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.

21st Century Cures Act

HR 6, the 21st Century Cures Act:  Renewed optimism for patients and researchers.

What is this 21st Century Cures Act?

This new bill in the House of Representatives is in the early stages of the legislative process. However, it has gone through more than a yearlong developmental process.  The latest version of the bill has been reduced to 199 pages.  Importantly, the Energy and Commerce Committee approved the bill unanimously on May 21 by a vote of 51-0, with obvious and enthusiastic bipartisan support!  When the bill came up for consideration before the entire House, the vote remained overwhelmingly bipartisan—members who voted in favor 344, against 77, abstain 12.

What is the Congress proposing in this new bill?

The current iteration of the bill has three main components: Discovery, Development, and Delivery.

Title 1 focuses on “Discovery”.

The 21st Century Cures Act has several goals that should energize academic physicians and scientists.  The bill proposes to re-invest in discovery research by increasing the NIH budget—currently $30.3 billion.  The committee proposes to increase the NIH budget to $31.8 billion in 2016; $33.3 billion in 2017; and $34.8 billion in 2018.  Importantly, the proposed NIH budget grows predictably over the next 3 years:  total increase is $4.5 billion (nearly 15%).

The 21st Century Cures Act also creates a dedicated innovation fund of an additional $2 billion/year from 2016 through 2020. This represents another $10 billion “to support biomedical research through funding of basic, translational, and clinical research” at the NIH.  This component of the NIH budget allows congressional appropriators to invest additional resources in scientific research without impacting current budget caps (per sequestration).

The 21st Century Cures Act is prescriptive in that it directs the NIH to invest in specified priority areas.  The bill specifies support for innovative research in such areas as biomarkers, precision medicine, infectious diseases, and antibiotics, for example.  In other priority areas, the 21st Century Cures Act directs the NIH to reserve funding specifically for “young emerging scientists”.  This subtitle in the Act includes also specific language regarding improved loan repayment programs.  Furthermore, the bill directs the NIH to create “capstone awards” to support the work of particularly outstanding scientists previously funded by the NIH.

Another priority area in the 21st Century Cures Act includes pediatrics research and directs the NIH to establish a “national pediatrics research network”. The network would be composed of research institutions operating as a consortium in order to pool resources and coordinated activities related to research on rare diseases or birth defects.  The bill also declares a “sense of Congress” that directs the NIH and FDA to work together and with the European Union, industry, and others to establish a “global pediatrics clinical trials network”.

The 21st Century Cures Act identifies other priority areas.  The bill specifies the need for the NIH to engage “in scientifically based strategic planning implemented in support of research priorities”.  This is a recurring requirement to be repeated at 5-year intervals.  In addition, the bill directs the NIH to improve access to clinical trials data by creating and then releasing de-identified clinical trials data sets, from qualified clinical trials, for use by other medical investigators.

These budget issues and priority areas represent some of the key features included in the current version of the 21st Century Cures Act.  Now that the House has acted, what will the Senate choose to do?

For additional information visit:

COMING next: The 21st Century Cures Act, Title 2 “Development”