title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Primary Care and Public Health Sciences, King's College London, 42 Weston Street, London, United Kingdom. jennifer.nicholas@kcl.ac.uk
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Nicholas
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Grieve
authors.forename: Martin C
authors.initials: MC
authors.lastname: Gulliford
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D015340:Epidemiologic Research Design; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000139:chemically induced*; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007600:Judgment; D008297:Male; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D006113:United Kingdom
chemical_list: D000927:Anticonvulsants; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones