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Real-world evidence in regulatory decision making

Real-world evidence can be used to show that a drug or medical device is safe and effective. The FDA has approved both drugs and medical devices based on regulatory submissions that have included real-world evidence. Here, we summarise a recent review which explores the contemporary applications of real-world evidence in regulatory decision-making.

Use of real-world evidence

The 21st Century Cures Act (2016) requires the FDA to assess the use of real-world evidence (RWE) for applications that include new drug indications and for satisfying post-approval. In 2017, the FDA also issued a final guidance document for medical devices, in which they stated that applicants could use real-world data (RWD) to support regulatory determinations under the right conditions. Although the FDA has yet to follow up with a guidance for pharmaceutical products, their 2018 framework for FDA’s Real-World Evidence Program outlined the potential applications of RWE for regulatory decision-making regarding the effectiveness of marketed products.

Approaches to real-world evidence regulatory submissions

Regulatory submissions that use submissions from RWD can come from a range of data sources, including claims data, electronic records, patient reported outcomes, registries and also public and private databases.

The role of RWD and RWE has been particularly important for rare diseases as well as for the expansion of labelling to a more broad or newly defined sub-population. Using a ‘totality of evidence’ approach, you can determine whether the new evidence from RWD sources or RWE analyses can add to the existing evidence to create a new evidence package that has value from a clinical and regulatory perspective.

Case examples

The authors discussed three pharmaceutical case examples for which RWE has been used for approvals and labelling changes. They also examined the label expansion of a medical device based on RWE.

Ibrance for male breast cancer

Authorities approved Ibrance for metastatic breast cancer in 2019. It was based on two large RCTs in women and was supported by clinical pharmacology and non-clinical toxicology studies. Evidence for clinical benefit in male breast cancer was noted from post-marketing reports, insurance claims data and also electronic health records. The FDA submission included evidence derived from RWD sources including: the IQVIA insurance database, Flatiron Health breast cancer database and the Pfizer global safety database.

Invega Sustenna for schizoaffective disorder

Invega Sustenna is a centrally active anti-psychotic. There have been several expansions to the label since its original approval in 2006. In 2018, experts approved a labelling change related to the time to treatment failure compared with oral anti-psychotics using an unconventional RWE clinical trial design.

Brineura for a form of Batten disease

Brineura is an enzyme replacement therapy for patients with late infantile neuronal ceroid lipofuscinosis type 2. The approval of Brineura in 2017 was an example of the FDA comparing a single-arm clinical study of a prospective drug treatment against a control obtained from RWD.

TAVR device

The FDA in 2011 approved the Sapien 3 device for Transcatheter Aortic Valve Replacement (TAVR). This was a novel approach that provided a minimally invasive alternative to open heart surgery. The FDA evaluated the clinical and functional data for this procedure from the Transcatheter Valve Therapy Registry to expand the indication for the TAVR-enabling device.


While RWE analysis will not replace RCTs, researchers are already using it as an effective support for drug and device labelling changes and for rare disease submissions. Selecting new indications and expansion targets is important where there is an opportunity for RWE analysis to provide credible evidence to an existing evidence base.

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Decision Making / FDA / Real World Evidence

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