External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real World Data Sources.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, though the direct comparability of ECs to concurrent controls is unknown. To develop IPF ECs by fit for purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry [PFF-PR]), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the BMS-986020 phase 2 RCT. After data curation, the rate of change in forced vital capacity (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. At 26 weeks, the rate of change in FVC was -32.71 mL (BMS-986020) versus -130.09 mL (BMS-placebo; difference, 97.4 mL, 95% 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. Both PFF-PR-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. IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, while 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.