Fig. 3

A directed acyclic graph of the modeling strategy. A A directed acyclic graph (DAG) of the drug attributable effect. In addition to the active treatment itself, patient demographics (age, sex, BMI), baseline Crohn’s disease activity (baseline CDAI, CRP, location), and treatment history (prior use of TNFis, current use of oral corticosteroids and immunomodulators) are all modelled as contributing to the drug attributable effect. The non-drug covariates are effect modifiers and are implicitly modeled as two-way interaction terms with the active drug. B A DAG of the drug independent effect (i.e., placebo effect). The same covariates except for the treatment term are modeled as effect modifiers and are implicitly represented as two-way interactions with the placebo effect. C Drug attributable and drug independent effects have additive effects on the overall clinical remission at week 8 (CDAI < 150), with any individual trial reflecting a noisy measurement of the true effect due to unmodeled heterogeneity in study design and execution (random effect)