- No need to select controls because information
about them is known theoretically.
CROSSOVER DESIGN
- Used for sporadic
exposures.
- The same individual can serve as a case or as a control several times without any prejudice to the study.
BASIC 2x2 TABLE FOR CASE-BASE STUDIES
- The marginal totals, a+b, and c+d, are fixed by design before data collection thus prevalence cannot be computed.
- The basic statistical parameter is the odds ratio = ad/bc.
- The source population for cases and controls must be the same.
CASE SELECTION
- Cases are sourced from clinical records, hospital discharge records, disease registries, data from surveillance programs, employment records, and death certificates.
- Cases are either all cases of a disease or a sample thereof.
- Only incident cases (new cases) are selected.
SELECTION OF CONTROLS
- Controls must be from the same population base as the cases and must be like cases in everything except having the disease being studied.
- Information comparability between the case series and the control series must be assured.
- Hospital, community, neighborhood, friend, dead, and relative controls are used.
- There is little gain in efficiency beyond a 1:2 case-control ratio unless control data is obtained at no cost.
PREVENTION OF CONFOUNDING
- Stratification,
- Matching,
- Restriction.
SOURCE OF EXPOSURE INFORMATION
- Interviews,
- Hospital records,
- Pharmacy records,
- Vital records,
- Disease registry,
- Employment records,
- Environmental data,
- Genetic determinants,
- Biomarkers,
- Physical measurements,
- Laboratory measurements.
STRENGTHS OF THE CASE-CONTROL DESIGN
- Computation of the OR
- Low cost,
- Short duration, convenient for subjects because they are contacted/interviewed only once.
WEAKNESSES OF THE CASE-CONTROL DESIGN
- OR is an approximation,
- Prevalence cannot be computed because marginal totals are fixed in advance,
- the time sequence between exposure and disease outcome is not clear,
- vulnerability to bias (misclassification, selection, and confounding).