# The 21st Century Cures Act (Division A of P.L. 114-255) > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/crs%3AR44720 ## Record - **Collection:** Congressional research report - **Document type:** CRS Report - **Published:** December 23, 2016 - **Citation:** R44720 ## Text The 21st Century Cures Act (Division A of P.L. 114-255) Amanda K. Sarata, Coordinator Specialist in Health Policy Updated December 23, 2016 Congressional Research Service 7-.... www.crs.gov R44720 The 21st Century Cures Act (Division A of P.L. 114-255) Summary The 21st Century Cures Act (P.L. 114-255) was signed into law on December 13, 2016, by President Barack Obama. On November 30, 2016, the House passed the House amendment to the Senate amendment to H.R. 34, the 21st Century Cures Act, on a vote of 392 to 26. The bill was then sent to the Senate where it was considered and passed, with only minor technical modification, on December 7, 2016, on a vote of 94 to 5. The law consists of three divisions:    Division A—21st Century Cures Act; Division B—Helping Families in Mental Health Crisis; and Division C—Increasing Choice, Access, and Quality in Health Care for Americans. CRS has published a series of reports on this law, one on each Division. This is the report for Division A of the law. This report provides a brief summary of each provision of the 21st Century Cures Act (Division A of P.L. 114-255), by title, subtitle, and section. The Division includes five titles, as follows: (1) Innovation projects and state responses to opioid abuse; (2) Discovery; (3) Development; (4) Delivery; and (5) Savings. Title I provides funding for biomedical research, including the Precision Medicine Initiative (PMI) and the Cancer Moonshot Initiative, for the opioid crisis response, and for the Food and Drug Administration (FDA) to support certain new activities authorized by the law. Title II, consisting of seven subtitles, requires or authorizes a number of activities to support biomedical research, including the reauthorization of the National Institutes of Health (NIH) and the reform of that agency through numerous administrative, reporting, and data access provisions. The Title includes provisions that support young investigators funded by NIH; pediatric research; collaborative research such as research on neurological disease; and precision medicine efforts, and specifically the PMI. Title III, consisting of ten subtitles, focuses on modifying the drug and device approval pathways at the FDA to support innovation, and specifically includes provisions that support patientfocused drug development and streamlined and clarified pathways to approval for drugs, combination products, antimicrobials, Orphan drugs, drugs for rare disease, and regenerative therapies. This Title also contains provisions making modifications to the medical device approval pathway and reforms to the FDA’s hiring process. Finally, it addresses FDA’s regulation of medical countermeasure and vaccine development. Title IV focuses on health care delivery, and includes provisions that together address the federal policies to promote the adoption and use of electronic health record (EHR) technology, as well as a handful of Medicare delivery provisions addressing telehealth services in Medicare, site-ofservice price transparency for certain Medicare services, Local Coverage Determinations (LCDs) under Medicare, and a technology and pharmaceutical ombudsman for Medicare. Title V provides savings for the Division, and includes Medicare and Medicaid savings; Patient Protection and Affordable Care Act (ACA, P.L. 111-148, as amended) savings, including Prevention and Public Health Fund (PPHF) and territory funding; and savings from the Strategic Petroleum Reserve (SPR) drawdown. Congressional Research Service The 21st Century Cures Act (Division A of P.L. 114-255) Contents Introduction ..................................................................................................................................... 1 Title I-Innovation Projects and State Responses to Opioid Abuse .................................................. 2 Section 1001. NIH Innovation Projects .............................................................................. 2 Section 1002. FDA Innovation Projects .............................................................................. 5 Section 1003. Account for the State Response to the Opioid Abuse Crisis ........................ 6 Title II- Discovery ........................................................................................................................... 7 Subtitle A- National Institutes of Health Reauthorization......................................................... 7 Section 2001. National Institutes of Health Reauthorization .............................................. 7 Section 2002. Eureka Prize Competitions........................................................................... 7 Subtitle B- Advancing Precision Medicine ............................................................................... 8 Sections 2011-2014. Precision Medicine Establishment and Data Protections .................. 9 Subtitle C- Supporting Young Emerging Scientists .................................................................. 9 Section 2021. Investing in the Next Generation of Researchers. ........................................ 9 Section 2022. Improvement of Loan Repayment Program. .............................................. 10 Subtitle D- National Institutes of Health Planning and Administration ...................................11 Section 2031. National Institutes of Health Strategic Plan ................................................11 Section 2032. Triennial Reports ........................................................................................ 12 Section 2033. Increasing Accountability at the National Institutes of Health .................. 12 Section 2034. Reducing Administrative Burden for Researchers ..................................... 13 Section 2035. Exemption of the National Institutes of Health from the Paperwork Reduction Act Requirements. ........................................................................................ 14 Section 2036. High-Risk, High-Reward Research............................................................ 15 Section 2037. National Center for Advancing Translational Sciences. ............................ 16 Section 2038. Collaboration and Coordination to Enhance Research .............................. 17 Section 2039. Enhancing the Rigor and Reproducibility of Scientific Research .............. 18 Section 2040. Improving Medical Rehabilitation Research at the National Institutes of Health ......................................................................................................... 19 Section 2041.Task Force on Research Specific to Pregnant Women and Lactating Women ........................................................................................................................... 19 Section 2042. Streamlining National Institutes of Health Reporting Requirements ......... 19 Section 2043. Reimbursement for Research Substances and Living Organisms .............. 20 Section 2044. Sense of the Congress on Increased Inclusion of Underrepresented Populations in Clinical Trials ......................................................................................... 20 Subtitle E- Advancement of the National Institutes of Health Research and Data Access .................................................................................................................................. 21 Sections 2051. Technical Updates to Clinical Trials Database ......................................... 21 Section 2052. Compliance Activities Reports................................................................... 21 Section 2053. Updates to Policies to Improve Data .......................................................... 22 Section 2054. Consultation ............................................................................................... 22 Subtitle F- Facilitating Collaborative Research ...................................................................... 23 Section 2061. National Neurological Conditions Surveillance System ............................ 23 Section 2062. Tick-Borne Diseases .................................................................................. 23 Section 2063. Accessing, Sharing, and Using Health Data for Research Purposes .......... 24 Subtitle G- Promoting Pediatric Research .............................................................................. 25 Section 2071. National Pediatric Research Network ........................................................ 25 Section 2072. Global Pediatric Clinical Study Network ................................................... 25 Congressional Research Service The 21st Century Cures Act (Division A of P.L. 114-255) Title III-Development .................................................................................................................... 26 Subtitle A-Patient Focused Drug Development ...................................................................... 26 Sections 3001-3004. Patient Experience Data, Patient-Focused Drug Development Guidance, Streamlining Patient Input, Report on Patient Experience Drug Development ...................................................................................... 26 Subtitle B-Advancing New Drug Therapies ........................................................................... 27 Section 3011. Qualification of Drug Development Tools ................................................. 27 Section 3012. Targeted Drugs for Rare Diseases .............................................................. 29 Section 3013. Reauthorization of Program to Encourage Treatments for Rare Pediatric Diseases .......................................................................................................... 30 Section 3014. GAO Study of Priority Review Voucher Programs ................................... 31 Section 3015. Amendments to the Orphan Drug Grants ................................................... 31 Section 3016. Grants for Studying Continuous Drug Manufacturing ............................... 32 Subtitle C-Modern Trial Design and Evidence Development ................................................. 33 Section 3021. Novel Clinical Trial Designs ...................................................................... 33 Section 3022. Real World Evidence.................................................................................. 33 Sections 3023-3024. Protection of Human Research Subjects, Informed Consent Waiver or Alteration for Clinical Investigations ............................................................ 34 Subtitle D-Patient Access to Therapies and Information ........................................................ 36 Section 3031. Summary Level Review ............................................................................. 36 Section 3032. Expanded Access Policy ............................................................................ 37 Sections 3033-3036. Regenerative Therapies ................................................................... 38 Section 3037. Health Care Economic Information ........................................................... 39 Section 3038. Combination Product Innovation ............................................................... 40 Subtitle E-Antimicrobial Innovation and Stewardship ........................................................... 42 Section 3041. Antibacterial Resistance Monitoring. ......................................................... 42 Section 3042. Limited Population Pathway. ..................................................................... 43 Section 3043. Prescribing Authority. ................................................................................ 44 Section 3044. Susceptibility Test Interpretive Criteria for Microorganisms; Antimicrobial Susceptibility Testing Devices................................................................ 44 Subtitle F-Medical Device Innovations................................................................................... 45 Section 3051. Breakthrough Devices ................................................................................ 45 Section 3052. Humanitarian Device Exemption ............................................................... 48 Section 3053. Recognition of Standards ........................................................................... 48 Section 3054. Certain Class I and Class II Devices .......................................................... 50 Section 3055. Classification Panels .................................................................................. 51 Section 3056. Institutional Review Board Flexibility ....................................................... 52 Section 3057. CLIA Waiver Improvements ...................................................................... 53 Section 3058. Least Burdensome Device Review ............................................................ 54 Section 3059. Cleaning Instructions and Validation Data ................................................. 55 Section 3060. Clarifying Medical Software Regulation ................................................... 56 Subtitle G-Improving Scientific Expertise and Outreach at FDA ........................................... 58 Section 3071. Silvio O. Conte Senior Biomedical Research and Biomedical Product Assessment Service .......................................................................................... 58 Section 3072. Hiring Authority for Scientific, Technical, and Professional Personnel........................................................................................................................ 59 Section 3073. Establishment of Food and Drug Administration Intercenter Institutes ......................................................................................................................... 59 Section 3074. Scientific Engagement ............................................................................... 60 Section 3075. Drug Surveillance ...................................................................................... 61 Congressional Research Service The 21st Century Cures Act (Division A of P.L. 114-255) Section 3076. Reagan-Udall Foundation for the Food and Drug Administration ............. 62 Subtitle H-Medical Countermeasures Innovation ................................................................... 62 Sections 3081-3085. Medical Countermeasures Innovation ............................................. 63 Section 3086. Encouraging Treatment for Agents that Present a National Security Threat ............................................................................................................................. 