Ethics Committees Selection in Italy under EU Regulation 536/2014: A Three-year Governance Analysis

The implementation of Regulation (EU) No. 536/2014 (CTR) introduced a reformed clinical trial governance system in Italy, based on a single national ethics opinion, replacing the previous decentralized model. This transition has raised important questions regarding how sponsors orient their choice of Ethics Committees (ECs) within the new regulatory framework. The aim of this study is to evaluate geographical trends in sponsor-proposed ECs for clinical trials in Italy between January 2022 and January 2025, and to examine their association with therapeutic area, trial phase, and population characteristics.

We conducted a retrospective three-year nationwide analysis based on data from the Italian Medicines Agency (AIFA) and the Clinical Trials Information System (CTIS). Adopting a longitudinal approach, descriptive and comparative evaluations were performed.

A total of 1,462 Clinical Trials (CTs) were identified, of which 1,135 (77.8%) involved sponsor-proposed Ethics Committees (ECs), including both legacy ECs operating under Directive 2001/20/EC and Territorial Ethics Committees (TECs) active since June 2023. A marked geographical imbalance emerged in sponsor proposals: 60.2% targeted ECs located in Northern Italy, 26.4% in Central Italy, and 13.4% in Southern Italy and the Islands, with additional intra-regional disparities. Non-commercial sponsors often chose TECs within their own region (64.7%), frequently within the same institution.

The results show a concentration of sponsor-proposed ECs in Northern Italy, together with marked intra-regional concentration patterns in regions hosting multiple ECs. The distribution of proposals also indicates that non-commercial sponsors frequently select TECs located within their own region and institution. In the most recent part of the observation period, a modest increase in proposals to Central TECs has been recorded.

This nationwide analysis provides a descriptive overview of sponsor-driven EC selection in Italy under the CTR, identifying inter-regional and intra-regional imbalances. While some changes in sponsor behavior are observed in the latest data, continued monitoring over time is required. The observed patterns may be potentially influenced by contextual and organisational factors, as well as by additional variables not directly assessed in the analysis. Future studies incorporating these variables will be important to confirm whether the trends identified here persist over time and to better clarify the factors contributing to their distribution.