On a model‐based approach to estimating efficacy in clinical trials

Abstract

Treatment efficacy is of primary importance in phase III clinical trials. Determining the true size of the treatment effect is often complicated by patient non‐compliance with the regimen. This paper examines a model‐based approach in the spirit of Efron and Feldman utilizing drug and placebo compliance information. One of the assumptioqs of this analysis is ‘comparability’ of drug and placebo compliance. Robustness in estimation of subgroup and population treatment effects when this assumption is violated is investigated in a simulation study. We find that even moderate non‐comparability (for example, normalized compliance correlations of 0.4) may produce severely biased estimates. The bias is modulated by the strength of the relationship between compliance and the response on placebo.