The 21st Century Cures Act, signed into law by President Obama on December 13, encourages biomedical research investment and facilitates innovation review and approval processes. Through National Institutes of Health (NIH) funding mechanisms, the act prioritizes certain areas of innovation and will likely steer both public and private funding priorities for years to come. The legislation also includes other provisions aimed at revamping NIH operations, streamlining research regulations, encouraging research collaboration, and expanding privacy protections for research subjects, among others.
This On the Subject summarizes key components of the new legislation that relate to broad research reforms. Our continuing coverage of the 21st Century Cures Act addresses additional titles and provisions, including research provisions related to the FDA and behavioral health.
The US Congress on December 7, 2016, approved the 21st Century Cures Act (Cures), substantial legislation intended to accelerate “discovery, development and delivery” of medical therapies by encouraging biomedical research investment and facilitating innovation review and approval processes. On December 13, President Obama signed the bill into law.
Through National Institutes of Health (NIH) funding mechanisms, the Cures legislation prioritizes certain areas of medical innovation—namely cancer care, regenerative therapies, neurotechnologies and precision medicine—and will likely steer both public and private funding priorities in those directions for years to come. The Cures legislation also includes a number of other provisions aimed at revamping NIH operations. Many of these provisions focus on reducing administrative burdens and enhancing collaboration both within the NIH and between the NIH and other agencies or divisions. Although some of these changes will have minimal impact on private industry, many of them indicate more streamlined processes that may benefit researchers and grantees, among others. On the other hand, an enhanced focus on preventing and eliminating duplicative research efforts may raise the bar for prospective NIH awardees.
In addition to NIH funding mechanisms, Cures contains a number of other important research-related provisions. These include lightening the administrative burden on researchers by streamlining and minimizing duplication between regulations, encouraging collaboration between stakeholders and expanding privacy protections for research subjects, among others.
This On the Subject summarizes key components of the new legislation that relate to broad research reforms. Other provisions, including research provisions related to the FDA and behavioral health will be examined through other On the Subject articles.
Funding NIH Initiatives
Section 1001 of the new Cures legislation provides the NIH with a dedicated, multi-year funding stream to support certain targeted research efforts, including the president’s Precision Medicine Initiative, the vice president’s Cancer Moonshot initiative, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and regenerative medicines. This section creates and funds the NIH Innovation Account to support these specific projects.
Precision Medicine Initiative. The president’s Precision Medicine Initiative encompasses funding streams, cross-agency directives and research ventures, all aimed at collecting and using genomic, lifestyle and other clinical data to help advance biomedical discoveries. A signature endeavor of the initiative is the development of a research cohort study of at least one million Americans who would participate by sharing genomic and clinical data, biospecimens and biofluids and other information for use by both researchers and participants themselves. The legislation authorizes a total of $1.45 billion over the next 10 years for this initiative.
Cancer Moonshot Initiative. Currently led by Vice President Biden, the Cancer Moonshot initiative within the NIH’s National Cancer Institute supports cancer research and focuses on accelerating cancer prevention, screening, treatment, and care. On December 5, 2016, the Senate amended Section 1001 of the Cures legislation in honor of Vice President Biden’s late son, renaming it the “Beau Biden Cancer Moonshot and NIH Innovation Projects.” This initiative is authorized to receive a total of $1.8 billion over the next 7 years.
BRAIN Initiative. The BRAIN Initiative focuses on accelerating the diagnosis and treatment of brain disorders, such as Alzheimer’s disease, by funding research into neurotechnologies. The legislation authorizes a total of $1.51 billion over the next 10 years for the BRAIN Initiative.
Regenerative Medicines. The legislation also provides a total of $30 million in funding over the next 3 years for NIH, in coordination with the FDA, to award grants and contracts for clinical research using adult stem cells. Interestingly, the legislation requires grant recipients to bring matching private dollars to the project. As this matching private dollar requirement is not a current feature of NIH-funded stem cell research, it could act as a barrier to funding for institutions or effectively limit the amount of funding they can receive from NIH.
Though the Innovation Account, which finances each of these initiatives, is fully funded by Cures, an appropriation will still be required each year in order to release funds. Nonetheless, the significant amount of funding earmarked for these initiatives highlights their role as high-priority areas of bipartisan interest and, for research entities, likely areas of significant growth over the next decade. Nor are these funding priorities only important for NIH scientists, as they present significant extramural funding opportunities for researchers focused in these areas.
The new legislation also reauthorizes the NIH for Fiscal Years 2018-2020 (the first reauthorization since 2006) and authorizes funding for each of those years ($34.8 billion in FY 2018, $35.6 billion in FY 2019 and $36.5 billion in FY 2020). While these levels are more robust that NIH’s current authorization, the year-to-year increases are less than those proposed in the original bill (which would have seen a $1.5 billion increase in authorization levels per year). With several large-scale NIH initiatives receiving dedicated funding through the NIH Innovation Account, increases to NIH’s funding may directly impact the number of grants NIH is able to award. Conversely, the Innovation funding could become an excuse for Congress to curb spending in other parts of the agency.
