Enhancing NIH Research on Autoimmune Disease (2022) / Chapter Skim
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6 Analysis of Institute and Center Autoimmune Disease Research Activity
6 Analysis of Institute and Center Autoimmune Disease Research Activity
Pages 345-412
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NIH's investment in autoimmune disease research has remained constant at about 2.8 percent of its total obligations between 2008 and 2020 (Figure 6-1) .1,2 From 2015 to 2020, total NIH obligations increased by 40 percent, whereas autoimmune disease spending increased by approximately 34 percent.
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346 FIGURE 6-1 NIH actual total obligations and autoimmune disease spending, FY 2008–2020.
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FIGURE 6-2 NIH autoimmune disease spending, FY 2008–2020. NOTE: FY, fiscal year.
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is not an institute but is included because of its funding contributions to autoimmune disease research. FY, fiscal year; IC, Institute or Center; 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 of Neurological Disorders and Stroke; OD, Office of the Director.
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.4 CHARACTERISTICS OF RESEARCH ACTIVITIES SUPPORTED BY ICS NIH uses 245 activity codes to characterize the funding mechanisms it employs to fund diverse activities. The committee focused on a select number of activity codes to characterize NIH- and IC-funded autoimmune disease research activities.
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is not an institute but is included because of its funding contributions to autoimmune disease research. FY, fiscal year; IC, Institute or Center; 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 of Neurological Disorders and Stroke; OD, Office of the Director.
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for trainees at the undergraduate, graduate, and postdoctoral levels. Research Career Development awards provide individual and Research Career Development institutional research training opK Programs portunities (including international)
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The OD spent an average of $10 million on autoimmune disease research grants, which was comparable to the average funding spent by other smaller ICs. U grants support research activities that NIH considers to be complex and of high-priority research areas.
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, and research program project and center (P) grants, FY 2008–2020 (in millions)
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SOURCE: NIH, 2021f. TABLE 6-5 Training Investment for Selected RCDC Spending Categories, FY 2020 RCDC Spending Research FY 2020 Category Fellowship Career Training Total Alzheimer's 10.9% 72.5% 16.5% $47,440,000 Autoimmune Disease 12.1% 76.9% 11.0% $43,646,000 Breast Cancer 0.8% 2.2% 0.0% $717,665,000 Cardiovascular 9.4% 64.3% 26.3% $144,080,000 COPD 12.2% 87.8% 0.0% $7,531,000 NOTE: COPD, chronic obstructive pulmonary disease; FY, fiscal year; RCDC, Research, Condition, and Disease Categorization.
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grants, in addition to traditional research grants. Table 6-6 shows IC funding of training grants that support the autoimmune disease research workforce.
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356 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 6-6 Training Grant Funding for Autoimmune Disease Research by IC and FY Training as a Percent of FY 2020 IC Year(s) F K T Obligations FY 2020 $171,195 $584,384 $0 NCI 0.01% Average FY 2008–2020 $100,885 $349,586 $0 FY 2020 $814,263 $2,085,385 $653,017 NIAID 0.06% Average FY 2008–2020 $492,310 $2,454,588 $561,823 FY 2020 $804,583 $4,432,189 $0 NHLBI 0.14% Average FY 2008–2020 $442,446 $2,737,751 $0 FY 2020 $79,212 $198,504 $0 NIGMS 0.01% Average FY 2008–2020 $135,591 $118,849 $0 FY 2020 $432,647 $3,359,470 $0 NINDS 0.16% Average FY 2008–2020 $586,329 $2,324,825 $0 FY 2020 $2,062,032 $11,311,126 $93,836 NIDDK 0.61% Average FY 2008–2020 $1,640,982 $9,848,175 $159,663 FY 2020 $82,851 $570,283 $0 NICHD 0.04% Average FY 2008–2020 $26,922 $553,745 $0 FY 2020 $36,611 $87,463 $0 NIEHS 0.01% Average FY 2008–2020 $67,663 $65,037 $0 FY 2020 $0 $0 $0 NCATS Average FY 2008–2020 $0 $0 $0 FY 2020 $0 $916,394 $0 NEI 0.11% Average FY 2008–2020 $14,717 $828,068 $0 FY 2020 $281,015 $8,247,061 $3,953,872 NIAMS 2.00% Average FY 2008–2020 $229,852 $7,926,922 $4,261,852 FY 2020 $64,926 $0 $0 NHGRI 0.01% Average FY 2008–2020 $4,994 $62,014 $0 FY 2020 $107,672 $0 $0 NIDCR 0.02% Average FY 2008–2020 $65,626 $139,637 $0 FY 2020 $0 $1,175,676 $85,655 OD 0.09% Average FY 2008–2020 $9,502 $491,711 $12,694 continued
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INSTITUTE AND CENTER AUTOIMMUNE DISEASE RESEARCH 357 TABLE 6-6 Continued NOTE: FY, fiscal year; IC, Institute or Center; 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 of Neurological Disorders and Stroke; OD, Office of the Director.
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FY, fiscal year; IC, Institute or Center; NIAID, National Institute of Allergy and Infectious Diseases; NCI, National Cancer Institute; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIGMS, National Institute of General Medical Sciences; NHLBI, National Heart, Lung, and Blood Institute; NINDS, National Institute of Neurological Disorders and Stroke.
