TJ ISSN 0300-8916 https://doi.org/ Tumori Journal 2018, Vol. 104(1) 15–21 © Fondazione IRCCS Istituto Nazionale dei Tumori 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.5301/tj.5000668 journals.sagepub.com/home/tmj ORIGINAL RESEARCH ARTICLE Classical oncology phase I trials are cohort studies aimed at identfying the maximum tolerated dose for cytotoxic agents or the optmal biological dose for target therapies or immunological drugs, and at determining the recommended dose and schedule according to which to administer the drug in the subsequent phase II studies. During phase I, a frst de- scripton of adverse events in a dose-dependent manner is also provided (2). Although the beneft to risk rato for patents included in phase I studies is perceived as low, and while the ethical bases of these studies have been questoned (3-5), their results are necessary for drug development. Since phase I clinical trials (CTs) are the frst step in human testng of experimental drugs, they ought to be conducted in compliance with established rigorous standards for the protecton of the rights, safety and well-being of the partcipants (6). In spite of the regulatons (7-11) requiring the implementaton of vigilant oversight by competent authorites and ethics commitees, and in spite of the regulatory agencies’ eforts to guarantee compliance (12), phase I trials have not been immune from tragedies. New requirements for phase I trials: a challenge for Italian clinical research Emanuela Marchesi 1,2 , Manuela Mont 3 , Oriana Nanni 3 , Lisete Bassi 4 , Martna Piccinni-Leopardi 5 , Celeste Cagnazzo 4 1 Scientfc Directon, Rizzoli Orthopedic Insttute, Bologna - Italy 2 Italian Sarcoma Group, Bologna - Italy 3 Isttuto Scientfco Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy 4 Clinical Research Ofce, Candiolo Cancer Insttute–Piemonte Foundaton for Oncology, Scientfc Insttutes for Research and Care, Candiolo (Turin) - Italy 5 Chemotherapy Unit, Rizzoli Orthopedic Insttute, Bologna - Italy Introducton Clinical research is crucial for advancing medical knowl- edge and patent care, and phase I trials represent the frst stage of the clinical development of a new drug, in which a small group of healthy volunteers or – in selected felds including oncology and for antretroviral drugs – patents receive the drug. The primary objectve is to evaluate the drug’s safety and tolerability (1). ABSTRACT Background: In 2015, the Italian Medicines Agency (Agenzia Italiana del Farmaco; AIFA) issued the Determinaton 809/2015 with new requirements for phase I clinical trials. Before it came into force, we explored the extent to which several Italian oncology centers were working to implement it. Methods: A survey was conducted among 80 Italian centers involved in clinical trials. Investgators and research coordinators were surveyed. Results: Answers from 42 insttutons were collected: among them 88.1% were involved in oncology research. In the last 5 years, 55% had conducted from 1 to 5 phase I trials, and only 16.7% more than 5. A third were involved in not-frst-in-human research and none with healthy volunteers. The majority (57.1%) of the centers did not run any projects and trials are non-commercial, and about 35%, no more than 2. While 9.5% already met the stan- dards for self-certfcaton, 71.4% were working to achieve them. Standard operatng procedures dedicated to research and the required good clinical practce training had been established by 57.1% and 76.2%, respectvely. Fify percent of laboratories were almost compliant with the Determinaton. Afer 10 months from its coming into force, 98 sites had applied for certfcaton, of which 34 were oncology units. Conclusions: The new AIFA Determinaton imposes a certfed organizatonal model on units and laboratories involved in phase I trials. Our results showed that great eforts were made to qualify for phase I research suggest- ing that other oncology units will apply for certfcaton in the near future. Predictably, Italy will set the pace as a highly qualifed country in which to conduct early-phase research. Keywords: AIFA determinaton 809/2015, Clinical trials, Oncology, Phase I units Accepted: June 13, 2017 Published online: August 7, 2017 Corresponding author: Dr. Emanuela Marchesi Scientfc Directon Orthopedic Rizzoli Insttute Via di Barbiano 1/10 40136 Bologna, Italy emanuela.marchesi@ior.it