64 Section 3087. Paperwork Reduction Act Waiver During a Public Health Emergency ..................................................................................................................... 65 Section 3088. Clarifying FDA Emergency Use Authorization ......................................... 65 Subtitle I-Vaccine Access, Certainty, and Innovation ............................................................. 66 Sections 3091-3093. Predictable Review Timelines of Vaccines by the ACIP, Review of Processes and Consistency of ACIP Recommendations, Encouraging Vaccine Innovation ........................................................................................................ 67 Title IV- Delivery .......................................................................................................................... 67 Sections 4001-4008. Policies to Promote the Adoption and Use of EHR Technology .................................................................................................................... 70 Section 4009. Improving Medicare Local Coverage Determinations ............................... 72 Section 4010. Medicare Pharmaceutical and Technology Ombudsman ........................... 73 Section 4011. Medicare Site-of-Service Price Transparency ............................................ 73 Section 4012. Telehealth Services in Medicare ................................................................ 74 Title V-Savings .............................................................................................................................. 75 Section 5001. Savings in the Medicare Improvement Fund ............................................. 75 Section 5002. Medicaid Reimbursement to States for Durable Medical Equipment ........ 75 Section 5003. Penalties for Violations of Grants, Contracts, and Other Agreements .................................................................................................................... 75 Section 5004. Reducing Overpayments of Infusion Drugs ............................................... 78 Section 5005. Increasing Oversight of Termination of Medicaid Providers ..................... 79 Section 5006. Requiring Publication of Fee-for-Service Provider Directory ................... 81 Section 5007. Fairness in Medicaid Supplemental Needs Trusts ..................................... 82 Section 5008. Eliminating Federal Financial Participation with Respect to Expenditures under Medicaid for Agents Used for Cosmetic Purposes or Hair Growth ........................................................................................................................... 83 Section 5009. Amendment to the Prevention and Public Health Fund ............................. 83 Section 5010. Strategic Petroleum Reserve Drawdown ................................................... 84 Section 5011. Rescission of Portion of ACA Territory Funding ....................................... 84 Section 5012. Medicare Coverage of Home Infusion Therapy ......................................... 85 Tables Table 1. CRS Experts List ............................................................................................................... 2 Appendixes Appendix. List of Acronyms ......................................................................................................... 88 Contacts Author Contact Information .......................................................................................................... 92 Congressional Research Service The 21st Century Cures Act (Division A of P.L. 114-255) Introduction The 21st Century Cures Act (P.L. 114-255) was signed into law on December 13, 2016, by President Barack Obama. On November 30, 2016, the House passed the House amendment to the Senate amendment to H.R. 34, the 21st Century Cures Act, on a vote of 392 to 26. The bill was then sent to the Senate where it was considered and passed, with only minor technical modification, on December 7, 2016, on a vote of 94 to 5.1 The law consists of three divisions:    Division A—21st Century Cures Act; Division B—Helping Families in Mental Health Crisis; and Division C—Increasing Choice, Access, and Quality in Health Care for Americans. CRS has published a series of reports on this law, one on each Division. This is the report for Division A of the law.2 Division A of the law provides funding for biomedical research—including the Precision Medicine Initiative (PMI) and the Cancer Moonshot Initiative—and for the opioid crisis response; modifies Food and Drug Administration (FDA) pathways for the approval of regulated medical products; and makes a number of reforms to the National Institutes of Health (NIH). Division A of the law also includes and builds on provisions from both the previously passed House bill, H.R. 6 (The 21st Century Cures Act, passed in July 2015), and a package of Senate medical innovation bills that were considered in the early part of 2016. As noted, both the House and the Senate considered previous legislation to support medical innovation, primarily through reforms to the NIH and changes to the drug, biologic and device approval pathways at the FDA. On February 3, 2015, Senators Lamar Alexander and Patty Murray, chairman and ranking Member of the Committee on Health, Education, Labor and Pensions, announced the start of a bipartisan initiative to "examine the process for getting safe treatments, devices and cures to patients and the roles of the [FDA] and the [NIH] in that process."1 This initiative culminated in a package of 19 bipartisan bills that were reported out of the Senate Health, Labor, Education, and Pensions (HELP) Committee in a series of three executive sessions held on February 9, 2016; March 9, 2016; and April 6, 2016. One of these 19 bills, The Adding Zika Virus to the FDA Priority Review Voucher Program Act (S. 2512), subsequently was passed by both chambers and signed into law on April 19, 2016 (P.L. 114-146). The Senate's medical innovation package was that chamber's companion effort to the House's 21st Century Cures initiative, which resulted in the House passage of H.R. 6, the initial version of the 21st Century Cures Act, on July 10, 2015, on a vote of 344 to 77. H.R. 6 was the result of a series of hearings and roundtable meetings hosted by the House Energy and Commerce Committee dating back to spring 2014. The hearings and roundtables focused on a broad range of topics, including modernizing clinical trials, incorporating patient perspectives into medical research and 1 The Congressional Budget Office's (CBO) score of H.R. 34 (Rules Committee Print 114-67, as amended by Amendment Number 5) is available at https://www.cbo.gov/sites/default/files/114th-congress-20152016/costestimate/H.R.34amendment5.pdf. 2 For information on Division B, see CRS Report R44718, The Helping Families in Mental Health Crisis Reform Act of 2016 (Division B of P.L. 114-255), coordinated by Erin Bagalman. Congressional Research Service R44720 · VERSION 5 · UPDATED 1 The 21st Century Cures Act (Division A of P.L. 114-255) regulatory processes, precision/personalized medicine, digital health care, and more. While it consisted of many different provisions, H.R. 6 was primarily focused on efforts to increase strategic investments in medical research at NIH and change some aspects of how the FDA executes its regulatory oversight mission with regard to the review and approval of new drugs, biologics, and medical devices. This report provides a brief summary of each provision of the 21st Century Cures Act (Division A of P.L. 114-255), by title, subtitle, and section.3 The Division includes five titles, as follows: (1) Innovation projects and state responses to opioid abuse; (2) Discovery; (3) Development; (4) Delivery; and (5) Savings. Most provision summaries include a brief background of current law in addition to a description of the new provision of law. Throughout the report, clarity takes priority over consistency. For example, some summaries are more detailed than others where such detail is necessary to highlight important changes. A list of acronyms used throughout this report can be found in Appendix of this report. Table 1. CRS Experts List Erin Bagalman Opioid epidemic funding Cliff Binder Medicaid, Fraud and abuse Kirsten J. Colello Medicaid supplemental needs trusts Agata Dabrowska FDA drug regulation Susannah Gopalan Telehealth in Medicare Frank Gottron Medical countermeasures innovation Jim Hahn Medicare Part B, Site-of-service price transparency Elayne J. Heisler Health care workforce and education Judith Johnson National Institutes of Health, FDA medical device and biologics regulation Sarah A. Lister Antimicrobial and vaccine development, Collaborative research, PPHF Annie Mach ACA territory funding Paulette Morgan Durable Medical Equipment Robert Pirog Strategic Petroleum Reserve drawdown C. Stephen Redhead Data privacy, Health Information Technology, Regulation of medical software Amanda Sarata Precision medicine, Clinical laboratory regulation Title I-Innovation Projects and State Responses to Opioid Abuse Section 1001. NIH Innovation Projects The National Institutes of Health (NIH) is the lead federal agency charged with performing and supporting biomedical and behavioral research. It also has major roles in training biomedical 3 Three sections are excluded from this report due to their technical, non-substantive nature: Section 1004 (Budgetary treatment), Section 3101 (Technical corrections), and Section 3102 (Completed studies). Congressional Research Service R44720 · VERSION 5 · UPDATED 2 The 21st Century Cures Act (Division A of P.L. 114-255) researchers and disseminating health information. Congress doubled the NIH budget from $13.65 billion to $27.1 billion in the five-year period from FY1998 to FY2003; during that period, annual increases in the 14%-15% range were the norm. Since then, increases from regular appropriations have been between 1.0% and 3.2% each year.4 The growth rate of the NIH budget has been at or below the rate of inflation, which for biomedical research in FY2015 is estimated to be 2.2%.5 NIH funding in FY2015 was 22% lower than the FY2003 level, the peak of the doubling period in constant 2012 dollars.6 A recent analysis of U.S. expenditures on biomedical research found that “U.S. government research funding declined from 57% (2004) to 50% (2012) of the global total, as did that of U.S. companies (50% to 41%), with the total U.S. (public plus private) share of global research funding declining from 57% to 44%. Asia, particularly China, tripled investment from $2.6 billion (2004) to $9.7 billion (2012) preferentially for education and personnel.”7 The United States continues to be the top supporter of both public and industry medical research. 8 However, some Members of Congress and many in the biomedical research community have expressed concern over the rapidly increasing investments being made by other countries in this area of research. Many of those who are concerned about the U.S. global position in biomedical research investment have made frequent calls for increased support for research at NIH. However, another recent analysis of U.S. biomedical research funding cautioned that the past pattern of rapid doubling of the NIH budget followed by slowdowns in federal funding “created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession—and making it difficult for seasoned investigators to produce their best work.”9 Rather than short-term infusions of cash that disappear, the authors recommend that greater emphasis be placed on the predictable and stable growth of federal funds for the research enterprise.10 In responding to questions raised by Senator Elizabeth Warren during a May 5, 2015, Senate hearing, NIH Director Francis Collins agreed that continued NIH budget increases— ranging from 3.7% annually to inflation plus 4% or 5%—would be preferred to a temporary larger investment that disappears.11 4 For further information, see CRS Report R43341, NIH Funding: FY1994-FY2017, by Judith A. Johnson. 5 The Biomedical Research and Development Price Index (BRDPI) is developed each year for NIH by the Bureau of Economic Analysis of the Department of Commerce. It reflects the increase in prices of the resources needed to conduct biomedical research—including personnel services, supplies, equipment—and indicates how much the NIH budget must change to maintain purchasing power. See http://officeofbudget.od.nih.gov/gbiPriceIndexes.html. 6 For further information, see CRS Report R43341, NIH Funding: FY1994-FY2017, by Judith A. Johnson. 7 Hamilton Moses, David H. M. Matheson, Sarah Cairns-Smith, et al., “The Anatomy of Medical Research: U.S. and International Comparisons,” Journal of the American Medical Association, vol. 313, no. 2 (January 13, 2015), pp. 174189. 8 Overall medical research funding in the United States was $117.2 billion in 2011. See Figure 8 on page 181 in Hamilton Moses, David H. M. Matheson, Sarah Cairns-Smith, et al., “The Anatomy of Medical Research: U.S. and International Comparisons,” Journal of the American Medical Association, vol. 313, no. 2 (January 13, 2015). 9 Bruce Alberts, Marc W. Kirschner, Shirley Tilghman, and Harold Varmus, “Rescuing U.S. biomedical research from its systemic flaws,” Proceedings of the National Academy of Sciences, vol. 111, no. 16 (April 22, 2014), pp. 57735777. 10 Ibid., p. 5775. 