National Academies Press: OpenBook

Enhancing NIH Research on Autoimmune Disease (2022)

Chapter:5 National Institutes of Health Autoimmune Disease Research Efforts

« Previous: 4 Crosscutting Issues in Autoimmune Diseases
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page289
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page290
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page291
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page292
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page293
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page294
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page295
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page296
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page297
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page298
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page299
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page300
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page301
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page302
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page303
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page304
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page305
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page306
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page307
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page308
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page309
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page310
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page311
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page312
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page313
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page314
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page315
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page316
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page317
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page318
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page319
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page320
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page321
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page322
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page323
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page324
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page325
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page326
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page327
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page328
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page329
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page330
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page331
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page332
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page333
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page334
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page335
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page336
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page337
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page338
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page339
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page340
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page341
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page342
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page343
Suggested Citation:"5 National Institutes of Health Autoimmune Disease Research Efforts." National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. doi: 10.17226/26554.
×
Page344

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

5 National Institutes of Health Autoimmune Disease Research Efforts NIH OVERVIEW AND ORGANIZATIONAL STRUCTURE Analyzing autoimmune disease research efforts at the National Institutes of Health (NIH) begins with an understanding of the funding, administrative structure, and authorities of the NIH and its constituent parts. For more than 130 years, NIH has been the federal agency primarily responsible for sponsoring and conducting basic, clinical, and transla- tional research (CRS, 2021); research training; and health information and dissemination in the United States. The agency is one of the 11 operating divisions in the U.S. Department of Health and Human Services (HHS).1 The stated mission of the NIH is to “seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and dis- ability” (NIH, 2017a). From its origin as the single-room Laboratory of Hygiene in 1887, the agency now executes its missions and goals through the Office of the Director (OD) and 27 Institutes and Centers (ICs) that focus on different areas of biomedical research (CRS, 2019). Appendix E includes the full list of the ICs and their missions. 1 The other 11 operating divisions are: Administration for Children and Families, Adminis- tration for Community Living, Agency for Healthcare Research and Quality, Agency for Tox- ic Substances and Disease Registry, Center for Faith-Based and Neighborhood Partnerships, Centers for Disease Control and Prevention, Centers for Medicare & Medicaid Services, Food and Drug Administration, Health Resources and Services Administration, Indian Health Service, and Substance Abuse and Mental Health Services Administration (see HHS, 2022). 289 PREPUBLICATION COPY—Uncorrected Proofs

290 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE The OD sets policy and coordinates the programs and activities of all NIH components. Legislation in 2006 and 2016 resulted in a number of changes at NIH (CRS, 2019). The NIH Reform Act of 2006,2 which implemented many recommendations from a National Academies of Sci- ences, Engineering and Medicine report that reviewed the structure and organization of the NIH, strengthened the OD to perform strategic plan- ning, created a standardized reporting system, and provided funding (Common Fund) for NIH-wide initiatives (CRS, 2019; NRC, 2003). The Act also required an integrated biennial report of NIH research activities. In response to the Act, the OD established the Division of Program Coor- dination, Planning, and Strategic Initiatives (DPCPSI) in 2006 (DPCPSI, 2021). DPCPSI oversees a number of program Offices that coordinate research activities on specific topics that previously reported to the Direc- tor of NIH, (DPCPSI, 2021). DPCPSI identifies and assists NIH in respond- ing to emerging scientific opportunities, develops resources for the sup- port of portfolio analyses and priority setting, and supports strategic planning, progress monitoring, evaluation, and reporting (CRS, 2019; DPCPSI, 2021). More recently, the 21st Century Cures Act3 directed the NIH Direc- tor to develop an NIH-wide strategic plan to expedite IC collaboration, provide guidance on investments made by NIH, and “leverage scientific opportunity, and advance biomedicine.” The first NIH-wide strategic plan covered fiscal year (FY) 2016 to 2020, and the most recent plan covers FY 2021 to 2025 (NIH, 2021d).4 The Act also changed guidance on reporting on NIH research activities from the earlier mandated biennial report to a triennial report, the most recent of which covered FY 2016 to 2018.5 Congress annually appropriates funds for NIH overall and the ICs specifically, and sometimes Congress qualifies funds with specific require- ments or instructions (NIH, 2021e). For example, Congress has required NIH to establish research programs, provided funding for research on spe- cific topics, and mandated that NIH create research centers or institutes. Today, NIH is the primary source of public funding for biomedical research in the United States with an annual discretionary budget author- ity of $40.3 billion6 for FY 2020 (NIH, 2020a; Viergever and Hendriks, 2016). Among federal agencies, NIH had the highest amount of discre- tionary funds in FY 2020 (Figure 5-1). Table 5-1 provides the trend in NIH appropriations from FY 2008 to 2020. 2 National Institutes of Health Reform Act of 2006, Public Law 109-482, 109th Cong. (January 15, 2007). 3 21st Century Cures Act, Public Law 114-225, 109th Cong. (December 13, 2016). 4 Available at: https://www.nih.gov/about-nih/nih-wide-strategic-plan, accessed No- vember 29, 2021. 5 Available at: https://dpcpsi.nih.gov/oepr/nih-triennial-report, accessed November 29, 2021. 6 This includes $80 million for Superfund Research activities (NIH, 2020a). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 291 FIGURE 5-1  Enacted HHS appropriations by agency (FY 2020). NOTES: “Amounts in this figure are generally drawn from or calculated based on data contained in the explanatory statement accompanying the FY 2020 LHHS omnibus (P.L. 116-94), available in the Congressional Record, vol. 165, no. 204, December 17, 2019, pp. H11061-H11161. Enacted totals for FY 2020 do not in- clude emergency-designated appropriations provided by P.L. 116-113, P.L. 116-123, P.L. 116-127, P.L. 116-136, or P.L. 116-139. For consistency with source materials, amounts in this figure generally do not reflect mandatory spending sequestration, where applicable, nor do they generally reflect transfers or reprogramming of funds pursuant to executive authorities.”1 ACF, Administration for Children and Families; ACL, Administration for Commu- nity Living; AHRQ, Agency for Healthcare Research and Quality; CDC, Centers for Disease Control and Prevention; CMS, Centers for Medicare and Medicaid Ser- vices; HRSA, Health Resources and Services Administration; SAMHSA, Substance Abuse and Mental Health Services Administration; OS, Office of the Secretary. SOURCE: CRS, 2020. 1 “Details may not add to totals due to rounding. The bar representing the combined mandatory and discretionary total for CMS has been abbreviated due to space constraints. When taking into account both mandatory and discretion- ary funding, CMS receives over 20 times the funding appropriated to either ACF or NIH in the FY 2019 LHHS omnibus. Amounts in this table (1) reflect all BA appropriated in the bill, regardless of the year in which funds become avail- able (i.e., totals do not include advances from prior-year appropriations, but do include advances for subsequent years provided in this bill); (2) have generally not been adjusted to reflect scorekeeping; (3) comprise only those funds provided (or requested) for agencies and accounts subject to the jurisdiction of the LHHS subcommittees of the House and Senate appropriations committees; and (4) do not include appropriations that occur outside of appropriations bills.” PREPUBLICATION COPY—Uncorrected Proofs

292 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-1  NIH Appropriations (FY 2008–2020) FY NIH Appropriations Percent Change 2008 $29,607,070,000  - 2009 $30,545,098,000 3.2% 2010 $31,238,000,000 2.3% 2011 $30,916,345,000 -1.0% 2012 $30,860,913,000 -0.2% 2013 $29,315,822,000 -5.0% 2014 $30,142,653,000 2.8% 2015 $30,311,349,000 0.6% 2016 $32,311,349,000 6.6% 2017 $34,300,999,000 6.2% 2018 $37,311,349,000 8.8% 2019 $39,313,000,000 5.4% 2020 $41,690,000,000 6.0% NOTE: FY, Fiscal Year. SOURCES: NIH, 2010, 2020b. Funding for NIH Institutes and Centers NIH funding goes primarily to the ICs to support research conducted through both extramural grants and intramural research projects (NIH, 2020a). Extramural grants account for more than 80 percent of NIH’s funding, while intramural support accounts for about 11 percent of NIH funding (NIH, 2020a, 2021d, 2021e). In 2020, NIH awarded approximately 50,000  competitive grants to approximately 300,000 researchers (NIH, 2020a, 2021e). NIH ICs have different missions that guide their activities, and may focus, for example, on a specific disease, organ system, life stage, field of science, or training or technology. The ICs also include the NIH Clinical Center, the National Library of Medicine, and The Center for Scientific Review (CSR). ICs plan and manage their own research program in coordination with the OD (NIH, 2021a, 2021e). ICs engage in strategic planning to set priorities and plan activities (NIH, 2015, 2021e). Figure 5-2 presents FY 2020 congressional appropriations for the ICs and OD. The varia- tion in the level of appropriation is notable, with the National Cancer Institute (NCI) receiving the largest amount of funding and the Fogarty International Center receiving the smallest. The level of IC appropriation PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 293 FIGURE 5-2  NIH Congressional appropriations by IC (FY 2020). NOTE: B&F; Buildings and Facilities; FIC, Fogarty International Center; FY, Fiscal Year; IC, Institutes and Centers; NCATS, National Center for Advancing Trans- lational Sciences; NCCIH, National Center for Complementary and Integrative Health; NCI, National Cancer Institute; NEI, National Eye Institute; NHGRI, National Human Research Institute; NHLBI, National Heart, Lung, and Blood Institute; NIA, National Institute of Aging; NIAAA, National Institute on Alco- hol Abuse and Alcoholism; NIAID, National Institute of Allergy and Infectious Diseases; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases; NIBIB, National Institute of Biomedical Imaging and Bioengineering; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human De- velopment; NIDA, National Institute on Drug Abuse; NIDCD, National Institute on Deafness and Other Communication Disorders; NIDCR, National Institute of Dental and Craniofacial Research; NIDDK, National Institute of Diabetes and Di- gestive and Kidney Diseases; NIEHS, National Institute of Environmental Health Sciences; NIGMS, National Institute of General Medical Sciences; NIMH, National Institute of Mental Health; NIMHD, National Institute on Minority Health and Health Disparities; NINDS, National Institute on Neurological Disorders and Stroke; NINR, National Institute of Nursing Research; NLM, National Library of Medicine; OD, Office of the Director. SOURCE: NIH, 2021h. PREPUBLICATION COPY—Uncorrected Proofs

294 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE correlates with the level of research, training, and other activities that the ICs that engage in these activities can support. NIH RESEARCH PROCESS Extramural Research Funding At NIH, 24 of the 27 ICs fund the extramural research program (NIH Central Resource for Grants and Funding Information, 2020), which supports research across the United States and beyond (NIH, 2021d). Extramural research can be categorized generally as “unsolicited” inves- tigator-initiated research or “solicited” targeted research (NIH Office of Extramural Research, 2021). Most applications submitted to NIH for research or research training, including fellowships, are investigator ini- tiated (NIH Office of Extramural Research, 2021). Investigator-initiated opportunities may be attractive to new investigators as a result of the freedom to create an application to pursue any area of science NIH sup- ports without waiting for a particular funding announcement. Moreover, new investigators pursuing investigator-initiated research opportunities receive a higher pay line than established investigators, whereas there is no pay differential for new investigators pursuing solicited research opportunities (NIAID, 2016). All applications are submitted in response to Funding Opportunity Announcements (FOAs), which are publicly avail- able documents in which NIH describes its intentions to make discre- tionary awards for which it selects the awardees and/or the amounts of funding via a competitive process.7 FOAs can range from an NIH-wide umbrella announcement that channels investigator-initiated research applications, to a single IC’s announcement to solicit applications for a clearly-defined scientific area in order to fulfill specific objectives8 (NIH Office of Extramural Research, 2021). The Center for Scientific Review (CSR) is the entry point for all NIH grant, fellowship, and cooperative agreement applications (CSR, 2021; Hodge, 2021). 7 Non-discretionary awards, which are uncommon, are made to specific recipients, in ac- cordance with statutory, eligibility, and compliance requirements. The award amount could be determined specifically or by formula (NIH Office of Extramural Research, 2021). 8 The most common FOA types are as follows. Program Announcements (PAs) are state- ments about a new or ongoing activity or program that may also invite applications for grant support. Requests for Applications (RFAs) solicit grant or cooperative agreement ap- plications in a well-defined scientific area to accomplish specific program objectives. Parent Announcements are omnibus announcements that enable applicants to submit investigator- initiated applications. Notices of Special Interest (NOSI) highlight a topic of interest and direct applicants to one or more FOAs (often Parent Announcements) to submit applications for the initiative (NIH Office of Extramural Research, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 295 CSR’s Division of Receipt and Referral reviews grant applications for completeness and compliance with NIH policies and makes two referral assignments for each application (Hodge, 2021; NIH). The first assign- ment is to one or more NIH ICs for potential funding based on guidelines that each IC provides to CSR for assignment purposes, and these guide- lines may include shared interests among different ICs (Hodge, 2021). The ICs’ assignment guidelines are not available to the public (Hodge, 2021). The second assignment is to either a CSR review group, the case for 75 percent of applications, or to IC review groups associated with solicited FOAs (Murrin, 2019). CSR scientific review groups, also called study sections, review the applications for scientific merit (CSR, 2020). Information on each study section, including its reviewers, topics covered, and overlap with related study sections, is available on the NIH website.9 There are two kinds of CSR study sections, chartered and special emphasis panels (CSR, 2020). Chartered, also called standing or recurring, study sections review most investigator-initiated research applications; the sections comprise members who are “primarily non-federal scientists with expertise in relevant scientific disciplines and current research areas” (NIH, 2018). Special emphasis panels perform reviews when the subject matter does not match up with a study section, when assigning a project to an appropriate study section might create a conflict of interest, or for cer- tain types of applications such as fellowships, Small Business Innovation Research, and Small Business Technology Transfer Research applications (CSR, 2020; Hodge, 2021; NIH, 2013). A special emphasis panel comprises temporary members whom CSR recruits based on expertise needed for each meeting. CSR assigns each application to a Scientific Review Officer (SRO) (NIH, 2013). An SRO is an extramural staff scientist who is the designated federal official responsible for ensuring an application meets peer-review requirements and for managing the review process (NIH, 2018; NIMH, 2021). The two-stage review process involves evaluation by a panel of pri- marily non-federal scientists, and approval by the IC Advisory Council/ Board and the IC Director (NIH, 2018, 2019a). In the first stage of review, assigned reviewers provide their prelimi- nary assessments and critiques to the SRO, who uses them to plan and frame the session with the fully convened study section (CSR, 2020; NIH, 2018). The section chair and the SRO partner to run the study section review meeting (NIH, 2018). At the meeting, the assigned reviewers pres- ent a critique of the application, and members then discuss the application 9 Available at https://public.csr.nih.gov/StudySections (accessed November 19, 2021). PREPUBLICATION COPY—Uncorrected Proofs

296 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE FIGURE 5-3  NIH CSR review process. NOTE: CSR, Center for Scientific Review; IC, Institute and Center; SRG, Scientific Review Group. SOURCE: Adapted from figure developed by the Congressional Research Service (CRS, 2019 739) using information from NIH 2016, 2018, 2019a. PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 297 in depth (Hodge, 2021; NIH, 2013, 2018). The members each provide a final overall impact score (Hodge, 2021; NIH, 2013, 2018). In the second stage of review, the Advisory Council or Board of the assigned IC, comprising “both scientific and public representatives selected for their expertise, interest, or activity in matters related to health and disease,” makes funding recommendations based on the results of the study section’s review and the IC’s programs and priorities (Hodge, 2021; NIH, 2013, 2018) The directors of the ICs make the final funding deci- sions (NIH, 2018). Figure 5-3 depicts an overview of the process. Chapter 6 discusses CSR study sections that review applications that focus on autoimmune diseases. The ICs use a similar process to review grant applications submitted in response to solicited FOAs, but they convene ad hoc special emphasis panels with expertise appropriate for each separate FOA (NIAID, 2020). NIH uses a broad range of activity codes to categorize funding mech- anisms for research activities. Extramural research activities are typically grants, contracts, or cooperative agreements (NIH, 2019b). Investigator- initiated research project grants, so-called R01 grants, are considered the traditional grant mechanism and constitute the largest single type of support NIH provides (NIH, 2021g). For the purpose of this study, the committee was also interested in fellowships, research career programs, training programs, and cooperative agreements. Table 5-2 provides a brief description of these grants. Intramural Research Funding The NIH Intramural Research Program (IRP) supports research con- ducted on the NIH campuses, and 23 of the 27 ICs have an intramu- ral component (IRP, 2021a; NIH, 2017b). Priority setting for intramural research projects is based on prior investigator success and innovative ideas, often in collaboration with investigators in other ICs or with extra- mural researchers. The IRP budget supports more than 1,200 principal investigators and 4,000 postdoctoral fellows who conduct basic, translational, and clinical research (IRP, 2021b, 2021c). IRP principal investigators receive a review of their work every four years, and the external reviews are primarily retrospective (IRP, 2021a; Kastner, 2021; Rider, 2021). The IRP approach represents NIH’s commitment to individual researchers rather than indi- vidual projects, as is the case with extramural investigators, providing support for high-risk, high-reward projects not easily funded by R01 projects and for long-term studies requiring stable funding. PREPUBLICATION COPY—Uncorrected Proofs

298 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-2  Select NIH Grant Types Type of Grant Category Purpose F Fellowship Programs “To provide individual research training opportunities (including international) to trainees at the undergraduate, graduate, and postdoctoral levels.” K Research Center Programs “To provide individual and institutional research training opportunities (including international) to trainees at the undergradu- ate, graduate, and postdoctoral levels.” P Research Program Projects “Program project/center grants are large, and Centers multi-project efforts that generally include a diverse array of research activities.”  R Research Projects “These grants may be awarded to individu- als at universities, medical and other health professional schools, colleges, hospitals, research institutes, for-profit organizations, and government institutions.” T Training Programs “To provide individual research training opportunities (including international) to trainees at the undergraduate, graduate, and postdoctoral levels.” U Cooperative Agreements A support mechanism frequently used for “high-priority research areas that require substantial involvement from NIH program or scientific staff.” SOURCE: NIH, 2019b. NIH Initiatives NIH supports a number of specific initiatives. Initiatives originate in a number of ways, which include externally through congressional man- dates, congressional language that is not a mandate, or direction from the Executive Branch (e.g., via HHS) as well as internally from the NIH OD, IC leadership and staff, or internal coordinating bodies. Directions from Congress or the Executive Branch are announced publicly, have specific goals, and may or may not have set-aside funding to support the goals. ICs may propose their own initiatives with or without dedicated fund- ing. NIH initiatives may also derive from and be coupled with private sector initiatives, with variable sharing of funds, Examples of the latter include large registries or clinical care consortia created by advocacy groups, strengthened in structure and resources by NIH or NIH-spon- sored research, that pharmaceutical companies can use. PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 299 Select NIH Autoimmune Research Efforts The previous discussion provided a brief overview of NIH funding and the process for awarding grants. The next section focuses more spe- cifically on autoimmune disease research activities. For the purpose of this report and the timeframe available to the committee to conduct its work, the committee chose to limit its review to the OD and 13 NIH ICs—the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Arthritis and Musculoskeletal Diseases (NIAMS), National Institute on Neurological Disorders and Stroke (NINDS), National Heart, Lung, and Blood Institute (NHLBI), NCI, National Eye Institute (NEI), National Institute of Dental and Craniofacial Research (NIDCR), National Institute of General Medical Sciences (NIGMS), National Institute of Envi- ronmental Health Sciences (NIEHS), Eunice Kennedy Schriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI), and National Center for Advancing Translational Sciences (NCATS)—that supported the major- ity of autoimmune disease research through intramural and extramural programs in FY 2020 based on the total amount of funding (see Figure 5-4).10 Table 5-3 presents the general mission statements of the select NIH ICs. The committee notes that of these, the general mission of six Institutes focus on diseases, and six focus on organ systems or anatomy. These ICs have different missions, favor different funding mechanism priorities, and focus on different autoimmune diseases. While they offer more detailed disease-specific interests in their website-searchable data- bases (Table 5-3), their reporting formats are not standardized, nor do they indicate how they choose diseases. Some listed diseases are common, such as rheumatoid arthritis, a focus of NIAMS, and some are exceedingly rare, such as autoimmune encephalitis, a focus of NINDS. Other diseases are lethal, such as vasculitis and systemic lupus erythematosus (SLE), which are areas of focus for NIAMS and NIDDK, while others are not lethal but cause life disruption treatable with today’s technologies, such as Hashi- moto’s thyroiditis and Graves’ disease, a focus of NIDDK. The complexity and diversity in the group of autoimmune diseases has contributed to how research and other efforts to understand the diseases are dispersed across NIH ICs, which in turn may lead to siloing of efforts if there are no systematic attempts to coordinate activities across NIH. Yet another per- spective can be seen when considering a disease such as Sjögren’s disease. Sjögren’s disease is a prototypical, multisystemic autoimmune disease. Its 10 The committee notes that many investigators funded by NIH also receive support from philanthropy, industry, and other private sector sources. The committee did not seek to quantify or outline the relative contributions of these other sectors. PREPUBLICATION COPY—Uncorrected Proofs

300 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE FIGURE 5-4  NIH autoimmune disease funding by IC (FY 2020). NOTE: The 13 ICs and OD contributed approximately 97 percent of total au- toimmune disease spending in FY 2020. NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIAID, National Institute of Allergy and Infectious Diseases; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases; NINDS, National Institute on Neurological Disorders and Stroke; NHLBI, National Heart, Lung, and Blood Institute; NCI, National Cancer Institute; NEI, National Eye Institute; NIDCR, National Institute of Dental and Craniofacial Research; NIGMS, National Institute of General Medical Sciences; NIEHS, National Institute of Environmental Health Sciences; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NHGRI, National Human Research Institute; NCATS, National Center for Ad- vancing Translational Sciences; OD, Office of the Director. SOURCE: NIH, 2021f. manifestations include mucosal and ocular abnormalities, arthritis, respi- ratory and renal failure, multiple autoantibodies, cytopenias, neuropathy, maternal autoantibody-induced neonatal disease, and lymphadenopathy and lymphoma. Because it involves so many organ systems, Sjögren’s disease does not have “a home” in NIH; NIAMS, NIAID, NEI, NINDS, NHLBI, NCI, NICHD, and NIDCR all can legitimately claim primary interest in grants focusing on this disease. In an effort to categorize the autoimmune diseases relevant to the ICs in Table 5-3, the committee had to gather information from a variety of sources since such information was not readily available from a sole source. The committee relied on presentations by invited speakers from the ICs during the committee’s information-gathering public sessions, publicly available information on the ICs’ websites, and committee mem- bers’ expert knowledge. The categorization of the ICs in Table 5-3, based on their mission statements and other publicly available information, reveals the broad and sometimes overlapping missions and focus areas PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 301 as they pertain to autoimmune diseases research. While there is some evidence of attempts to coordinate funding and research efforts among the ICs, it was difficult for the committee to assess how effective these efforts were, as discussed later in this chapter. Table 5-3 summarizes the autoimmune disease research focus of each IC, which range from basic to translational and clinical research. Strategic Planning for Autoimmune Disease Research at NIH ICs engage in a strategic process to set research priorities. In an effort to understand if and how the various ICs prioritize autoimmune diseases as part of their overarching institutional plans and vision planning, the committee reviewed the strategic plans for the 13 ICs that funded most of the autoimmune diseases work in FY 2020. The strategic plans offer insights into what the institutes consider to be the most pressing issues that they can tackle within their mission and vision, as well as those issues that will hold the most promise for advancing their respective fields. Complicating the committee’s review of the strategic plans was the fact that there is no standardized approach and timeline by which the ICs release their report (Table 5-4). Some ICs, such as NCI, release plans as part of the annual budget planning process to the President and Congress. Other institutes—NIAMS, NIDDK, and NIGMS—release 5-year plans, while others—NHGRI, NIEHS, and NICHD—release reports periodically at intervals of 6 to 10 years. The committee found information about past reports to assess the frequency of the strategic planning process for some of the ICs, including NIAID, NHLBI, and NEI. This lack of standard- ization across ICs and consistency in the release of strategic plans for individual ICs has important implications since it may pose an obstacle for ICs to coordinate their strategic planning efforts, and subsequently, their funding and research efforts for autoimmune diseases. While the timeframe covered by some of the strategic plans overlap, the plans are at various stages of implementation. Regarding the process for strategic planning, not all the ICs docu- ment their approach, so the committee was unable to fully evaluate how the ICs identified scientific and programmatic priorities outlined in the strategic plans. Some of the ICs, as discussed in the section below, go through a detailed process spanning one to two years that includes issu- ing a Request for Information (RFI) to solicit stakeholder feedback on their proposed themes or areas of focus. Broad and varied stakeholder input is essential for comprehensively surveying the field and ensuring that the priorities identified reflect what a variety of stakeholder groups consider as the most pressing issues. PREPUBLICATION COPY—Uncorrected Proofs

302 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-3  Missions and Autoimmune Diseases of Focus of Select NIH ICs Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National “The mission of Rheumatic Diseases/Conditions “Supports basic, Institute of the NIAMS is to (Systemic Lupus Erythematosus translational, Arthritis and support research (SLE); Inflammatory Arthritis and clinical Musculoskeletal into the causes, (Rheumatoid Arthritis; research, Skin Diseases treatment, and Ankylosing Spondylitis; and including (NIAMS) prevention of Psoriatic Arthritis); Inflammatory clinical trials and arthritis and Myopathies; Scleroderma; observational musculoskeletal Sjögren’s Syndrome; studies, and and skin diseases; Antiphospholipid Syndrome; and mechanistic the training of Vasculitis (Giant Cell Arteritis, studies with basic and clinical ANCA-Associated Vasculitis, a focus on scientists to Granulomatosis with Polyangitis, mechanisms of carry out this and Behçet’s disease); Skin disease”—basic research; and the Diseases/Conditions (Psoriasis, immunology, dissemination of Pemphigus, Bullous Pemphigoid, inflammation, information on Atopic Dermatitis (Eczema), end-organ research progress Alopecia Areata, Vitiligo and damage and in these diseases” Hidradenitis suppurativa); repair; genomics, (NIAMS, 2021b). Autoinflammatory Syndromes proteomics and (Tumor necrosis factor receptor- other “Omics”; associated periodic fever pain and fatigue; syndrome (TRAPS), Cryopyrin- behavioral and associated periodic syndromes biopsychosocial (CAPS) and Systemic Juvenile factors Idiopathic Arthritis (sJIA) contributing to (Mancini, 2021). disease severity and quality of life and patient reported outcomes; health disparities and special populations, e.g., pediatrics and pregnancy; traininng basic and clinical scientists to perform this research; and disseminating research and progress in these diseases (Mancini, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 303 TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National “The mission of Type 1 Diabetes; Crohn’s Invests in Institute of the NIDDK is Disease; Inflammatory Bowel “a vigorous, Diabetes and to conduct and Disease (IBD); Ulcerative investigator- Digestive support medical colitis; SLE– Lupus Nephritis; initiated research and Kidney research and Celiac Disease; Autoimmune portfolio that Diseases research training Hepatitis; Autoimmune supports (NIDDK) and to disseminate Thyroid diseases – Hashimoto’s crosscutting science-based disease and Graves’ disease; science that information on Autoimmune pancreatitis; and can be broadly diabetes and other Glomerulonephritis – IgA and applied to many endocrine and membranous; primary sclerosing disease-specific metabolic diseases; cholangitis; and primary biliary research areas; digestive diseases, cholangitis (Spain, 2021). supporting nutritional pivotal clinical disorders, and studies and obesity; and trials, with kidney, urologic, a focus on and hematologic substantial diseases, to participation improve people’s of groups at health and quality highest risk; of life” (NIDDK, promoting a 2021a; Spain, 2021). steady and diverse pool of talented new investigators; fostering exceptional research training and mentoring opportunities; and ensuring that science- based health information reaches patients, their families, health care providers, and the public through communications and outreach” continued PREPUBLICATION COPY—Uncorrected Proofs

