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Case-Control Studies

Observational studies allowing researcher to be a passive observer of natural events occurring in individuals with the disease/condition of interest (cases) who are compared with people who do NOT have the condition of interest (controls); conducted in a retrospective fashion


Reasons to select a Case-Control Study

1. Unable to force group allocation; unethical/not feasible
2. Limited resources such as time, money, and subjects
3. Disease of interest is rare in occurrence and little is known about its associations/causes
4. Prospective exposure data is difficult/expensive to obtain and/or very time inappropriate


Strengths of Case Control Study

1. Good for assessing multiple exposures of one outcome
2. Useful when diseases are rare
3. Useful in determining associations
4. Less expensive than interventional
5. Useful when ethical issues limit interventional studies
6. Useful when disease has a long induction/latent period


Weaknesses of Case Control Study

1. Can't demonstrate causation
2. Can be impacted by unassessed confounders
3. Retrospective; can't control for other exposures or potential changes in amount of study-exposure during study frame
4. Can be impacted by various biases, most importantly selection and recall/assessment bias
5. Limited by available data


Selection of Cases

Defined by the investigator using accurate, medically-reliable, efficient data sources; applied to all study participants objectively, consistently, accurately, and with validity; best criteria are clinically supportable/definable


Goal of Control Selection

To assess for the presence of an association between exposure and known condition of interest by selecting non-disease individuals from the sample population which produced the cases; controls should represent the baseline risk of exposure in the general/reference population


Major determinant in whether a conclusion is valid in case-control studies?

The way controls are selected


How to select control populations

Must be selected irrespective of exposure status; can come from population of the state, community, or neighborhood, from an institution or organization as long as any illnesses in controls are unrelated to the exposure(s) being studied, from relatives/friends/spouse. or from those who participated in the same picnic or convention but did NOT get sick (outbreak sources of controls)


Case-Crossover Design

Subjects are their own controls during the other times they don't have the acute change in risk; only case-control study that can attempt to address issue of temporality


Nested Case-Control Studies

Case-control studies conducted after, or out of, a prospective previous study type (cohort or interventional study); subjects in cohort study, ultimately developing disease/outcome, are defined as cases for the subsequent case-control study to evaluate other exposures


Survivor Sampling

Sample of non-diseased individuals (survivors) at end of study period


Base Sampling

Sample of non-diseased individuals at start of study period


Risk-Set Sampling

Sample of non-diseased individuals during study period at same time when case was diagnosed


Selection Bias

Related to the way subjects are chosen for study; usually more of a concern for control selection and less of a concern during case-crossover study designs


Recall Bias

Related to the amount/specificity that cases or controls recall past events differently


Individual Matching

Matches individuals based on specific patient-based characteristics; useful for controlling confounding characteristics


Group Matching

Proportion of cases and proportion of controls with identical characteristics are matched (if 41% of cases are males, 41% of controls need to be male); cases must be selected first