11 U.S. Congress, Senate Committee on Health, Education, Labor, and Pensions, Continuing America’s Leadership: Realizing the Promise of Precision Medicine for Patients, 114th Cong., 1st sess., May 5, 2015. Congressional Research Service R44720 · VERSION 5 · UPDATED 3 The 21st Century Cures Act (Division A of P.L. 114-255) The Advisory Committee to the Director of NIH, authorized under PHSA Section 222, provides “advice on matters pertinent to NIH mission responsibilities in the conduct and support of biomedical research.”12 Provision Section 1001 establishes the “NIH Innovation Account” in the Treasury, to which specified amounts are transferred for each of FY2017 through FY2026. Such amounts from the account are authorized to be appropriated to the NIH Director for the purpose of carrying out the NIH Innovation Projects. Amounts appropriated from this account are available until expended. Specifically, the provision authorizes appropriations to support     the Precision Medicine Initiative, specified amounts for FY2017 through FY2026, total not to exceed $1.455 billion; the Brain Research through Advancing Innovative Neurotechnologies Initiative (BRAIN Initiative), specified amounts for FY2017 through FY2026, total not to exceed $1.511 billion; cancer research, specified amounts for FY2017 through FY2023, total not to exceed $1.8 billion; and regenerative medicine using adult stem cells, specified amounts for FY2017 through FY2020 that total $30 million; no funds are to be appropriated for this activity after FY2020. This research is to be undertaken in coordination with the FDA. Within six months of enactment, the NIH Director must submit to the specified congressional committees a work plan including the proposed allocation of funds authorized to be appropriated for each year, FY2017 through FY2026, for the NIH Innovation Projects. Prior to submitting the work plan, the NIH Director must seek recommendations on the allocations of funds and the contents of the proposed work plan from the Advisory Committee to the Director of NIH. The work plan must include recommendations from this Advisory Committee, the amount of money to be obligated or expended in each fiscal year for each NIH Innovation Project, a description and justification of each such project, and a description of how each such project supports the strategic research priorities identified in the NIH Strategic Plan. Not later than October 1 of each year, FY2018 through FY2027, the Director of NIH must submit to the specified congressional committees a report including the amount of money obligated or expended in the prior fiscal year for each NIH Innovation Project, a description of any such project using funds provided by this section, and whether such projects are advancing the strategic research priorities identified in the NIH Strategic Plan. The specified House and Senate committees may request an update on the allocation of funding under this section or the description of the NIH Innovation Projects, which the NIH Director must provide in the form of additional reports or testimony. Section 1001 specifies that these funds may be used only for NIH Innovation fund projects (notwithstanding any transfer authority in any appropriations act). The section also specifies that amounts in the account are not available until appropriated in subsequent appropriations acts. Notably, the amounts subsequently appropriated (i.e., the budget authority and the resulting outlays) for FY2017 through FY2026, up to the amounts transferred, are to be subtracted from any cost estimates provided for purposes of budget controls. Effectively, 12 NIH, Advisory Committee to the Director, Charter, at http://acd.od.nih.gov/charter.htm. Congressional Research Service R44720 · VERSION 5 · UPDATED 4 The 21st Century Cures Act (Division A of P.L. 114-255) the appropriations from the account will not be counted against any spending limits, such as the statutory discretionary spending limits; that is, the amounts appropriated from the account will be considered outside those limits for FY2017 through FY2026. Section 1001 sunsets on September 30, 2026. Section 1002. FDA Innovation Projects The Food and Drug Administration (FDA) regulates the safety of foods (including dietary supplements), cosmetics, and radiation-emitting products; the safety and effectiveness of drugs, biologics (e.g., vaccines), and medical devices; and public health aspects of tobacco products. FDA’s budget (i.e., its total program level) has two funding streams: annual appropriations (i.e., discretionary budget authority, or BA) and industry user fees. In FDA’s annual appropriations, Congress sets both the total amount of appropriated funds and the total amount of user fees that the agency is authorized to collect and obligate for that fiscal year. Appropriated funds are largely for the Salaries and Expenses account, with a much smaller amount for the Buildings and Facilities account. The different user fees contribute only to the Salaries and Expenses account. Between FY2012 and FY2016, FDA’s total program level increased from $3.832 billion to $4.745 billion. Although congressionally appropriated funding increased by 9% over that time period, user fee revenue increased more than 50%. In FY2016, user fees accounted for 42% of FDA’s total program level.13 The Science Board to the FDA is an advisory committee that provides “advice to the Commissioner and other appropriate officials on specific complex scientific and technical issues important to FDA and its mission, including emerging issues within the scientific community.” Among other things, the Science Board is also tasked with providing, where requested, “expert review of Agency sponsored intramural and extramural scientific research programs.” Provision Section 1002 establishes the “FDA Innovation Account,” to which a total of $500 million is authorized to be transferred over a nine-year period (FY2017-FY2025).14 It specifies that amounts in the account are not available until appropriated in subsequent appropriations acts and that once made available, these amounts are available until expended. The amounts from the account are authorized to be appropriated to the FDA Commissioner for the purpose of carrying out the FDA Innovation Projects specified as activities under subtitles A through F of Title III (e.g., Subtitle A—Patient Focused Drug Development, Subtitle B—Advancing New Drug Therapies, Subtitle F—Medical Device Innovations), as well as Section 3073 of this Act establishing FDA Intercenter Institutes; these activities are described later in this report. The amounts subsequently appropriated (i.e., the budget authority and the resulting outlays) for FY2017 through FY2025, up to the amounts transferred, are to be subtracted from any cost estimates provided for purposes of budget controls. Effectively, the appropriations from the account will not be counted against any spending limits, such as the statutory discretionary 13 CRS Report R44576, The Food and Drug Administration (FDA) Budget: Fact Sheet, by Agata Dabrowska and Susan Thaul. 14 For each of fiscal years 2017 through 2025, the following amounts are authorized to be transferred to the FDA Innovation Account: $20 million in FY2017; $60 million in FY2018; $70 million in FY2019; $75 million in FY2020; $70 million in FY2021; $50 million in FY2022; $50 million in FY2023; $50 million in FY2024; $55million in FY2025. Congressional Research Service R44720 · VERSION 5 · UPDATED 5 The 21st Century Cures Act (Division A of P.L. 114-255) spending limits; that is, the amounts appropriated from the account will be considered outside those limits for FY2017 through FY2025. Within six months of enactment, the FDA Commissioner is required to submit to the specified congressional committees a work plan including the proposed allocation of funds authorized to be appropriated for each fiscal year (FY2017 through FY2025) for the FDA Innovation Projects. Prior to submitting the work plan, the FDA Commissioner must seek recommendations on the allocations of funds and the contents of the proposed work plan from the Science Board. The work plan must include recommendations from the Science Board, the amount of money to be obligated or expended in each fiscal year for each FDA Innovation Project, and a description and justification of each such project. Section 1002 requires the FDA Commissioner, not later than October 1 of each fiscal year 2018 through 2026, to submit to the specified congressional committees a report including the amount of money to be obligated or expended in each fiscal year for each FDA Innovation Project, a description of any such project using funds provided by this section, and how the activities are advancing public health. The specified House and Senate committees may request an update on the allocation of funding under this section or the description of the FDA Innovation Projects, which the FDA Commissioner must provide in the form of additional reports or testimony. Section 1002 specifies that these funds may be used only for FDA Innovation fund projects (notwithstanding any transfer authority in any appropriations act). Section 1002 sunsets on September 30, 2025. Section 1003. Account for the State Response to the Opioid Abuse Crisis The Substance Abuse and Mental Health Services Administration (SAMHSA) administers block grants authorized by PHSA Title XIX and numerous other grants authorized by PHSA Title V, as well as other activities. Each state that receives a block grant from SAMHSA is required to submit to the HHS Secretary a report about block grant funds received in the preceding fiscal year—including the purposes for which funds were expended, the state’s activities under the block grant, and the recipients of block grant funds. Provision Section 1003 establishes the “Account for the State Response to the Opioid Abuse Crisis” in the Treasury, to which $500 million is transferred for each of FY2017 and FY2018. Such amounts from the account are authorized to be appropriated to the HHS Secretary for use as grants to support state responses to opioid abuse. Specifically, the provision authorizes appropriations to support two categories of grants to states: (1) grants “for the purpose of addressing the opioid abuse crisis” and (2) grants for activities that supplement opioid-related activities undertaken by the state agency that administers the substance abuse block grant. Section 1003 requires that such funds (1) shall not be used for any other purpose (notwithstanding any transfer authority in any appropriations act) and (2) shall be subject to the same requirements as SAMHSA’s substance abuse prevention and treatment programs under PHSA Titles V and XIX. It further requires a state receiving such a grant to include specified information about the use of the grant in the report already required in connection with the block grants. The amounts in the account are not available until appropriated in subsequent appropriations acts. Notably, the amounts subsequently appropriated (i.e., the budget authority and the resulting outlays) for FY2017 and FY2018, up to the amounts transferred, are to be subtracted from any cost estimates provided for purposes of budget controls. Effectively, the appropriations from the Congressional Research Service R44720 · VERSION 5 · UPDATED 6 The 21st Century Cures Act (Division A of P.L. 114-255) account will not be counted against any spending limits, such as the statutory discretionary spending limits; that is, the amounts appropriated from the account will be considered outside those limits for FY2017 and FY2018. Title II- Discovery Subtitle A- National Institutes of Health Reauthorization Section 2001. National Institutes of Health Reauthorization NIH derives its statutory authority from the Public Health Service Act of 1944 (PHSA), as amended.15 PHSA Section 301 grants the HHS Secretary broad permanent authority to conduct and sponsor research.16 In addition, PHSA Title IV, “National Research Institutes,” authorizes in greater detail various activities, functions, and responsibilities of the NIH Director and the institutes and centers.17 The last major NIH reauthorization was the NIH Reform Act of 2006 (P.L. 109-482). The NIH Reform Act, in PHSA Section 402A, authorized total funding levels for NIH appropriations for FY2007 ($30,331,309,000), FY2008 ($32,831,309,000), and such sums as necessary for FY2009. Overall NIH authorization expired at the end of FY2009 and has not been extended by Congress. Annual appropriations, together with Section 301 of the PHSA, have provided authority for NIH programs to continue from FY2009 to the present. Provision Section 2001 amends PHSA Section 402A, to authorize appropriations for NIH in FY2018 ($34,851,000,000), FY2019 ($35,585,871,000), and FY2020 ($36,472,442,775). Section 2002. Eureka Prize Competitions Section 105 of the America COMPETES Reauthorization Act of 2010 (P.L. 111-358) provides federal agencies with broad authority to carry out programs designed to stimulate innovation through prize competitions.18 Before passage of P.L. 111-358, only certain federal agencies had the authority to initiate prize competitions. The White House Office of Science and Technology Policy (OSTP) publishes annual reports on the implementation of Section 105 as required by P.L. 111-358.19 Currently a number of federal government agencies, including NIH, sponsor challenges or prize competitions in science and medical research. A current list of such challenges is available on the Challenge.gov website.20 A search of the website on December 8, 2016, resulted in 15 competitions conducted by NIH or one of the NIH ICs. Examples of research topics covered in the various challenges include breast cancer genetics, antimicrobial resistance, and drug abuse and addiction research. 15 42 U.S.C. §§201-300mm-61. 16 42 U.S.C. §241. 17 42 U.S.C. §§281-290b. 18 For more information, see CRS Report R43880, The America COMPETES Acts: An Overview, by Heather B. Gonzalez. 19 Office of Science and Technology Policy, “Implementation of Federal Prize Authority: Fiscal Year 2015 Progress Report,” August 2016, at https://www.whitehouse.gov/sites/default/files/fy2015_competes_prizes_report.pdf. 20 https://www.challenge.gov/list/. Congressional Research Service R44720 · VERSION 5 · UPDATED 7 The 21st Century Cures Act (Division A of P.L. 114-255) Provision Section 2002 requires the NIH Director, under authorities in 15 U.S.C. §3719, to support prize competitions for one or both of the following goals: (1) identifying and funding areas of biomedical science that could realize significant advancements through a prize competition and (2) improving health outcomes, particularly with respect to human diseases and conditions such as those that are serious and represent a significant disease burden in the United States. With regard to the second goal, the prize competition may also target human diseases and conditions where public and private investment in research is disproportionately small relative to federal government expenditures for prevention and treatment activities and those diseases and conditions with potential for a significant return on investment. The section requires the NIH Director to collect information on the effect of prize competition innovations on advancing biomedical science or improving health outcomes and the effect of the innovations on federal expenditures. This information must be included in the NIH triennial report, required in PHSA Section 403. Subtitle B- Advancing Precision Medicine Precision medicine is a relatively new term for what has traditionally been called personalized medicine, the idea of providing health care to individuals based on specific patient characteristics. On February 25, 2016, the White House hosted a Precision Medicine Initiative (PMI) Summit to mark the one-year anniversary of the initiative’s launch, first announced in the 2015 State of the Union address. In the first year, the PMI’s three key entities—National Institutes of Health (NIH), Food and Drug Administration (FDA), and the Office of the National Coordinator for Health Information Technology (ONC)—began work in this area. The FY2017 President’s budget requests a total of $309 million