Real-world evidence can change the course of regulatory decisions. In February 2023, the U.S. Food and Drug Administration (FDA) approved Skyclarys (omaveloxolone) for the treatment of the rare neurological condition Friedreich’s ataxia (FA) on the basis of both clinical trial data and matched analyses with real-world patients in a natural history study. While ultimately accepted, regulators did critique the sponsor’s lack of prespecified analysis plan for their real-world analyses, highlighting increased demand for proactive and transparent RWE strategy.
This critique is well in line with ISPE/ISPOR initiative to integrate open science practices into routine workflows for pharmacoepidemiologists—an initiative that was front and center in several informative ISPE sessions including Building Transparency and Reproducibility into the Practice of Pharmacoepidemiology and Outcomes Research. These sessions were great reminders that transparency should extend through the lifecycle of RWE from published protocols and analysis plans to data conformance to facilitate reproducibility by regulatory and other decision-making bodies. Based on the traffic around our poster synthesizing and operationalizing data conformance standards, interest in putting recommendations into practice is high.
Our presented case series on the evaluation of RWE by regulatory and HTA bodies showcases other ways to translate regulatory and HTA feedback into action. In studies of seven therapies, including Skyclarys, the FDA showed greater RWE acceptance than EMA. HTA acceptance was more mixed; the same evidence might be accepted by one, rejected by another, and not considered by a third. However, across agencies, similar concerns were expressed and the handling of prognostic variables, missing data, and residual confounding were identified as areas of improvement.
The lessons for sponsors are clear: Engage early, design RWE that can pre-empt known concerns, and build strategies that anticipate the evidentiary bar across markets.
Want to sharpen your RWE approach? Landmark can help translate regulatory feedback into evidence packages that align with best practices. Whether you need help identifying prognostic variables (see Shivani Aggarwal’s recently published work on this topic), data landscaping to assess data completeness, or methodological support to answer questions about residual confounding, our experts are at your service.