title: Estimation of time-dependent rate ratios in case-control studies: comparison of two approaches for exposure assessment.
abstract: OBJECTIVE
  In pharmacoepidemiology, it is well recognized that the rate of adverse events may vary as a function of the cumulative duration of the drug exposure and/or the time since the end of the exposure. In case-control studies, two different approaches have been used to estimate temporal effects of drug exposure: the time-windows (T-Ws) approach and the duration-specific (D-S) approach. We decided to conduct a simulation study to compare the two approaches when the rate ratios (RRs) vary as a function of the cumulative duration of exposure and/or the time since the end of exposure.
  
  
  METHODS
  We generated three cohorts of 500,000 individuals in which the rate of the event was varying as a function of the cumulative duration of exposure and the time since the end of exposure. For each cohort, a nested case-control analysis was performed using both the D-S and the T-Ws approaches. In the T-Ws approach, a RR is estimated within specific periods of time prior to the outcome, while a RR is estimated within periods of cumulative duration of exposure and time since the end of exposure in the D-S approach.
  
  
  RESULTS
  We found that the RRs obtained from the D-S approach exactly corresponded to the RRs obtained from the cohort analyses, while the RRs obtained from the T-Ws approach generally not. RRs obtained from the T-Ws approach were difficult to interpret in terms of the effect of the duration and timing of the exposure.
  
  
  CONCLUSIONS
  The D-S approach should be used to investigate the duration-related effects of exposure in case-control studies.
authors.affiliation: Mathematics and Statistics Department, Université de Montréal, Montreal, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lefebvre
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Angers
authors.forename: Lucie
authors.initials: L
authors.lastname: Blais
mesh_terms: D016022:Case-Control Studies; D006801:Humans; D017891:Pharmacoepidemiology / Q000379:methods*; D013997:Time Factors