304 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National The mission of Type 1 Diabetes; Systemic Lupus Supports Institute of NIAID is “to Erythematosus; Rheumatoid research that Allergy and conduct and Arthritis; Pemphigus; investigates Infectious support basic Vitiligo; Membranous the role of the Diseases and applied Nephropathy; Scleroderma; immune system, (NIAID) research to better Multiple Sclerosis; ANCA- highlighting understand, treat, associated vasculitis; Crohn’s basic immune and ultimately disease; and IgG4-related mechanisms; prevent infectious, disease; IBD; Autoimmune the role of the immunologic and Lymphoproliferative Syndrome microbiome; the allergic diseases. (ALPS), Autoimmune development of (NIAID, 2017) Polyendocrinopathy- novel immune NIAID has a Candidiasis-ectodermal strategies to unique mandate, Dystrophy (APECED); and earlier detect, which requires Autoinflammatory Disease diagnose, treat the Institute (Barron, 2021) and prevent to respond to disease; the emerging public application health threats” of knowledge (Barron, 2021). of immune mechanisms to develop immunotherapies; and the use of improved animal models; and support clinical trial networks and investigator- initiated clinical trials to evaluate immune-based treatment, such as cellular therapies, tolerance approaches, and other courses of action, each with integrated mechanistic studies (McNamara, 2021) PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 305 TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National “The mission Multiple Sclerosis; Neuromyelitis Supports basic, Institute of of NINDS is to Optica; MOG-Antibody translational and Neurologic seek fundamental associated disorders; clinical research; Disease and knowledge about Myasthenia Gravis; Guillain- research that Stroke (NINDS) the brain and Barré syndrome; Autoimmune identifies gaps nervous system encephalitis (i.e. Anti-N-methyl in research and and to use that D-aspartate receptor); Transverse public health knowledge to myelitis; Acute disseminated needs; training reduce the burden Encephalomyelitis; and a talented and of neurological Paraneoplastic syndromes (Utz, diverse research disease” (NINDS, 2021) workforce; 2020). supports the development of tools and resources to enable discoveries; and communicating and collaborating with all stakeholders, including the public (Utz, 2021) National Heart, “The mission of Vasculitis – Immune Supports basic, Lung and the NHLBI is to Thrombocytopenia; Autoimmune translational and Blood Institute provide global hemolytic anemia; Autoimmune clinical research (NHLBI) leadership for a thrombocytopenic purpura; in the causes research, training, coexisting diseases of and coexisting and education systemic SLE (Atherosclerosis; diseases of program to Hypertension; Platelet autoimmune promote the activity); coexisting diseases diseases prevention and of Rheumatoid Arthritis; treatment of heart, and coexisting diseases of lung, and blood Scleroderma (Systemic Sclerosis, diseases and SSC), myocarditis (Kirby, 2021) enhance the health of all individuals so that they can live longer and more fulfilling lives” (NHLBI, 2014). continued PREPUBLICATION COPY—Uncorrected Proofs

306 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National Eye The mission of the Autoimmune uveitis; Supports basic, Institute (NEI) NEI is to conduct autoimmune retinopathy; translational, and support autoimmune dry eye diseases and clinical research, training, (DED) including Sjögren’s (NEI, studies of the health information 2021c) causes and dissemination, and mechanisms of other programs autoimmune with respect diseases of the to blinding eye. Ongoing eye diseases, projects include visual disorders, neuroretinal mechanisms of autoimmunity, visual function, ocular surface preservation of mucosal sight, and the immunity, and special health the role of problems of the microbiota and blind (NEI, 2021a, their products 2021c). in these contexts (NEI, 2020) PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 307 TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National “The mission of Environmental triggers of Invests in Institute of the NIEHS is to autoimmune disease (NIEHS, research to Environmental discover how 2021). ”advance Health Sciences the environment research on (NIEHS) affects people environmental in order to triggers of promote healthier disease; foster lives” (NIEHS, training and 2018; Rider, 2021).  development of young environmental health scientists and practitioners; enhance translation of knowledge from research to disease prevention; and develop improved safety assessment research on chemicals and other environmental factors” continued PREPUBLICATION COPY—Uncorrected Proofs

308 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National “As a leading Inflammatory diseases Invests in Human Genome authority in the (Kastner, 2021) research that Research field of genomics,” evaluates genetic Institute the mission of influences on the (NHGRI) NHGRI is “to development of accelerate scientific autoimmune and and medical inflammatory breakthroughs diseases that improve human health … by driving cutting- edge research, developing new technologies, and studying the impact of genomics on society” (NHGRI, 2018). National Cancer The mission of Supports Institute (NCI) NCI is “to lead, research conduct, and investigating support cancer the role of research across immunotherapy the nation to in the induction advance scientific of autoimmune knowledge and disease, (e.g., help all people live checkpoint longer, healthier inhitors) lives” and immune (NCI, 2018). regulation PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 309 TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National The mission of Supports Institute NIGMS mission research of General is “to support investigating Medical fundamental basic Sciences biomedical research immunology and (NIGMS) that increases the regulation of understanding of T-cell immunity life processes and (NIGMS, 2018; lays the foundation NIH, 2021f) for advances in disease diagnosis, treatment, and prevention” (NIGMS, 2018). “NIGMS- funded scientists investigate how living systems work at a range of levels, from molecules and cells to tissues, whole organisms, and populations. The Institute also supports research in certain clinical areas, primarily those that affect multiple organ systems. To assure the vitality and continued productivity of the research enterprise, NIGMS provides leadership in training the next generation of scientists, enhancing the diversity of the scientific workforce, reducing disparities, and developing research capacities throughout the country” (NIGMS, 2021). continued PREPUBLICATION COPY—Uncorrected Proofs

310 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National The mission Rheumatoid arthritis, Sjögren’s Supports basic, Institute of of “NIDCR syndrome, lupus, and Psoriatic translational and Dental and is to advance Spectrum Diseases (NIH et al., clinical research, Craniofacial fundamental 2021b) including Research knowledge about mechanistic (NIDCR) dental, oral, and studies with craniofacial (DOC) a focus on health and disease mechanisms of and translate disease—basic these findings immunology, into prevention, inflammation, early detection, and end-organ and treatment damage strategies that improve overall health for all individuals and communities across the lifespan” (NIDCR, 2021a). National “The mission of Supports Institute of the NICHD is research of Child Health to lead research of immune and Human and training to tolerance in Development understand human reproduction and (NICHD) development, immunoregulatory improve mechanisms reproductive (NICHD, 2020; health, enhance the NIH et al., lives of children 2021c) and adolescents, and optimize abilities for all” (NICHD, 2019). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 311 TABLE 5-3 Continued Types of Research Supported for Autoimmune Diseases Relevant Autoimmune IC Name Mission to Missiona Diseases National Center “The NCATS Supports for Advancing mission is to translation Translational catalyze the research on Sciences generation autoimmune (NCATS) of innovative diseases, methods and including technologies that support for the will enhance the Rare Diseases development, Clinical Research testing and Network implementation consortia of diagnostics and focusing on therapeutics across myesthenia a wide range of gravis and human diseases vasculitis and conditions” (Bamias et al., (NCATS, 2021a). 2017) aDisease lists are not intended to be comprehensive; sources included NIH websites and presentations delivered to the committee. A blank cell indicates that while the IC’s mission may not focus on autoimmune diseases specifically, its research may benefit autoimmune disease research indirectly or may involve autoimmune diseases as a result of its broad mission. PREPUBLICATION COPY—Uncorrected Proofs

312 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 5-4  Recent Strategic Plans Available From NIH ICs That Fund Autoimmune Disease Research IC Name Current Strategic Plan Years Plan Period NIAMS FY 2020–2024 5 years NIDDK 2021–2025 5 years NIAID 2017 N/A NINDS FY 2021–2026 6 years NHLBI FY 2016 N/A NEI 2021–2025 5 years NIEHS FY 2018–2023 6 years NHGRI 2020a 10 yearsb NCI FY 2023 1 year NIGMS 2021–2025 5 years NIDCR 2021-2026 6 years NICHD 2020 N/A NCATS 2016 N/A a The plan offers ten bold predictions of what might be realized in human genomics by 2030 (Green et al., 2020). b Based on schedule of previous plan. NOTE: FY, Fiscal Year; IC, Institutes and Centers; NCATS, National Center for Advancing Translational Sciences; NCI, National Cancer Institute; NEI, National Eye Institute; NHGRI, National Human Genome Research Institute; NHLBI, National Heart, Lung, and Blood Institute; NIAID, National Institute of Allergy and Infectious Diseases; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIDCR, National Institute of Dental and Craniofacial Research; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIEHS, National Institute of Environmental Health Sciences; NIGMS, National Institute of General Medical Sciences; NINDS, National Institute on Neurological Disorders and Stroke. SOURCE: Green et al., 2020; NCATS, 2016; NCI, 2021a; NEI, 2021b; NHLBI, 2016; NIAID, 2021b; NIAMS, 2020b; NICHD, 2019; NIDCR, 2020; NIDDK, 2021b; NIEHS, 2018; NIGMS, 2021; NINDS, 2020. The various strategic plans reference autoimmune diseases and issues of autoimmunity to varying degrees or not at all, as the discussion below notes for each individual IC. The institutes that funded the most autoim- mune diseases research and whose missions and focus align directly with autoimmune diseases—NIAMS, NIDDK, and NIAID—were more likely to mention the autoimmune diseases in their strategic plan. NIEHS, which is not a major funder of autoimmune diseases research, made mention of autoimmune diseases in its recent plan (FY 2018 to 2023) (NIEHS, 2018). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 313 NIAMS The current NIAMS strategic plan covers FY 2020 to 2024 and includes a section on scientific objectives that are disease and tissue specific, one of which is to advance and speed systemic rheumatic and autoimmune diseases research, and crosscutting themes of focus for NIAMS. The cross- cutting scientific themes NIAMS identified acknowledge that most of the scientific challenges and opportunities transcend a single disease area or organ (NIAMS, 2020b). The four themes identified are all relevant to autoimmune diseases: • “Precision medicine for arthritis and musculoskeletal and skin diseases” (NIAMS, 2020b). This involves, but is not limited to, leveraging new technologies and computational tools to improve knowledge of the molecular basis of health and disease. • “Shared mechanisms in health and among diseases.” Focus areas include immunity and inflammation and the effects of envi- ronmental exposures. • “Patient-centric approaches to health and disease.” Capturing patient-reported perspectives using tools such as the Patient- Reported Outcomes Measurement Information System (PRO- MIS®) as part of the research process. • “Health and disease in diverse populations.” Promoting the relevance of NIAMS-funded research in groups that have been historically underrepresented in biomedical research in order to effect health equity for all populations. The report also identifies aspirations or thematic issues that are ger- mane to multiple diseases or conditions at NIAMS and those that hold the most promise for the future given the NIAMS portfolio (NIAMS, 2020b). The two most relevant for autoimmune diseases are: • “Biomarkers will guide the choice of the most effective therapy for each individual rheumatoid arthritis patient […and] • “Preventive therapy will delay the onset of autoimmune diseases like lupus and rheumatoid arthritis” (NIAMS, 2020b). Independently of its IC-specific strategic plans, NIAMS published the Action Plan for Lupus Research in 2015, intending that it supplement ongo- ing long-term plans as well as the work of the Lupus Federal Working Group (LFWG) and the Autoimmune Diseases Coordinating Committee (ADCC) (NIAMS, 2015). More information on these organizations appears later in this chapter. PREPUBLICATION COPY—Uncorrected Proofs

314 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE NIDDK NIDDK established a Working Group of Council, comprising 44 exter- nal scientists and patient advocates to provide input during the strategic planning process for its most recent strategic plan, the institute published in December 2021 (NIDDK, 2021b, 2021c). It issued an RFI in 2020 to seek input from different stakeholders, “including the scientific research com- munity; patients and caregivers; health care providers and health advo- cacy organizations; scientific and professional organizations; federal agen- cies; and other stakeholders, including interested members of the public,” on the thematic considerations for the 5-year strategic plan (NIDDK, 2021b). After developing a draft strategic plan, NIDDK issued another RFI for the period August 10–31, 2021 to elicit feedback on the draft. The strategic plan includes four major goals: • “Advance understanding of biological pathways and environ- mental contributors to health and disease […and] • Advance pivotal clinical studies and trials for prevention, treat- ment, and cures in diverse populations […and] • Advance research to disseminate and implement evidence-based prevention strategies and treatments in clinics and community settings, to improve the health of more people, more rapidly and more effectively […and] • Advance stakeholder engagement — including patients and other participants as true partners in research”(NIDDK, 2021c). NIAID The most recent NIAID-wide strategic plan is from 2017, and devel- opment of new one is not yet scheduled.11 The budget and planning page of NIAID’s website12 does include strategic plans for various dis- eases and conditions and research areas, such as COVID-19, hepatitis B, tickborne disease research, vaccine adjuvants, and tuberculosis (NIAID, 2021b). NIAID’s last published strategic plan (NIAID, 2017) outlined the Institute’s then-current research priorities to inform its future decision making. The plan identified four scientific areas of focus, one of which is “allergy, immunology, and immune-mediated diseases,” including auto- immune disease. For this specific area, it emphasizes applying under- standing of the human immune system in continuing to support immu- nology research that provides preclinical information that is crucial to 11 Personal communication. Susan Cooper, M.Sc., Director, Office of Program Planning, Operations, and Scientific Information, NIAID, September 7, 2021. 12 Available at https://www.niaid.nih.gov/about/budget-planning. PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 315 developing new strategies to diagnose, treat, and prevent infectious and immune-mediated diseases. Another area of emphasis involves support- ing clinical trial networks committed to treating and preventing allergic and autoimmune diseases and to preventing graft rejection. A third and final area of emphasis identified for this scientific area involves determin- ing the precise mechanisms of human immune regulation (NIAID, 2017). NINDS NINDS organized its FY 2021 to 2026 strategic plan by focus areas that are not disease specific (NINDS, 2020). The four areas are: • “Science: Support and perform rigorous and important neurosci- ence research. • Training and Diversity: Fund and conduct neuroscience research training and career development programs to ensure a vibrant, talented, and diverse neuroscience workforce. • Communications: Promote dynamic communication and diverse stakeholder engagement to accelerate scientific progress and reduce the burden of neurological disorders. • Workforce Culture: Create and sustain a supportive work culture for the NINDS workforce that becomes the model for biomedical research and the neuroscience community” (NINDS, 2020). While the strategic plan does not mention specific autoimmune dis- eases, NINDS seeks to advance research on the basic science and mecha- nisms of nervous system function in order to advance efforts to prevent and treat neurological disorders. In addition, NINDS will support the development and validation of biomarkers and outcome measures that are required to enable better and targeted therapeutic options for patients. The strategic plan also indicates as part of its science focus that is has a goal of supporting work to prevent neurological disorders and advance health equity (NINDS, 2020). As part of its crosscutting strategies, the plan indicates NINDS’s intention to rely primarily on investigator-initiated research for its funded portfolio, but notes that productive collaborations and partnerships are essential as scientific advances highlight intersections between the inter- ests of NINDS and other organizations (NINDS, 2020). NHLBI The most recent strategic plan available for NHLBI is from 2016 (NHLBI, 2016). This report is organized according to four goals, 8 strategic PREPUBLICATION COPY—Uncorrected Proofs

