How FDA’s Focus on Overall Survival Redefines Trial Success

In a recent video interview with Applied Clinical Trials, Ananth Kadambi, VP of real-world evidence and modeling solutions at Certara, outlined the operational hurdles sponsors face as the FDA increasingly requires overall survival (OS) as the primary endpoint in oncology studies. He emphasized the importance of pre-specified safety monitoring, analytical subgroup planning, and strategies to minimize patient dropouts. This regulatory shift places equal weight on demonstrating efficacy and safety, with implications for post-approval monitoring and patient access. Kadambi noted that model-informed drug development and real-world evidence can support more efficient trial designs. For clinical operations teams, the focus will be on strengthening patient tracking and engaging data monitoring committees earlier in the process to balance trial efficiency with regulatory and payer demands in complex oncology indications.

ACT: How does this shift toward OS reflect broader concerns around post-approval safety, and what does it mean for how trial success is measured moving forward?

Kadambi: Trial success going forward will clearly be reflective of both efficacy and safety, and the agency is clearly interested in mitigating undetectable safety risks as early on in the process as possible. The other consideration here, which is not necessarily related directly to clinical trials per se, is related to success post market. I'll just point out that the success of drug development is not necessarily getting regulatory approval, it's ensuring that the patients who need the drug get access to it at an affordable price point, so the reimbursement story and payer discussions are really a critical piece of this that I think are often overlooked.

By planning earlier during the clinical trial stage for assessment of those real-world effectiveness type of endpoints, there will be a shorter bridge for sponsors to cross once they get to the reimbursement side of things. It's not just about trial success, it's about successful launch and successful access of the drugs by the right patients at the right time.