HR 6, the 21st Century Cures Act, Title 2 “Development”

HR 6, the 21st Century Cures Act, Title 2 “Development”


What is the Congress proposing in this new act?


In the previous SSCI HeLP Line, I discussed Title 1, “Discovery”, of the 21st Century Cures Act.   This part of the Act invests in research by providing additional funding for the NIH.  However, the Congress perceives that application of scientific research discoveries is not efficient enough to meet patient needs.  Title 2 of the 21st Century Cures Act addresses that perception, requiring that the FDA streamline its processes to speed the pace of FDA reviews of new drugs and medical devices.

Currently, the FDA approves most new medications within 6-10 months, perhaps faster than other comparable regulatory bodies. The FDA approval process relies on data derived from pivotal clinical trials—the highest level of scientific evidence that demonstrates efficacy.  Many believe that the FDA process is already efficient, given the complexity of the research and the high quality of scientific evidence required to establish benefit for innovative therapies.  By requiring changes to the FDA’s current processes, an unintended consequence of the new 21 Century Cures Act may be an accentuation of the conflict between a desire for a speedier FDA review process and the need to demonstrate efficacy and safety with scientifically rigorous studies.

In addition to process improvements, the 21st Century Cures Act directs the FDA to develop procedures for use of data from other study designs and methods of data analysis. Specifically, the Act discusses clinical trial methodologies like adaptive trial designs and use of Bayesian analytical methods.  These are robust designs and analytical methods, but other suggestions are not.  For example, the 21 Century Cures Act directs the Secretary to develop programs to evaluate the use of “clinical experience” in the drug and device review process.  Clinical investigators know that clinical experience alone rarely contributes key scientific evidence concerning efficacy. In addition, the Act suggests use of smaller or shorter-duration clinical trials, observational studies like case-control studies, and registries.  All of these methods are much less rigorous than randomized clinical trials to establish efficacy and safety.

The bill also encourages the FDA to rely more on biomarkers and intermediate, surrogate measures rather than actual clinical end-points when assessing efficacy of both drugs and devises. However, improvement in intermediate variables does not always translate to improved patient outcomes.  For example, a treatment may show positive preliminary results by reducing tumor size but does not lead to improved patient survival.  In this case, improvement in a surrogate variable does not establish efficacy because it does not improve patient outcomes.

Under the Subtitle, “Streamline Clinical Trials”, the Act enumerates alterations of waivers for informed consent to patient volunteers in clinical trials. They offer a new exception when clinical testing poses “no more than minimal risk”.  This exception concerns some physicians and scientists given the vagueness in defining “minimal risk”.  Perhaps this exception is offered to facilitate comparative effectiveness trials where the competing treatments are already FDA approved drugs and devices with known risks and adverse effects.

Title 2 “Development” specifies 15 subtitles and other topics that deal extensively with review processes and decision-making at the FDA. For additional information about these other issues go to

Also see J Avorn, AS Kesselheim. The 21st Century Cures Act:  Will it take us back in time?  New Eng J Med 2015; 372: 2473-2475.

COMING NEXT: 2016 Congressional Omnibus spending bill:  Something for everyone.