316 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE objectives, 132 research priorities, and 12 critical challenges, the latter of which the strategic plan defines as obstacles to scientific progress, which when overcome, will result in significant impact. The report’s fifth stra- tegic objective—developing and optimizing new diagnostic and thera- peutic strategies to prevent, treat, and cure heart, lung, blood, and sleep diseases—states that one of its critical challenges is to understand the immune system from a systems biology perspective as a means of design- ing more efficacious treatment strategies for chronic inflammatory and autoimmune heart, lung, blood, and sleep diseases. This critical challenge was the only explicit reference to autoimmune diseases in the strategic plan. The critical challenges, along with a set of compelling questions, constitute NHLBI’s strategic research priorities (NHLBI, 2016). The NHLBI plan mentions that investigator-initiated projects will continue to be the Institute’s primary focus, but it also acknowledges the importance of NHLBI-solicited research initiatives supported by new FOAs and that the plan’s strategic research priorities will shape the devel- opment of future FOAs and other activities (NHLBI, 2016). NEI On November 1, 2021, NEI released a strategic plan for 2021 to 2025 (NEI, 2021b). This strategic plan is the ninth comprehensive plan for the institute since it was established; the plan prior to the current plan was published in August 2012. The new plan has seven areas of emphasis within three research domains: “1) Visual system in health and diseases; 2) Capitalizing on emerging fields; and 3) Preventing vision loss and enhancing wellbeing” (NEI, 2021b). One of the focus areas within the first research domain is “immune system and eye health,” (NEI, 2021b) which will address how NEI can develop crosscutting program priorities and overarching goals for ocular immunology, infection, and inflamma- tion biology. As part of this goal, NEI’s focus is to support research that develops targeted therapeutics for ocular immune-related diseases and improve imaging, biomarkers, and data analytics to support precision medicine for immune-mediated eye diseases, among other research goals. As with some of the other ICs, NEI points to how it leverages partner- ships both within and outside of NIH to advance its mission and research priorities (NEI, 2021b). NIEHS The most recent version of the NIEHS strategic plan spans the years 2018 to 2023 and is organized around three themes: PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 317 • “Advancing environmental health sciences • Promoting translation – data to knowledge to action • Enhancing environmental health sciences through stewardship and support” (NIEHS, 2018). Inflammation effects that result in autoimmune disorders is one major area of research interest identified for the first theme. In addition, NIEHS’s goals for advancing environmental health sciences include supporting research on the effects of the environment on biological systems and processes, which may have implications for many diseases, including autoimmune diseases (NIEHS, 2018). NHGRI NHGRI released its current strategic plan in 2020, following versions it issued in 2003 and 2011 (Green et al., 2020). In the plan, NHGRI identi- fied four interrelated strategic areas that are at “the forefront of genomics” or are opportunities for human genomics in the next decade (Green et al., 2020). These areas are not disease specific, but overarching principles for genomics research that fall into the categories of: • “Guiding principles and values for human genomics • Sustaining and improving a robust foundation for genomics • Breaking down barriers that impede progress in genomics • Compelling genomics research projects in biomedicine” (Green et al., 2020) While NHGRI funds and conducts some research on autoimmune diseases, its strategic vision does not mention them specifically (Green et al., 2020). It is conceivable that some of the details identified in the broad categories delineated above may have implications for several diseases, including autoimmune diseases. NCI NCI releases an institutional plan and budget annually for submis- sion to the President and Congress. A summary document of the most current version, for FY 2023 (NCI, 2021a), highlights four focus areas: (1) clinical trials, (2) computer-based drug design, (3) precision preven- tion, and (4) tumor dynamics. The first highlighted area of the FY 2023 plan could have implications for autoimmune disease research in that a focus on expanding telemedicine into clinical trials could increase access to autoimmune disease trials in underserved communities. Similarly for PREPUBLICATION COPY—Uncorrected Proofs

318 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE the third highlighted area, a focus on precision-medicine approaches to prevention could aid in developing personalized prevention approaches for autoimmune diseases based on genetics, family history, environmental exposures, and behaviors. The FY 2022 summary document (NCI, 2021b) highlighted four focus areas including “cancer drug resistance, molecular diagnostics for cancer treatment, obesity and cancer, and cancer survivorship.” The FY 2021 plan summary (NCI, 2019a) identified three opportunities in cancer research: “the immune system and microbiome, artificial intelligence, and implementation science.” The FY 2021 plan’s first area of research, which focuses on harnessing the immune system in the development of immunotherapies, may have implications for individuals with autoim- mune diseases, as trials for existing immunotherapies have excluded these individuals (NCI, 2019b). NIGMS NIGMS released its current strategic plan in 2021. True to NIGMS’s mission, which is crosscutting in nature to support biomedical research in general, the plan (NIGMS, 2021) is organized around five goals that include sustaining support for investigator-initiated research and invest- ing in developing a skilled and diverse biomedical research workforce. NIGMS has supported some autoimmune diseases-focused research, so its goals may have relevance for the field of autoimmune diseases. NIDCR NIDCR released an RFI in August 2019 to solicit stakeholder input for its 2020 to 2025 strategic plan, but decided to postpone the plan release following the retirement of the former director in December 2019 and pending the installation of a new director who would provide new lead- ership and direction for the institute (NIDCR, 2021b). The FY 2021–2026 strategic plan will be organized around five priority areas, all of which could potentially have a bearing on autoimmune diseases, such as SLE and Sjögren’s disease, that involve dental, oral, and craniofacial (DOC) diseases (NIDCR, 2021b). These include: • “Advancing cross-disciplinary fundamental research in the bio- medical, behavioral, social, and environmental sciences and driv- ing translation toward early diagnosis, prevention, and treatment of DOC diseases and conditions across the lifespan. • Developing more precise and individualized ways of managing and preventing DOC diseases. PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 319 • Accelerating research translation and the uptake of new discover- ies into oral and general healthcare practices that reduce health inequities and disparities and improve oral health outcomes for individuals and communities worldwide. • Nurture future generations of DOC researchers and oral health professional scholars who can address existing and emerging challenges driven by personalized and public health needs and a continually evolving landscape of science and technology advances. • Expanding existing partnerships and create new ones to advance the NIDCR research enterprise and increase its reach and impact” (NIDCR, 2021b). NICHD NICHD’s most recent strategic plan is for the year 2020, having released its previous two strategic plans in 2000 and 2012. The report is organized around five themes, which include an emphasis on under- standing the biological basis of development; promoting gynecologic, andrologic, and reproductive health; promoting healthy pregnancies and lifelong wellness; improving the health of children and adolescents as they transition into adulthood; and safe, effective therapies and devices for pregnant women, children, and individuals with disabilities. While the strategic plan does not focus on specific diseases or conditions, the plan mentions how the results from NICHD-funded researchers working with maternal mouse models that showed the persistence of fetal cells post-delivery could offer insight into diseases that affect women, includ- ing autoimmune diseases (NICHD, 2019). NCATS NCATS was established in 2011 and has published a strategic plan from 2016 (NCATS, 2016). The Center’s research is not disease specific but rather focuses on disease commonalities and the translational process. The NCATS strategic plan is organized around four strategies, and the first, and most relevant for autoimmune diseases, is to conduct and sup- port innovative research to reveal fundamental scientific and operational principles of translational science to drive the development and dissemi- nation of novel medical interventions. Among several objectives listed to support this strategy are (1) “to identify biological commonalities among diseases and use insight into shared mechanisms and pathways to test and treat multiple human diseases and conditions” (NCATS, 2016), and (2) to “drive development of medical interventions for rare diseases that PREPUBLICATION COPY—Uncorrected Proofs

320 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE lack safe and effective treatments” (NCATS, 2016). The plan also points out obstacles that can limit the progress of translational science such as a lack of data interoperability; “a shortage of qualified biomarkers to diag- nose disease and measure treatment response”; and “inadequate devel- opment and measurement of appropriate clinical outcome measures or endpoints, including patient-reported outcomes.” While no diseases are named in the plan, translational science research could benefit the field of autoimmune diseases (NCATS, 2016). In summary, the committee notes the inherent difficulty in assessing the priorities of the ICs as it pertains to autoimmune diseases (as discussed earlier in this chapter). While ICs develop their strategic plans indepen- dently, on different schedules, and focus on broad thematic issues, there are sufficient commonalities in the themes and priority areas highlighted across the strategic plans that the committee reviewed to indicate that the process could benefit from a concerted effort. For example, some of the ICs, such as NIAMS and NEI, highlighted the development of biomarkers that will aid in the delivery of precision medicine. NIAID, NIAMS, and NIEHS all prioritized additional research on the basic science and mechanisms of the human immune system, and NIAMS also mentions the importance of understanding the effects of environmental exposures, which is a shared goal with NIEHS. Beyond scientific issues, a few of the ICs, such as NIDDK and NIAMS, highlight other priority areas such as the importance of the patient as partner in the research process, and NIAMS and NCATS call for the use of patient-reported outcomes in research. Better coordination in strategic planning and priority setting efforts across the ICs could enable the ICs to harness their expertise and resources effectively to address the pressing issues in autoimmune diseases research. CONGRESSIONAL ACTIONS AND NIH AUTOIMMUNE DISEASE RESEARCH On numerous occasions, Congress has issued mandates pertaining to autoimmune disease research at NIH. Constituents, advocacy groups, and other stakeholders who request congressional action on autoimmune diseases research have contributed greatly to such action, often through organized advocacy efforts (Autoimmune Association, 2021; Keenan, 2020). These mandates provide direction and in some cases funding for specific activities NIH-wide or at the IC level. This section provides an illustrative selection of specific mandates. The National Institutes of Health Revitalization Act of 199313 directed multiple ICs to pursue research on specific autoimmune diseases. The 13 National Institutes of Health Revitalization Act of 1993, Public Law 103-43, 103rd Cong., 1st sess. (June 10, 1993). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 321 Act tasked NIAMS to develop a plan to expand research into etiology, prevention, diagnosis, treatment, and rehabilitation of arthritis affecting children; to establish a disease center for this purpose; and to make recom- mendations for expanding funding for such research. The Act encouraged NIAID to collaborate with external entities to research chronic fatigue syndrome, issue research grants to study it, establish an extramural study section to review related research, appoint experts on the disease to appropriate NIH advisory committees and boards, and report on NIH’s work and priorities involving the disease. The Act also enabled NEI to issue grants to support a variety of basic and clinical research on diabetes and the eye and to improve patient care. Furthermore, the Act directed NINDS to conduct and support research on multiple sclerosis, particu- larly the effects of genetics and hormonal changes on disease progression. Congress did not include appropriations language for these efforts. One directive that has been renewed over many years is the Special Statutory Funding Program for Type 1 Diabetes Research, or Special Dia- betes Program, a special appropriation for research on type 1 diabetes that NIDDK administers on behalf of the HHS Secretary in collaboration with multiple ICs and the Centers for Disease Control and Prevention (CDC) and with input from the  Diabetes Mellitus Interagency Coordinating Committee. Begun in 1998, the Special Diabetes Program established collaborative research consortia and clinical trials networks dedicated to preventing, treating, and curing type 1 diabetes. Annual funding for the program has grown over time from $30 million to the current level of $150 million.14 The Children’s Health Act of 200015 called for the NIH Director to “expand, intensify, and coordinate research and other activities involving autoimmune diseases among the institutes.” It also requested establishing an Autoimmune Diseases Coordinating Committee (ADCC) to coordinate activities across NIH and with other federal health programs. Its members would include representatives of germane NIH ICs, federal departments, and agencies, including CDC and the Food and Drug Administration (FDA). The ADCC was to create a plan for “conducting and supporting a broad range of research and education activities relating to biomedical, psychosocial, and rehabilitative issues, including studies of the dispro- portionate impact of such diseases on women.” It was to determine NIH priorities for autoimmune diseases, which would “reflect input from a broad range of scientists, patients, and advocacy groups.” Planning was to include: research to identify the reasons for the incidence and prevalence 14 Consolidated Appropriations Act, 2021, Public Law 116-260, 116th Cong. 2nd sess. (December 27, 2020). 15 Children’s Health Act of 2000, Public Law 106-310, 106th Cong. 2nd sess. (October 17, 2000). PREPUBLICATION COPY—Uncorrected Proofs

