External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources.
Am J Respir Crit Care Med
; 208(5): 579-588, 2023 09 01.
Article
em En
| MEDLINE
| ID: mdl-37384378
ABSTRACT
Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, but the direct comparability of ECs versus concurrent controls is unknown. Objectives:
To develop IPF ECs by fit-for-purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the phase II RCT of BMS-986020.Methods:
After data curation, the rate of change in FVC from baseline to 26 weeks among participants receiving BMS-986020 600 mg twice daily was compared with the BMS-placebo arm and ECs using mixed-effects models with inverse probability weights. Measurements and MainResults:
At 26 weeks, the rates of change in FVC were -32.71 ml for BMS-986020 and -130.09 ml for BMS-placebo (difference, 97.4 ml; 95% confidence interval [CI], 24.6-170.2), replicating the original BMS-986020 RCT. RCT ECs showed treatment effect point estimates within the 95% CI of the original BMS-986020 RCT. Pulmonary Fibrosis Foundation Patient Registry ECs and EHR ECs experienced a slower rate of FVC decline compared with the BMS-placebo arm, resulting in treatment-effect point estimates outside of the 95% CI of the original BMS-986020 RCT.Conclusions:
IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, whereas ECs from real-world data sources, including registry or EHR data, do not. RCT ECs may serve as a potentially useful supplement to future IPF RCTs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar Idiopática
/
Fonte de Informação
Tipo de estudo:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2023
Tipo de documento:
Article