gms | German Medical Science

Background: Single-arm trials (SATs) have gained popularity in pharmaceutical research over the past years, despite frequent criticism because SATs have no control groups. Under certain conditions, supplementing SATs with external control arms (ECAs) can improve the identification of a medicines treatment effect. However, there has never been a comprehensive evaluation of the feasibility of supplementing ECAs to SATs on a large scale.

Materials and Methods: We include all SATs concerning breast cancer (BC) or amyotrophic lateral sclerosis (ALS) treatments registered in the EU. Trials were excluded if they did not only concern BC or ALS, were extension studies to previous controlled trials, or evaluated imaging methods. The feasibility assessment was based on five selected German Real-World Data (RWD) sources.

The main outcome measure was the number and percentage of trials for which all important inclusion and exclusion criteria and at least one primary endpoint could be identified in real-world data sources.

Results: Seventeen out of the 379 BC SATs and 2 of the 11 ALS SATs could feasibly be supplemented with ECAs derived from RWD sources. Of the BC trials, 93 had at least one outcome ascertainable in a RWD source, and 70 trials had all inclusion and exclusion criteria recorded in a RWD source. Nine trials on ALS had at least one primary endpoint ascertainable in RWD sources, and two had all inclusion and exclusion criteria recorded in a RWD source.

Conclusion: Supplementing SATs with RWD-based ECAs is rarely feasible for the two phenotypes investigated when all inclusion and exclusion criteria are supposed to match. Our study highlights the need to design SATs with limitations of the source of external controls in mind.