for the PMI: $4 million to FDA, $5 million to ONC, and the remaining $300 million to NIH. Precision medicine research efforts rely on the collection of large amounts of health and other data; therefore, access to this data may be a concern in the context of this type of research. The sharing of genetic and genomic data among private individuals, researchers, and the federal government has, at times, prompted concerns that the information, if collected or retained by a federal executive branch agency, could be subject to public release pursuant to the Freedom of Information Act (FOIA). FOIA, however, specifies nine categories of information that may be exempted from the rule of disclosure, allowing agencies to withhold applicable records. Exemption 3 allows agencies to withhold applicable records if the data are specifically exempted from disclosure by a statute other than FOIA, if that statute meets criteria laid out in FOIA. These types of Exemption 3 statutes are often referred to as b(3) exemptions because they are authorized in 5 U.S.C. §552(b)(3). As a mechanism for addressing compelled disclosure of research data, NIH currently issues Certificates of Confidentiality pursuant to PHSA Section 301(d) (42 U.S.C. §241(d)) at the request of an investigator. A Certificate of Confidentiality protects investigators from being compelled to disclose information that would identify research subjects in any civil, criminal, administrative, legislative, or other proceeding. In this way, having a Certificate of Confidentiality can help promote participation in research by adding an additional layer of privacy protection. At the other end of the spectrum, the sharing of research data—specifically, genomic data generated by NIH-funded research—has also received attention in the context of precision medicine. NIH has established a comprehensive policy for the sharing of genomic data that “applies to all NIH-funded research that generates large-scale human or non-human genomic data Congressional Research Service R44720 · VERSION 5 · UPDATED 8 The 21st Century Cures Act (Division A of P.L. 114-255) as well as the use of these data for subsequent research.” This policy requires investigators to outline their data-sharing plans as part of their funding applications; if investigators fail to submit the required data, NIH may withhold funding. Sections 2011-2014. Precision Medicine Establishment and Data Protections Provisions Title II, Subtitle B, has four sections (Sections 2011-2014) that together aim to support precision medicine by (1) codifying the PMI; (2) requiring issuance of Certificates of Confidentiality to investigators of federally funded research; (3) protecting identifiable, sensitive information from release under FOIA; and (4) requiring the sharing of NIH-supported research data in certain circumstances. Section 2011 codifies the President’s Precision Medicine Initiative (PMI) in a new PHSA Section 498E, by encouraging the HHS Secretary to establish and carry out the PMI, and by allowing specified components and authorities in the carrying out of the PMI as well as identifying requirements of the initiative, including, for example, complying with existing law and regulation regarding human research subjects protections. It also requires, not later than one year after enactment, the HHS Secretary to submit a report to Congress on relevant data access policies and procedures, and consultation with experts in the development of those policies. Section 2012 amends PHSA Section 301(d) to require the HHS Secretary to issue a Certificate of Confidentiality to research investigators of research funded wholly or in part by the federal government in which sensitive, identifiable information is collected to protect the privacy of research participants. The section prohibits the individual with the certificate from disclosing sensitive information about the research participants, with certain exceptions, as specified, and would make this type of information immune from the legal process. In addition, the section requires that these protections exist in perpetuity and that the HHS Secretary must minimize the burden to researchers of compliance with this section, and must coordinate across involved HHS entities. The requirements of this section become effective 180 days after the date of enactment of the act. Section 2013 amends PHSA Section 301 to allow the HHS Secretary to exempt from disclosure under FOIA exemption (b)(3) specified biomedical information that identifies an individual or that has an associated risk that the information may be reidentified. The HHS Secretary is required to make each such exemption available in writing and to the public, upon request. However, this does not limit individual research participants access to their own data. Section 2014 amends PHSA Section 402(b) to allow the HHS Secretary to require recipients of NIH grants or agreements to share data generated from such NIH grants or agreements in a manner consistent with all applicable federal law regarding human subject protections, propriety interests, confidential commercial information, and intellectual property. Subtitle C- Supporting Young Emerging Scientists Section 2021. Investing in the Next Generation of Researchers. Congress has had a long-standing interest in developing the future biomedical research workforce. Recent concerns have focused on ways to reduce the time between when young investigators complete their training and when they receive their first independent NIH research grant (i.e., achieve research independence). NIH has created a number of initiatives to shorten this Congressional Research Service R44720 · VERSION 5 · UPDATED 9 The 21st Century Cures Act (Division A of P.L. 114-255) time, in part to better retain young investigators in biomedical research. The Departments of Labor, Health and Human Services, and Education, and Related Agencies Appropriations Act, 2016 (P.L. 114-113, Division H), instructed the NIH Director to enter into a contract with the National Academy of Sciences (NAS) to conduct a comprehensive study of the policies affecting the next generation of researchers in the United States. Provision Section 2021 amends Part A of Title IV of the PHSA by adding a new Section 404M, which establishes the Next Generation of Researchers Initiative (the Initiative) within the office of the NIH Director. The Initiative requires the NIH Director to coordinate all NIH policies and programs focused on promoting and providing opportunities for new researchers and for promoting earlier research independence. Among other things, the NIH Director would have to coordinate with relevant agencies, professional associations, and academic institutions to improve and update information on the biomedical workforce to inform training, recruitment, and retention programs of biomedical researchers. In establishing the Initiative, the NIH Director is required to consider recommendations made by NAS in its study on the next generation of researchers. Not later than two years after completion of the NAS study, the NIH Director would be required to submit a report to specified congressional committees regarding any actions taken by NIH with respect to the NAS recommendations. Section 2022. Improvement of Loan Repayment Program. NIH funds seven loan repayment programs for researchers. Three of these are intramural programs that provide educational loan repayment benefits to researchers in exchange for undertaking research while employed by NIH. Intramural loan repayment programs support researchers from disadvantaged backgrounds, those who are investigating AIDS, and those undertaking general research (including general research by physicians during their fellowship training). Four of these programs help extramural researchers repay their educational loans. These funds are awarded competitively to researchers who are employed by a qualifying educational institution. Specific programs are available to extramural researchers investigating health disparities, undertaking contraception and infertility research, engaging in clinical research, and examining pediatric-related topics. Researchers may receive up to $35,000 per year in loan repayment benefits under each of these programs. Under current law, appropriations for loan repayments remain available until the end of the second fiscal year after they are appropriated. Provision Section 2022 renames PHSA Section 487A “Intramural Loan Repayment Program” and consolidates existing NIH intramural loan repayment programs. Specifically, it (1) transfers the authority to administer these program from the HHS Secretary to the NIH Director; (2) increases annual loan repayment amounts from a maximum of $35,000 to a maximum of $50,000; and (3) provides loan repayment benefits for individuals who conduct research in areas of emerging scientific or workforce needs, in addition to individuals who conduct research on AIDS, and clinical researchers from disadvantaged backgrounds. In addition, Section 2022 authorizes the NIH Director to amend the categories eligible for intramural loan repayment as scientific and workforce priorities change. Finally, the section prohibits the NIH Director from entering into a loan repayment contract with individuals unless they have substantial amounts of educational loans relative to income as determined by the NIH Director and permits amounts appropriated for new loan repayment contracts to remain available until the end of the second fiscal year after they are appropriated. Congressional Research Service R44720 · VERSION 5 · UPDATED 10 The 21st Century Cures Act (Division A of P.L. 114-255) Section 2022 similarly amends the NIH’s extramural loan repayment program. Specifically, it (1) retitles PHSA 487B “Extramural Loan Repayment Program,” (2) transfers authority for the program from the HHS Secretary to the NIH Director, (3) increases loan repayment amounts to a maximum of $50,000 per year, (4) prohibits the NIH Director from entering into a loan repayment contract with individuals unless they have substantial amounts of educational loans relative to income as determined by the NIH Director, and (5) permits amounts appropriated for new loan repayment contracts to remain available until the end of the second fiscal year after they are appropriated. In addition, Section 2022 retains authorization for current topics eligible for extramural loan repayment (contraception and infertility, pediatric research, minority health disparities, clinical research, and clinical research conducted by individuals from disadvantaged backgrounds). The section makes extramural researchers who are conducting research in an area of emerging scientific or workforce need eligible for loan repayment benefits, and it authorizes the NIH Director to amend the categories eligible for extramural loan repayment as scientific and workforce priorities change. Finally, Section 2022 repeals existing authorizations for NIH loan repayment programs in PHSA Sections 464z, 487C, 487E, and 487F. It requires a GAO report, not later than 18 months after enactment, that (1) reports on NIH efforts to attract, retain, and develop emerging scientists, including underrepresented individuals in the sciences; (2) reports on the research areas where individuals are receiving increased loan repayment amounts; and (3) analyzes the impact of changes included in this act on addressing workforce shortages. Subtitle D- National Institutes of Health Planning and Administration Section 2031. National Institutes of Health Strategic Plan PHSA Section 402(b)(5) specifies that the NIH Director “shall ensure that scientifically based strategic planning is implemented in support of research priorities as determined by the agencies of the National Institutes of Health.” Current law does not direct NIH Institutes and Centers (ICs) to coordinate or collaborate in the development of IC strategic plans. NIH provides access to many of its strategic plans on the agency’s website.21 The NIH Reform Act of 2006 (P.L. 109482) enhanced the authority of the NIH Director’s Office to perform strategic planning and provided for trans-NIH initiatives by enacting the Common Fund into law and requiring strategic planning for the fund. The Common Fund is part of the Office of the Director and is intended to support research in emerging areas of scientific opportunity, public health challenges, and knowledge gaps that might benefit from collaboration between two or more ICs. Provision Section 2031 amends PHSA Section 402 by adding a new subsection (m), which describes a strategic plan for NIH. Within two years of enactment, and once every six years thereafter, the NIH Director, in consultation with the IC Directors, must develop and submit to the appropriate committees of Congress, and post on the NIH website, a six-year NIH Strategic Plan. The NIH Strategic Plan is expected to provide direction to the biomedical research investments made by NIH, facilitate IC collaboration, leverage scientific opportunity, and advance biomedicine. The NIH Strategic Plan must identify research priorities, such as advancement of treatment, cure and prevention of health conditions, emerging scientific opportunities, and rising public health 21 See for example http://report.nih.gov/strategicplans/#tab2. Congressional Research Service R44720 · VERSION 5 · UPDATED 11 The 21st Century Cures Act (Division A of P.L. 114-255) challenges. The research strategy must address the disease burden in the United States, including rare diseases, and the many factors that contribute to health disparities. Other elements to be included in the NIH Strategic Plan are (1) coordination of research among the ICs; (2) priorities for funding research through the Common Fund; (3) training the biomedical workforce; and (4) collaboration with other agencies and departments. The individual IC strategic plans are required to be prepared regularly, to be informed by the NIH Strategic Plan, and to have a common template. The NIH Director must consult with the IC directors, researchers, patient advocacy groups, and industry leaders when developing the strategic plan. Section 2032. Triennial Reports PHSA Title IV establishes numerous reporting requirements for the NIH Director related to the activities of the agency. Specifically, PHSA Section 403(a) requires the NIH Director to submit to Congress biennially a report on NIH activities. Among other things, the report must include an assessment of the state of biomedical and behavioral research, and details of all the research activities conducted or supported by the ICs of NIH. Provision Section 2032 amends PHSA Section 403(a) by replacing the biennial reporting requirement of the NIH Director with a triennial requirement. The section adds new, and clarifies existing, reporting requirements, including a description of intra-NIH activities and funding made available for conducting and supporting research that involves collaboration between an IC and one or more other ICs. Section 2033. Increasing Accountability at the National Institutes of Health PHSA Section 405 specifies that the National Cancer Institute Director is appointed by the President and the Directors of the other NIH Institutes are appointed by the HHS Secretary. Each NIH Institute Director reports directly to the NIH Director. Research supported by NIH is first evaluated by a peer review system.22 Scientists who seek to compete for NIH research funding must submit detailed applications describing the research they plan to undertake. NIH considers the applications under a two-tiered system of peer review. First, the applications are reviewed for scientific and technical merit by committees composed of nongovernment scientists who are experts in the relevant fields of research. Each application is thoroughly discussed and given a score representing the average of the scores assigned by the reviewers. That score becomes the main determinant in whether an applicant will receive funding from an IC for the research proposal. The funding decisions are fine-tuned by a second level of peer review in the ICs, when the applications are considered for program relevance by the IC’s National Advisory Councils or Boards, which are composed of scientific and lay representatives. Section 202 of the Labor/HHS/ED Appropriations Act, 1993, states at the end of the section that the payment of compensation to consultants or individual scientists appointed for limited periods of time is “not to exceed the per diem rate equivalent to the maximum rate payable for seniorlevel positions,” which is “not less than 120% of the minimum rate of basic pay payable for GS– 15 of the General Schedule; and ... not greater than the rate of basic pay payable for level III of the Executive Schedule.”23 22 Peer review requirements described in PHSA Section 492. 