A decade of clinical trials in Italy (2016-2025): trends, regulatory transformation and biotechnological evolution

Italy represents one of major hubs for clinical research in Europe, nevertheless comprehensive long-term analyses of its clinical trial landscape under evolving regulatory frameworks remain limited. This study examines the trends of clinical trials submitted to the Italian Medicines Agency (AIFA) over a 10-year period, evaluating the impact of the COVID-19 pandemic, the transition to Regulation (EU) No. 536/2014 (CTR) and the introduction of the EU Clinical Trials Information System (CTIS).

All clinical trial applications submitted to AIFA between January 2016 and December 2025 were analysed, integrating data from the Osservatorio sulla Sperimentazione Clinica dei medicinali (OsSC), the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), and the CTIS. Trials were categorised by year, therapeutic area and Investigational Medicinal Product (IMP) characteristics, and were further analysed by phase, sponsor profile, and study population.

A total of 7,449 clinical trials were submitted over 10 years, showing overall stability with marked fluctuations: a pandemic-driven peak in 2021 (n = 864), a regulatory transition through 2023 (n = 688) and a recovery in 2025 (n = 838). Oncology dominated the therapeutic area distribution, followed by neurological diseases, though both declined; immune-related diseases increased steadily, alongside cardiovascular and respiratory areas. Biological IMPs increased, chemical compounds declined and antibody-drug conjugates tripled by 2025, signaling a biotechnological shift. Phase II and III trials predominated, confirming Italy's role in confirmatory research. Phase I showed the most consistent growth, especially post-pandemic, while Phase IV decreased. Commercial sponsors dominated and recovered faster post-COVID-19, while non-commercial research declined. The elderly (≥65 years) and paediatric populations remained systematically underrepresented.

The Italian clinical trials setting appears resilient with a tendency toward increased activity, a strong oncology focus, and developments in other areas. It remains highly attractive for industry-sponsored trials yet structurally imbalanced. Persistent weaknesses include limited support for non-commercial research, systematic underrepresentation of key populations and, a decline in independent post-marketing studies. Targeted policy interventions are needed to strengthen academic research capacity and better align clinical research with national and European public health priorities.