Leveraging Real-World Evidence: A Paradigm Shift in Regulation.

The study methodology and regulatory frameworks for real-world data collection is quickly evolving, opening new avenues to use valid and robust real-world evidence (RWE) to support regulatory decision making. Although the Food and Drug Administration has historically accepted specific applications of RWE to support regulatory determinations, significant progress has been made in recent years to examine conditions in which this information can be used to support specific types of premarket decisions. Of note, hybrid study designs that incorporate aspects of randomized clinical trials, including randomization and pragmatic outcomes, are expected to be a driving factor to accelerate the adoption of RWE in regulatory contexts. Generation of RWE to better understand effectiveness and safety of orthopaedic- and trauma-related devices requires careful planning, but it is achievable as demonstrated by the Bioventus Observational Non-Interventional EXOGEN Studies (BONES) clinical development program. This article examines the role of RWE in regulatory decision making and reviews key concepts in RWE study design methodology to facilitate creation of valid scientific evidence in support of marketing authorizations.