Design and Evaluation of an External Control Arm Using Prior Clinical Trials and Real-World Data.

ABSTRACT:

Purpose

We discuss designs and interpretable metrics of bias and statistical efficiency of "externally controlled" trials (ECT) and compare ECT performance to randomized and single-arm designs.

Experimental design

We specify an ECT design that leverages information from real-world data (RWD) and prior clinical trials to reduce bias associated with interstudy variations of the enrolled populations. We then used a collection of clinical studies in glioblastoma (GBM) and RWD from patients treated with the current standard of care to evaluate ECTs. Validation is based on a "leave one out" scheme, with iterative selection of a single-arm from one of the studies, for which we estimate treatment effects using the remaining studies as external control. This produces interpretable an

SUBMITTER: Ventz S 

PROVIDER: S-EPMC6697596 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature