How RWE and Predictive Modeling Support OS-Focused Trial Designs

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: What role can real-world evidence and predictive modeling play in supporting OS-focused designs without compromising speed or patient access?

Kadambi: I think real-world evidence and predictive modeling are an integral part of what I'll call an integrated evidence framework, and I'll back up a little bit. This will be a slightly longer answer than you probably want, but I already mentioned this evidence gap between regulators and payers, and I think one approach that can help bridge this gap earlier in the process is to bring these tools, like real-world evidence and model informed drug development to bear earlier on in development. By using these tools and generating a more global or comprehensive package of information that considers things from all angles, earlier on, you can still go through the normal process of generating the RCT based evidence that are still, in most cases, the gold standard for the agencies, while filling in the gaps with other pieces of evidence that you might not collect during your clinical studies for either ethical or practical considerations, and have a more fully-baked story for the agency that not only satisfies their requirements, but also gives you a leg up on, as I mentioned earlier, future conversations that you'll have to get reimbursement for your drug and enable patient access after launch. Bringing these tools to the forefront, in short, can help keep the process lean and mean, if you will, despite the fact that, on the surface, this guidance suggests that trials are going to have to be longer, potentially in order to capture these safety endpoints. I think the MIDD and real-world evidence tools that are available are really critical part of keeping the process efficient while still satisfying the high bar that the agencies and the and the payers set.