Background: In 2018 FDA released its RWE Framework to further the use of RWE and evaluate the potential use of RWE to support new indications for approved drugs and to satisfy post-approval study requirements. Based on the Framework, potential areas for use of RWE include labeling for effectiveness, changes in dose, dose regimen, or route of administration changes, new population (s); or adding comparative effectiveness or safety information.
Objectives: To conduct a scoping review and identify the attributes where RWE was recognized by the FDA as substantial, supportive, or not-fit-for integration into regulatory decision making for efficacy.
Methods: We assessed FDA drug reviews between 2018-2022 where RWE was included to support efficacy by reviewing product labels, Multi-Disciplinary Reviews, Administration and Correspondence Documents, company materials (press releases), PubMed , and clinicaltrials.gov.
Results: We identified 19 cases where of RWE for efficacy was evaluated by the FDA. Of these, 8 cases were identified as substantial or primary evidence, 5 as supportive evidence, and the remaining 6 cases were classified as not adequate for regulatory decision making. Among the cases where RWE contributed to substantial or supportive evidence of efficacy, the following patterns were observed: • Regulatory Strategy Agreement - Early agreement on RWE proposals with regulators • Indication and Natural History of Disease Strategy – Importance of classifying unmet medical needs, homogeneous indications, rare disease, and known biological pathway • Methodological Rigor and Trust in Data Preparation – Predefined statistical analysis plan using methods to reduce bias/confounding/informative censoring and sensitivity analyses • Change in Treatment Paradigm and Drug Effect - Agreement with regulator on what effect size is sufficient to overcome concerns about biases
Conclusions: We identified four key attributes which may advance the FDA’s goal of using RWE in regulatory decision making for efficacy.
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