The importance of real world evidence in the 21st Century Cures Act


On December 13, 2016, the 21st Century Cures Act, which requires the FDA to produce a framework and guidance for evaluating real world evidence (RWE) in the context of drug approvals, was signed into law by Congress. Critics, however, have taken issue with other parts of the act, claiming these will ultimately serve to erode the drug approval process, potentially leading to increased risks for patients taking FDA-approved drugs. Unfortunately, this muddies the waters regarding the usefulness of RWE in supporting drug approval decisions, but it certainly highlights the issues surrounding the inclusion of multiple provisions within single legislative acts.

What exactly is RWE, and how will its inclusion in drug regulatory decisions be helpful? The FDA previously issued draft guidance on the inclusion of RWE for medical devices on July 27, 2016, but didn’t follow suit with similar guidance for drugs. Now the agency is required to do so.  According to the Cures Act, RWE is defined as “data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials (RCT)”. This can be taken to mean any data that can be collected from real life medical practice settings, including electronic medical records and insurance claims, and also from patient registries. Drug developers and health regulatory agencies have traditionally relied exclusively upon RCT to support drug development and approval decisions, and those seeking approval in the US will now be encouraged to include RWE in submissions.

RWE is defined as “data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials (RCT)”

RWE has already been in use in assessing drug reimbursement decisions by health technology agencies (HTAs), and an analysis published at PharmaForum on January 27, 2015 evaluating nearly 1,840 decisions globally found that just 6% of these decisions included observational RWE data. Of these, 77% resulted in a positive reimbursement decision, compared to 67% resulting in positive decisions for those cases not incorporating RWE. While the number of those decisions including RWE was rather small, making it difficult to draw conclusions on the significance of the correlation, what is actually most important is revealed in the individual case studies. These include instances where developers used RWE to show increased durability of response, increased survival, quality of life or economic value for their drugs. 

Now with the FDA moving ahead to provide a framework for inclusion of RWE in approval decisions, there will be robust opportunities to demonstrate increased efficacy, safety, and economic value in settings beyond RCTs. The stage is set for a paradigm shift in the drug approval process based on the inclusion of RWE that should more substantially prove or disprove a drug’s safety and effectiveness. Therefore, the usefulness of its inclusion should not be diminished by criticism of other provisions of the recently enacted 21st Century Cures Act.