Development, review, and activation of thoracic oncology investigator-initiated trials

Abstract

Background: Investigator-initiated trials (IITs) may address important biological and clinical questions that may not be prioritized by pharmaceutical sponsors. However, little is known about the process by which IIT proposals are evaluated and activated. Methods: We performed a retrospective study of IIT concepts submitted through the Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC), which comprises 13 institutions in the U.S. and Canada, from 2014 (consortium inception) to 2024. We compared approved and disapproved concepts using chi-squared tests, Fisher’s exact tests, and Wilcoxon Rank-Sum tests. Results: Among a total of 68 presented IIT concepts, 60 (88%) received consortium approval a median of 30 days (interquartile range [IQR] 31-59 days) after submission. Concepts submitted by junior faculty were more likely to be approved than those from full professors (P=0.003). Of the 60 concepts subsequently submitted to pharmaceutical sponsors, 15 (25%) were approved, 43 (72%) were disapproved, and 2 (3%) remain under review. The median time between concept submission to a sponsor and the sponsor’s decision was 61 days (IQR 31-183 days). Concepts with shorter projected durations were more likely to be approved by the pharmaceutical sponsor (P=0.05). For sponsor-approved IIT concepts, median overall time from initial submission to trial activation was 18 months. Conclusions: Only a small proportion of proposed investigator-initiated cancer clinical trials are successfully activated following a prolonged development process. Given the importance of IITs in addressing real-world, practical questions and the growing professional challenges facing clinical research physician faculty, further attention to IIT development facilitators and barriers is warranted.