In their Perspective article (June 25 issue),1 Avorn and Kesselheim argue that the 21st Century Cures Act, which is currently being debated in Congress, would lower the regulatory standards of the Food and Drug Administration (FDA) by giving it greater discretion to approve drugs on the basis of less rigorous data. In particular, the authors argue that the legislation would authorize the FDA to “rely” on observational analyses, which are less rigorous than randomized controlled trials (RCTs). But the Cures Act does not diminish the FDA’s standards for requiring that new medical products are safe and effective. Rather, it recognizes that recent developments in genomics, systems biology, electronic data systems, and other fields can provide additional tools and resources to support better premarketing and postmarketing regulation and more efficient development of drugs and medical devices.
The authors note that the FDA now relies on evidence beyond RCTs. Patients with coexisting conditions or rare diseases are not studied much in traditional RCTs; further progress in precision medicine is likely to make RCTs even more difficult. The Cures Act facilitates the use of new types of evidence, enabling a more comprehensive understanding of risks and benefits for particular patients. The authors argue that such uses of adaptive trials, Bayesian statistics, biomarkers and surrogate end points, and data from postmarketing registries and surveillance systems will adversely affect the FDA’s ability to approve safe and effective drugs. However, as the authors state, such tools have been valuable in many situations. For example, progress in therapies for the human immunodeficiency virus and the hepatitis C virus reflects the use of validated biomarkers. The point of the legislation on biomarkers is to develop better evidence on other markers that could be valuable for evaluating treatments for currently unmet needs. Similarly, the point of developing better evidence on patient-reported outcomes, and better systems for studying clinical experience, is to better assess the disease experience of particular groups of patients.
As such, the legislation’s provisions can increase the feasibility, efficiency, and influence of RCTs by enabling them to be better targeted and more effectively designed — and perhaps to be carried out in more routine clinical practice. The law empowers the FDA to use its expertise to guide the development of better science for the regulation of medical products.
Better evidence and up-to-date regulatory science are the best foundation for regulatory decisions and meaningful progress in biomedical innovation. They are also the best way to avoid turning back the clock on new opportunities to develop safe and effective treatments for unmet medical needs.