FDA Draft Guidance On Overall Survival in Oncology Trials: What Sponsors Need To Know

By John McIntyre, PhD and Nick Richardson, DO, MPH

The FDA’s August 2025 draft guidance on Approaches to the Assessment of Overall Survival (OS) in Oncology Clinical Trials marks a pivotal shift in regulatory expectations for cancer drug development. Historically regarded as the gold standard efficacy endpoint, OS is now positioned not only as a measure of therapeutic benefit but also as a critical safety endpoint. Sponsors are being called on to assess OS in all randomized oncology studies supporting marketing approval, even when it is not a primary endpoint. The guidance lays out an expectation for sponsors to conduct interim harm analyses, incorporate long-term follow-up, minimize missing data, and carefully address intercurrent events such as crossover and subsequent therapies.

The FDA discourages crossover trial designs and emphasizes robust, pre-specified statistical methods, including sensitivity analyses and simulations to assess uncertainty and rule out harm. By reframing OS as both an efficacy and safety measure, the FDA signals that oncology sponsors must integrate survival data into trial strategy from early development through regulatory submission.