23 P.L. 102-394 and 5 U.S.C. §5376. Congressional Research Service R44720 · VERSION 5 · UPDATED 12 The 21st Century Cures Act (Division A of P.L. 114-255) Provision Section 2033 amends PHSA Section 405 with regard to the appointment and terms of the Director of the National Cancer Institute and the directors of other NIH ICs. It requires that directors of ICs be appointed by the HHS Secretary acting through the NIH Director. The Director of the National Cancer Institute continues to be appointed by the President. It specifies five-year terms for the IC Directors who are appointed by the HHS Secretary acting through the NIH Director, and authorizes the NIH Director to remove an IC Director prior to the end of a five-year term if necessary. It permits the director of an IC to be reappointed at the end of a five-year term, with no limit to the number of terms served. It requires that, if the office of a director of an IC becomes vacant before the end of a five-year term, the director appointed to fill the vacancy begin a new five-year term (as opposed to finishing the five-year term of the previous director). Each current IC Director is deemed to be appointed for a five-year term as of the date of enactment. Section 2033 specifies that the compensation limitations in Section 202 of the Labor/HHS/ED Appropriations Act, 1993, related to time-limited appointments of consultants and individual scientists, do not apply to directors appointed under this new authority.24 The section adds a new requirement that before a new research grant is made by an IC, the IC Director will review and approve the award, taking into consideration the mission of the IC, the scientific priorities identified in the strategic plan, “programs or projects funded by other agencies on similar research topics and advice by staff and the advisory council or board of such national research institute or national center.” Section 2033 also requires the HHS Secretary to submit a report to Congress, not later than two years following enactment, “on efforts to prevent and eliminate duplicative biomedical research that is not necessary for scientific purposes.” Among other things, the report must “describe how the HHS Secretary operationally distinguishes necessary and appropriate scientific replication from unnecessary duplication, and provide examples of instances where the HHS Secretary has identified unnecessarily duplicative research and the steps taken to eliminate the unnecessary duplication.” Section 2034. Reducing Administrative Burden for Researchers The Federal Demonstration Partnership (FDP) is “a cooperative initiative among 10 federal agencies and 119 institutional recipients of federal funds, sponsored by the National Academies, with a purpose of reducing the administrative burdens associated with federal research grants and contracts.”25 In 2005 and 2012, FDP conducted surveys of principal investigators of federally funded projects to determine the impact of federal regulations and requirements on the research process. In both surveys, researchers reported spending 57% of their time engaged in research and 43% of their time in completing pre- and post-award requirements. “The most commonly experienced administrative responsibilities included those related to federal project finances, personnel, and effort reporting. These were also among the most time-consuming responsibilities. For researchers engaged in projects that required human or animal subjects, the related Institutional Review Board (IRB) and Institutional Animal Care and Use Committee (IACUC) 24 Ibid. 25 Sandra L. Schneider et al., Federal Demonstration Partnership (FDP) 2012 Faculty Workload Survey: Executive Summary, April 2014. Congressional Research Service R44720 · VERSION 5 · UPDATED 13 The 21st Century Cures Act (Division A of P.L. 114-255) requirements were by far the most time-consuming. Other areas viewed as particularly timeconsuming were those involving clinical trials, subcontracts, and cross-agency differences.”26 Provision Section 2034 includes a series of requirements that aim to address the administrative burden on researchers funded by NIH and other federal agencies. First, it directs the HHS Secretary, within two years of enactment, to lead a review by research funding agencies of all financial conflict-ofinterest regulations and policies and to make revisions to harmonize the policies and reduce the administrative burden on researchers, as appropriate. It also requires the HHS Secretary to update this policy and, in doing so, take into account certain specified considerations regarding financial interest disclosures. Second, it requires the NIH Director to implement measures that aim to reduce the administrative burdens experienced by primary NIH grant awardees related to monitoring grant sub-recipients. Third, the HHS Secretary, in consultation with the NIH Director, is required to evaluate financial expenditure reporting procedures and requirements for NIH funding recipients and take appropriate action to avoid duplication of effort and minimize burden to funding recipients. Fourth, within two years of enactment, the HHS Secretary, in consultation with the NIH Director, the Secretary of Agriculture, and the FDA Commissioner, must complete a review of regulations and policies for the care and use of laboratory animals and make appropriate revisions to reduce administrative burden on investigators. Fifth, the HHS Secretary is required to clarify the applicability of OMB Uniform Guidance requirements regarding documentation of personnel expenses for entities receiving HHS grants. Finally, within one year of enactment, the OMB Director is required to establish a Research Policy Board, consisting of up to 10 federal and 9 to 12 nonfederal members, as specified, to provide the NIH Director and other members of the federal government with information on the effects of regulations related to federal research requirements. The board makes recommendations on harmonizing regulations and policies to minimize administrative burden across federal research agencies. Within two years of enactment, and once thereafter, the board must submit a report to specified offices in OMB, the heads of relevant federal departments and agencies, and specified House and Senate committees. The report must provide recommendations on scientific research policy, including regulatory benefits and burdens. The board will sunset on September 30, 2021. The section also requires that GAO, within four years of enactment, conduct an evaluation of board activities regarding its purpose and responsibilities and submit a report to Congress. Section 2035. Exemption of the National Institutes of Health from the Paperwork Reduction Act Requirements. The Paperwork Reduction Act (PRA, 44 U.S.C. Chapter 35), enacted in 1980 and amended in 1995, established the Office of Information and Regulatory Affairs (OIRA) in the Office of Management and Budget (OMB). Congress required that agencies seek OIRA permission before collecting information from the public. The first of 11 stated purposes was to “minimize the paperwork burden for individuals ... and other persons resulting from the collection of 26 http://sites.nationalacademies.org/cs/groups/pgasite/documents/webpage/pga_087823.pdf; http://sites.nationalacademies.org/PGA/fdp/PGA_055749. Congressional Research Service R44720 · VERSION 5 · UPDATED 14 The 21st Century Cures Act (Division A of P.L. 114-255) information by and for the Federal Government.”27 The PRA requires that federal agencies receive clearance from OIRA before requesting most types of information from the public.28 PRA clearance is required when standardized information is collected from 10 or more respondents within a 12-month period.29 PRA does not apply to certain types of scientific research, including collections that are neither sponsored nor conducted by the agency and those that are subject to a clinical exception.30 Provision Section 2035 amends PHSA Section 301 by adding a subsection stating that the PRA does not apply to the collection of information during the conduct of NIH research. Section 2036. High-Risk, High-Reward Research Other transaction (OT) authority is a special vehicle used by certain federal agencies for obtaining or advancing research and development (R&D).31 An OT is not a contract, grant, or cooperative agreement, and there is no statutory or regulatory definition of “other transaction.” Only those agencies that have been provided OT authority may engage in other transactions. Generally, OT authority is created because the government needs to obtain leading-edge R&D from commercial sources, but some companies (and other entities) are unwilling or unable to comply with the government’s procurement regulations and certain procurement statutes that govern contracts. Provision Section 2036 adds a new PHSA Section 402(n) to allow the NIH Director to approve requests by IC Directors, or program officers within the Office of the Director, to engage in transactions other than a contract, grant, or agreement with respect to projects that carry out (1) the Precision Medicine Initiative, or (2) “research that represents important areas of emerging scientific opportunities, rising public health challenges, or knowledge gaps that deserve special emphasis and would benefit from conducting or supporting additional research that involves collaboration between 2 or more [ICs], or would otherwise benefit from strategic coordination and planning.”32 This provision also requires internal NIH reporting on the use of this authority and requires the HHS Secretary, through the NIH Director, to submit a report to Congress evaluating the activities under this new subsection by September 30, 2020. 27 44 U.S.C. §3501. 28 For further information about the PRA, see CRS Report RL30590, Paperwork Reduction Act Reauthorization and Government Information Management Issues (out of print; available to congressional clients from the author on request), and CRS Report RL32397, Federal Rulemaking: The Role of the Office of Information and Regulatory Affairs, coordinated by Maeve P. Carey. 29 See NIH, Office of Science Policy, Genetics, Health and Society, What is the Paperwork Reduction Act?, at http://osp.od.nih.gov/faq/what-paperwork-reduction-act; and HHS, Frequently Asked Questions About PRA / Information Collection, at http://www.hhs.gov/ocio/policy/collection/infocollectfaq.html. 30 Cass R. Sunstein, Facilitating Scientific Research by Streamlining the Paperwork Reduction Act Process, Executive Office of the President, Office of Management and Budget, December 9, 2010, https://www.whitehouse.gov/sites/ default/files/omb/memoranda/2011/m11-07.pdf. 31 For further information, see U.S. Government Accountability Office, DOD Research: Acquiring Research by Nontraditional Means, GAO/NSIAD-96-11, March 29, 1996, https://www.gpo.gov/fdsys/pkg/GAOREPORTSNSIAD-96-11/pdf/GAOREPORTS-NSIAD-96-11.pdf. 32 PHSA Section 402(b)(7)(A)(i). Congressional Research Service R44720 · VERSION 5 · UPDATED 15 The 21st Century Cures Act (Division A of P.L. 114-255) Section 2037. National Center for Advancing Translational Sciences. Prior to FDA approval, medical products are tested in a clinical trial using human volunteers to see how the products compare to standard treatments or to no treatment. FDA uses the data from clinical trials to determine whether to approve a manufacturer’s application for marketing a medical product. Clinical trials are conducted in three phases. Phase I trials try to determine dosing, document how a drug is metabolized and excreted, and identify acute side effects. Usually, a small number of healthy volunteers (between 20 and 80) are used in Phase I trials. Phase II trials include more participants (about 100-300) who have the disease or condition that the product potentially could treat. In Phase II trials, researchers seek to gather further safety data and preliminary evidence of the drug’s beneficial effects (efficacy), and they develop and refine research methods for future trials with this drug. Sometimes Phase II clinical trials are divided into Phase IIA (to assess dosing requirements) and Phase IIB (to study efficacy). If the Phase II trials indicate that the drug may be effective—and the risks are considered acceptable, given the observed efficacy and the severity of the disease—the drug moves to Phase III. In Phase III trials, the drug is studied in a larger number of participants with the disease (approximately 1,000-3,000). This phase further tests the product’s effectiveness, monitors side effects and, in some cases, compares the product’s effects to a standard treatment, if one is already available. As more and more participants are tested over longer periods of time, the less common side effects are more likely to be revealed.33 Under current law in PHSA Section 479, NIH’s National Center for Advancing Translational Sciences (NCATS) may develop and provide infrastructure and resources for all phases of clinical trials research; however, it may support clinical trial activities only through the end of Phase IIA, with specific exceptions. NCATS may support clinical trial activities through the end of Phase IIB for treatment of a rare disease or condition if (1) it gives public notice for a period of at least 120 days of NCATS’s intention to support the clinical trial activities in Phase IIB; (2) no public or private organization provides credible written intent to NCATS that the organization has timely plans to further the clinical trial activities or conduct clinical trials of a similar nature beyond Phase IIA; and (3) NCATS ensures that support of the clinical trial activities in Phase IIB will not increase the federal government’s liability beyond the award value of the center’s support. This section does not authorize the HHS Secretary to disclose trade secret information or other privileged or confidential information. Provision Section 2037 amends PHSA Section 479 to extend NCATS’s authority to support clinical trial activities through the end of Phase IIB (instead of Phase IIA) and extends the exception for treatment of a rare disease or condition through the end of Phase III (instead of Phase IIB). It adds material to the NCATS annual/biennial report regarding methods and tools developed since the previous report and whether such methods and tools are being used by the FDA to support medical product reviews. Under the Cures Act, the next NCATS report, following enactment, will include a complete list of all such methods and tools developed by research supported by NCATS. 