Tracking a Decade of Phase I Clinical Trials in Italy: Trends and Insights from National and European Registries Amid Regulatory Change

ELEONORA DE PAOLA^1,2LUNA DEL BONO^1,3DIEGO ALEJANDRO DRI²RAFFAELLA MAIONE²SANDRA PETRAGLIA²FABRIZIO GALLICCIA²GIOVANNI GORI^3*

• ¹School of Specialization in Hospital Pharmacy, Department of Pharmacy, University of Pisa, Italy, Pisa, Italy
• ²Agenzia Italiana del Farmaco, Rome, Italy
• ³Clinical Pharmacology Centre for Drug Investigation, Pisa University Hospital, Pisa, Italy, Pisa, Italy

Introduction: 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 studies. 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. Methods: A systematic extraction of data was conducted from the Italian Osservatorio sulla Sperimentazione Clinica (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 January 1, 2015, and January 30, 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. Results: 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. Conclusion: 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.