2026/05/05 by Victor A. Kiri · 1 citation
Mathematics · Economics, Econometrics and Finance · #Statistical Methods in Clinical Trials #Advanced Causal Inference Techniques #Health Systems, Economic Evaluations, Quality of Life
paper · doi:10.1002/cpt.70316
A single-arm trial with an external control arm (ECA) is one in which the patients in the control group do not participate in the trial. The number of approved ECA trials is on the increase, due largely to their practical advantages. To assist this process, we have developed an ECA Viability Checklist as a framework for making initial assessments of the viability of the ECA in meeting regulatory requirements. Its purpose is to inform exploratory discussions with regulatory agencies, who would expect study sponsors to establish the appropriateness of the proposed design, including data sources and statistical analyses. The Checklist is based on the guidance documents by the United States Food and Drug Administration (FDA), European Medicines Agency (EMA), and the UK Medicines & Healthcare products Regulatory Agency (MHRA), using data from 40 FDA-approved ECA trials across different therapeutic areas. It is structured on the critical aspects of design and analytical considerations on the use of real-world data and past trials, presented as 10 thematic questions with recommendations on possible solutions to issues arising from each theme. We evaluated the Checklist against 4 FDA-approved ECA trials. Ideally, all responses should be affirmative to be most confident of regulatory acceptance of the proposed ECA; non-affirmative responses would require an adequate rationale, guided by the associated recommendations for progression. The Checklist will enable decision-makers to conduct an initial viability assessment of the proposed ECA and make an informed decision on the required next steps to help ensure acceptance of the design.