The authorization process of observational studies in Italy: exploring two decades of Ethics Committee approval data.

Abstract

Introduction: The recent guideline from the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) on observational studies prompts a broader reflection on the impact of regulations on clinical research and real-world evidence. While regulations are necessary to ensure ethical and scientific standards, their effectiveness in improving research quality is unclear. It is also uncertain whether these regulations strengthen clinical research or create bureaucratic obstacles. This quantitative, "before and after" study investigates the impact of the 2008 AIFA guideline and the 2018 General Data Protection Regulation (GDPR) on the complexity of ethical evaluation processes. As a secondary outcome, we also aimed to investigate whether the duration and probability of suspensions were influenced by intrinsic study characteristics (study design, rare disease, genetic data, post-authorization safety study).

Materials: The study analyzed the ethical evaluation process of 112 observational multicenter studies with 2,875 submissions from 2002 to 2022, included in the database of Medineos srl. The number of suspensions observed in each evaluation process was a surrogate endpoint of complexity of evaluation process.

Methods: Descriptive analyses and survival analysis were used to evaluate the total evaluation time, and a logistic model was applied to assess the probability of receiving a suspension.

Results: The median (and interquartile range) evaluation time for "pre-AIFA" submissions was 70 (41-133) days, whereas it was 75 (45-122) days for "post-AIFA" submissions. The median evaluation time was 68 (41-113) days without suspension and 127 (84-180) days with suspension. Post-AIFA submissions had a higher likelihood of suspension. The median evaluation time for "pre-GDPR" submissions was 70 (42-123) days, whereas it was 90 (63-140) days for "post-GDPR" submissions. AIFA guidelines slightly increased evaluation time and the likelihood of suspension, suggesting improved quality control. GDPR increased evaluation time due to privacy evaluations but did not affect suspension probability. Intrinsic study factors did not impact evaluation duration or suspension probability.

Conclusions: Although more extensive analyses are necessary, this study suggests that past changes in Italian regulations have affected the evaluation by the Ethics Committee (EC) and have also impacted the conduct of the observational studies. The data generated can be useful for monitoring the future impact of the recently published new AIFA guideline.