News Feature | December 9, 2016

FDA Officials Discuss Merits And Dangers Of Real-World Evidence

By Jof Enriquez,
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Fifteen officials from the U.S. Food and Drug Administration (FDA), through an article in the New England Journal of Medicine (NEJM), acknowledge the positive impact of real-world evidence on patient care, safety surveillance, and regulatory practice, but also warn of the pitfalls such evidence could entail if not vetted according to existing evidentiary standards.

FDA Commissioner Robert Califf, deputy commissioner for medical products and tobacco Rachel Sherman, and director of the Center for Drug Evaluation and Research (CDER) Janet Woodcock, wrote that a concrete meaning of real-world evidence (RWE) remains "elusive" because many types of information other than randomized, controlled clinical trials can qualify as RWE, according to the Regulatory Affairs Professional Society (RAPS).

The officials acknowledge in the article that RWE “can inform therapeutic development, outcomes research, patient care, research on health care systems, quality improvement, safety surveillance, and well-controlled effectiveness studies.”

Yet, they warn that, in using RWE, “the confluence of large data sets of uncertain quality and provenance, the facile analytic tools that can be used by nonexperts, and a shortage of researchers with adequate methodologic savvy could result in poorly conceived study and analytic designs that generate incorrect or unreliable conclusions."

In previous related draft guidance, the agency considers RWE to include: large simple trials, or pragmatic clinical trials, prospective observational or registry studies, retrospective database studies, case reports, administrative and healthcare claims, electronic health records (EHR), data obtained as part of a public health investigation or routine public health surveillance, data from registries (e.g., device, procedural, or disease registries), data from electronic systems used in health care delivery, data contained within medical devices, and data obtained from tracking patient experience during care, including in home-use settings.

“But these data sources also raise concerns," the FDA officials wrote in the journal article published this week. "EHR and claims data are not collected or organized with the goal of supporting research, nor have they typically been optimized for such purposes, and the accuracy and reliability of data gathered by many personal devices and health-related apps are unknown. Furthermore, the use of any of these sources, including social media, raises important questions about the quality of the data they provide and about privacy.”

The officials wrote that in order to realize the full promise of RWE, "we must be clear about what it is and how it can be used most effectively, and we must have appropriate expectations about what it can tell us."

To help clarify what constitutes RWE and how FDA plans to incorporate it into the regulatory decision-making process, "The FDA is developing guidance on the use of ‘real-world evidence’ — health care information from atypical sources, including electronic health records, billing databases, and product and disease registries — to assess the safety and effectiveness of drugs and devices," they wrote in the article.

The guidance will cover how RWE can be used to assess safety and effectiveness in both premarketing and postmarketing regulatory requirements.

An expedient guidance will be welcomed by industry, as the 21st Century Cures Act (which cleared Congress this week and is likely to be signed into law by President Obama) directs FDA to formally evaluate RWE in approving new drugs and devices.

Under the landmark legislation, FDA within two years is tasked to evaluate the potential use of RWE to help support the approval of a new indication for a drug or to help support or satisfy postapproval requirements, according to RAPS.

FDA had said previously that it intends to leverage real-world evidence from clinical registries, electronic health records, and medical billing claims with unique device identifiers, for its National Evaluation System for Healthcare Technology (NEST) surveillance program.

In April, it submitted its RWE user fee proposal that includes a $10 million allocation to establish and operate a coordinating center, projects to improve RWE data sources and increase their use, and assignment of 15 full-time employees who will develop and implement the framework for using RWE for premarket decision-making by supporting the work of the coordinating center.

Under the reauthorized Prescription Drug User Fee Act (PDUFA VI), FDA plans to conduct a public workshop and launch a pilot project, or methodology development projects, to identify how RWE can contribute to regulatory decisions, according to RAPS.