Within-person study designs had lower precision and greater susceptibility to bias because of trends in exposure than cohort and nested case–control designs

Abstract 

Objective

To compare precision and apparent bias between cohort, nested case–control, self-controlled case series, case–crossover, and case–time–control study designs.

Study Design and Setting

Study designs were implemented to evaluate the association between thiazolidinediones (TZDs) and heart failure, TZDs and fracture, and liver enzyme–inducing anticonvulsants and fracture.

Results

Effect estimates were similar for the cohort and case–control study; for the association between TZDs and fracture in women, the hazard ratio was 1.36 (1.18, 1.56) and odds ratio (OR) was 1.44 (1.21, 1.70). For this clinical example, the self-controlled case series gave upward bias when follow-up was censored at the outcome (incidence rate ratio [IRR], 7.08; 4.96, 10.09) but was otherwise unbiased (IRR, 1.41; 1.14, 1.75). The retrospective case–crossover OR was 3.24 (2.18, 4.80), which was reduced by either bidirectional sampling (OR, 1.20; 0.98, 1.46) or with the case–time–control design (OR, 1.40; 1.09, 1.81). Findings on apparent bias were similar for the other two clinical examples. In each clinical example, within-person designs had considerably lower precision than the cohort or case–control study designs.

Conclusion

When long-term exposures are analyzed, within-person study designs may have lower precision and greater susceptibility to bias. Bias may be reduced by sampling follow-up both before and after the outcome or with the case–time–control study design.

Keywords: Epidemiologic research design, Bone fractures, Heart failure, Thiazolidinediones, Antiepileptics, Drug toxicity