case-control study

**Design (outcome → exposure):** - Select cases (disease present) and controls (disease absent, from the same source population). - Look backward to measure exposure history in both groups. - Compare the odds of exposure in cases vs. controls.

**Measure of association:** Odds ratio = (a×d)/(b×c) from the 2×2 table, or the odds of exposure in cases divided by the odds of exposure in controls. - OR > 1: exposure is associated with higher odds of disease (risk factor). - OR = 1: no association. - OR < 1: exposure is associated with lower odds of disease (protective). - It cannot directly give incidence, prevalence, or relative risk, because the investigator fixes the number of cases and controls. When the disease is rare (the "rare disease assumption"), OR ≈ RR.

**Strengths:** - Quick, inexpensive, and needs relatively few subjects. - Efficient for rare diseases (e.g., vaginal clear cell adenocarcinoma and in utero DES exposure). - Efficient for diseases with long latency. - Can examine multiple exposures for one outcome.

**Weaknesses:** - Cannot establish temporality as reliably as a cohort study, so it cannot prove causation. - Cannot calculate incidence or relative risk. - Prone to **recall bias**: cases remember exposures differently than controls. - Prone to **selection bias**: controls are not representative of the source population (e.g., Berkson bias with hospital-based controls). - Prone to confounding, which is addressed by matching, restriction, or multivariate (logistic regression) analysis.

**Control selection:** Controls should come from the same population that produced the cases, so that they would have been identified as cases had they developed the disease. Common sources are population-based, hospital-based, and matched controls. Matching improves comparability but can lead to overmatching.

**Comparison with other designs (high-yield):** - Cohort study: exposure → outcome, can be prospective or retrospective, gives relative risk and incidence, and is best for common diseases or rare exposures. - Cross-sectional study: measures exposure and disease at one time point, gives prevalence, and cannot establish temporality. - Case series/case report: descriptive, with no control group. - Randomized controlled trial: experimental, the gold standard for causation.

**Step 1/2 pearls:** - Stem clues: "patients with X compared with matched individuals without X," "odds ratio," "retrospectively reviewed." - Case-control is the observational design best suited to a rare disease. - Nested case-control studies sample cases and controls from within a defined cohort, which reduces recall bias.