by Chris Rota
figures by Dan Utter
In the twilight of the Obama administration, a rare event of compromise between Democrats and Republicans resulted in the successful passage of the 21st Century Cures Act. While the law has a number of implications for healthcare, especially in the area of mental health, its greatest effects are likely to be seen in the area of biomedical research. The law calls for a collective $4.8 billion dollars in new research funding to be made available over the next ten years with a focus on spurring the development of new therapies for a variety of diseases, particularly cancer. Furthermore, the law seeks to lower the barriers that this next generation of therapies will have to hurdle in order to obtain FDA approval, such as expanding the use of so-called “real world evidence” to supplement conventional clinical trial data. Lastly, the act lays legal groundwork for the development of networks to share data between research and healthcare institutions across the country, which will become increasingly necessary to support a cohesive national research agenda. As the potential scope of these changes is vast, it is paramount that the members of the scientific and medical communities, as well as the general public, understand exactly what the 21st Century Cure Act prescribes and what they can expect to see happen as it becomes implemented.
A windfall for translational researchers, but not for basic scientists
The vast majority of the $4.8 billion prescribed by the law will be earmarked for addressing questions about how to apply our current knowledge to directly improve human health, a category broadly termed “translational research.” As summarized in Figure 1, the largest chunk of this funding will go towards the Beau Biden Cancer Moonshot, a signature program of Vice President Joe Biden that aims to propel innovative strategies for innovative cancer treatments, such as immunotherapy. Two other research efforts spearheaded by the White House, the Precision Medicine Initiative and the BRAIN Initiative, will also receive comparable funding. The Precision Medicine Initiative seeks to gather health data from a large cohort of Americans to identify genetic and lifestyle factors that could be used to better predict who will develop certain diseases. The BRAIN Initiative, meanwhile, seeks to develop new tools to allow us to unravel the structural complexity of the human brain, with the goal of using this structure as a means to understand how the brain functions. An additional portion of the money is designated for research involving human stem cells, which hold great promise for treating a wide variety of injuries and degenerative disorders.
While researchers focused on translational medicine will benefit greatly from this influx of money, scientists investigating more fundamental scientific questions are likely to be disappointed. Federal investment in basic science, which seeks to understand important natural principles without regard to future usefulness, has been declining steadily for decades and would remain on the back-burner with this new law. While a section of the law does call for the creation of “Eureka Prizes” by the NIH to reward breakthrough discoveries in basic science, it provides no mechanism for funding these awards, and they are likely to pale in comparison to the incentives being offered for translational research. As scientific inequality continues to fester, it remains to be seen whether the next Congress or new President will address this issue.
Loosening the reins of the FDA
Besides the new money that it offers for translational research, the 21st Century Cures Act will also affect the way the government approves potential therapies for use in the clinic. The process of drug development is long and arduous, and entering this process has become an increasingly risky gamble in recent years, as success depends heavily on the results of large-scale clinical trials. One major change made by the Act will be to enhance the ability of companies to submit data gathered outside of the context of such trials as part of their applications for FDA approval, classified broadly as “real world evidence.” Some examples of this data would be exploratory drug trials or anecdotal clinical data, both of which are routinely gathered in academic hospitals or small biotech companies, but have been traditionally frowned upon by the FDA. This new move raises the possibility for these types of data, typically filed away as minor details on the final application, to become valuable support for a therapy’s efficacy and safety. Though changes will be gradual, it is possible to envision a future where several small investigational studies and a cadre of assorted clinical data form a solid platform for an FDA application, as envisioned in Figure 2. In addition to altering the application process, the Act will also allow the FDA to offer new fast-track review procedures specifically for stem cell therapies and new antibiotics. Such procedures offer accelerated approval to therapies for intractable diseases where no current treatments exist, or therapies that show highly significant improvement over the current standard of care. Taken together, these changes will grease the wheels for many new treatments to enter the national healthcare market and hopefully allow innovative therapies to succeed.
First steps toward national data sharing
As a final part of its vision, the Act attempts to set up mechanisms for encouraging collaboration and data sharing between researchers, as well as between researchers and healthcare professionals. One specific section calls for the formation of official working groups to discuss the expanding use of personal health information in research, including how to safely share such information between institutions, as well as how to gather more information from patients. In certain cases, such as with neurological diseases, the NIH will be mandated by the law to form national networks for gathering and sharing clinically relevant information to aid in therapy development. While the majority of its recommendations are very broad, together they represent an effort to increase the accessibility of patient data to researchers and unlock its potential to inform therapeutic development.
Moving forward into the 21st Century
From its name alone, the goal of the 21st Century Cures Act is clear: to promote the development and dissemination of modern treatments for age-old diseases. The blueprint that the Act lays out for achieving this goal is to fund more researchers interested in these diseases, accelerate the approval of more therapies, and provide more information about how these therapies work in the clinic. However, successfully enacting this plan will take more than pen strokes in the Oval Office. It will require increased cooperation and communication among the scientific, medical, and regulatory communities, as well as new tools for managing, analyzing, and securely sharing the ever-growing volume of available clinical data. While the United States’ precise scientific path through the next decade remains uncertain, the 21st Century Cures Act has attempted to fix our final destination.
Chris Rota is a first year graduate student in the Biological and Biomedical Sciences PhD program at Harvard Medical School.
For further information:
See the full text of the 21st Century Cures Act here:
Or, read more about the Cancer Moonshot in our recent series here:
http://sitn.hms.harvard.edu/flash/2017/cancer-moonshot-musings-part-precision-prevention/