322 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE of the diseases; basic research of causes; epidemiologic studies on disease frequency and progression, including disparities among sexes and racial and ethnic groups; improvement of screening techniques; and clinical research to develop treatments. The ADCC was also to plan information and education programs for the public and medical community. The ADCC would issue reports to Congress on autoimmune disease-related activities conducted or supported by NIH and the cost of NIH activi- ties for each disease, and would identify appropriate future projects for consideration by NIH or other research entities. Congress authorized appropriations for FY 2001 through 2005, but the language did not include amounts. The Children’s Health Act of 2000 also asked NIAMS and NIAID to expand and intensify programs for research and other activities involv- ing juvenile arthritis and related conditions. Congress authorized NIAMS and NIAID to be appropriated “such sums as may be necessary” for FY 2001 through FY 2005. In addition, the Act directed NIDDK to conduct or support long-term epidemiology studies in those who have or who are at risk for type 1 diabetes in order examine the causes, characteristics, and complications of the disease, and to undertake an effort to support regional clinical research centers for preventing, detecting, treating, and curing juvenile arthritis and related conditions. NIH was to join HHS in a national effort to increase “research and development of prevention strategies, including consideration of vaccine development, coupled with appropriate ability to evaluate the effectiveness of such strategies in large clinical trials of children and young adults.” NIDDK was to be appropri- ated sums for FY 2001 through 2005, but the Act did not specify what those sums should be. Another statute Congress passed in 2000 was the Public Health Improvement Act,16 which included directives to extend and intensify the study of SLE and charged NIAMS with coordinating with other ICs doing work related to SLE. NIAMS was asked to conduct or support research to include investigating the reasons for the preponderance of SLE in women, including African American women; basic research on disease causes; epidemiologic studies to examine disease progression, its frequency, and difference between sexes and racial and ethnic groups; development of improved diagnostic techniques; and clinical research to develop and evaluate new treatments. The Act also directed NIAMS to develop infor- mation and education programs for the health care community and the public. It was authorized appropriations for FY 2001 through 2003, but the Act did not specify sums. 16 Public Health Improvement Act, Public Law106-505, 106th Cong., 2nd sess. (November 13, 2000). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 323 Congress enacted the Rare Diseases Act of 200217 with the intent of increasing the study of rare diseases and disorders—“defined as those affecting fewer than 200,000 individuals in the United States”—and the Act includes Crohn’s disease as an example of a rare disease. NIH created the Office of Rare Diseases in 1993, but it lacked statutory authorization, so the Act requested that NIH establish the Office within the OD. The Act directed the Office to recommend a varied research and educational agenda and to promote coordination and cooperation across the NIH ICs and those they supported, and, in collaboration with directors of other ICs, it was enabled to make cooperative agreements and to award grants to regional centers of excellence on rare diseases. Other duties specified for the Office included promoting the establishment of an information clearinghouse on rare and genetic diseases for the public and medical community, liaising with national and international organizations, report- ing biennially on the activities that had and should occur, and reporting annually to Congress. The Office was appropriated “such sums as already have been appropriated for FY 2002, and $4,000,000 for each of the FY 2003 through 2006” for the purpose of cooperative agreements or grants for the regional centers of excellence for rare diseases. Congress enacted the Pancreatic Islet Cell Transplantation Act of 200418 to “increase the supply of pancreatic islet cells for research, to pro- vide for better coordination of Federal efforts and information on islet cell transplantation.” Annual reports prepared by the NIDDK-led Diabetes Mellitus Interagency Coordinating Committee were directed to evaluate the federal activities and programs related to pancreatic islet transplan- tation and research, recommend legislation to increase the supply of pancreas tissue for islet cell transplantation, and address the adequacy of federal funding. The Act did not provide funding authorization or appropriation amounts. The American Recovery and Reinvestment Act of 200919 was a fiscal stimulus package developed in response to the Great Recession. Of the money appropriated to NIH, $7,400,000,000 was transferred to the ICs and the Common Fund,20 in proportion to the appropriations otherwise made to them for FY 2009. The funds were to be used to “support additional scientific research,” and money was to be consolidated with and used 17 RareDiseases Act of 2002, Public Law 107-280, 107th Cong., 2nd sess. (November 6, 2002). 18 PancreaticIslet Cell Transplantation Act of 2004, Public Law 108-362, 108th Cong., 2nd sess. (October 25, 2004). 19 American Recovery and Reinvestment Act of 2009, Public Law 111–5, 111th Cong., 1st sess. (February 17, 2009). 20 Not included among the recipients were the National Institutes of Health–Buildings and Facilities, the Center for Scientific Review, the Center for Information Technology, the Clinical Center, and the Global Fund for HIV/AIDS, Tuberculosis and Malaria. PREPUBLICATION COPY—Uncorrected Proofs

324 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE for “the same purposes as the appropriation or fund to which [it] was transferred.” In addition, $1,800,000,000 was appropriated to the NIH for repair, renovation, and construction of non-federal and NIH facilities and for instrumentation and research equipment. The 21st Century Cures Act,21 enacted in 2016 to expedite the discov- ery, development, and delivery of new treatment and cures, appropriated $4.8 billion to biomedical research. While autoimmune disease research was not specifically named in the Act, the crosscutting nature of autoim- mune disease research could enable it to benefit from the funding desig- nated for NIH initiatives such as the NIH Beau Biden Cancer Moonshot, the Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, and the Precision Medicine Initiative. In addition, funding was directed to the Next Generation of Researchers Initiative to help support new researchers, sustain research careers, and promote growth, stability, and diversity of the biomedical research workforce. In 2018, the National Clinical Care Commission Act22 established an HHS Commission, which included NIH as a member, to evaluate and make recommendations on how to better leverage and coordinate federal programs related to as many as two metabolic or autoimmune diseases with insulin-related etiology. In making its recommendations, the Act instructed the Commission to consider preventing and reducing the dis- eases and complications, “gaps in Federal efforts to support clinicians in providing integrated high-quality care,” “improvement in and improved coordination of Federal education and awareness activities related to the prevention and treatment of the diseases,” methods for dissemination of educational materials, and opportunities for consolidating overlap in federal programs related to the diseases. The Commission was to submit an operating plan, which could include a budget for the Commission’s activities, and a final report to the HHS Secretary and Congress, and it decided to focus on type 1 and type 2 diabetes. Congress did not appro- priate funds for the Commission’s operation, and an HHS Joint Funding Agreement supported the Commission’s activities (National Clinical Care Commission, 2018). Relevant Bills or Resolutions That Did Not Pass There have been congressional actions directed to NIH autoimmune disease research efforts that Congress did not pass into law. One example is a bill that members of Congress submitted twice—the NIH Office of 21 21st Century Cures Act, Public Law 114-255, 114th Cong., 2nd sess. (December 13, 2016). 22 National Clinical Care Commission Act, Public Law 115-80, 115th Cong., 1st sess. (November 2, 2017). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 325 Autoimmune Diseases Acts of 199823 and 199924—which called for estab- lishing an Office of Autoimmune Diseases in the NIH OD. The 1999 bill was introduced by then Senator Joseph Biden (see Appendix F). Accord- ing to that proposed bill, the Director of the Office, consulting with the ADCC, was to recommend an agenda for autoimmune disease research across the ICs. The Director of the Office was also to promote coordina- tion and cooperation among the ICs involved in autoimmune disease research and those supported by their research; promote NIH allocation of resources for such research; annually report on the research, including identifying projects that should be conducted or supported; and serve as the principal advisor to HHS, NIH, CDC, and FDA and other agen- cies regarding autoimmune diseases. The 1999 bill authorized a FY 2000 appropriation of $950,000 (20 percent more than that of the 1998 bill) as well as “such sums necessary for fiscal years 2001 and 2002.” While both bills required establishing or operating the ADCC, and the ADCC had been formed by the time of the 1999 bill, the establishment and duties of the ADCC were not required by statute until The Children’s Health Act of 2000. In the 2000 Act, the ADCC was directed to carry out certain duties that had been outlined for the proposed NIH Office of Autoim- mune Diseases. Other select examples of congressional action are the Scleroderma Research and Awareness Act (Congresses of 2009–2010, 2011–2012, and 2013–2014)25,26,27 requesting the director of NIAMS to “expand, inten- sify, and coordinate” research of the disease; the Psoriasis and Psoriatic Arthritis Research, Cure, and Care Act of 2007,28 2009,29 and 2011,30 which encouraged the Director of NIH to “explore the development of a virtual Center of Excellence for Collaborative Discovery in Psoriasis and Comor- bid  Research  or some other mechanism through which public  and  pri- 23 NIH Office of Autoimmune Diseases Act of 1998, HR 4873, 105th Cong., 2nd sess., Congres- sional Record 144, no. 150, daily ed. (October 20, 1998); H 11695. 24 NIH Office of Autoimmune Diseases Act of 1999, S 1897, 106th Cong., 1st sess., Congres- sional Record 145, no. 157, daily ed. (November 9, 1999); S 14407. 25 Scleroderma Research and Awareness Act of 2010, HR 2408, 111th Cong., 1st sess., Congres- sional Record 155, no. 74, daily ed. (May 14, 2009); H 5664. 26 Scleroderma Research and Awareness Act of 2011, HR 1672, 112th Cong., 1st sess., Congres- sional Record 157, no. 57, daily ed. (May 2, 2011); H 2933. 27 Scleroderma Research and Awareness Act, S 1239, 113th Cong., 1st session, Congressional Record 159, no. 94, daily ed. (June 27, 2013) S 5498. 28Psoriasis and Psoriatic Arthritis Research, Cure, and Care Act of 2007, HR 1188, 110th Cong., 1st sess., Congressional Record 153, no. 30, daily ed. (February 16, 2007); H 1895. 29 Psoriasis and Psoriatic Arthritis Research, Cure, and Care Act of 2009, HR 930, 111th Cong., 1st sess., Congressional Record 155, no. 27, daily ed. (February 10, 2009); H 1156. 30 Psoriasis and Psoriatic Arthritis Research, Cure, and Care Act of 2011, S 1107, 112th Cong., 1st sess., Congressional Record 157, no. 74, daily ed. (May 26, 2011); S 3427. PREPUBLICATION COPY—Uncorrected Proofs

326 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE vate sector findings regarding psoriasis and its comorbid conditions can be regularly shared  and  leveraged”; the Prevention, Awareness, and Research of Autoimmune Disease Act of 200631 (as well as during the 2003–2004 Congress32), which required NIEHS to award grants to research environmental triggers of autoimmune diseases in genetically predis- posed people; and the Women’s Autoimmune Diseases Research and Pre- vention Act (Congresses of 2001–200233 and 2003–200434), which directed the ADCC to include research on the causes of autoimmune diseases in women, particularly genetic, hormonal, and environmental factors; devel- opment of information and education programs on risk factors, including hormonal and environmental factors; and community outreach to histori- cally underserved populations of women in its plan for NIH activities. CURRENT COORDINATION OF AUTOIMMUNE DISEASE AT NIH Role and Function of Autoimmune Diseases Coordinating Committee NIH established the Autoimmune Disease Coordinating Committee (ADCC) in 1998 in response to congressional interest in the autoimmune diseases and the need to coordinate activities across the ICs and with other federal health programs and activities for autoimmune diseases (ADCC, 2000).35 The inaugural ADCC membership consisted of repre- sentatives of the ICs that are engaged in autoimmune diseases research, and members from other federal departments and agencies that focus on autoimmune diseases, such as CDC, Veterans Administration, and FDA.36 In addition, although Congress did not require it, the ADCC extended membership invitations to advocacy groups and representatives from 31 Prevention, Awareness, and Research of Autoimmune Disease Act of 2006, HR 6214, 109th Cong., 2nd sess., Congressional Record 152, no. 123, daily ed. (September 27, 2006); H 7674. 32 Prevention, Awareness, and Research of Autoimmune Disease Act, HR 3359, 108th Cong., 1st sess., Congressional Record 149, no. 148, daily ed. (October 21, 2003); H 9811. 33 Women’s Autoimmune Diseases Research and Prevention Act, HR 5104, 107th Cong., 2nd sess., Congressional Record 148, no. 93, daily ed. (July 11, 2002); H 4552. 34 Women’s Autoimmune Diseases Research and Prevention Act, HR 370, 108th Cong., 1st sess., Congressional Record 149, no. 14, daily ed. (January 27, 2003); H 170. 35 Children’s Health Act of 2000, Public Law 106–310, 106th Cong. (October, 17, 2000), H.R. 4365. Departments of Labor, Health And Human Services, And Education, And Related Agencies Appropriation Bill, 1998, HR 105-205, 105th Cong., 1st sess. (July 25, 1997). Departments Of Labor, Health And Human Services, And Education And Related Agencies Ap- propriation Bill, 1998, 105th Cong., 1st sess. (July 24, 1997): Senate Report 105-58. 36 Children’s Health Act of 2000, Public Law 106–310, 106th Cong., 2nd sess. (October, 17, 2000), H.R. 4365. PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 327 private autoimmune disease organizations.37 The current membership of ADCC remains similar, and the membership of advocacy groups has only continued to grow, providing these stakeholders with a greater voice (NIAID, 2021a). NIAID is the current chair of the ADCC. In the first two years of its existence, ADCC had several major accom- plishments, as documented in its first report released in 2000 (ADCC, 2000). The committee analyzed information on autoimmune diseases research funding and research at the NIH and established multi-IC col- laborative working groups for autoimmune diseases. ADCC was also instrumental in enhancing coordination and facilitating private and pub- lic partnerships for autoimmune research both within the ICs and with private disease organizations. In FY 1999, NIH “committed more than $393 million” to support autoimmune disease research (ADCC, 2000). A congressional conference report38 stated that NIAID was being appropri- ated more funding for FY 1999 than the House and Senate had requested, urged NIAID to expand autoimmune disease research, and pointed to ADCC to provide greater coordination and focus for such research, which likely facilitated ADCC’s charge. ADCC released reports in 2000, 2002, and 2005, each with a different focus and purpose. ADCC’s initial report summarized the state of autoim- mune research and funding at NIH and identified the major challenges facing autoimmune diseases research (ADCC, 2000): 1. “Development of a mechanism-based, conceptual understanding of autoimmune disease; 2. Translation of this knowledge into new, broadly applicable strate- gies for treatment and prevention of multiple diseases; and 3. Development of sensitive tools for early and definitive diagnosis, disease staging, and identification of at-risk individuals.” The subsequent ADCC report in 2002 (ADCC, 2002) was an autoim- mune diseases research plan that had been requested by Congress, and it was informed by an expert panel that identified priority areas for autoim- mune diseases research and considerations for implementing the research plan. The research plan had four major areas of emphasis: • “reducing the burden of disease; • enhancing understanding of disease etiology; 37 Personal communication. Ellen Goldmuntz, MD, PhD, Section Chief, Rheumatologic Autoimmune Disease Section, NAID. August 11, 2021. 38 Omnibus Consolidated and Emergency Supplemental Appropriations Act, 1999. Public Law 105-277, 105th Cong. (October 21, 1998). Conference Report 105-825 to accompany H.R. 4328. PREPUBLICATION COPY—Uncorrected Proofs

