Using Bayesian Evidence Synthesis Methods to Incorporate Real-World Evidence in Surrogate Endpoint Evaluation.

Objective

Traditionally, validation of surrogate endpoints has been carried out using randomized controlled trial (RCT) data. However, RCT data may be too limited to validate surrogate endpoints. In this article, we sought to improve the validation of surrogate endpoints with the inclusion of real-world evidence (RWE).

Methods

We use data from comparative RWE (cRWE) and single-arm RWE (sRWE) to supplement RCT evidence for the evaluation of progression-free survival (PFS) as a surrogate endpoint to overall survival (OS) in metastatic colorectal cancer (mCRC). Treatment effect estimates from RCTs, cRWE, and matched sRWE, comparing antiangiogenic treatments with chemotherapy, were used to inform surrogacy patterns and predictions of the treatment effect on OS from the treatment effect on PFS.

Results

Seven RCTs, 4 cRWE studies, and 2 matched sRWE studies were identified. The addition of RWE to RCTs reduced the uncertainty around the estimates of the parameters for the surrogate relationship. The addition of RWE to RCTs also improved the accuracy and precision of predictions of the treatment effect on OS obtained using data on the observed effect on PFS.

Conclusion

The addition of RWE to RCT data improved the precision of the parameters describing the surrogate relationship between treatment effects on PFS and OS and the predicted clinical benefit of antiangiogenic therapies in mCRC.