Because No One is Immune to the Law
January 23, 2020 - United States, FDA, Biotech, Healthcare, Pharma, Regulatory, Cell + Gene Therapy

FDA and Real-World Evidence in 2019

A New Year's Gift for Patent Applicants?

Around the end of 2018, FDA published the “Framework for FDA’s Real-World Evidence Program” (the “Framework”).[1] The Framework is to provide a basis for the agency in evaluating the potential use of real-world evidence (RWE) in regulatory decisions involving drug and biological products.[2] The Framework laid out a “three-part approach” identifying data quality, study design, and regulatory requirements as focal points of the evaluation. In addition, the Framework pointed to the importance of data standards in enabling efficient processing of real-world data (RWD), from which RWE is derived. In 2019, to refine its understanding of these four areas (data quality, study design, regulatory requirements, and data standards) in the context of RWE, FDA coordinated a multifaceted effort including demonstration projects, development of guidance documents, the Sentinel System, and active engagement with sponsors and other stakeholders.

In 2019, FDA expanded some of its existing demonstration projects, while funding new ones. In April, Aetion announced that FDA and Brigham and Women’s Hospital/Harvard Medical School will expand the scope of their demonstration project to include predicting seven ongoing randomized control trials (RCTs) with RWE, in addition to the original scope of replicating 30 completed RCTs.[3] In August, a San Francisco-based company Syapse announced that it will work with FDA to assess the potential of RWE especially in the context of precision medicine.[4] While some have criticized these studies,[5] demonstration projects seem to remain a core part of FDA’s Real-World Evidence Program (the “Program”).

In May, FDA published a draft guidance entitled “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics.”[6] The industry reaction was mixed, some cautioning while others encouraging the use of RWE.[7] Notably, some of the pharmaceutical companies asked the agency to consider data from Expanded Access programs as a source of RWD, in response to the draft.[8] While expanding the scope of RWD in such a way may incentivize companies to more actively engage in FDA’s Expanded Access and Right to Try programs,[9] it remains to be seen how the agency’s subsequent treatment of RWE interacts with the level of industry participation in those programs.

The Sentinel contract in September marked another step forward in FDA’s endeavor to incorporate RWE into its regulatory practice. According to Jacqueline Corrigan-Curay, FDA’s Director of CDER’s Office of Medical Policy, the contract “will really enable FDA to continue to grow its own RWE capabilities.”[10] The contract will fund up to $220 million for five years starting in 2019, for the next phase of the Sentinel System,[11] which is to become a platform that generates RWE for FDA.[12]

Lastly, FDA supported and sponsored workshops to exchange insights with stakeholders. In July, through a public workshop titled “Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes,” FDA explored the potential use of RWD not only in single-arm trials but also in randomized clinical trials.[13] Also in July, FDA sponsored a workshop titled “FDA-AACR Real-world Evidence Workshop,” discussing the use of large genomic databases and digital data as RWD, among other things.[14] In October, at a conference entitled “Developing Real-World Data and Evidence to Support Regulatory Decision-Making,” FDA and various stakeholders exchanged thoughts on the key evaluation areas laid out in the Framework.[15] Through these workshops, FDA has shown that it is open to a wide range of creative solutions, while understanding that it may have to take one step at a time.[16]

In parallel with its pursuit under the Program, FDA in September announced a Technology Modernization Action Plan.[17] In justifying the timeliness of this plan, FDA explained that a modernized technical infrastructure will be necessary for the agency to accept and process RWD and to derive RWE for its regulatory decision-making, specifically referring to the Framework and the Program. This explanation seems to reach beyond the scope of the Program (and the congressional mandate by the 21st Century Cures Act), which simply sets out to evaluate the potential use of RWE.[18]

Finally, it is worth noting how RWE continued to play a role in supporting drug approvals in 2019, especially in the context of cancer and rare diseases. For instance, FDA’s Oncology Drugs Advisory Committee last month unanimously recommended accelerated approval of a drug (tazemetostat) for a rare form of cancer,[19] where the approval was supported in part by a Natural History Study.[20] Further, FDA in April approved a new indication of a drug (palbociclib) primarily based on RWD such as electronic health records and post-marketing reports.[21] The approval is one of the rare cases where FDA accepted RWE to support an effectiveness decision (rather than a safety evaluation), and will serve as a precedent for future drug approvals. Given FDA’s willingness apparent in the Framework to further explore the use of RWE in effectiveness decisions, it seems likely that RWE will play a bigger role in drug approval processes in 2020.

