De Paola Eleonora, Del Bono Luna, Dri Diego Alejandro, Maione Raffaella, Petraglia Sandra, Galliccia Fabrizio, Gori Giovanni
Clinical Trials Office, Italian Medicines Agency (AIFA), Rome, Italy.
Department of Pharmacy, School of Specialization in Hospital Pharmacy, University of Pisa, Pisa, Italy.
Front Pharmacol. 2025 Aug 29;16:1661186. doi: 10.3389/fphar.2025.1661186. eCollection 2025.
The global clinical research landscape has expanded significantly over the past decade, yet Europe has witnessed a decline in its share of clinical trial activity, especially in early-phase trials. This study aims to characterize the evolution of Phase I clinical trials in Italy from January 2015 through the completion of the European regulatory transition under Regulation (EU) 536/2014 (30 January 2025), by analyzing trends in trial submissions, sponsor typologies, study designs, and participant populations.
A systematic extraction of data was conducted from the Italian (OsSC), European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) and the EU Clinical Trials Information System (CTIS), covering all Phase I trials submitted to the Agenzia Italiana del Farmaco (AIFA; Italian Medicines Agency), the Competent Authority for clinical trials in Italy, between 1 January 2015, and 30 January 2025. Trials were categorized by sponsor type, authorization outcome, therapeutic area, study design, investigational medicinal product (IMP) classification, and participant population characteristics. Descriptive and comparative analyses were conducted.
A total of 1,051 Phase I clinical trials were submitted during the study period, accounting for 14.4% of all clinical trial applications in Italy. Commercial sponsors dominated (90.6%), and oncology was the leading therapeutic area (69.6%). The overall regulatory authorization rate was high, with no statistically significant difference between commercial and non-commercial sponsors (89.5% vs. 86.9%, respectively; p > 0.05). Trials exclusively involving healthy volunteers were limited (3.4%). Among the 3,777 IMPs analyzed, chemical compounds prevailed (66.1%), followed by biologics (28.7%) and Advanced Therapy Medicinal Products (ATMPs, 3.3%), the latter showing a steady increase over the decade. Non-commercial sponsor trials more frequently included pediatric and vulnerable populations, thus underlining their distinct contribution to underrepresented areas of clinical research.
While Phase I trial activity in Italy remained stable over the past decade, structural imbalances persist-including limited non-commercial engagement, strong therapeutic concentration in oncology, and underuse of healthy volunteer models. Strengthening infrastructure for early development, supporting academic-led studies, and promoting broader inclusion in study populations may help consolidate recent progress and foster a more balanced national research ecosystem.
在过去十年中，全球临床研究格局显著扩大，但欧洲在临床试验活动中的份额却有所下降，尤其是在早期试验方面。本研究旨在通过分析试验提交趋势、申办者类型、研究设计和受试人群，描述意大利2015年1月至2014年第536/2014号法规（2025年1月30日）规定的欧洲监管过渡期结束期间的I期临床试验演变情况。
从意大利（OsSC）、欧盟药品监管当局临床试验数据库（EudraCT）和欧盟临床试验信息系统（CTIS）中系统提取数据，涵盖2015年1月1日至2025年1月30日期间提交给意大利药品管理局（AIFA；意大利药品管理机构）的所有I期试验，该机构是意大利临床试验的主管当局。试验按申办者类型、授权结果、治疗领域、研究设计、试验用药品（IMP）分类和受试人群特征进行分类。进行了描述性和比较性分析。
在研究期间共提交了1051项I期临床试验，占意大利所有临床试验申请的14.4%。商业申办者占主导地位（90.6%），肿瘤学是主要治疗领域（69.6%）。总体监管授权率较高，商业和非商业申办者之间无统计学显著差异（分别为89.5%和86.9%；p>0.05）。仅涉及健康志愿者的试验有限（3.4%）。在分析的3777种试验用药品中，化学化合物占主导（66.1%），其次是生物制品（28.7%）和高级治疗药品（ATMPs，3.3%），后者在十年间呈稳步上升趋势。非商业申办者的试验更频繁地纳入儿科和弱势群体，从而突出了它们对临床研究中代表性不足领域的独特贡献。
虽然意大利在过去十年中I期试验活动保持稳定，但结构失衡依然存在，包括非商业参与有限、肿瘤学治疗集中度高以及健康志愿者模型使用不足。加强早期开发基础设施、支持学术主导的研究以及促进更广泛地纳入受试人群，可能有助于巩固近期进展并培育更平衡的国家研究生态系统。
