Predicting Treatment Effects of a New-to-Market Drug in Clinical Practice Based on Phase III Randomized Trial Results.
Clin Pharmacol Ther
; 114(4): 853-861, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37365904
ABSTRACT
Trial results may not be generalizable to target populations treated in clinical practice with different distributions of baseline characteristics that modify the treatment effect. We used outcome models developed with trial data to predict treatment effects in Medicare populations. We used data from the Randomized Evaluation of Long-Term Anticoagulation Therapy trial (RE-LY), which investigated the effect of dabigatran vs. warfarin on stroke or systemic embolism (stroke/SE) among patients with atrial fibrillation. We developed outcome models by fitting proportional hazards models in trial data. Target populations were trial-eligible Medicare beneficiaries who initiated dabigatran or warfarin in 2010-2011 ("early") and 2010-2017 ("extended"). We predicted 2-year risk ratios (RRs) and risk differences (RDs) for stroke/SE, major bleeding, and all-cause death in the Medicare populations using the observed baseline characteristics. The trial and early target populations had similar mean (SD) CHADS2 scores (2.15 (SD 1.13) vs. 2.15 (SD 0.91)) but different mean ages (71 vs. 79 years). Compared with RE-LY, the early Medicare population had similar predicted benefit of dabigatran vs. warfarin for stroke/SE (trial RR = 0.63, 95% confidence interval (CI) = 0.50 to 0.76 and RD = -1.37%, -1.96% to -0.77%, Medicare RR = 0.73, 0.65 to 0.82 and RD = -0.92%, -1.26% to -0.59%) and risks for major bleeding and all-cause death. The time-extended target population showed similar results. Outcome model-based prediction facilitates estimating the average treatment effects of a drug in different target populations when treatment and outcome data are unreliable or unavailable. The predicted effects may inform payers' coverage decisions for patients, especially shortly after a drug's launch when observational data are scarce.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Acidente Vascular Cerebral
/
Embolia
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos