Ethics review or compliance check? an empirical analysis of 6740 requests for information in Belgian clinical trial evaluations (2017-2024).

Abstract

The EU Clinical Trials Regulation (CTR) was introduced to harmonize clinical trial evaluations across Member States while upholding participant protection and ethical integrity. This study analyzes 6740 Requests for Information (RFIs) issued by Belgian Medical Research Ethics Committees (MRECs) across 266 trial dossiers evaluated between 2017 and 2024, spanning both the CTR pilot phase and the initial CTIS implementation. Using framework content analysis, we examined the number and content of RFIs in relation to trial outcomes, sponsor type (commercial vs. non-commercial), and the MREC's role as Reporting Member State (RMS) or Member State Concerned (MSC).Results show a decline in total RFIs over time, mainly due to a reduction in typographical and linguistic remarks, yet significant variability persists in the formulation and scope of ethical feedback. While statistical and methodological concerns remained central in Part I evaluations, RFIs increasingly addressed newer challenges such as decentralized trials, e-consent, and data collection on ethnicity. Part II RFIs continued to focus heavily on informed consent documents. We further observed that MSCs raised fewer RFIs than RMSs for Part I, prompting reflection on the necessity and efficiency of full multi-state review in this section.The study also highlights a growing emphasis on regulatory compliance-sometimes at the expense of ethical deliberation-and the limited authority of policy advisors to correct inconsistencies, despite their expertise. We recommend clearer guidance, formalized roles for policy advisors in quality control, improved pre-submission processes, and limited direct communication between MRECs and sponsors. These findings support ongoing efforts to improve ethics review efficiency and quality under the CTR, with broader relevance for harmonization across Europe.