External Controls – Evolving Regulatory Approaches

This paper examines the benefits and challenges of using supplemental and external controls in regulatory submissions. Data platforms are an integral part of the ecosystem, enabling trial sponsors to access and use patient data from real-world settings and prior clinical trials. The paper recommends specific steps data platforms can take to support sponsors in meeting health authority expectations.

This keynote presentation by Mark McClellan, Director of the Duke-Margolis Institute for Health Policy and former commissioner of the U.S. Food and Drug Administration, provides a thought-provoking analysis of the current state of Real-World Data and Evidence in regulatory use. Major themes include “regulatory grade” RWD/E, audit readiness and data fitness, learning health systems, and fit-for-purpose clinical trial design.

Following the keynote, a panel of experts discussed what’s on the regulatory horizon, from the use of alternative data sources to novel trial designs to AI-generated evidence.

Innovative trial designs that make use of the totality of available evidence can reduce the burden on patients and meaningfully improve the drug development process. In February 2023, the FDA released for public comment “Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products” (Docket FDA-2022-D-2983).

The draft guidance received over 200 responses from industry sponsors, patient advocacy organizations, academic research institutions, nonprofit consortia, and patients. In July 2023, CRDSA convened a roundtable panel of experts to discuss issues raised by commenting organizations and explore ways to ensure the expanded use of alternative control trial designs in regulatory submissions. The August 2023 report, “FDA Draft External Controls Guidance: Situation Analysis and Recommendations,” summarizes the roundtable discussion, key regulatory challenges, and recommended actions.