Reducing Administrative and Regulatory Burdens on Researchers
In addition to certain structural and administrative changes within the agency, the Cures legislation provides for review of and changes to a number of NIH rules and requirements that have historically been associated with significant administrative burdens. For example, the director of NIH is directed to review and revise as necessary NIH’s regulations and policies related to financial conflict of interest disclosures for all research-funding agencies (e.g., to minimize duplicative requirements). The NIH director is also directed to ease the administrative burdens associated with the monitoring of grant subrecipients, as long as those subrecipients meet certain requirements with respect to auditability and risk of noncompliance. Additionally, Section 2034 of the act permits the NIH director to utilize alternative grant structures that “may include collaborative grant models allowing for multiple primary awardees” to reduce the need for monitoring grant subrecipients.
Cures has also introduced new initiatives to promote efficiency and streamline research funded by NIH. By December of 2018, the secretary of HHS is required to report on the steps taken and procedures in place to prevent and eliminate unnecessary and duplicative biomedical research. A similar provision focuses on medical rehabilitation research at the National Center for Medical Rehabilitation Research at the NIH, which requires the HHS secretary and other agency heads to review its programs and take steps to coordinate across agencies to prevent duplication. These changes appear to reflect a desire to streamline research and preserve research funds without hampering contributions to scientific knowledge. The same section, however, also appears to require the directors of NIH’s national research institutes and centers to personally review applications for competitive R-series grants made to their respective centers and make the final approval decision. As part of their sign-off, the directors must consider other projects on similar topics that are already funded by other agencies. This added requirement has the potential to significantly slow the grant approval process and may frustrate the act’s overall focus on simplification and streamlining.
As part of the overall effort to streamline and simplify, the Cures legislation places a premium on collaboration among NIH’s own research institutes and centers, with other federal agencies and with the private sector. There are several checks in place in the act to ensure these efforts are sustained and substantial. Cures directs the director of NIH and other heads of national research institutes to encourage and foster collaborative efforts. It also requires the director of NIH and the heads of each national research institute or center within the NIH to include in their formal triennial reports the exact amount of funding made available for collaborative research. Other provisions that encourage or require collaborative efforts with the private sector include:
In carrying out the Precision Medicine Initiative, the secretary may collaborate with private industry and develop public-private partnerships. Section 2011 of the Cures Act requires the secretary, in his or her report on the Initiative, to explain what steps have been taken with respect to consulting with experts.
In promoting and providing opportunities for new researchers and earlier research independence, the director of the NIH shall coordinate with, among others, “professional and academic associations and academic institutions” under Section 2021 of the act in order to better inform programs related to “the training, recruitment, and retention of biomedical researchers.”
Section 2031 of the act requires the NIH director to consult with “researchers, patient advocacy groups, and industry leaders” in developing the NIH Strategic Plan.
The NIH will be represented on a Working Group, established by Section 2063 of the act, in which the research community, patients, experts in civil rights, health information technology developers, experts in data privacy and security, health care providers and bioethicists will also be represented, on the uses and disclosures of protected health information for research.
Streamlining FDA and Human Subjects Research Requirements
In recognition of the additional compliance burden placed on researchers subject to both FDA and Common Rule regulatory regimes governing human subjects research, Section 3023 of the Cures Act directs the HHS secretary to harmonize these regulations—found at 21 C.F.R. pt. 50 and 45 C.F.R. pt. 46, respectively—within three years from Cures’ enactment. Specifically, the secretary will be modifying and updating both the FDA and Common Rule regulations to:
Minimize instances of “regulatory duplication and unnecessary delays”;
Align with current practices in the context of multisite and cooperative research projects; and
Facilitate the use of collaboration and shared review and oversight pathways among entities engaged in human subjects research.
In developing these changes, the legislation instructs the HHS secretary to consult with various stakeholders, including researchers, providers, drug and device developers, as well as engaging with local stakeholders to ensure the protection of vulnerable populations. This initiative is good news for researchers, on whom the regulatory burden will be minimized in the context of human subjects research. Nonetheless, this legislation does not address all the areas in need of harmonization, nor does it address divergences between FDA, Common Rule, and Health Insurance Portability and Accountability Act (HIPAA) regulations.
Streamlining Research Use of Health Data
Cures’ broad emphasis on facilitating research is reflected in efforts to remove certain barriers to leveraging the existing HIPAA preparatory to research pathway set forth at 45 CFR § 164.512(i)(1)(ii). The preparatory to research pathway allows researchers to review protected health information (PHI) in connection with activities that proceed and help prepare for the conduct of an actual research study; for example, identifying potential subjects or refining a research protocol. The current pathway does not permit PHI to leave the premises of the applicable covered entity during such activities. In the current digital world, this premises requirement—a reflection of a world of medical record departments in hospital basements with paper records—is no longer well suited. Section 2063 of the Cures legislation modernizes this requirement by specifying that a researcher’s remote access of PHI held within a covered entity’s electronic record system does not constitute the removal of the PHI from the covered entity’s premises, provided that HIPAA-compliant privacy and security safeguards are maintained by the covered entity and researcher, and where the researcher does not copy or otherwise retain the protected health information. While Cures directly addresses questions posed by covered entities about remote access, further legislative or regulatory activity may be necessary to clarify what constitutes the “premises” of the covered entity, as so many covered entities do not maintain local storage (digital or otherwise) of the records but rather rely on business associates. In addition, Cures does not provide direction as to any required harmonization of HIPAA and the Common Rule with respect to how such preparatory to research activities should be structured given that the Common Rule’s definition of outright research in 45 CFR § 46.102(d) includes “research development.”
