In December 2016, President Obama signed into law the 21st Century Cures Act, which “builds on FDA’s ongoing efforts to advance medical product innovation and ensure that patients get access to treatments as quickly as possible, with continued assurance from high quality evidence that they are safe and effective,” according to FDA Commissioner Robert M. Califf, M.D.
The act aims to improve FDA’s ability to hire and retain scientific experts. Given the tremendous advances in biological sciences, engineering, information technology and data science, it has been an ongoing challenge for the FDA to recruit and retain experts in specialized areas to complete work and meet growing responsibilities. “Preventive, diagnostic and therapeutic strategies will become more complex with much greater potential for benefit and in some cases, greater risk if used without adequate evidence to exclude risks that exceed potential benefits,” says Califf.
The FDA hopes that Cures will enhance ongoing efforts to better incorporate the patient’s voice into FDA’s decision-making.
Cures will also support efforts to modernize and improve efficiency in clinical trial design. This has been an FDA priority for decades, but Califf says that exciting new approaches are now available, and that they need to develop a common understanding of which designs should be used for which clinical issues. “In cancer, for example, we’re already weighing the use of common control trials, which share a control arm, involve multiple different drugs for the same indication, and may even involve different companies” he explains. “One of the benefits of using a common control arm is that the overall number of patients who need to be recruited and enrolled decreases, thereby optimizing clinical trial resources and potentially shortening the time it takes to get a new study off the ground.”
The FDA uses expedited programs (fast track, priority review, accelerated approval, and breakthrough therapy) for drugs and biologics more than comparable drug and biologic regulators in other countries use theirs and, as a result, the FDA is the first to approve a majority of novel drugs compared to foreign counterparts.
For devices, this past year was the first full year of operation for the FDA’s expedited access pathway (EAP) program, which helps speed the development and availability of certain medical devices that demonstrate the potential to address unmet medical needs for life-threatening or irreversibly-debilitating diseases or conditions. To date, 24 devices have been granted access to the EAP program. Cures builds on EAP by creating the breakthrough device pathway.
The law establishes other new programs as well:
Limited Population pathway: This helps streamline the development programs for certain antibacterials and antifungals intended to treat targeted groups of patients suffering from serious or life-threatening infections where unmet need exists due to lack of available therapies. Approvals of these antimicrobials are expected to rely on data primarily targeting these limited populations. The statement “Limited Population” will appear prominently next to the drug’s name in labeling, which will provide notice to healthcare providers that the drug is indicated for use in a limited and specific population of patients. The limited population statement, additional labeling statements describing the data, and FDA review of promotional materials, will help assure these drugs are used narrowly to treat these serious and life-threatening infections while additional evidence is generated to assess safety and effectiveness for broader use.
Development of regenerative medicine products: A new program designates drugs as regenerative advanced therapies and takes appropriate actions to improve the efficiency of development and to enhance the exchange of information among FDA, researchers and developers. An especially important element of this program is the creation of a research network and a public-private partnership to assist developers in generating definitive evidence about whether their proposed therapies indeed provide clinical benefits that are hoped for.
Califf notes that much still needs to be done to spur product development. There have yet to be successful therapies identified for certain diseases, such as Alzheimer’s disease, where underlying scientific knowledge is still lacking. “In addition, we are only at the early stage in building a national evidence generation system based on registries, claims data, and electronic health records that will be a rich source of post-market data and an avenue for conducting more efficient research.” Last week, a consensus of FDA leadership was published on the use of real world evidence in the New England Journal of Medicine, focusing on the misperception that randomized trials and real world data are incompatible. The use of randomization within the context of clinical practice will constitute a major advance in evidence generation and the FDA is actively encouraging proposals with this combination of randomized trials conducted in real world practice. Cures provides support for continued exploration of the use of real world evidence in the regulatory context.
The law also addresses drug firms providing healthcare economic information to payers and formulary committees. This complex area will require careful delineation of principles to guide information exchange to enable these entities to appropriately assess the value of drugs.
With Cures, Califf says ,“We are excited about the major advances in NIH funding, and welcome the increasing focus on rigorous translational science and data sharing reflected in the bill.
“Furthermore, the funding of opioid addiction treatment and mental health services is a major positive element for our country and consistent with tremendous needs that we recognize.”