Inter-hospital heterogeneity in the authorizations of off-label cancer drugs: A project by Associazione Italiana di Oncologia Medica

Purpose: This project aimed to describe variability of local evaluations of off-label cancer drug requests by submitting a list of identical requests to different Italian centers. Methods: In October 2024, oncology unit directors listed in the AIOM Libro Bianco were invited to participate, evaluating 11 clinical cases with solid tumors through their internal approval process. Supporting evidence was retrospective in two cases, based on phase II trials in seven, and phase III trials in two. Inter-rater agreement was measured using Fleiss’ kappa. Results: Seven centers completed evaluations. Two cases were approved by all centers, both with a rare cancer with scant alternatives. The mean number of centers approving the individual requests was 5.36/7 (76.6%) with a poor inter-rater agreement (kappa 0.009, 95% CI -0.120 to 0.138). Single centers approved a mean of 8.4 requests (76.6%). The mean number of centers that approved requests was 5.5 for requests based on retrospective studies, 5.3 for those based on phase II trials, and 5.5 for those based on phase III trials. There was no correlation between estimated cost and chance of approval. Conclusions: There is a significant inter-hospital variability in off-label oncology drug evaluations, leading to potential disparities in patient’s access to care.