An Expanded Role for Real-World Evidence in FDA Approvals for Drug Registration

Real-world evidence (RWE) is gaining prominence in the drug approval process for promising and breakthrough treatments.

RWE is clinical evidence derived from real-world data (RWD) – that is, data related to patient health status and/or the delivery of health care that are generated in clinical practice, outside of randomized controlled trials. Pharmaceutical companies have been working with the US Food and Drug Administration (FDA) to explore new ways to use RWE to support new drug applications (NDAs), supplemental new drug applications (sNDAs), and pre-marketing approvals (PMAs) for medical devices. This can be especially important for new therapies that target rare but serious illnesses with unmet need, where single-arm trials are often conducted due to the lack of effective therapies and low feasibility of a parallel-arm controlled trial. In these and other cases, RWE can play a role in complementing and contextualizing a drug’s usage, benefits (in terms of efficacy), and risks (in terms of safety) in order to support accelerated approval or in support of confirmatory trials for regular approval after contingency approval is granted.

Bavencio® (avelumab), a drug used to treat Merkel cell carcinoma, a rare and lethal form of skin cancer, provides an example of this in practice. Merck KGaA and Pfizer used RWE from a retrospective observational study to benchmark and contextualize results from their single-arm trial with respect to real-world outcomes in patients treated with chemotherapy. The FDA agreed that the trial efficacy and safety data presented in conjunction with RWE were sufficient to support avelumab’s accelerated approval. As a result, avelumab gained accelerated approval only 3 years after its investigational new drug (IND) filing, approximately 1.8 years shorter than the median for other drugs in expedited programs.¹ (See timeline.)

The FDA is continuing to explore approaches and methods for optimizing the use of RWE in its evaluation of NDAs, sNDAs, PMAs, and post-marketing studies. The 21st Century Cures Act, which aims to accelerate the process of bringing new remedies to patients, required the FDA to develop a comprehensive plan for incorporating RWE into regulatory decisions. In December 2018, the agency released a new framework that will “serve as a roadmap for more fully incorporating RWD and RWE into the regulatory paradigm."² In addition, it has developed an open-source app, MyStudies, to facilitate patient input of RWD that can be used in support of traditional clinical trials.

Increased use of RWE in the drug approval process necessitates expertise in clinical trials, regulatory epidemiology, health economics and outcomes research (HEOR), and especially observational research methodology. RWE has the potential to both accelerate approval timelines and reduce the costs of drug development, as long as pharmaceutical companies engage in early and ongoing dialogue with the FDA, and are careful to uphold established standards of evidence – including standards for Good Clinical Practice (GCP) and 21 CFR Part 11 requirements. ■

Mei Sheng Duh, Managing Principal
Maral DerSarkissian, Managing Principal
Priyanka Bobbili, Vice President