Fig. 1

Study overview. A Clinical trials were found using clinicaltrials.gov and sought for retrieval on the YODA and Vivli platforms. Individual participant data (IPD) from trials that collected CDAI scores at week 8 visits were then aggregated and harmonized. B Two linear mixed effect models—placebo-attributable and ADA-attributable—were developed from the harmonized data to partition the CDAI reduction based on baseline covariates (age, sex, BMI, etc.). Disease activity reduction was partitioned into placebo attributable (square) and drug-attributable (circle) effects. IPD (solid lines) were used to predict or simulate data (dashed lines). C Using the adalimumab (ADA) attributable model, we simulated the outcomes of the placebo group from the ustekinumab (UST) trials under a counterfactual scenario where they had instead been assigned to receive ADA. D Results from a simulated head-to-head trial were compared against a recently completed head-to-head trial, SEAVUE, to externally validate the proposed method