Figure 3. Causal diagram representing confounding for non-randomized therapies.

A₀ represents assignment to the experimental arm, A₁ the non-randomized treatment received at disease relapse, Y death, L₁ prognostic factors that affect the clinicians’ choice of A₁ (e.g. performance status, comorbidities, frailty scale, toxicity, center, type of health insurance coverage, bone marrow, liver and renal function), and U the unmeasured determinants of those factors and of death. Conventional statistical methods adjust for the factors L₁ by conditioning on them, e.g., adding them as covariates in an outcome regression model, which will generally induce selection bias in the estimates.