SummaryTune in to episode 2 of our discussion covering why the FDA is so interested in real-world evidence and how they are approaching it.
Listen to the Other Podcasts in This Series
Nancy: Hello and welcome to the second installment of our three-part series, “Real-World Evidence: Is It a Game Changer for the FDA?” I’m Dr. Nancy Beck, a director in Avalere Health’s Regulatory Science and Commercial Strategy practice. I’m joined today by my colleague Dr. Brenda Huneycutt, a vice president in the practice.
Brenda: Hi, Nancy. Last time we talked about what real-world evidence (RWE) is and the promise it holds for improving the efficiency of medical product development and approval. Today we’ll take a closer look at:
- What is driving the emphasis on RWE at the FDA?
- The FDA’s approach
First to drivers. Concerns about the costs of clinical trials along with a desire for a broader evidence base for medical decision-making led to RWE provisions in both the 21st Century Cures Act and the Prescription Drug User Fee Act (PDUFA) VI commitment letter. These provisions require FDA to:
- Hold at least one public workshop on RWE by September 2018
- Develop a draft framework on potential RWE sources and uses by Dec 2018
- Initiate activities to address key RWE considerations by September 2019, which could include pilots
- Publish draft guidance on the use of RWE by September 2021 and revised guidance by March 2023
Nancy, you’ve been following the FDA activities. What can you tell us about the Agency’s approach?
Nancy: Given the timelines you just mentioned, these activities are largely underway. The public kick-off to these the FDA activities was a September 2017 workshop held in collaboration with the Duke-Margolis Center for Health Policy. A white paper and framework were presented, illustrating 3 major ways the FDA might use RWE—including satisfying post-market commitments, label expansions and revisions, and new approvals. Although there were no surprises, the meeting did provide some clarity on how agency leaders are thinking about RWE.
While there is still a lot of talk about ensuring that the study design, data collection, and analytical methods are fit for regulatory purpose, we have officially moved past talking about “if” RWE can be used. We’re now talking about “how” and “when” RWE can be used. For example, recommendations for improving the transparency and reproducibility of RWE for healthcare decision-making were published in October 2017 by a joint task force of ISPOR (International Society for Pharmacoeconomics and Outcomes Research) and ISPE (International Society for Pharmacoepidemiology). And the National Academies are holding a series of three workshops on the use of RWE in medical product development. The second meeting, held in early March, centered around developing recommendations to guide researchers in determining when RWD might be useful.
Brenda: When you say recommendations, are you talking about developing specific standards or something more like general guidelines?
Nancy: The intent is more in the spirit of guidelines or best practices. What characteristics of a data source, study design, and analytical method should be considered in determining whether they are appropriate to answer a given question or research aim with sufficient confidence? For example, how do you determine whether a data source is accurate enough to identify the right population, the treatment or product of interest, the right outcome, or detect potential safety issues?
Brenda: And for the FDA, of course, the issue is whether the question can be answered with sufficient confidence for a regulatory decision. So, where we’re at now is that a significant amount of information gathering, and thinking has already occurred, and now it is a matter of CDER—the Center for Drug Evaluation and Research at FDA—coming to agreement internally and pulling the information together in a way that reflects their needs. I say CDER, because CDRH—the Center for Devices and Radiological Health—has already published a guidance on the use of RWE for medical devices. I imagine we can look to that guidance for an idea of what we may see from CDER.
Nancy: Yes, I think so, and certainly in terms of thinking around best practices. Development of best practices is a necessary step toward building confidence in the use of RWE, but what is still missing are use cases and practical experience. We can talk about recommendations, but until someone starts testing the recommendations, we’re not going to get very far.
The FDA does have significant learnings from 10 years of hands-on experience standing up and running Sentinel, but that experience primarily involves the use of claims data to assess post-market safety. FDA needs experience with additional types of data to answer questions of efficacy that would be needed to support decisions about label changes and new approvals.
Brenda: So what we need are some pilot demonstration projects. The FDA is required to initiate activities to address outstanding concerns around the use of RWE by September 2019 which could include pilot projects. Do we have any ideas as to how the FDA may approach those?
Nancy: We do, but we’ll save that for the next podcast, where we’ll explore what companies should be doing to prepare for resulting benefits. The FDA has encouraged sponsors to come to them with proposed pilots to help address key considerations and build confidence in the use of RWE. This is a great opportunity to test new approaches and understand first-hand what RWE the FDA may consider and in what contexts to answer the question of “when” RWE can be used.
Brenda: In our third and final podcast, we’ll explore those possibilities, looking at some use cases to illustrate ways companies can capitalize on RWE. Tune in to find out the answer to whether real-world evidence is a game changer? Thanks to everyone for listening.
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