Emulating Randomized Trials by Observational Database Studies: The RCT-DUPLICATE Initiative in COPD and Asthma.
Samy SuissaSebastian SchneeweissWilliam B FeldmanHelen TesfayeShirley V WangPublished in: American journal of epidemiology (2024)
Observational studies are increasingly used to provide real-world evidence in regulatory decision-making. The RCT-DUPLICATE initiative conducted observational studies emulating two trials in patients with asthma and three in COPD. For each trial, new-user cohorts were constructed from two 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 6,494 asthma patients per arm, the hazard ratio (HR) of a serious asthma-related event with budesonide-formoterol versus 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 4,365 COPD patients per arm, the HR of a COPD exacerbation with triple therapy versus 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 randomized trials, likely from the forced discontinuation of treatments prior to randomization in the trials, not mimicable in the observational analyses.
Keyphrases
- chronic obstructive pulmonary disease
- lung function
- study protocol
- phase iii
- end stage renal disease
- phase ii
- clinical trial
- cystic fibrosis
- healthcare
- ejection fraction
- newly diagnosed
- air pollution
- chronic kidney disease
- allergic rhinitis
- peritoneal dialysis
- decision making
- randomized controlled trial
- type diabetes
- prognostic factors
- patient reported outcomes
- adipose tissue
- emergency department
- patient reported
- artificial intelligence
- social media
- acute respiratory distress syndrome
- weight loss
- smoking cessation
- health insurance