Real-world evidence and regulatory decision-making: A round-up of readings on progress to date, and what’s to come
Contributing writer, Aetion
In recent years, the U.S. Food and Drug Administration (FDA) and other global regulatory and health technology assessment (HTA) bodies have increasingly turned to real-world evidence (RWE) to inform their decision-making. With the need for current data to support the understanding of and response to the ongoing pandemic, the FDA is “approaching the generation of RWE for COVID-19 with a sense of urgency,” shared Amy Abernethy, M.D., Ph.D., Principal Deputy Commissioner of Food and Drugs at the FDA.
FDA Commissioner Stephen Hahn, M.D., expressed that this urgency has increased the FDA’s comfort level with using real-world data (RWD), which could lead to shifts in how the agency uses it going forward: “The more experience we have with RWE, the more confidence we will have in using it for product decisions.”
Aetion is staying up to date on all things regulatory-grade RWE, and has been closely tracking on any guidances and instances in which RWE has been submitted to FDA, which we share in our FDA Decision Alerts. Below, we share a roundup of content as reported by our team and collaborators to help you get up to speed on recent RWE-supported FDA decisions, as well as the foundational projects, guidances, and recommendations that have shaped the agency’s use of RWE thus far, and predictions for the work ahead.
RWE-supported FDA decisions
Learnings from three FDA decisions on external control arm submissions in oncology
In advance of the FDA’s guidance on RWE, we can learn when and how RWE is likely to be considered regulatory-grade from studies that were already submitted. We share insights gleaned from three external control arm submissions in which the FDA did not deem the evidence regulatory-grade—and outline pitfalls to avoid when submitting RWE studies.
The surge in FDA approvals supported by RWE:
A look at three recent FDA decisions
According to an Aetion analysis of 2019 new drug and biologic submissions, one in two FDA approvals for new drug applications and biologics license applications included RWD in the submission package. Read more to learn about the role RWE played in three recent FDA decisions.
Lessons from four recent FDA decisions in infectious disease
RWE has proven to be especially useful in infectious disease research; it supported five of the eight FDA approvals for interventions targeting infectious diseases in 2019. Here, we analyze four of these approvals, which highlight how RWE can support label expansion and postmarketing safety reporting.
Foundations and demonstration projects
Framework for FDA’s Real-World Evidence Program:
Dr. Sebastian Schneeweiss considers implications for biopharma
When the FDA unveiled its strategy for incorporating RWD in regulatory decision-making in 2018, Sebastian Schneeweiss, M.D., Sc.D., of Brigham and Women’s Hospital and Harvard Medical School, and Co-Founder of Aetion, answered questions from biopharma on the key principles detailed in the framework, their significance for industry, and how to prepare for the FDA’s 2021 RWE guidance document. We share his comments here, including why assessing data fitness for purpose is key to any RWD study.
Methods, approaches, and predictions:
Dr. Jessica Franklin discusses RCT DUPLICATE
The landmark, FDA-funded study RCT DUPLICATE sees researchers attempting to replicate the results of 30 completed randomized controlled trials (RCTs) and predict the results of seven ongoing trials—an effort to demonstrate where, when, and how RWE can support the approval and regulation of drugs. We spoke with Jessica Franklin, Ph.D., of Brigham and Women’s hospital, leader of the project, on her process for selecting studies and therapeutic areas to focus on, and what she expects to learn.
RWE guidances and comments shared
The epidemiology of databases:
Four principles of generating RWE
In response to the Framework for FDA’s Real-World Evidence Program, Aetion shared recommendations for the agency as it explores the use of RWE in regulatory decision-making. We share those comments in a series of three articles, which explore how to integrate RWE across the drug lifecycle. Here, we share four principles underpinning the generation of RWE to ensure validity and transparency.
Writing the perfect cover letter:
A look at the FDA’s forthcoming guidance on submitting RWE studies
In another milestone in the developing infrastructure surrounding regulatory-grade RWE, the FDA released draft guidance encouraging sponsors to use a templated, uniform cover letter on submissions that contain RWE. Aetion submitted comments on the positioning of the cover letter, the terms it includes, and the data sources, technology, and process used to generate and submit RWE studies. Read our thoughts here.
FDA’s Technology Modernization Action Plan:
Three ways to prepare for the coming RWE infrastructure
FDA’s Technology Modernization Action Plan aims to create a formalized process for RWE submissions and reviews, a step that advances the previously mentioned guidance on a uniform cover letter for RWE submissions. Learn what biopharma can expect from the plan, and how to prepare for forthcoming FDA guidance on RWE.
Priorities for modernizing ClinicalTrials.gov:
Five ideas to facilitate transparency in observational research
ClinicalTrials.gov, the world’s largest public clinical registry and results database, is slated for an update, and, to prepare, the National Library of Medicine requested input from various stakeholders to inform its modernization efforts. We share five recommendations from RWD scientists to help facilitate transparency in observational research.
Looking ahead: Future opportunities to advance RWE
The case for regulator-HTA collaboration on RWE methodology standards
As regulators and HTA bodies commit to using RWE to inform decision-making, collaboration while developing methodology and standards will ensure we realize RWE’s potential. As we look ahead, we explore approaches to developing standards for high-quality RWE that satisfy both groups’ evidence requirements.
What’s ahead for the use of RWE by regulators and HTAs?
Q&A with Dr. Lucinda Orsini of ISPOR
As Associate Chief Science Officer of the Professional Society for Health Economics and Outcomes Research (ISPOR), Lucinda Orsini, D.P.M., M.P.H., works with members to advance the perception of and standards around RWE generation and use. Dr. Orsini shares the work ISPOR is doing around RWE, and offers perspectives on the opportunities and challenges for regulators and HTAs as they continue to adopt RWE to support decision-making.
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