Emulating randomized trials by observational database studies: the RCT-DUPLICATE initiative in COPD and asthma

• Suissa, Samy ^[1] ; Schneeweiss, Sebastian ^[2] ; Feldman, William B ^[2] ; Tesfaye, Helen ^[2] ; Wang, Shirley V ^[2]
  1. [1] Centre for Clinical Epidemiology, Lady Davis Institute Jewish General Hospital , Montreal, Quebec ,
  2. [2] Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital , 1620 Tremont St Suite 3030, Boston, MA,
• Localización: American journal of epidemiology, ISSN-e 1476-6256, ISSN 0002-9262, Vol. 194, Nº. 5, 2025, págs. 1152-1159
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • Abstract Observational studies are increasingly used to provide real-world evidence in regulatory decision-making. The RCT-DUPLICATE initiative conducted observational studies emulating 2 published randomized trials in patients with asthma and 3 in chronic obstructive pulmonary disease (COPD). For each trial, new-user cohorts were constructed from 2 US healthcare claims databases, comparing initiators of the study and comparator drugs, matched on propensity scores. Proportional hazards models were used to compare the treatments on study outcomes. The observational studies involved more subjects than the corresponding trials, with treatment arms well-matched on baseline characteristics. An asthma example involved emulation of the 26-week FDA-mandated D5896 trial. With 6494 asthma patients per arm, the hazard ratio (HR) of a serious asthma-related event with budesonide-formoterol vs budesonide was 1.29 (95% CI, 0.63-2.65) compared with 1.07 (95% CI, 0.70-1.65) in the trial. A COPD example is the emulation of the one-year IMPACT trial. With 4365 COPD patients per arm, the HR of a COPD exacerbation with triple therapy vs dual bronchodilators was 1.08 (95% CI, 1.00-1.17) compared with 0.84 (95% CI, 0.78-0.91) in the trial. We found mainly discordant results between observational analyses and their emulated randomized trials, likely from the forced discontinuation of treatments prior to randomization in the trials, not mimicable in the observational analyses. This article is part of a Special Collection on Pharmacoepidemiology.