33 FDA, Inside Clinical Trials: Testing Medical Products in People, What Happens in a Clinical Trial? http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143531.htm. Congressional Research Service R44720 · VERSION 5 · UPDATED 16 The 21st Century Cures Act (Division A of P.L. 114-255) Section 2038. Collaboration and Coordination to Enhance Research Racial and ethnic minorities traditionally have been underrepresented in clinical trials. For example, according to a 2011 report from an FDA-sponsored conference, “African Americans represent 12% of the U.S. population but only 5% of clinical trial participants and Hispanics make up 16% of the population but only 1% of clinical trial participants.”34 Biological differences (e.g., genetic differences) may affect how people process or respond to medical products. This variation could make a treatment less effective or perhaps more toxic for individuals with specific genotypes. Therefore, it is important to study in clinical trials the safety and effectiveness of medical products in a broadly representative sample of people who will likely use the products following FDA approval. PHSA Section 492B requires the NIH Director to include women and minorities in NIH-funded clinical research and to conduct or support outreach to recruit minorities and women into clinical research. Section 492B(d) requires the NIH Director, in consultation with the directors of the NIH’s Office of Research on Women’s Health and the Office of Research on Minority Health, to develop guidelines regarding the requirements under Section 492B.35 Provision Section 2038 amends PHSA Section 402(b), requiring the NIH Director, in assessing research priorities, to assemble accurate data on study populations in clinical research that specifies the inclusion of women, members of minority groups, relevant age categories (including pediatric subgroups), and other demographic variables. The data must be disaggregated by research area, condition, and disease categories and made publically available on the NIH website. The NIH Director is required to foster collaboration between the ICs that conduct research on human subjects, allow for an increase in the number of subjects studied, and utilize a diverse study population with special consideration of the determinants that contribute to health disparities. Section 2038 amends PHSA Section 492B to make the biennial report a triennial report and requires that the report contain specified data on the number of women and members of minority groups included in clinical research projects conducted during the reporting period. Section 2038 amends PHSA Section 486 to specify that the coordinating committee for the Office of Research on Women’s Health will include NIH IC Directors or their senior staff-level designees. Section 2038 adds a new PHSA Section 404N, Population Focused Research, which requires the NIH Director to encourage efforts to improve research related to the health of sexual and gender minority populations through the increased participation of such groups in clinical research. The HHS Secretary, in collaboration with the NIH Director and taking into account the recommendations of the National Academy of Medicine, is required to continue to support research for the development of appropriate measures related to reporting health information of sexual and gender minority populations. Within two years of enactment, the HHS Secretary is required to disseminate and make public such measures. Section 2038 also amends PHSA Section 464z-3, adding that the National Institute on Minority Health and Health Disparities Director may foster partnerships between the ICs and may 34 FDA, For Consumers, Clinical Trials Shed Light on Minority Health, at http://www.fda.gov/ForConsumers/ ConsumerUpdates/ucm349063.htm. 35 See “NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research,” at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. Congressional Research Service R44720 · VERSION 5 · UPDATED 17 The 21st Century Cures Act (Division A of P.L. 114-255) encourage the funding of collaborative research to achieve the goals of NIH related to minority health and health disparities. Section 2038 requires the NIH Director, within two years of enactment and taking into consideration the findings of the working group established under Section 2039, to develop policies for basic research to assess relevant biological variables, including sex, and how differences between male and female cells, tissues, or animals may be studied and permits the NIH Director to amend these policies as appropriate. It also requires the NIH Director to (1) consult with the Office of Research on Women’s Health, the Office of Laboratory Animal Welfare, and appropriate members of the scientific and academic communities; and (2) conduct outreach in developing (and updating) policies on the influence of sex as a variable in basic research, among other requirements. With respect to clinical research involving women and minorities, the NIH Director must, within one year of enactment, update the guidelines established under PHSA Section 492B(d) to reflect the science regarding sex differences and improve adherence to the requirements of Section 492B of the PHSA, among other things. Section 2038 requires the NIH Director, within six months of enactment, to convene a workshop of experts on pediatrics and older populations to provide input on appropriate age groups to be included in research studies. Within six months of the workshop, the NIH Director must determine if it is necessary to update NIH policies “on the inclusion of relevant age groups in clinical studies.” The Director is required to make available to the public the findings and conclusions of the workshop and the updates to policies. The Director must ensure that agerelated data reported in the triennial report are made publicly available on the NIH website. Section 2039. Enhancing the Rigor and Reproducibility of Scientific Research Research supported by NIH is evaluated by a peer review system.36 Scientists competing for NIH funding submit detailed applications describing their research plan. NIH considers the applications under a two-tiered system of peer review. First, the applications are reviewed for scientific and technical merit by committees composed of nongovernment scientists who are experts in the relevant fields of research. Each application is thoroughly discussed and given a score, which becomes the main determinant in whether an applicant will receive IC funding. A second level of review occurs in the ICs when the applications are considered for program relevance by the IC’s National Advisory Councils or Boards, composed of scientific and lay representatives. The peer review system does not necessarily evaluate the applications for reproducibility. Provision Section 2039 requires the HHS Secretary, acting through the NIH Director, to convene a working group to make recommendations for a formal policy to enhance the rigor and reproducibility of NIH-funded scientific research. The working group must consider various specified factors, including, for example, preclinical and clinical experiment design and methods of statistical analysis. It also requires the NIH Director, not later than 18 months after enactment, to consider the recommendations and develop or update policies as appropriate. Finally, the NIH Director must issue a report to the HHS Secretary and Congress, within two years of enactment, regarding the recommendations and any subsequent policy changes. This section does not authorize the HHS Secretary to disclose trade secret information or other privileged or confidential information. 36 Peer review requirements described in PHSA Section 492. Congressional Research Service R44720 · VERSION 5 · UPDATED 18 The 21st Century Cures Act (Division A of P.L. 114-255) Section 2040. Improving Medical Rehabilitation Research at the National Institutes of Health PHSA Section 452 established in 1990 the National Center for Medical Rehabilitation Research (the Center) within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at NIH to conduct and support research, and disseminate information, on the rehabilitation of individuals with physical disabilities. It also required the NIH Director to create a Medical Rehabilitation Coordinating Committee and a National Advisory Board on Medical Rehabilitation Research. The section also requires NICHD Director—in collaboration with the Director of the Center, the Coordinating Committee, and the Advisory Board—as created by this section—to develop, and periodically revise and update, a comprehensive plan for medical rehabilitation research. Provision Section 2040 amends PHSA Section 452 instructing the Director of the Center—in collaboration with the Director of the Institute, the coordinating committee, and the advisory board—to develop and, not less than every five years, revise and update a comprehensive plan for medical rehabilitation research. The research plan must include goals and objectives for such research. Prior to revising and updating the research plan, the Director of the Center must report to the coordinating committee and the advisory board on the progress made toward achieving the research goals and objectives, and provide recommendations for revising and updating the plan. Within 30 days of revising and updating the plan, the Director of the Center is required to transmit the plan to the President, and to specified congressional committees. In addition, Section 2040 requires the HHS Secretary, along with the other federal agencies, to review their medical rehabilitation research programs and take action to avoid duplication among those programs through actions such as entering into interagency agreements. Finally, Section 2040 defines medical rehabilitation research as “the science of mechanisms and interventions that prevent, improve, restore, or replace lost, underdeveloped, or deteriorating function.” Section 2041.Task Force on Research Specific to Pregnant Women and Lactating Women Provision Within 90 days of enactment, Section 2041 requires the HHS Secretary to establish a Task Force on Research Specific to Pregnant and Lactating Women. The section specifies the duties, membership, meeting schedule, and reporting requirements of the task force, which would be terminated two years after its establishment, with an option for a two-year extension. It requires the HHS Secretary, not later than two years after enactment, to update regulations and guidance, as appropriate, regarding the inclusion of pregnant women and lactating women in research. This section does not authorize the HHS Secretary to disclose trade secret information or other privileged or confidential information. Section 2042. Streamlining National Institutes of Health Reporting Requirements PHSA Title IV establishes numerous reporting requirements for the NIH Director related to the activities of the agency. Specifically, PHSA Section 403(a) requires the NIH Director to submit to Congressional Research Service R44720 · VERSION 5 · UPDATED 19 The 21st Century Cures Act (Division A of P.L. 114-255) Congress biennially a report on NIH activities. Among other things, the report must include an assessment of the state of biomedical and behavioral research, and details of all the research activities conducted or supported by the ICs of NIH. Provision Section 2042 modifies or eliminates a number of different NIH reporting requirements. Within two years of enactment, the heads of each IC must submit to the NIH Director a report on the amount of funding made available for conducting or supporting research that involves collaboration between a given IC and at least one other IC. This information will be included in the triennial report required by Section 403(a), as amended by Section 2032. It also (1) eliminates an annual reporting requirement regarding the number of experts and consultants whose services are used by NIH; (2) makes a minor modification to the doctoral degree reporting requirement; (3) makes a technical correction to a vaccine reporting requirement; (4) changes the NCATS annual report to a biennial report; (5) eliminates the report on Centers of Excellence; (6) eliminates the periodic reports on rapid HIV testing; and (7) eliminates the National Institute on Nursing Research biennial report. Section 2043. Reimbursement for Research Substances and Living Organisms PHSA Section 301(a) establishes the general research authorities of the Public Health Service through the HHS Secretary. Specifically, it requires the HHS Secretary to “conduct in the Service, and encourage, cooperate with, and render assistance to other appropriate public authorities, scientific institutions, and scientists in the conduct of, and promote the coordination of, research, investigations, experiments, demonstrations, and studies relating to the causes, diagnosis, treatment, control, and prevention of physical and mental diseases and impairments of man.” As part of these authorities, the HHS Secretary is authorized to make available substances and living organisms for biomedical and behavioral