Am J Respir Crit Care Med. 2023 Jun 29. doi: 10.1164/rccm.202210-1947OC. Online ahead of print.
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, though the direct comparability of ECs to 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 [PFF-PR]), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the BMS-986020 phase 2 RCT.
METHODS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: 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.
PMID:37384378 | DOI:10.1164/rccm.202210-1947OC
