CORNERSTONE Insights: Beyond the Clinical Trial – Saving Time and Costs by supporting FDA applications with Real-World Evidence

April 3, 2019

By Nicole Ferko, Senior Director

The use of Real-World Evidence (RWE) has been rapidly expanding in recent years and has become an integral component to demonstrating the value of health technologies, including medical devices. This type of evidence can be defined as data relating to patient health status and/or the delivery of healthcare routinely collected from a variety of sources, including electronic health records, claims databases, and product registries. RWE can reflect a wide spectrum of methodologies, ranging from observational studies conducted within an existing dataset to studies involving planned interventions with or without randomization. A central theme of RWE studies is that data are collected under routine conditions with limited influence of protocol-driven factors. Recent recommendations (1) are available on the development of high-quality RWE.

RWE is not only playing an increasing role in coverage and reimbursement decisions, but under the right conditions, can also be used to make regulatory decisions.  The 21st Century Cures Act (2), enacted in 2016, requires the FDA to evaluate use of RWE in new drug indications. In 2017, the FDA issued a final guidance document (3) on RWE in regulatory decision-making for medical devices. The FDA relies on scientifically robust methods and approaches to determine whether submitted RWE is of sufficient quality to support a regulatory decision.

Given the richness of data that can be provided from RWE sources, as well as the relative ease of retrieving such information, RWE can help to reduce time and costs associated with data generation for regulatory purposes. For FDA medical device applications, potential applications of RWE may include support for Premarket Approval Application (PMA), De Novo requests, petitions for reclassification of a medical device, and relabeling of a device to include additional indications for use. RWE may also be used to update product labeling to include new information on safety and effectiveness, and for post-approval studies that are imposed as a condition of device approval.

One recent example of a successful use of RWE for an FDA submission involved the NeuWave Medical Certus 140 2.45 GHz ablation system. In this example, the predicate device was indicated for ablation (coagulation) of soft tissue in the surgical setting (not cardiac). A 510(k) application was submitted to update the Certus 140 indications for use to also include partial or complete ablation of non-resectable liver tumors. To support the indication expansion, the sponsor provided non-clinical bench, in vivo testing, as well as meta-analytic data based on randomized and real-world observational studies published in peer-reviewed literature. Based on this evidence, the FDA granted approval (4) for the new indication requested for this device. Use of meta-analytic evidence that included existing real-world evidence saved the sponsor time and money compared with traditional evidence-generation methods for obtaining such approvals.

Many other successful uses of RWE by the FDA exist, and use of RWE can be expected to increase in the coming years. If such evidence is collected using robust data methods, it may provide not only an efficient use of resources for health technology manufacturers, but also more applicable information as wider populations can be studied under routine conditions.


  1. Berger ML et al. Good practices for real-world data studies of treatment and/or comparative effectiveness: Recommendations from the joint ISPOR-ISPE Special Task Force on real-world evidence in healthcare decision-making. Pharmacoepidemiol Drug Saf 2017; 26: 1033-1039. Available at:
  2. 21st Century Cures Act. Available at:
  3. Food and Drug Administration. Use of real-world evidence to support regulatory decision-making for medical devices. Guidance for industry and FDA staff. August 31, 2017. Available at:
  4. Food and Drug Administration. Approval letter for Neuwave Inc. October 24, 2018. Available at:

CORNERSTONE Insights is a blog where staff from Cornerstone Research Group provide commentary on topical issues related to market access, health technology assessment, and value communications.

Copyright © 2019. All Rights Reserved. Cornerstone Research Group