In short, FDA in 2019 tapped into multiple channels to gather input from stakeholders and also to broaden its own experience with RWD and RWE. Although the exact outcome of these endeavors remains to be seen in 2020, the agency appears to be slowly but surely getting ready to incorporate more RWE into its regulatory decisions.

[1] Framework for FDA’s Real-World Evidence Program, FDA (December 2018)

[2] Webinar: Framework for FDA’s Real-World Evidence Program, FDA (March 2019)

[3] FDA Expands Real-World Evidence Partnership with Brigham and Women’s Hospital and Aetion, PR Newswire

[4] Syapse Announces Research Collaboration with the FDA Focused on the Regulatory Use of Real-World Evidence (August 2019)

[5] Attempt to Replicate Clinical Trials with Real-World Data Generates Real-World Criticism, Too, Matthew Herper (July 2019)

[6] Draft Guidance: Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics, FDA (May 2019)

[7] Industry Reaction Mixed to FDA Draft Guidance on Real World Data and Evidence, Thomas Sullivan (September 2019)

[8] Gilead and Novartis Seek to Expand What FDA Considers as Real-World Data and Real-World Evidence, Zachary Brennan (July 2019)

[9] Public Meeting Report: Leveraging Real World Treatment Experience from Expanded Access Protocols, Silver Spring (November 2018); Pre-Approval Access and Real-World Evidence: A Win-Win Proposition, Jane Reese-Coulbourne (November 2017); Working Group on Compassionate Use & Preapproval Access Frequently Asked Questions (“If companies see expanded access programs as a source of valuable RWE, they may become more willing to run expanded access programs alongside their clinical trials.”)

[10] Developing Real-World Data and Evidence to Support Regulatory Decision-Making, FDA & Duke-Margolis Center for Health Policy (October 2019)

[11] Harvard Pilgrim Health Care Institute Funded up to $220 Million for The Next Phase of FDA Sentinel System, Harvard Department of Population Medicine (September 2019)

[12] Sentinel System: Five-Year Strategy 2019-2023, FDA (January 2019)

[13] Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes, FDA & Duke-Margolis Center for Health Policy (July 2019),;

[14] FDA-AACR Workshop: Real-world Evidence, FDA & AACR (July 2019),;

[15] Developing Real-World Data and Evidence to Support Regulatory Decision-Making, FDA & Duke-Margolis Center for Health Policy (October 2019)

[16] E.g., Developing Real-World Data and Evidence to Support Regulatory Decision-Making, FDA & Duke-Margolis Center for Health Policy (October 2019) (“We know that today data (does) not just seamlessly flow from the EHR or claims data for use in research. Today we’re going to hear maybe how we might get one step closer to that: whether that will require re-imagination of the EHR and the clinical work flow to capture data that is relevant to both quality practice and research … or maybe it’s more relying on natural language processing and artificial intelligence.”)

[17] FDA’s Technology Modernization Action Plan, FDA (September 2019)

[18] Webinar: Framework for FDA’s Real-World Evidence Program, FDA (March 2019)

[19] FDA Panel Recommends Approval of Epizyme Drug for Rare Cancer, Alaric Dearment (December 2019)

[20] NDA211723: Tazemetostat for the Treatment of Patients with Metastatic or Locally Advanced Epithelioid Sarcoma Who Are Not Eligible for Curative Surgery, Epizyme (December 2019)

[21] U.S. FDA Approves Ibrance® (Palbociclib) for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer (April 2019)