E3 – Real-World Evidence: Is It a Game Changer for the FDA?

  • This page as PDF


We discuss 3 steps companies should complete now to take advantage of the FDA’s priority to advance the adoption of RWE to support agency decision making.
“Companies should consider developing a policy strategy to engage with the FDA and other stakeholders to help the Agency advance their RWE initiatives.” Brenda Huneycutt, Avalere

This interview was originally published as a podcast. The audio is no longer available, but you can read the transcript below. For updates on our newly released content, visit our Insight Subscription page.

Explore Other Interviews in This Series

E1 – Real-World Evidence: Is It a Game Changer for the FDA?

E2 – Real-World Evidence: Is It a Game Changer for the FDA?


Brenda: Hello and welcome to the third and final installment of our three-part series, “Real-World Evidence: Is It a Game Changer For the FDA?” I’m Dr. Brenda Huneycutt, a vice president in Avalere Health’s Regulatory Science and Commercial Strategy practice. I’m joined today by my colleague Ernest Voyard, a director in the practice who previously spent time as a regulatory counsel in FDA’s Office of Prescription Drug Promotion – we will get to that later.

Ernest: Hi, Brenda. I know you have already discussed what real world evidence, or RWE is, what is driving the emphasis on RWE at the FDA, and the FDA’s approach. Today we are going to talk about how product manufacturers (sponsors) can use RWE in product development – for example, getting approval for a new indication – and what companies should be doing now.

Brenda: That’s right! As FDA Commissioner Scott Gottlieb says: “The more widespread use of RWE can make our medical product development process more efficient, and help lower the costs of development.” So, let’s talk about a few RWE uses that the 21st Century Cures Act directs the FDA to focus on – RWE to support or satisfy post-approval study requirements and RWE to support the approval of a new indication – as well as supporting new approvals of drugs to treat rare diseases.

Ernest: One public example is the use of a patient registry to meet a post-marketing commitment for the drug Kalydeco®. Vertex is conducting a 3-year, single arm, observational study of all patients registered in the U.S. Cystic Fibrosis Foundation Patient Registry who have a newly designated CFTR gene mutation shown to be responsive to Kalydeco®. This study will evaluate select patient outcomes, including lung function, and select cystic fibrosis complications. When completed, the study, will meet the post-marketing commitment.

Brenda: Vertex also used Cystic Fibrosis patient registries to support a new indication for Kalydeco®. More than five years of RWE demonstrating the product’s safety and efficacy supported FDA’s decision to grant a new indication expanding the populations treated to those with additional, I believe almost 20, CFTR gene mutations.

Ernest: In the device space, registries have also been used to expand indications for the Sapien 3® artificial heart valve. For example,  the label was expanded to include use of the device when a first device fails – called a valve-in-valve treatment—based on a study of 625 patients who had undergone this procedure off-label. A registry was also the basis for revising the label to remove reference to specific access points on the body for insertion of the device (for example, transfemoral or transapical), allowing alternative access points not previously indicated, based on the outcomes of about 500 patients who had undergone such off-label insertions.

Brenda: In the rare disease space, RWE has been used to support approval of a number of products, including Carbaglu® to treat N-acetylglutamate synthase deficiency based on a retrospective case series of 23 patients, and Cholbam® to treat bile acid synthesis disorders based on a 54 patient case series from an expanded access trial. In addition, RWE can serve as a historical control, as it did to support the approval of Ceprotin® to treat severe congenital Protein C deficiency.

Ernest: As the FDA becomes more and more comfortable with RWE for these purposes, we expect to see more examples of the use of RWE to support new approvals and new indications, satisfying post-marketing commitments, and for other uses such as determining the feasibility of certain clinical studies.

Brenda: Let’s turn to a related topic for a moment. Ernest, what about promotional issues? Is there anything about RWE that companies should consider when promoting their products?

Ernest: When it comes to promoting their products, I think that one area for sponsors to pay attention to is health care economic Information, or HCEI, provided to payors, formulary committees and other similar entities. The 21st Century Cures Act amended FDAMA Section 114 in some notable ways. For example, by changing the requirement that HCEI claims made to “formulary committees, payers, and other similar entities” from“directly related to the indication” to simply “related to the indication”, the Act, and the recently published guidance, seems to clear up some of the questions about the use of RWE in this type of promotion. In the past, I think sponsors were hesitant to step into this area because RWE might not always “directly” relate to the indication—I mean the patient mix in the real world is never the same as a clinical trial—but removing that “directly” language makes it clear that RWE can be an appropriate source for the development of HCEI. The examples in the guidance of what qualifies as “related to”—duration of therapy, patient subgroups, length of hospital stay—makes it clear the FDA is trying to be flexible. That being said, the agency did set some guideposts—for example, sponsors shouldn’t focus HCEI RWE on patients not found within the indicated population for the product.

Brenda: Do you expect the FDA’s stance on promotion in general to change? What should companies be looking out for?

Ernest: Well, as I mentioned, the FDA earlier, the FDA just released a final version of its payor communication guidance. It also just released a final version of its guidance covering “Medical Product Communications That Are Consistent With the FDA-Required Labeling.” As everyone digests these guidances, I think it will become clear that both will have an impact on the use of RWE in drug promotion.

Brenda: That is clearly very important for companies to get ahead of. To wrap up, what are three actions we think all companies should do now to take advantage of the FDA’s priority to advance the adoption of RWE to support Agency decision-making?

Ernest: First, conduct an assessment of your whole company. What RWE data sources do you currently have and on what terms; what are your current RWE capabilities; and what experience do you already have using RWE with FDA or with EMA or other regulatory agencies around the world. Identifying gaps can inform your RWE strategy moving forward, and getting everyone up to speed on what might already be happening throughout the company helps too.

Brenda: I agree and would add that companies should consider developing a policy strategy to engage with the FDA and other stakeholders to help the Agency advance their RWE initiatives. This can include participating in public meetings, submitting comments to FDA regarding draft guidances, and meeting with the Agency.

Ernest: And third, companies should map out a product development RWE strategy for specific products, and possibly for pilot projects with the FDA. In addition, companies should think about collaborations, especially with patient groups. And don’t forget your patient engagement strategy!

Brenda: Well, there you have it. Do you think real-world evidence is a game changer? We think it very well might be! And in any event, companies need to be thinking about it now. You can reach out to myself or Ernest to have a more in-depth conversation on RWE via our website avalere.com or if you would like to remain updated on the latest RWE news follow us on Twitter @avalerehealth and LinkedIn @Avalere Health.

Thanks to everyone for listening.

To learn more about RWE-related work, connect with us.

From beginning to end, our team synergy
produces measurable results. Let's work together.

Sign up to receive more insights about Regulatory Strategy and FDA Policy
Please enter your email address to be notified when new Regulatory Strategy and FDA Policy insights are published.

Back To Top