Construction and application of a disease progression model for the placebo group in clinical trials of idiopathic pulmonary fibrosis

The aim of this study is to quantitatively describe the characteristics of disease progression and its influencing factors in the placebo group of idiopathic pulmonary fibrosis clinical trials, and to provide evidence for the optimal design of clinical trials. PubMed, Embase and Cochrane Library were searched for placebo-randomized controlled trials on IPF up to November 12, 2024. We conducted a time-course modeling analysis of the placebo group based on commonly reported evaluation indicators in clinical trials. Using the established model, we simulated the distribution of the placebo effect for each index under various conditions and applied this to provide a quantitative external control. A total of 32 studies were included. Common evaluation measures in clinical trials include all-cause mortality, forced vital capacity (FVC), 6-minute walk distance (6MWD) and Diffusing Capacity of the Lung for Carbon Monoxide (DLCO). Based on the final model, this study simulated typical effect sizes after different times of placebo intervention. Subgroup analysis showed that background treatment and gender also showed consistent trends in the effects on the above efficacy indicators. The potential utility of this model in drug effectiveness evaluation is demonstrated through a preliminary case study. This study established a disease progression model for the placebo group based on common evaluation indicators in IPF clinical trials. This model helps conserve valuable clinical resources for rare diseases and promotes the development of new drugs. The study strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Supplementary Material) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration ID: CRD42024557923).