328 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE • improving diagnosis, treatment, and prevention; and increasing training, education; and • information dissemination activities.” The report underscored the importance of leveraging scientific and clinical knowledge to inform multiple autoimmune diseases and coor- dinating efforts to efficiently utilize available resources in both federal and private agencies, among others (ADCC, 2002). The report also called for Congress to appropriate additional funds in support of research in autoimmunity. Congress authorized funding for developing the ADCC research plan through amendments to the Children’s Health Act of 2000 (ADCC, 2002). A resolution submitted in the House in 200439 called for increase in appropriations to carry out the autoimmune diseases research. The committee, however, was unable to find additional information on appropriations for the research plan or its implementation. The final ADCC report published in 2005 summarized progress made since the publication of the research plan in 2002 and pointed to funded and soon-to-be funded activities that signify NIH’s commitment to mak- ing progress in the areas identified in the research plan and encouraged continued investments in those areas. ADCC reports ceased after the NIH Reform Act of 2006, which consolidated all the disparate reports required by law from NIH ICs in one comprehensive biennial report to Congress. As of FY 2016, NIH has further consolidated biennial reporting into a triennial report (ADCC, 2005). The amount of NIH reporting to Congress on autoimmune diseases has changed over time. ADCC reports ran 33 to145 pages. In the NIH biennial reports for the years FY 2006 to 2009, the autoimmune disease section, which included type 1 diabetes, ran 14 to 19 pages, and in the reports for FY 2010 to 2013, including a new section on type 1 diabetes, autoimmune disease reporting ran 9 to 12 pages. For the FY 2014 to 2015 report, including a new diabetes section that intermixed type 1 and type 2 diabetes, autoimmune disease reporting ran 17 pages. In the most recent report, the first triennial report for the period FY 2016 to 2018, after including the section combining type 1 and type 2 diabetes, the content on autoimmune disease totaled 21 pages. The field of autoimmune disease research at NIH has expanded over time, yet the amount of reporting 39Expressing the sense of the House of Representatives with respect to the level of funding pro- vided to the National Institutes of Health for carrying out the Autoimmune Diseases Research Plan., H.Res.610, 108th Cong. 2nd sess. (April 28, 2004). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 329 to Congress on NIH activities and priorities in the field appears to have diminished.40 While ADCC continues to be active to date, the committee was unable to identify information from publicly available sources to indicate the extent to which ADCC’s activities contribute to research and funding priorities at NIH. The agenda for the last ADCC public meeting held in May 2020 focused on celiac disease, a topic the group pursued after con- gressional language addressed concerns about the disease, and featured invited speakers who addressed research gaps and opportunities, and unmet needs according to patients (ADCC, 2020). As a follow-up to this meeting, “NIH plans to develop a Research, Condition, and Disease Cat- egory (RCDC) report for celiac disease within the NIH Research Portfolio Online Reporting Tools (RePORT) website” (NIH, 2021c). Establishing a celiac disease RCDC category will make all NIH-funded projects related to celiac disease available in a publicly accessible format. In addition, in FY 2021, NIAID is “developing a Notice of Special Interest to encourage investigator-initiated celiac disease research.” The ADCC is now using the process it used for celiac disease to explore other gaps and topics of interest to the community.41 An earlier public meeting held in April 2019 introduced the Accelerating Medicines Partnerships (AMP), a collabora- tive initiative for autoimmune diseases sponsored by NIAMS, NIAID, and other non-NIH partners (ADCC, 2019). Currently, the IC representatives on ADCC convene regularly to review shared priorities and activities, but information about these meetings is not available to the public, so the committee is unable to report on the scope of current ADCC activities.42 Since its establishment, ADCC has played a role in coordinating research activities for autoimmune diseases across the ICs and with non- NIH external partners. Based on the review of available public infor- mation about ADCC, and interviews with NIAID representatives, the committee notes that ADCC functions as a convener of ICs and external partners and provides a forum for ICs to share information and coordi- nate their activities on autoimmune disease research. Outside of ADCC meetings, ICs may decide to develop or support collaborative research activities influenced in part by their participation in ADCC meetings, but this was difficult to assess from public documents. Currently, ADCC has 40 The committee is aware that information on autoimmune diseases may appear in the biennial and triennial reports in sections other than the autoimmune disease and diabetes sections. The intention was to estimate the clearly indicated content on autoimmune disease in the reports. 41 Personal communication. Ellen Goldmuntz, MD, PhD, Section Chief, Rheumatologic Autoimmune Disease Section, NAID. August 11, 2021. 42 Personal communication. Ellen Goldmuntz, MD, PhD, Section Chief, Rheumatologic Autoimmune Disease Section, NAID. May 11, 2021. PREPUBLICATION COPY—Uncorrected Proofs

330 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE no dedicated funding or staff; NIH staff who support ADCC operations do so as part of their general work responsibilities. Other Modes of Coordination and Collaboration The committee investigated other mechanisms by which the NIH coordinates and collaborates on autoimmune disease research, both across the NIH and external to the NIH. For example, NIH established the Center for Human Immunology, Autoimmunity, and Inflammation as an NIH-wide “intramural initiative designed to study the human immune system” (NIH, 2012). Originally, its operation was supported jointly by several ICs, and this coordination and collaboration resulted in a study on human response to influenza vaccine that was collectively useful.43 However, the center could not sustain this funding model, partly because of difficulties in reaching agreement on projects that could yield benefit to all contributors, and eventually the Center was placed in NIAID. NIH and FDA created the intramural NIH–FDA Immunology Interest Group in the 1990s as a part of an effort to foster interaction among scien- tists across both NIH and FDA, then located on the Bethesda campus.44 It is one of the largest of such NIH groups and has led to offshoot groups. Speakers invited from within and outside NIH deliver weekly video seminars that anyone can view, and a large and active Listserv of some 1,500 listees further encourages collaboration. The Immunology Interest Group connects trainees and younger investigators with more established investigators across NIH and external experts, with a major vehicle being an annual workshop internal to NIH and FDA where approximately 400 attendees present abstracts and posters on active and unpublished work. The workshop, which the ICs jointly support, includes talks by intramural and extramural investigators who interact with trainees. At the request of Congress, NIH established the NIAMS-led Lupus Federal Working Group (LFWG) in 2003 to facilitate collaboration on SLE “among NIH components, other federal agencies, voluntary and pro- fessional organizations, and industry groups with an interest in lupus” (NIAMS, 2019). With the help of LFWG and others, NIAMS published The Future Directions of Lupus Research in 2007, intended to guide the U.S. investment in SLE research (NIAMS, 2020a) and a follow-up Action Plan 43 Personal communication. Daniel Kastner, MD, PhD, Scientific Director, Division of In- tramural Research Head, Inflammatory Disease Section, National Human Genome Research Institute, NIH, August 30, 2021. 44 Personal communication. Pamela L. Schwartzberg, M.D., Ph.D, Chief, Cell Signaling and Immunity Section, NIAID; Senior Investigator, NHGRI, NIH, September 3, 2021. PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 331 for Lupus Research in 2015 (NIAMS, 2020a).45 The latter was intended to “inform priority-setting processes among all lupus-related organizations” (NIAMS, 2015, 2020a) but not to dictate approaches to research or to compete with NIAMS’s strategic plans.46 In addition to inviting experts to deliver talks, LFWG meetings serve as a forum for hearing patient concerns and disseminating information among members. The National Institutes of Health Reform Act of 200647 directed NIH to establish DPCPSI, which sits within the NIH OD (DPCPSI, 2021). One of the Division’s responsibilities is to coordinate the research and activi- ties of the various Offices that operate within the OD, such as the Office of AIDS Research and the Office of Research on Women’s Health (ORWH) (DPCPSI, 2021). The missions of these Offices vary, but in general they serve to enhance and promote the research of focus by coordinating and integrating activities across NIH’s intramural and extramural activities, as well as to stimulate and support research, disseminate research results, educate the public, and foster the development of a workforce for the field (OBSSR, 2021; ORWH, 2021b; SGMRO, 2021). Establishing an Office requires having a research focus that cuts across most NIH ICs, with the Office addressing concerns, particularly roadblocks, that the ICs share.48 For example, NIH-funded researchers were inconsistent in the ways they recorded sex in clinical and animal trials, and while it was unlikely that a single IC would undertake advancing the policies and tools to cap- ture this data in a uniform manner, it was appropriate for ORWH to do so. Similarly, ORWH initiated the Building Interdisciplinary Research Careers in Women’s Health program, a career development program, which “connects junior faculty to senior faculty with a shared interest in women’s health and sex differences research” (ORWH, 2021a). DPCPSI’s budget funds the activities of the NIH Offices and their staffs. Although the Offices can fund research, most can only do so by collaborating with one or more ICs. Each Office has a coordinating committee of IC repre- sentatives that serves as a primary coordinating hub to identify areas of need, gather consensus, and identify funding opportunities. The Offices release strategic plans, and the NIH triennial report to Congress describes Office activities. 45 Available at https://www.niams.nih.gov/about/working-groups/lupus-federal/ac- tion-plan (accessed December 6, 2021). 46 Personal communication. Marie Mancini, PhD, Program Director, Systemic Autoim- mune Diseases Biology, Division of Extramural Research, NIAMS, NIH, September 7, 2021. 47 PL 109-482. 48 Personal communication. James M. Anderson, M.D., Ph.D., DPCPSI Director, September 7, 2021. PREPUBLICATION COPY—Uncorrected Proofs

332 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE Opportunities for IC Collaboration During the CSR Review Process Independent of the efforts of ADCC to coordinate autoimmune research activities, ICs can take steps among themselves to coordinate their research interests. The CSR review process, as noted earlier, presents an opportunity for ICs to collaborate on research activities, including col- laborating on research funding for autoimmune diseases. CSR reviews all unsolicited grant applications and assigns them the appropriate IC for funding according to guidelines the ICs provide (Hodge, 2021). Those guidelines direct CSR on how to address grant applications that tackle areas of shared interest for multiple ICs. ICs may also “bid” to be part of grants that they have an interest in, which offers an opportunity for ICs to collaborate on studies that can leverage their mutual expertise and resources.49 Since the committee did not have further access to materials governing this process or additional details on the process, it is unclear how well this process works and the frequency with which ICs bid on and collaborate on projects. Major NIH Initiatives Involving Collaboration A number of recent and ongoing initiatives provide evidence of col- laboration on autoimmune research across ICs as well as including other federal agencies and external organizations and researchers. Institute representatives, during their meetings with the committee, along with information on IC websites, highlighted the major initiatives below. Collaborations Among ICs Clinical Islet Transplant (CIT) Consortium.50 Type 1 diabetes (CIT Consortium, 2021). • Collaborators include:  NIDDK  NIAID  Principal investigators and research centers in the United States and Sweden • Description: “The CIT Consortium is a network of clinical centers and a data coordinating center established in 2004 to conduct 49 According to multiple NIH speakers who spoke at the committee’s public information- gathering sessions (Goldmuntz, 2020; Hodge, 2021; McNamara, 2021). 50 Website available at https://www.citisletstudy.org/what.html (accessed December 2, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 333 studies of islet transplantation in patients with type 1 diabetes. Studies conducted by the CIT Consortium focus on improving the safety and long-term success of methods for transplanting islets, the insulin-producing cells of the pancreas, in people whose own islets have been destroyed by the autoimmune process that char- acterizes type 1 diabetes.” Principal areas of focus include:  “improving the isolation and viability of islets  reducing complications of the islet transplant procedure, (e.g., bleeding and clotting in the blood vessels of the liver)  reducing the side effects of immunosuppression  achieving good blood sugar control without hypoglycemia  following the fate of islets after transplantation and determin- ing why donor islets sometimes fail  evaluating new ways to safely prevent immune rejection of donor tissues” Autoantigens and Neoantigens Function in the Etiology and Patho- physiology of Type 1 Diabetes. Type 1 diabetes (NIH et al., 2021d). • Collaborators include:  NIDDK  NIAID • Description: The purpose of this initiative is to characterize the “function of neoepitopes and neoantigens in type 1 diabetes. This includes the function that post-translational modifications might have in the humoral and cell mediated autoimmune responses and overall in the etiology and pathophysiology of type 1 diabetes.” Autoimmune Centers of Excellence (ACEs).51,52 SLE, type 1 diabetes, inflammatory bowel disease, multiple sclerosis, pemphigus vulgaris, psoriasis, scleroderma, rheumatoid arthritis, and Sjögren’s disease (ACE, 2020). 51 Website available at https://www.autoimmunitycenters.org/mission.php (accessed December 2, 2021). 52 Autoimmunity Centers of Excellence Progress Report 2021 is available at https://www. autoimmunitycenters.org/ACE%20Public%20Progress%20Report%20Jan-31-2022%20DAIT. pdf (accessed March 3, 2022). PREPUBLICATION COPY—Uncorrected Proofs

