Considerations raised during the regulatory and ethics review of platform clinical trials in infectious diseases

Abstract

Background Platform trials can address more than one clinical research question simultaneously and allow for the addition or removal of arms over time. The scientific and operational complexity of platform trials may give rise to specific challenges. In this study, we evaluate the considerations raised during the regulatory and ethics review of five infectious disease platform trials. Methods Considerations raised during the review of five platform trials (ECRAID-Prime, RECOVERY, RECLAIM, REMAP-CAP, and SNAP) between 31 January 2022 and 28 March 2025, and sponsor responses were analyzed using content analysis. A single consideration could include multiple questions or remarks, and these were each treated as individual comments in the analysis. Results Findings were categorized under four main themes: (i) clinical trial application, (ii) recruitment and informed consent, (iii) participant safety and data protection, and (iv) methodology. We identified 1,218 comments, of which 93 (7.6%) specifically related to the platform trial design. Related to the methodology, regulators frequently requested more details about interim analyses, including triggers, correction for multiplicity, and stopping rules. Conclusions Less than 10% of the comments was directly related to the platform trial design. These were usually resolved by providing additional explanation. No comments were identified in areas where feedback was anticipated by the research team, such as response adaptive randomization or confidentiality of interim results. Effective evaluation of platform trials requires sponsors to highlight platform trial-specific features in clinical trial applications, and for regulatory bodies to be adequately prepared to evaluate them.