Which of the following statements is true? For a case-control study to provide valid estimates:

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Re-stating the question: For a case-control study to provide valid estimates, which statement is true? The answer options are:
- a. The controls must be sampled independently of exposure
- b. The cases must be representative of all persons in the target population
- c. The controls must be representative of the general population in the country in which the study is conducted
- d. The controls must be sampled independently of the outcome

Option a: The controls must be sampled independently of exposure. In a case-control study, exposure status is the variable of interest that is compared between cases (with disease) and controls (without disease). To avoid selection bias, controls should be selected without regard to their exposure status; i.e., the sampling of controls must be independent of exposure. This ensures that the exposure distribution among controls reflects the exposure distribution in the source population that gave rise to the cases. Thus, this statement aligns with proper case-control design principles.

Option b: The cases must be representative of all persons in the target population. This is not strictly required. What matters is that the cases represent the cases that would arise in the source population from which the cases and controls are drawn. Requiring representativeness of all persons in the broader target population is overly stringent and often impractical. This makes the statement false as written.

Option c: The controls must be representative of the general population in the country in which the study is conducted. The ideal is that controls come from the same source population as the cases, i.e., the population from which the cases arose, not necessarily the general population of the country. Asking for general population representativeness at the country level is too broad and can introduce bias if the source population is more restricted (e.g., hospital-based cases). This renders the statement incorrect.

Option d: The controls must be sampled independently of the outcome. While the outcome here refers to exposure status, in case-control studies the critical independence requirement is that controls be selected independently of exposure, not the outcome. The outcome is disease status (case or control), which is by design different between groups; sampling controls independent of exposure is the key criterion. Therefore, this statement is misleading and not the correct standard principle.

Summary: Among the options, only option a correctly captures the necessary condition for valid case-control estimates—that controls be sampled independently of exposure. The other statements misstate the needed representativeness or selection criteria by tying control selection to broader population representations or to the outcome in ways that can introduce bias.

EPI 201 Week 6 - Case-control & matched studies

Which of the following statements is true? For a case-control study to provide valid estimates:

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