PS37: Innovations for Improving Go/No-Go Decision-Making Through Multiple Endpoint Integration

As an objective and authoritative measure of both safety and efficacy overall survival has been the gold standard for oncology drug approvals. Recent innovations in US regulatory policy established several pathways to expedite the review process for emerging therapies for serious conditions with unmet medical need. Accelerated Approval, one such mechanism, provides early market access on the basis of improvements in surrogate endpoints such as objective response rate, progression-free survival, and duration of response. Accelerated approvals, which require sponsors to conduct subsequent confirmatory phase III trials, have emphasized indolent hematologic malignancies and solid tumors where randomized trials with an overall survival primary endpoint would result in significant delays or be impractical because of the rareness of the target population. In the last four years alone, however, more than 16 cancer indications have been withdrawn from previous accelerated approvals after negative phase III trials failed to demonstrate benefits for overall survival when compared to standard-of-care therapies. This has propelled further refinements in US regulatory policy, with Project Frontrunner and revised guidance for pursuing accelerated approval. Researchers at the FDA's Oncology Center of Excellence published an article in 2023 describing complex, "irreconcilable differences" between surrogate endpoints and overall survival which vary by drug class, the natural history of the disease, availability of subsequent therapies, and the safety profile of the experimental therapy. This session was devised to bring together leading experts in regulatory policy, machine learning, and clinical trial design to discuss the latest innovations in multivariate modeling techniques for oncology endpoints as well as the implications of these innovations for decision-makers. Moreover, the speakers in this session will propose statistical solutions to address Project Confirm, an initiative launched by the FDA's Oncology Center of Excellence in December of 2024 to promote the transparency of outcomes related to accelerated approval for oncology indications.