Another of the provisions in Cures requires NIH to foster and encourage collaboration among NIH-funded human subjects research projects that collect similar data. While the goals of this provision—to increase the subject population size and diversity—are valuable, it remains an open question whether such collaboration would be embraced, or even feasible, in our current national research environment, in which securing funding is a deeply competitive process and significant research findings are often fiercely protected prior to publication.
Changes to the Research Process
The Cures legislation also lays the groundwork for potentially significant changes to the research process for both federally and privately funded researchers. The general intent and reoccurring theme of Cures is stated best in Section 2034 of the act: to “harmonize existing policies and reduce administrative burden on researchers while maintaining the integrity and credibility of research findings and protections of human participants.” Despite this intent, certain new provisions in Cures have the potential to create additional regulatory and compliance hurdles for researchers. For instance, research entities seeking funding may be required to conform with new or modified policies with respect to the reproducibility of NIH-funded scientific research, preclinical and clinical experiment design, the types of variables that should be measured and analyzed (e.g., social and other determinants that contribute to health disparities), proper levels of rigor in statistical methodology and analysis and data sharing. The legislation requires the director of NIH to convene a working group to address these issues, and based on the group’s recommendations, the director is required to develop or update policies as appropriate.
Separate from this working group, the legislation also permits the director of the NIH to require researchers to share scientific data, to the extent feasible, generated from any NIH-funded research. Cures does not set forth details about what this data sharing requirement would entail; however, in the future, this may pose additional compliance hurdles for NIH awardees.
Changes to Certificates of Confidentiality
Cures also expands data privacy protections for research subjects by revising NIH’s certificate of confidentiality authority. Certificates of confidentiality generally protect against compulsory legal demands, such as court orders and subpoenas, for certain identifying information about a research participant. The NIH has a current process to grant certificates of confidentiality, but such authority is discretionary and limited to certain types of research (e.g., studies tackling certain mission areas of the NIH). Section 2012 of Cures newly requires the NIH to issue such certificates for federally funded research that collects “identifiable, sensitive information,” and permits the NIH to issue certificates for privately-funded research collecting the same. The new legislation expands the scope of the certificate and affirmatively prohibits certificate holders from disclosing or providing the name of research subjects—or any information, document or biospecimens containing identifiable, sensitive information collected during the research—to persons not connected with the research. There are limited exceptions to this disclosure prohibition (e.g., subject consent and medical treatment); however, one exception that may exist to further Cures’ data sharing goals permits disclosures made for the purposes of other scientific research that complies with applicable federal human subjects research regulations. It also explicitly protects such information created or compiled for research purposes against compulsory legal demands (unless a subject consents).
The act also introduces a new information standard: “identifiable, sensitive information.” Cures defines this as information about an individual that is gathered or used during the course of research through which an individual is identified or for which there is “at least a very small risk” that the individual could be identified via a combination of the information, the request and other available data sources. It is not directly clear how this new standard and new requirement reconcile with other research-related information specifications, such as the statistical de-identification standard under HIPAA, but the standards do appear substantially similar.
Key Areas of Focus
In addition to funding, however, the legislation directs the NIH (and, in certain instances, the FDA and other HHS agencies) to consider a host of other, broader focal points. In doing so, Cures creates opportunities for the NIH and others to think critically about specific areas of potential improvement in current research processes and priorities and to pursue such improvements. Important focal points include:
Addressing pressing, current public health crises (e.g., antimicrobial resistance, opioid epidemic);
Supporting research innovations and the next generation of scientists; and
Evaluating and modernizing current research infrastructure (e.g., via exploring diversity among research participants, reevaluating laboratory animal regulations and policies, and creating a new global pediatric clinical study network and a new task force on research regarding pregnant and lactating women).
While the new administration may not choose to actively pursue improvements in these areas, the statute includes a number of tools that the NIH may utilize if it chooses to do so. First, as part of the new Research Policy Board created under Cures, the NIH has the opportunity to work with the heads of other departments and agencies to overhaul research regulations and prioritize research aims across funding agencies. The legislation also includes funding mechanisms that give NIH significant control in structuring the funding of new scientific innovations. These include the Eureka Prize competitions and the Next Generation of Researchers Initiative, the latter of which could result in significantly more grant award opportunities for early-stage researchers. Cures also permits national institutes and centers within NIH, with approval from the director, to use alternate transaction structures to fund “high-risk, high-reward research,” and encourages the support of such “cutting-edge” research to address major current health challenges. Should it choose to do so, these tools likely give the NIH significant latitude to direct funding—and, moreover, policy—as it deems fit, based on its review and evaluation activities.