Evaluating RWE from Observational Studies in Regulatory Decision-Making: Lessons Learned from Trial Replication Analyses

Observational (non-interventional) studies—typically involving analyses of real-world data (RWD) from administrative claims and electronic health records—can broaden our understanding about the effectiveness of medical products, but questions remain about the credibility of observational studies using data generated for non-research purposes (secondary use of health data). As part of its Real-World Evidence (RWE) Program, FDA is evaluating the potential role of observational studies in contributing to evidence of drug product effectiveness. This virtual conference will consider attributes of observational study design and conduct to better understand considerations for using evidence from observational studies to inform regulatory decisions.  

The meeting will focus on sharing preliminary results from ongoing trial replication efforts to better understand strengths and limitations of observational studies when considering their potential use to answer questions about drug product effectiveness and inform regulatory decision-making. The conference will explore challenges with data adequacy, bias in observational studies that may impact causal inference, including provider- and patient-based perceptions of the assigned treatment and differential adherence to treatment. Panel discussions will explore how benefits can be realized, identify gaps in knowledge, and consider strategies for addressing those gaps.

Background reading:

• Hernán MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. Am J Epidemiol. 2016 Apr 15;183(8):758-64. doi: 10.1093/aje/kwv254. Epub 2016 Mar 18. PMID: 26994063; PMCID: PMC4832051. (link)
• Franklin JM, Pawar A, Martin D, Glynn RJ, Levenson M, Temple R, Schneeweiss S. Nonrandomized Real-World Evidence to Support Regulatory Decision Making: Process for a Randomized Trial Replication Project. Clin Pharmacol Ther. 2020 Apr;107(4):817-826. doi: 10.1002/cpt.1633. Epub 2019 Oct 25. PMID: 31541454. (link)
• Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, Pawar A, Bessette LG, Lee H, Garry EM, Gautam N, Schneeweiss S. Emulating Randomized Clinical Trials with Nonrandomized Real-World Evidence Studies: First Results from the RCT DUPLICATE Initiative. Circulation. 2020 Dec 17. doi: 10.1161/CIRCULATIONAHA.120.051718. Epub ahead of print. PMID: 33327727. (link)

Funding for this workshop was made possible in part by a cooperative agreement from the U.S. Food and Drug Administration Center for Drug Evaluation and Research. The views expressed in written workshop materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsements by the U.S. Government.