research. Provision Section 2043 amends PHSA Section 301(a) allowing the HHS Secretary, where research substances and living organisms are made available to researchers through contractors, to direct the contractors to collect payments for the costs incurred while making these substances and organisms available. These amounts would be credited to the appropriations accounts that incurred such costs and would be available until expended. Section 2044. Sense of the Congress on Increased Inclusion of Underrepresented Populations in Clinical Trials PHSA Section 492B requires that the NIH Director ensure that clinical research conducted or supported by NIH include members of minority groups as subjects. Each IC advisory council must prepare biennial reports describing the manner in which the IC has complied with this requirement. The report is submitted to the IC Director and is included in the biennial report under PHSA Section 403. Provision Section 2044 states that it is the sense of Congress that the National Institute on Minority Health and Health Disparities should include within its strategic plan ways to increase representation of underrepresented populations in clinical trials. Congressional Research Service R44720 · VERSION 5 · UPDATED 20 The 21st Century Cures Act (Division A of P.L. 114-255) Subtitle E- Advancement of the National Institutes of Health Research and Data Access Sections 2051. Technical Updates to Clinical Trials Database Sponsors of clinical trials for drugs, biologics, and devices regulated by the FDA are required to submit registration and summary results information to ClinicalTrials.gov, the clinical trial registry and results data bank operated by NIH’s National Library of Medicine (NLM) pursuant to PHSA Section 402 subsections(i)-(j). Subparagraph 402(j)(2)(B) requires the NIH Director to ensure that the public may, in addition to keyword searching, search the entries in the data bank by various specified criteria, including the disease or condition being studied, the name of the drug or device under investigation, and the location of the clinical trial. The NIH Director is instructed to add search categories as deemed necessary and to ensure that the data bank is easy to use, and that its entries are easily compared. Under PHSA Section 402(j), those responsible for specified clinical trials of FDA-regulated products have been required to submit registration information to ClinicalTrials.gov since December 2007, submit summary results information for clinical trials of approved products since September 2008, and submit adverse events information since September 2009. The section also required the HHS Secretary, by rulemaking, to expand the requirements for submission of summary results information, and authorized the HHS Secretary to use rulemaking to make other changes in the requirements for submission of registration and results information. In November 2014, HHS published a proposed rule to clarify and expand requirements for the submission of clinical trial registration and results information to ClinicalTrials.gov. The comment period was extended until March 23, 2015; about 900 comments were received. The final rule was published on September 21, 2016, and is expected take effect on January 18, 2017.37 Provision Section 2051 amends PHSA Section 402(j)(2)(D), regarding posting of data, by adding new language requiring the NIH Director to inform responsible parties of the option to request that information for a medical device clinical trial be publically posted prior to the date of clearance or approval. Section 2051 adds language that defines “combination product” for purposes of this database. Section 2052. Compliance Activities Reports PHSA Section 402(i)-(j) delineates the requirements for the clinical trials database but currently does not require the submission of a report to Congress. Provision Section 2052 requires the HHS Secretary, acting through the NIH Director and in collaboration with the FDA Commissioner, to submit to Congress, not later than two years after enactment, a report that “describes education and outreach, guidance, enforcement, and other activities undertaken to encourage compliance with Section 402(j) of the PHSA” (i.e., with submission to the clinical trials database). 37 NIH provides information on selected events, policies, and laws related to the development and expansion of Clinical Trials.gov at https://clinicaltrials.gov/ct2/about-site/history. Congressional Research Service R44720 · VERSION 5 · UPDATED 21 The 21st Century Cures Act (Division A of P.L. 114-255) This section also requires the HHS Secretary, acting through the NIH Director and in collaboration with the FDA Commissioner, to submit to Congress a report on registered clinical trials, as specified, including activities undertaken by the HHS Secretary to educate responsible persons about compliance with the requirements in Section 402(j). The HHS Secretary must submit an initial report not later than two years after the compliance date of the final rule implementing Section 402(j) of the PHSA. Two follow-up reports are required, which include information on actions taken to enforce compliance with the ClinicalTrials.gov reporting requirements. Section 2053. Updates to Policies to Improve Data PHSA Section 492B requires the NIH Director to include women and minorities in NIH-funded clinical research and to conduct or support outreach to recruit minorities and women into clinical research. Section 492B(c) requires the NIH Director to “ensure that the trial is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect women or members of minority groups, as the case may be, differently than other subjects in the trial.” Provision Section 2053 amends PHSA Section 492B(c), adding that the NIH Director must consider whether grant award recipients conducting research related to the inclusion of women and minority populations in clinical research have complied with the reporting requirements of ClinicalTrials.gov. The NIH Director must also take such compliance into consideration when awarding any future grants to such an entity. The Director of NIH must encourage the reporting of results to ClinicalTrial.gov “through any additional means determined appropriate by the Director.” Section 2054. Consultation PHSA Section 402(i)-(j) requires that the HHS Secretary consult with FDA, NIH, and the Centers for Disease Control and Prevention (CDC) prior to establishing the “data bank of information on clinical trials for drugs for serious or life-threatening diseases and conditions.” In addition, it requires that the HHS Secretary consult with experts in risk communication to ensure that posted information regarding the database is not misleading to patients or the lay public. The HHS Secretary must also consult with other federal agencies to ensure that clinical trial information is submitted to the database. Provision Section 2054 requires, within 90 days of enactment, the HHS Secretary to consult with relevant federal agencies, including FDA, the Office of the National Coordinator for Health Information Technology, and NIH, as well as other stakeholders (including patients, researchers, physicians, industry representatives, and developers of health information technology), to receive recommendations to improve ClinicalTrials.gov, including improvements in usability, functionality, and search capability. Congressional Research Service R44720 · VERSION 5 · UPDATED 22 The 21st Century Cures Act (Division A of P.L. 114-255) Subtitle F- Facilitating Collaborative Research Section 2061. National Neurological Conditions Surveillance System The PHSA does not explicitly authorize or require surveillance of neurological diseases in general, although the HHS Secretary may conduct such activities under general authorities in PHSA Title III. Surveillance is explicitly authorized for certain specified neurological disorders (e.g., amyotrophic lateral sclerosis and autism spectrum disorder).38 Provision Section 2061 adds a new PHSA Section 399S-1, which requires the HHS Secretary, through the CDC Director and in consultation with specified parties, to establish a National Neurological Conditions Surveillance System by enhancing and expanding relevant surveillance infrastructure and activities. The system may include a registry. In establishing the system, the HHS Secretary is required to collect and manage information in order to facilitate research and, as is practicable, to include information on incidence and prevalence, demographics, risk factors, and diagnostic and progression markers.39 Additional data elements may include the natural history, prevention, detection, management, and treatment approaches for the diseases, and the development of outcome measures. The HHS Secretary initially may address a limited number of neurological diseases. The section also authorizes the HHS Secretary to award grants, contracts, or cooperative agreements with public or private nonprofit entities to implement this provision. The HHS Secretary must make information and analysis obtained from the system available to other federal health agencies and state and local agencies, and, as appropriate and subject to federal privacy laws, to researchers and the public. Within one year of the establishment of a system under this section and biennially thereafter, the HHS Secretary must provide to Congress and the public an interim report on such system. A report on implementation of this section is due to Congress four years after enactment. The section authorizes to be appropriated $5 million for each of fiscal years 2018 through 2022 to carry out activities under this section. Section 2062. Tick-Borne Diseases The HHS Secretary is given broad authority to conduct research related to disease under Title III of the PHSA. Specifically, the HHS Secretary is required to conduct research, investigations, experiments, demonstrations, and studies relating to the causes, diagnosis, treatment, control, and prevention of disease.40 The act does not explicitly address tick-borne diseases, but HHS agencies do carry out research and public health activities on tick-borne diseases under the Secretary’s general authority. 38 PHSA Section 399S; 42 U.S.C. §280g-7 and PHSA Section 399AA; 42 U.S.C. §280i. 39 A disease marker is a substance or other measurable parameter that can be used to identify the presence or severity of a health condition. A progression marker is one that could indicate worsening or improvement in the condition over time. 40 PHSA Section 301 et seq.; 42 U.S.C. §241 et seq. Congressional Research Service R44720 · VERSION 5 · UPDATED 23 The 21st Century Cures Act (Division A of P.L. 114-255) Provision Section 2062 requires the HHS Secretary to continue to conduct or support epidemiological, basic, translational, and clinical research related to vector-borne diseases, including tick-borne diseases. It also requires the HHS Secretary to ensure that the triennial report of the NIH Director to Congress41 includes information on NIH activities with respect to tick-borne diseases. The section also requires the HHS Secretary to establish a working group to review the status of research on tick-borne diseases and relevant federal activities, and to report on such activities and any recommended changes every two years. The section provides requirements related to the working group’s membership, responsibilities, meeting frequency, and reporting. The working group is subject to the Federal Advisory Committee Act (FACA), and will terminate six years after enactment. Section 2063. Accessing, Sharing, and Using Health Data for Research Purposes The Health Information Portability and Accountability Act (HIPAA) privacy rule describes the circumstances under which HIPAA-covered entities such as health plans and health care providers are permitted to use or disclose individually identifiable health information (i.e., protected health information, or PHI) without an individual’s written authorization.42 In general, covered entities may use or disclose PHI for the purposes of treatment, payment, and other routine health care operations with few restrictions.43 The disclosure of PHI to researchers generally requires an individual’s authorization unless an Institutional Review Board (or equivalent Privacy Board) waives the authorization.44 A covered entity may, however, allow researchers access to PHI to prepare a research protocol, provided the PHI is not removed from the covered entity. The privacy rule traditionally has required authorizations to be study-specific; authorizations for future research were prohibited. In a January 2013 final rule, HHS permitted authorizations for future research if a sufficiently clear description of the future research is provided.45 Provision Section 2063 instructs the HHS Secretary, within one year of enactment, to issue guidance clarifying some of the privacy rule’s restrictions on researchers’ access to PHI. First, the HHS Secretary is required to clarify that the rule’s provision prohibiting researchers from removing PHI during preparation of a research protocol permits remote access to PHI by researchers, provided appropriate security and privacy safeguards are in place and the PHI is not copied or retained by the researchers. Second, the Secretary is required to clarify the circumstances under which a HIPAA authorization to use or disclose PHI for future research contains sufficient information; for example, the authorization (1) sufficiently describes the purposes such that it would be reasonable for an individual to expect that the PHI could be used or disclosed for future 41 This report is required under PHSA Section 403, 42 U.S.C. §283, as amended by this act. 42 The HIPAA privacy rule is codified at 45 C.F.R. Part 164, Subpart E. 43 45 C.F.R. §164.506. 44 45 C.F.R. §164.512(i)(1)(i). 