334 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE • Collaborators include:  NIAID  NIDDK  NIH ORWH  Clinical research sites and principal investigators • Description: “ACEs conduct collaborative basic and clinical research on autoimmune diseases. Close interaction between cli- nicians and basic researchers accelerates the discovery, develop- ment, and translation of therapies for autoimmune diseases from the lab to use in the clinic.” The principal areas of focus include:  Encouraging and enabling collaborative research—“across scientific disciplines, across medical specialties, and between basic and clinical scientists—in the search for effective treat- ments for autoimmune diseases”  Evaluating the safety and efficacy of treatment strategies for autoimmune diseases  Exploring the immune mechanisms underlying the agents evaluated in these ACE clinical trials Office of Rare Diseases Research.53 A rare disease is defined as “a condition that affects fewer than 200,000 people in the United States,” which includes some autoimmune diseases (NCATS, 2021b). • Collaborators include:  The Office sits in NCATS but is NIH-wide (NCATS, 2021a) • Description: This Office facilitates and coordinates NIH-wide activities that involve research for a broad range of rare diseases, including autoimmune diseases. Duties of the Office include:  Developing and maintaining a centralized database on rare diseases.  Coordinating and providing liaison with organizations world- wide concerned with rare diseases research and orphan prod- ucts development.  Advising the Office of the Director on matters related to NIH- sponsored research involving rare diseases.  Responding to information and policy requests about rare diseases. 53 Website available at https://ncats.nih.gov/about/center/org/ordr (accessed December 2, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 335 Collaborations Among ICs and External Agencies, Organizations, and Industry Myasthenia Gravis Rare Disease Network (MGNet).54 Myasthenia gravis and its subtypes (Rare Diseases Clinical Research Network, 2021). • Collaborators include:  NCATS  NINDS  Myasthenia Gravis Foundation of America  Industry (not named)  Academic medical centers • Description: The “Myasthenia Gravis Rare Disease Network serves as a centralized, international consortium for physicians, scientists, patient advocacy groups, as well as industry partners to develop resources and implement ideas to enhance discovery, treatment, and advocacy for the patient community. The imme- diate goals of MGNet are to further define how patients respond to conventional treatments over time, evaluate a novel drug for therapy of some forms of MG, find biological markers of the disease (biomarkers), and encourage new scientists to engage in research on MG.” Accelerating Medicines Partnership® (AMP®) Program including Autoimmune and Immune-Mediated Diseases (AMP® AIM).55 Rheuma- toid arthritis, SLE, psoriatic spectrum diseases, and Sjögren’s disease (NIAMS, 2021a; NIH, 2021b). • Collaborators include:  NIAMS  NIAID  NIDCR (NIH et al., 2021a)  ORWH  FDA (NIH, 2021b)  European Medicines Agency  Multiple biopharmaceutical and life science companies  Multiple nonprofit organizations • Description: The purpose of the AMP® and AMP® AIM pro- gram is to establish disease teams that will focus on autoimmune and immune-mediated diseases, including rheumatoid arthritis, 54 Website available at https://www.rarediseasesnetwork.org/mgnet (accessed December 2, 2021). 55 The AMP® AIM program expands and builds upon the AMP® RA/SLE program. PREPUBLICATION COPY—Uncorrected Proofs

336 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE SLE, psoriatic spectrum diseases, and Sjögren’s disease, with the goal of developing a thorough understanding of the cellular and molecular disease pathways and identifying novel targets for intervention. Immune Tolerance Network (ITN).56 Type 1 diabetes, SLE, multiple sclerosis (Immune Tolerance Network, 2021). • Collaborators include:  NIAID  NIDDK  The Juvenile Diabetes Research Foundation  Clinical sites and investigators worldwide • Description: ITN’s purpose is “to advance the clinical applica- tion of immune tolerance by performing high-quality clinical tri- als of emerging therapeutics integrated with mechanism-based research. In particular, [they] aim to establish new tolerance thera- peutics, develop a better understanding of the mechanisms of immune function and disease pathogenesis, [and] identify new biomarkers of tolerance and disease.” ITN conducts research on organ and cellular transplantation, autoimmune diseases, allergy, asthma, and type 1 diabetes. ITN collaborates with academic, government, and industry leaders to develop and fund cutting- edge immune tolerance research. Environmental Determinants of Diabetes in the Young (TEDDY) Study.57 Type 1 diabetes (Teddy Study Group, 2008). • Collaborators include:  NIDDK  NIAID  NICHD  NIEHS  CDC  Juvenile Diabetes Research Foundation  Clinical centers in the United States and Germany, Sweden, and Finland • Description: The long-term goal of the TEDDY study—an obser- vational study that enrolled 8,668 participants with a 2025 estimated completion date—“is the identification of infectious 56 Website available at https://www.immunetolerance.org (accessed December 2, 2021). 57 Website available at https://teddy.epi.usf.edu (accessed December 2, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 337 agents, dietary factors, or other environmental agents, including psychosocial factors which trigger [type 1 diabetes] in geneti- cally susceptible individuals or which protect against the disease. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse [type 1 diabetes] (Clinicaltrials.gov, 2021). Type 1 Diabetes Trial Net (TrialNet).58 Type 1 diabetes (TrialNet, 2018). • Collaborators include:  NIDDK  NIAID (ADCC, 2005)  NICHD (NIH et al., 2021e)  National Center for Complementary and Alternative Medicine (NIH et al., 2021e)  Juvenile Diabetes Research Foundation (TrialNet, 2018)  American Diabetes Association  Helmsley Charitable Trust  International network of researchers • Description: TrialNet is an international network of researchers exploring ways to prevent, delay, and reverse the progression of type 1 diabetes (TrialNet, 2018). TrialNet was established in response to the Surgeon General’s Report Healthy People 2000, which identified diabetes as a national health objective for the nation. In response to the report, Congress created the Diabetes Research Working Group to develop a plan for diabetes research. One of the group’s recommendations was to conduct additional research studies and clinical trials on type 1 diabetes prevention. SUMMARY NIH is the primary funding agency for biomedical research, including autoimmune disease research. In 2020, NIH spent more than $1 billion on autoimmune disease research. Currently, 12 of 24 ICs provide the major- ity of funding to support extramural investigator-initiated autoimmune disease research, and 11 of 24 ICs provide funding to support intramural autoimmune disease research programs. Each IC has a different mission, and often has different research priorities and focuses on different auto- immune diseases than the other ICs. The autoimmune disease research focus of each IC ranges across basic, translational, and clinical research, and sometimes ICs have overlapping missions in autoimmune disease 58 Website available at https://www.trialnet.org (accessed December 2, 2021). PREPUBLICATION COPY—Uncorrected Proofs

338 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE research. These overlapping missions could impede the coordination of autoimmune disease research programs. The committee identified evidence of attempts to coordinate funding and research efforts, but it was difficult for the committee to assess the effectiveness of these efforts. While ADCC continues to be active to date, the committee was unable to determine the extent to which ADCC’s activ- ities contribute to setting research and funding priorities for autoimmune disease research at the NIH. The lack of standardization of the process of strategic planning across ICs and consistency in the release of strategic plans by individual ICs has important implications, since it may pose an obstacle for ICs in coordinating their strategic planning efforts, and subsequently, their funding and research efforts for autoimmune diseases. REFERENCES ACE (Autoimmunity Centers of Excellence). 2020. Welcome to the autoimmunity centers of excellence. https://www.autoimmunitycenters.org (accessed August 5, 2021). ADCC (Autoimmune Diseases Coordinating Committee). 2000. Report of the Autoimmune Diseases Coordinating Committee. National Institutes of Health. ADCC. 2002. Autoimmune Diseases Coordinating Committee: Autoimmune diseases research plan. National Institutes of Health. ADCC. 2005. Progress in autoimmune diseases research. National Institutes of Health: Autoim- mune Diseases Coordinating Committee. ADCC. 2019. NIH autoimmune diseases coordinating committee agenda. https://www.niaid.nih. gov/sites/default/files/2019-ADCC-Agenda.pdf (accessed July 3, 2021). ADCC. 2020. Celiac disease-focused autoimmune disease coordinating committee (ADCC) meeting agenda. https://www.niaid.nih.gov/sites/default/files/2020-ADCC-Agenda.pdf (ac- cessed July 3, 2021). Autoimmune Association. 2021. Autoimmune Association impact on fighting autoimmune dis- eases. https://autoimmune.org/about-us/our-impact/ (accessed December 6, 2021). Bamias, G., K. O. Arseneau, and F. Cominelli. 2017. Mouse models of inflammatory bowel disease for investigating mucosal immunity in the intestine. Current Opinion in Gastro- enterology 33(6):411–416. Barron, K. S. 2021. Autoimmunity research in the division of intramural research. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 3, March 4, Webinar. CIT (Clinical Islet Transplantation) Consortium. 2021. Clinical Islet Transplantation Consor- tium: Welcome. https://www.citisletstudy.org/ (accessed August 5, 2021). Clinicaltrials.gov. 2021. TEDDY - The environmental determinants of diabetes in the young. https://clinicaltrials.gov/ct2/show/NCT00279318 (accessed March 1, 2022). CRS (Congressional Research Service). 2019. The National Institutes of Health (NIH): Back- ground and congressional issues. Congressional Research Service. CRS. 2020. Labor, health and human services, and education: FY2020 appropriations. https:// www.everycrsreport.com/reports/R46492.html (accessed August 4, 2021). CRS. 2021. National Institutes of Health (NIH) funding: FY1996–FY2022. CSR (Center for Scientific Review). 2020. Study sections. https://public.csr.nih.gov/Study Sections (accessed August 4, 2021). CSR. 2021. About CSR. https://public.csr.nih.gov/AboutCSR (accessed November 29, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 339 DPCPSI (Division of Program Coordination, Planning, and Strategic Initiatives). 2021a. About DPCPSI. https://dpcpsi.nih.gov/about (accessed October 27, 2021). Goldmuntz, E. 2020. Charge to the comittee. Paper read at NASEM Committee for the As- sessment of NIH Research on Autoimmune Diseases: Meeting 1, November 18, 2020, Webinar. Green, E. D., C. Gunter, L. G. Biesecker, V. Di Francesco, C. L. Easter, E. A. Feingold, A. L. Felsenfeld, D. J. Kaufman, E. A. Ostrander, W. J. Pavan, A. M. Phillippy, A. L. Wise, J. G. Dayal, B. J. Kish, A. Mandich, C. R. Wellington, K. A. Wetterstrand, S. A. Bates, D. Leja, S. Vasquez, W. A. Gahl, B. J. Graham, D. L. Kastner, P. Liu, L. L. Rodriguez, B. D. Solomon, V. L. Bonham, L. C. Brody, C. M. Hutter, and T. A. Manolio. 2020. Strategic vision for improving human health at the forefront of genomics. Nature 586(7831):683–692. HHS (Health and Human Services). 2022. HHS agencies & offices. https://www.hhs.gov/ about/agencies/hhs-agencies-and-offices/index.html (accessed January 14, 2022). Hodge, D. 2021. NIH peer review, a CSR perspective. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 2 (Continuation), February 1, 2021, Webinar. Immune Tolerance Network. 2021. Developing, funding & conducting clinical trials in immune tolerance. https://www.immunetolerance.org (accessed August 5, 2021). IRP (Intramural Research Program). 2021a. Organization and leadership. https://irp.nih.gov/ about-us/organization-and-leadership (accessed November 4, 2021). IRP. 2021b. Principal investigators. https://irp.nih.gov/our-research/principal-investigators (accessed Augutst 2, 2021). IRP. 2021c. What is the IRP? https://irp.nih.gov/about-us/what-is-the-irp (accessed No- vember 4, 2021). Kastner, D. 2021. Horror autoinflammaticus: Autoimmune disease research in the NHGRI intra- mural research program. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 3, March 3, 2021, Webinar. Keenan, A. 2020. Study background. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 1, Webinar. Kirby, R. 2021. NHLBI—committee for the assessment of NIH research on autoimmune diseases. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 2 (Continuation), February 1, 2021, Webinar. Mancini, M. 2021. Autoimmune disease research at the National Institute of Arthritis and Mus- culoskeletal and Skin Diseases. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 2 (Continuation), February 1, 2021, Webinar. McNamara, J. 2021. Autoimmune disease research supported by extramural NIAID. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 2 (Continuation), February 1, 2021, Webinar. Murrin, S. 2019. Vetting peer reviewers at NIH’s Center for Scientific Review: Strengths and limi- tations. Office of Inspector General. https://oig.hhs.gov/oei/reports/oei-01-19-00160. asp. National Clinical Care Commission. 2018. Operating plan: 2018–2021. https://health.gov/ sites/default/files/2019-09/nccc_three_year_operating_plan.pdf (accessed January 14, 2022). NCATS (National Center for Advancing Translational Sciences). 2016. NCATS strategic plan. Bethesda, MD: NCATS. https://ncats.nih.gov/strategicplan (accessed March 3, 2022). NCATS. 2021a. About the center. https://ncats.nih.gov/about/center (accessed December 1, 2021). NCATS. 2021b. FAQs about rare diseases. https://rarediseases.info.nih.gov/diseases/pages/ 31/faqs-about-rare-diseases (accessed December 6, 2021). PREPUBLICATION COPY—Uncorrected Proofs

