Preparing for the Operational Burden of OS Requirements in Oncology Trials

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 should clinical operations teams prepare for the cost and resource implications of this guidance, particularly in complex oncology indications with long survival curves?

Kadambi: The clinical operations teams will have their work cut out for them a little bit. As I mentioned earlier, one of the key things at the design phase is they're going to need to spend a lot more attention to making sure that patients are being tracked appropriately. I think I already mentioned the need to minimize the number of dropouts in the study and that every patient counts, and so the infrastructure associated with tracking patients, etc., will necessarily be somewhat increased. We'll also need, probably, to loop in independent data monitoring committees earlier on in the process than they normally would. While clinical operations is not my area of expertise, I can imagine there would be some additional overhead associated with that as well.

The other piece is, I think, more on the statisticians that are supporting the clinical operations team in terms of all of the pre-planning they're going to need to do to ensure that the bar that's set by the agency in this guidance for pre-specified analyses and pre-specification of subgroups is met.