Combining data from expanded access programs and conventional clinical trials: a statistical application to vemurafenib

Patients suffering from seriously debilitating or life-threatening conditions who are not eligible for further treatments or any clinical trials, may resort to ‘expanded access’: pre-approval access to investigational treatments. These programs are increasingly used to generate data in patients that are older, frailer, and therefore not suited for clinical trials. As these programs are non-randomized, several selection bias issues need to be accounted for.

This research investigates statistical methods to incorporate data from expanded access programs in the analyses of (randomized) controlled trials. In this work, we will illustrate novel techniques on the basis of trial data and expanded access data for vemurafenib. Although expanded access is not primarily seen as research-oriented, we sought to improve the useability of data from all patients that are treated in this setting with experimental medicine. This project will yield direct insights, via scientific publications and statistical methodology, that are directly beneficial to regulators, drug developers and (bio)statisticians. This project is different from proposal 6476, as we will cover a different drug under investigation (with various differing data sources).