45 Department of Health and Human Services, Office of the Secretary, “Modifications to the HIPAA Privacy, Security, Enforcement, and Breach Notification Rules Under the Health Information Technology for Economic and Clinical Health Act and the Genetic Information Nondiscrimination Act; Other Modifications to the HIPAA Rules; Final Rule,” 78 Federal Register 5566, 5611, January 25, 2013. Congressional Research Service R44720 · VERSION 5 · UPDATED 24 The 21st Century Cures Act (Division A of P.L. 114-255) research; (2) states that the authorization will either expire at a specified time or will remain valid unless revoked by the individual; and (3) provides revocation instructions to the individual. Finally, Section 2063 requires the HHS Secretary, within one year of enactment, to convene a working group to study the uses and disclosures of PHI for research purposes. The working group must include various specified federal and nonfederal members, and must report to the HHS Secretary within one year of its establishment with recommendations on whether the uses and disclosures for research purposes should be modified, as specified. The HHS Secretary must submit the report to Congress and make it publicly available, at which time the working group shall terminate. Subtitle G- Promoting Pediatric Research Section 2071. National Pediatric Research Network In 2013, PHSA Section 409D(d) established the NIH Pediatric Research Network “in order to more effectively support pediatric research and optimize the use of Federal resources.”46 Provision Section 2071 amends PHSA Section 409(D)(d) to (1) eliminate language telling the NIH Director to consult with the Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development but (2) retains language telling the NIH Director to collaborate with the ICs that carry out pediatric research, (3) amends language to require the NIH Director (it had previously been permitted) to award funding to support the pediatric research consortia, and (4) require that support for the pediatric research consortia not exceed five years. Section 2072. Global Pediatric Clinical Study Network Provision Section 2072 expresses the sense of Congress that (1) NIH should encourage a global pediatric clinical study network through funding to support new and early stage investigators; (2) the HHS Secretary should engage with clinical investigators and international authorities, including those in the European Union, during the formation of the network to encourage their participation; and (3) the HHS Secretary should continue to encourage and facilitate the network after it is established. 46 Section 409D(d) was added to the PHS Act by P.L. 113-55, the Prematurity Research Expansion and Education for Mothers who deliver Infants Early Reauthorization Act, or the PREEMIE Reauthorization Act, which was signed into law on November 27, 2013. Congressional Research Service R44720 · VERSION 5 · UPDATED 25 The 21st Century Cures Act (Division A of P.L. 114-255) Title III-Development47 Subtitle A-Patient Focused Drug Development The Food and Drug Administration Safety and Innovation Act (FDASIA; P.L. 112-144) expanded FDA’s authorities and strengthened the agency’s ability to safeguard and advance public health.48 FDASIA added a new FFDCA Section 569C “Patient Participation in Medical Product Discussion,” facilitating increased involvement of patients earlier in the regulatory process for medical product review. Section 569C directs the HHS Secretary to develop and implement strategies to solicit the views of patients during the medical product development process and consider the perspectives of patients during regulatory discussions by (1) fostering participation of a patient representative who may serve as a special government employee in appropriate agency meetings with medical product sponsors and investigators; and (2) exploring means to provide for identification of patient representatives who do not have any, or have minimal, financial interests in the medical products industry. Sections 3001-3004. Patient Experience Data, Patient-Focused Drug Development Guidance, Streamlining Patient Input, Report on Patient Experience Drug Development Provisions Section 3001 amends FFDCA Section 569C by adding a new subsection (b), “Statement of Patient Experience,” requiring the HHS Secretary, upon approval of a new drug application (NDA), to make public any patient experience data and related information submitted and reviewed as part of the application. “Data and information” refers to patient experience data, information on patient-focused drug development tools, and other relevant information, as determined by the HHS Secretary. “Patient experience data” is defined as (1) data that are collected by any persons (including patients, family members and caregivers of patients, patient advocacy organizations, disease research foundations, researchers, and drug manufacturers); and (2) are intended to provide information about patients’ experiences with a disease or condition, including—(A) the impact of such disease or condition, or a related therapy, on patients’ lives; and (B) patient preferences with respect to treatment of such disease or condition. Section 3002 requires the HHS Secretary, acting through the FDA Commissioner, to develop a plan to issue draft and final guidance, over a period of five years, regarding the collection of patient experience data and the use of such data in drug development. This section specifies the contents of the guidance documents (e.g., methods that could be used to collect and submit patient experience data, and methodologies, standards, and technologies that could be used to collect and analyze clinical data for regulatory decisionmaking). Section 3003 exempts FDA from the Paperwork Reduction Act clearance process when requesting patient experience data under sections 3001 and 3002 of the 21st Century Cures Act. 47 Subtitle J, “Technical Corrections,” is not summarized in this report. 48 FDA, The Food and Drug Administration Safety and Innovation Act (FDASIA) Section 1137: Patient Participation in Medical Product Discussions Report on Stakeholder Views, February 19, 2016; see http://www.fda.gov/downloads/ ForPatients/About/UCM486859.pdf. Congressional Research Service R44720 · VERSION 5 · UPDATED 26 The 21st Century Cures Act (Division A of P.L. 114-255) Section 3004 requires the HHS Secretary, acting through the FDA Commissioner, to publish on the FDA website, no later than June 1 of 2021, 2026, and 2031, a report “assessing the use of patient experience data in regulatory decision-making, in particular with respect to the review of patient experience data and information on patient-focused drug development tools....” Subtitle B-Advancing New Drug Therapies Section 3011. Qualification of Drug Development Tools Lengthy clinical trials have been found to contribute to the high cost of drug development. In clinical settings where the disease course is long and an extended period of time would be required to measure the intended clinical benefit of a drug, surrogate endpoints—based on the measurement of biomarkers—may be used to determine the clinical benefit of a product, rather than clinical endpoints. Surrogate endpoints “enable smaller, faster, and thus cheaper clinical trials. In addition, pharmaceutical companies argue that using surrogates means that fewer patients are exposed during testing, and beneficial new medications reach the market faster. The main disadvantage of these endpoints is that favorable effects on surrogates do not automatically translate into benefits to health.”49 A number of drugs have been approved on the basis of surrogate endpoint data and, after adoption into medical practice, have been shown to be harmful through clinical trials or other subsequent analysis.50 The FDA uses surrogate endpoints in about half of new drug approvals.51 The Institute of Medicine defines a clinical endpoint as “a characteristic or variable that reflects how a patient [or consumer] feels, functions, or survives. Death is one example of a clinical endpoint.”52 IOM defines “surrogate endpoint” in the following way: a biomarker that is intended to substitute for a clinical endpoint. A surrogate endpoint is expected to predict clinical benefit (or harm or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence. For example, blood pressure has served as a surrogate endpoint for morbidity and mortality due to cardiovascular disease in trials of several classes of antihypertensive drugs. A surrogate endpoint represents a special use of a biomarker, in which the biomarker substitutes for a clinical endpoint.53 FDASIA (P.L. 112-144) amended FFDCA Section 506 (on fast track products) by adding the following: “The HHS Secretary shall ... establish a program to encourage the development of surrogate and clinical endpoints, including biomarkers, and other scientific methods and tools that can assist the HHS Secretary in determining whether the evidence submitted in an application is reasonably likely to predict clinical benefit for serious or life-threatening conditions for which significant unmet medical needs exist.”54 49 Staffan Svensson, David B. Menkes, and Joel Lexchin, "Surrogate Outcomes in Clinical Trials—A Cautionary Tale," JAMA Internal Medicine, vol. 173, no. 8 (April 22, 2013), pp. 611-612. 50 Staffan Svensson, David B. Menkes, and Joel Lexchin, “Surrogate Outcomes in Clinical Trials—A Cautionary Tale,” JAMA Internal Medicine, vol. 173, no. 8 (April 22, 2013), Supplementary Online eTable. 51 Jerry Avorn and Aaron S. Kesselheim, “The 21st Century Cures Act—Will It Take Us Back in Time?,” The New England Journal of Medicine, June 3, 2015, http://www.nejm.org/doi/full/10.1056/NEJMp1506964. 52 IOM, Perspectives on Biomarker and Surrogate Endpoint Evaluation: Discussion Forum Summary, January 18, 2011, p.6. 53 Ibid. 54 FFDCA §506(d)(2). Congressional Research Service R44720 · VERSION 5 · UPDATED 27 The 21st Century Cures Act (Division A of P.L. 114-255) Provision Section 3011 adds a new FFDCA Section 507, “Qualification of Drug Development Tools,” which requires the HHS Secretary to establish a process for the qualification of drug development tools. A drug development tool is defined to include (1) a biomarker; (2) a clinical outcome assessment; and (3) any other method, material, or measure that the HHS Secretary determines aids drug development and regulatory review. Under new FFDCA Section 507, the HHS Secretary is allowed to accept a qualification submission based on factors that include its scientific merit, and the HHS Secretary is allowed to prioritize review of a qualification submission based on factors including, for example, the severity, rarity, or prevalence of the disease being targeted or the availability or lack of an alternative treatment. The HHS Secretary is allowed, through grants or other specified mechanisms, to consult with biomedical research consortia and may consider their recommendations in review of the qualification submission. “Biomedical research consortia” is defined as collaborative groups that may take the form of public-private partnerships and may include, among others, government agencies, institutions of higher education, patient advocacy groups, industry representatives, clinical and scientific experts, and other relevant individuals. The HHS Secretary is required to carry out a full review of the qualification package and to determine if the drug development tool at issue is qualified for its proposed context of use. A qualified drug development tool is allowed to be used to obtain approval or licensure of a drug or biologic or to support a product’s investigational use. The HHS Secretary is allowed to rescind or modify the granted qualification if he or she determines the drug development tool is not appropriate for the proposed context; if the HHS Secretary does this, the requestor would be granted a meeting, upon request, with the HHS Secretary to discuss the basis of the decision. New FFDCA Section 507 requires the HHS Secretary to make public on the FDA website, and update at least biannually, information about the qualification submissions, the HHS Secretary’s determinations in response to the submissions, and any subsequent modifications to the HHS Secretary’s determinations, among others. It also specifies that nothing in this section is to be construed to allow the HHS Secretary to release any information contained in an application for approval or licensure of a drug or biologic that is confidential commercial or trade secret information; in addition, nothing in the section is allowed to be construed as altering the standards of evidence for approval or licensure of a drug or biologic or to limit the Secretary’s authority to approve or license such products. The section also requires the HHS Secretary, not later than three years after enactment, to publish draft guidance to implement new FFDCA Section 507, in consultation with the biomedical research consortia and other interested parties through a collaborative public process. The guidance is required to, for example, provide “a conceptual framework describing appropriate standards and scientific approaches to support the development of biomarkers.” The HHS Secretary is required to issue final guidance not later than six months after the comment period for the draft guidance closes. To inform the guidance, the HHS Secretary is required, in consultation with the biomedical research consortia, to develop a taxonomy for the classification of biomarkers for use in drug development. The HHS Secretary is required to make this publicly available not later than two years after enactment and to finalize the taxonomy not later than one year after the public comment period closes. The section requires the HHS Secretary, not later than two years after enactment, to convene a public meeting regarding the qualification process under new FFDCA Section 507. The HHS Secretary is also required to publish a report on FDA’s website, not later than five years after enactment, to include specified information. Congressional Research Service R44720 · VERSION 5 · UPDATED 28 The 21st Century Cures Act (Division A of P.L. 114-255) Section 3012. Targeted Drugs for Rare Diseases Precision medicine is a relatively new term for what has traditionally been called personalized medicine (or targeted medicine), the idea of providing health care to individuals based on specific patient characteristics. This approach relies on companion diagnostics to target drugs and biological products to specific subsets of patients. Rare diseases often have genetic origins, and advances in medicine have resulted in the development of new treatments that work by targeting the genetic mutations that cause these diseases. It is inherently difficult to develop drugs for rare diseases because of the small patient population available to conduct clinical trials, so targeted therapies are generally first developed for patients with the most frequent disease-causing mutations. However, to provide therapies for the full spectrum of certain genetic rare diseases, additional targeted therapies would need to be developed. Targeted therapies, because they may be treating small subsets of patients, sometimes qualify as “orphan drugs.” Such drugs are called orphan drugs because firms may lack the financial incentives to sponsor products to treat small patient populations. Orphan drugs receive their designation pursuant to FFDCA Section 526(a),55 a designation that was created by the Orphan Drug Act (P.L. 97-414) to encourage firms to develop pharmaceuticals to treat rare diseases and conditions by providing an extended period of market exclusivity. FFDCA Section 526(a) defines “rare disease or condition” as any [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/crs%3AR44720. Public record. Not legal advice.