The Future of Italian Phase I Trials Regulation: Lessons from a Nationwide Survey

Celeste Cagnazzo^1*Linda Penolazzi¹Stefano Stabile²Veronica Franchina³Irene Federici⁴Francesca Mannozzi⁵Alessandra Ferrari⁶Marta Betti⁷Sata Testoni⁵

• ¹Ospedale Infantile Regina Margherita, Torino, Italy
• ²Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy
• ³L'Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte, Messina, Italy
• ⁴Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
• ⁵IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy
• ⁶Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
• ⁷Azienda Ospedaliero - Universitaria SS Antonio e Biagio e Cesare Arrigo - Alessandria, Alessandria, Italy

Background: Phase I trials are critical for drug development and require rigorous oversight. In Italy, AIFA Determination 809/2015 introduced mandatory standards and a self-certification model, nearly a decade ago. Its sustainability and impact now warrant reassessment. Methods: A nationwide cross-sectional survey (March–April 2024) was conducted among professionals involved in phase I trials. A 19-item questionnaire explored institutional characteristics, certification processes, quality structures and perceptions of the Determination. Descriptive analyses were performed. Results: Sixty-two professionals responded, mainly Data Managers/Clinical Research Coordinators and Quality Assurance officers. Most centers conducted both industry and nonprofit studies. Certification of both clinical units and laboratories was common, but timelines varied widely and preparation was resource-intensive. Over half of inspected centers reported major or critical deviations and voluntary suspensions of certification were not infrequent. Clinical Trial Quality Teams were established in most centers, though key roles were often outsourced. Respondents identified procedure drafting and staff training as the most burdensome requirements and considered parts of the Determination outdated, particularly regarding team composition and personnel qualifications. Comparative references with other European frameworks (e.g., Spain and the United Kingdom) highlight differences in implementation models and timelines. Conclusions: While AIFA Determination 809/2015 has strengthened safety and quality culture, it imposes significant operational burdens, especially on academic institutions. Targeted revision appears necessary to maintain high standards while improving sustainability and competitiveness of Italian phase I research.