340 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE NCI (National Cancer Institute). 2018. National Cancer Institute overview and mission. https:// www.cancer.gov/about-nci/overview (accessed August 6, 2021). NCI. 2019a. Annual plan & budget proposal for fiscal year 2021. Bethesda, MD: National Cancer Institute. NCI. 2019b. Study tests immunotherapy in people with cancer and autoimmune diseases. https:// www.cancer.gov/news-events/cancer-currents-blog/2019/immunotherapy-cancer- autoimmune-diseases-clinical-trial (accessed August 5, 2021). NCI. 2021a. Annual plan & budget proposal for fiscal year 2023. Bethesda, MD. https://www. cancer.gov/research/annual-plan/2023-annual-plan-budget-proposal-aag.pdf (ac- cessed January 14, 2022). NCI. 2021b. NCI annual plan & budget proposal for fiscal year 2022. Bethesda, MD: National Cancer Institute. https://www.cancer.gov/research/annual-plan (accessed August 4, 2021). NEI (National Eye Institute). 2020. Immunoregulation section. https://www.nei.nih.gov/ research/research-labs-and-branches/laboratory-immunology/immunoregulation- section (accessed August 6, 2021). NEI. 2021a. National Eye Institute (NEI). nih.gov/about-nih/what-we-do/nih-almanac/ national-eye-institute-nei (accessed August 6, 2021). NEI. 2021b. National Eye Institute strategic plan: Vision for the future 2021–2025. Bethesda, MD: National Eye Institute. NEI. 2021c (unpublished). NEI strategic plan 2021 draft for public comment. Bethesda, MD: National Eye Institute. NHGRI (National Human Genome Research Institute). 2018. NHGRI vision and mission. https://www.genome.gov/about-nhgri/NHGRI-Vision-and-Mission (accessed Au- gust 6, 2021). NHLBI (National Heart, Lung, and Blood Institute). 2014. The NHLBI mission statement. https://www.nhlbi.nih.gov/about/mission-statement (accessed November 8, 2021). NHLBI. 2016. Charting the future together: The NHLBI strategic vision. Bethesda, MD: National Heart, Lung, and Blood Institute. NIAID (National Institute of Allergy and Infectious Diseases). 2016. Unsolicited, investigator- initiated research. https://www.niaid.nih.gov/grants-contracts/unsolicited-investiga- tor-initiated-research (accessed December 16, 2021). NIAID. 2017. NIAID strategic plan 2017. Bethesda, MD: National Institute of Allergy and Infectious Diseases. NIAID. 2020. Solicited, NIAID-requested research. https://www.niaid.nih.gov/grants-con- tracts/solicited-niaid-requested-research (accessed January 4, 2022). NIAID. 2021a. Autoimmune Diseases Coordinating Committee member organizations. https:// www.niaid.nih.gov/about/autoimmune-diseases-coordinating-committee-members (accessed July 3, 2021). NIAID. 2021b. Budget & planning. https://www.niaid.nih.gov/about/budget-planning (ac- cessed August 4, 2021). NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases). 2015. Action plan for lupus research. Bethesda, MD: NIAMS. https://www.niams.nih.gov/about/ working-groups/lupus-federal/action-plan (accessed March 3, 2022). NIAMS. 2019. Lupus Federal Working Group. https://www.niams.nih.gov/about/working- groups/lupus-federal (accessed November 2, 2021). NIAMS. 2020a. The future directions of lupus research. https://www.niams.nih.gov/about/ future-directions-lupus-research (accessed November 2, 2021). NIAMS. 2020b. Strategic plan fiscal years 2020-2024: Turning discovery into health Bethesda, MD. NIAMS. 2021a. Accelerating Medicines Partnership® (AMP®) Program. https://www.niams. nih.gov/grants-funding/funded-research/accelerating-medicines (accessed December 6, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 341 NIAMS. 2021b. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-institute-arthri- tis-musculoskeletal-skin-diseases-niams (accessed August 6, 2021). NICHD (Eunice Kennedy Shriver National Institute of Child Health and Human Devel- opment). 2019. NICHD strategic plan 2020. Bethesda, MD: Eunice Kennedy Shriver National Institute of Child Health and Human Development. NICHD. 2020. Implementing a Maternal Health and Pregnancy Outcomes Vision for Everyone (IMPROVE) initiative. https://www.nichd.nih.gov/research/supported/IMPROVE (accessed December 6, 2021). NIDCR. 2020. 20202025 NIDCR strategic plan. https://www.nidcr.nih.gov/about-us/strate- gic-plan/2020-2025 (accessed August 5, 2021). NIDCR. 2021a. Mission. https://www.nidcr.nih.gov/about-us/mission (accessed December 1, 2021). NIDCR. 2021b. NIDCR strategic plan 2021–2026. https://www.nidcr.nih.gov/about-us/ strategic-plan (accessed December 6, 2021). NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases). 2021a. Mission & vision. https://www.niddk.nih.gov/about-niddk/meet-director/mission-vision (ac- cessed December 1, 2021). NIDDK. 2021b. NIDDK strategic plan for research. https://www.niddk.nih.gov/about-niddk/ strategic-plans-reports/planning-process-for-niddk-strategic-plan (accessed August 4, 2021). NIDDK. 2021c. Strategic plan for research: Pathways to health for all. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases. NIEHS (National Institute of Environmental Health Sciences). 2018. Advancing environmen- tal health sciences improving health. Bethesda, MD: National Institute of Environmental Health Sciences. NIEHS. 2021. Autoimmune disease and immunotoxicology. https://www.niehs.nih.gov/re- search/supported/health/autoimmune/index.cfm (accessed August 6, 2021). NIGMS (National Institute of General Medical Sciences). 2018. Mission. https://www. nih.gov/about-nih/what-we-do/nih-almanac/national-institute-general-medical- sciences-nigms (accessed November 8, 2021). NIGMS. 2021. National Institute of General Medical Sciences 5-year strategic plan 2021-2025. Bethesda, MD: National Institute of General Medical Sciences. NIH (National Institutes of Health). Receipt and referral. https://grants.nih.gov/grants/ receipt-referral.htm (accessed October 27, 2021). NIH. 2010. History of congressional appropriations, fiscal years 2000–2009. https://officeofbud- get.od.nih.gov/pdfs/FY21/Approp%20History%20by%20IC%20FY%202000%20-%20 FY%202009%20(V).pdf (accessed December 6, 2021). NIH. 2012. Biennial report of the director: Fiscal years 2008 & 2009. https://report.nih.gov/ biennialreport0809/Default.aspx (accessed November 11, 2021). NIH. 2013. What happens to your grant application: A primer for new applicants. https://public. csr.nih.gov/sites/default/files/2017-10/NewApplicantsGrantApplicationPrimer.pdf (accessed August 4, 2021). NIH. 2015. NIH-wide strategic plan, fiscal years 2016–2020. Bethesda, MD: National Institutes of Health. NIH. 2016. Report of the director—National Institutes of Health: Fiscal years 2014 and 2015. Bethesda, MD: National Institutes of Health. NIH. 2017a. Mission and goals. https://www.nih.gov/about-nih/what-we-do/mission-goals (accessed October 27, 2021). NIH. 2017b. The NIH intramural research program. https://www.nih.gov/research-training/ lasker-clinical-research-scholars/nih-intramural-research-program (accessed Novem- ber 24, 2021). PREPUBLICATION COPY—Uncorrected Proofs

342 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE NIH. 2018. Peer review. https://grants.nih.gov/grants/peer-review.htm#Overview (accessed August 4, 2021). NIH. 2019a. NIH peer review: Grants and cooperative agreements. Bethesda, MD: National Institutes of Health. NIH. 2019b. Types of grant programs. https://grants.nih.gov/grants/funding/funding_pro- gram.htm (accessed September 3, 2021). NIH. 2020a. Budget. https://www.nih.gov/about-nih/what-we-do/budget (accessed July 3, 2021). NIH. 2020b. History of congressional appropriations, fiscal years 2010–2019. https://officeofbud- get.od.nih.gov/pdfs/FY21/Approp%20History%20by%20IC%20FY%202010%20-%20 FY%202019%20(V).pdf (accessed December 6, 2021). NIH. 2021a. About the office of the NIH director. https://www.nih.gov/institutes-nih/nih- office-director (accessed October 27, 2021). NIH. 2021b. Accelerating Medicines Partnership® (AMP®). https://www.nih.gov/research- training/accelerating-medicines-partnership-amp (accessed December 6, 2021). NIH. 2021c. FY 2022 congressional justification: Department of Health and Human Services. https://officeofbudget.od.nih.gov/pdfs/FY22/br/NIH%20FY%202022%20CJ%20Sig- nificant%20Items.pdf (accessed on December 6, 2021). NIH. 2021d. NIH-wide strategic plan. https://www.nih.gov/about-nih/nih-wide-strategic- plan (accessed October 27, 2021). NIH. 2021e. NIH-wide strategic plan, fiscal years 2021–2025. Bethesda, MD: National Institutes of Health. NIH. 2021f. NIH reporter database. https://reporter.nih.gov (accessed March 3, 2022). NIH. 2021g. Research grants (R series). https://www.nidcd.nih.gov/funding/types/research- grants-r-series (accessed September 3, 2021). NIH. 2021h. Supplementary appropriation data table for history of congressional appropriations, fiscal years 2020–2021. https://officeofbudget.od.nih.gov/pdfs/FY21/Approp%20His- tory%20by%20IC%20FY%202020%20-%20FY%202021%20(V).pdf (accessed September 2, 2021). NIH, NIAMS, NIAID, NIDCR, and ORWH. 2021a. Accelerating Medicines Partnership Autoim- mune and Immune-Mediated Diseases: Disease teams for rheumatoid arthritis, lupus, psoriatic spectrum diseases, and Sjögren’s syndrome (UC2 clinical trial optional). https://grants.nih. gov/grants/guide/rfa-files/RFA-AR-21-015.html (accessed December 6, 2021). NIH, NIAMS, NIAID, NIDCR, and ORWH. 2021b. Notice of intent to publish a funding oppor- tunity announcement for Accelerating Medicines Partnership Autoimmune and Immune-Me- diated Diseases: Disease teams for rheumatoid arthritis, lupus, psoriatic spectrum diseases and Sjögren’s syndrome (UC2 clinical trial optional). https://grants.nih.gov/grants/guide/ notice-files/NOT-AR-21-013.html (accessed December 6, 2021). NIH, NICHD, and NIAID. 2021c. Development of the fetal immune system (R01 clinical trial not allowed). https://grants.nih.gov/grants/guide/pa-files/PAR-20-298.html (accessed December 6, 2021). NIH, NIDDK, and NIAID. 2021d. The autoantigens and neoantigens function in the etiology and pathophysiology of type 1 diabetes (R01 clinical trial optional). https://grants.nih.gov/ grants/guide/rfa-files/rfa-dk-21-004.html (accessed August 5, 2021). NIH, NIDDK, NIAID, NICHD, and NCCAM. 2021e. Type 1 diabetes trialnet: Clinical centers (U01). https://grants.nih.gov/grants/guide/rfa-files/rfa-dk-08-011.html (accessed December 6, 2021). NIH Central Resource for Grants and Funding Information. 2020. About the office of extra- mural research (OER) at NIH. https://grants.nih.gov/aboutoer/intro2oer.htm (accessed November 24, 2021). PREPUBLICATION COPY—Uncorrected Proofs

AUTOIMMUNE DISEASE RESEARCH EFFORTS 343 NIH Office of Extramural Research. 2021. NIH grants policy statement. https://grants.nih. gov/grants/policy/nihgps/html5/section_2/2.3.5_types_of_funding_opportunity_ announcements__foas_.htm (accessed November 19, 2021). NIMH (National Institute of Mental Health). 2021. Extramural review branch. https://www. nimh.nih.gov/about/organization/nimh-extramural-research-programs (accessed No- vember 29, 2021). NINDS. 2020. Strategic plan 2021-2026: Investing in the future of neuroscience. Bethesda, MD: National Institutes of Health. NRC (National Research Council). 2003. Enhancing the vitality of the National Institutes of Health: Organizational change to meet new challenges. Washington, DC: The National Academies Press. OBSSR (NIH Office of Behavioral and Social Sciences Research). 2021. About OBSSR. https:// obssr.od.nih.gov/about/mission-and-history (accessed November 2, 2021). ORWH. 2021a. Building interdisciplinary research careers in women’s health (BIRCWH). https:// orwh.od.nih.gov/career-development-education/building-interdisciplinary-research- careers-in-womens-health-bircwh (accessed November 2, 2021). ORWH (NIH Office of Research on Women’s Health). 2021b. The Office of Research on Women’s Health: A history of fostering diversity and inclusion in biomedical research. https://orwh. od.nih.gov/about/mission-history/office-research-womens-health-history-fostering- diversity-and-inclusion (accessed November 2, 2021). Rare Diseases Clinical Research Network. 2021. The myasthenia gravis rare disease network (MGNet). https://www.rarediseasesnetwork.org/mgnet (accessed August 5, 2021). Rider, L. G. 2021. Autoimmune disease research supported by intramural NIEHS. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 3, March 4, 2021, Webinar. SGMRO (NIH Sexual & Gender Minority Research Office). 2021. About SGMRO. https:// dpcpsi.nih.gov/sgmro (accessed November 2, 2021). Spain, L. M. 2021. Extramural autoimmune disease research supported by NIDDK. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 3, March 4, 2021, Webinar. TEDDY Study Group. 2008. The environmental determinants of diabetes in the young (TEDDY) study. Annals of the New York Academy of Sciences 1150:1–13. TrialNet. 2018. Who we are. https://www.trialnet.org/about-us/who-we-are (accessed De- cember 6, 2021). Utz, U. 2021. NINDS funding strategy—NIH research on multiple sclerosis. Paper read at NASEM Committee for the Assessment of NIH Research on Autoimmune Diseases: Meeting 2 (Continuation), February 1, 2021, Webinar. Viergever, R. F., and T. C. C. Hendriks. 2016. The 10 largest public and philanthropic funders of health research in the world: What they fund and how they distribute their funds. Health Research Policy and Systems 14(1):12. PREPUBLICATION COPY—Uncorrected Proofs

PREPUBLICATION COPY—Uncorrected Proofs

Next: 6 Analysis of Institute and Center Autoimmune Disease Research Activity »
Enhancing NIH Research on Autoimmune Disease Get This Book
×
Buy Prepub | $74.00 Buy Paperback | $65.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Autoimmune diseases occur when the body's immune system malfunctions and mistakenly attacks healthy cells, tissues, and organs. Strong data on the incidence and prevalence of autoimmune diseases are limited, but a 2009 study estimated the prevalence of autoimmune diseases in the U.S. to be 7.6 to 9.4 percent, or 25 to 31 million people today. This estimate, however, includes only 29 autoimmune diseases, and it does not account for increases in prevalence in the last decade. By some counts, there are around 150 autoimmune diseases, which are lifelong chronic illnesses with no known cures. The National Academies of Sciences, Engineering, and Medicine was asked to assess the autoimmune disease research portfolio of the National Institutes of Health (NIH).

Enhancing NIH Research on Autoimmune Disease finds that while NIH has made impressive contributions to research on autoimmune diseases, there is an absence of a strategic NIH-wide autoimmune disease research plan and a need for greater coordination across the institutes and centers to optimize opportunities for collaboration. To meet these challenges, this report calls for the creation of an Office of Autoimmune Disease/Autoimmunity Research in the Office of the Director of NIH. The Office could facilitate NIH-wide collaboration, and engage in prioritizing, budgeting, and evaluating research. Enhancing NIH Research on Autoimmune Disease also calls for the establishment of long term systems to collect epidemiologic and surveillance data and long term studies (20+ years) to study disease across the life course. Finally, the report provides an agenda that highlights research needs that crosscut many autoimmune diseases, such as understanding the effect of environmental factors in initiating disease.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!