Effect Estimates in Randomized Trials and Observational Studies: Comparing Apples With Apples

Am J Epidemiol. 2019 Aug 1;188(8):1569-1577. doi: 10.1093/aje/kwz100.


Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

Keywords: antiretroviral initiation; causal inference; per-protocol effect; target trial.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Epidemiologic Methods*
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Observational Studies as Topic*
  • Randomized Controlled Trials as Topic*
  • Research Design*


  • Anti-Retroviral Agents