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National Center for Advancing Translational Sciences (NCATS) was not included in the figure because it became an Institute in 2012; In FY 2020, NCATS spent $226,174 on autoimmune disease research grants and an average of $493,918 per year over the FY 2008–2020 period.
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FY, fiscal year; IC, Institute or Center; NIAID, National Institute of Allergy and Infectious Diseases; NCI, National Cancer Institute; NICHD, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIGMS, National Institute of General Medical Sciences; NHLBI, National Heart, Lung, and Blood Institute; NINDS, National Institute of Neurological Disorders and Stroke.
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FY, fiscal year; IC, Institute or Center; NIAMS, National Institute of Arthritis ind Musculoskeletal and Skin Diseases; NIEHS, National Institute of Environmental Health Sciences; NEI, National Eye Institute; NIDCR, National Institute of Dental and Craniofacial Research.
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did not have any P grant spending between 2012 and 2020. IC, Institutes and Centers; FY, Fiscal Year; NIAID, National Institute of Allergy and Infectious Diseases; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Disorders; NCI, National Cancer Institute; NHLBI, National Heart, Lung, and Blood Institute; NIGMS, National Institute of General Medical Sciences; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NINDS, National Institute of Neurological Disorders and Stroke.
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NIDDK solicited research funding was 2.7 times higher than NIAID funding for this grant type. Intramural research activities represent 17.3 percent of NIH funding for autoimmune disease research in FY 2020. A total of 50 intramural principal investigators conduct autoimmune disease research, which may include basic, translational, and clinical studies. However, the committee notes that there is a relative lack of intramural principal investigators who focus on epidemiology and autoimmune diseases.
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and Combined Total Cost of Funded Autoimmune Disease Research. Grants without an FOA were not included in the analysis.
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TABLE 6-7 Intramural, Investigator-Initiated, and Solicited Autoimmune Disease Research by IC, FY 2020 and Average FY 2008–2020 IC Intramural Investigator-Initiated Solicited Average Average Average FY 2020 FY FY 2020 FY FY 2020 FY 2008–2020 2008–2020 2008–2020 NCI $14,270,000 $10,882,000 $11,684,000 $10,347,000 $9,416,000 $2,074,000 NIAID $34,006,000 $21,769,000 $187,328,000 $107,751,000 $55,735,000 $42,976,000 NHLBI $11,701,000 $4,077,000 $59,078,000 $39,906,000 $5,593,000 $14,307,000 NIGMS $0 $0 $15,026,000 $10,947,000 $629,000 $1,744,000 NINDS $13,474,000 $9,765,000 $54,562,000 $50,127,000 $11,350,000 $3,113,000 NIDDK $7,566,000 $4,921,000 $185,951,000 $127,257,000 $153,690,000 $120,316,000 NICHD $1,964,000 $3,444,000 $7,844,000 $8,163,000 $709,000 $1,855,000 NIEHS $4,724,000 $7,439,000 $4,602,000 $4,202,000 $2,101,000 $1,170,000 NCATS $2,606,000 $1,564,000 $590,000 $472,000 $2,801,000 $2,801,000 NEI $14,983,000 $9,614,000 $18,624,000 $10,587,000 $376,000 $128,000 NIAMS $35,790,000 $28,182,000 $86,159,000 $72,297,000 $25,767,000 $20,573,000 NHGRI $7,003,000 $3,945,000 $65,000 $371,000 $3,401,000 $6,688,000 NIDCR $4,930,000 $7,740,000 $13,950,000 $6,191,000 $0 $1,350,000 OD $0 $0 $3,316,000 $4,668,000 $11,595,000 $15,929,000 continued 365
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FY, fiscal year; IC, Institute or Center; 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 of Neurological Disorders and Stroke; OD, Office of the Director.
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These diseases include inflammatory bowel disease (IBD) , multiple sclerosis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematous (SLE)
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. NOTES: Percentages in the figure sum to more than 100 percent because grants can be associated with more than one autoimmune disease.
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. NOTES: Percentages in the figure sum to more than 100 percent because grants can be associated with more than one autoimmune disease.
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. Figure 6-18 shows NIAID-funded FIGURE 6-12 Top 10 activity codes for autoimmune disease research (N=8,470)
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FIGURE 6-13 Number of R01 grants by autoimmune disease, FY 2008–2020 (N=3,042)
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372 FIGURE 6-14 Number of non-competing continuation R01 grants by autoimmune disease, FY 2008–2020 (N=2,751)
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To assess the level of collaboration among ICs, the committee examined co-funded autoimmune disease research grants for FY 2008–2020. To accomplish this, the committee used NIH RePORTER data to identify administrative ICs funding autoimmune disease research grants and corresponding funding ICs that contributed to the total cost of grants during this period.
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374 FIGURE 6-15 New R01 grants by autoimmune disease, FY 2008–2020 (N=1,892)
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. NOTES: Percentages do not sum to 100 percent because the figure includes only the top 10 funding ICs and does not include grants without a funding IC listed in NIH RePORTER.
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NIDDK was not necessarily the sole funder of each grant. FY, fiscal year; IC, Institute or Center; NIDDK, National Institute of Diabetes and Digestive Kidney Diseases.
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NIAID was not necessarily the sole funder of each grant. FY, fiscal year; IC, Institute or Center; NIAID, National Institute of Allergy and Infectious Diseases.
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NIAMS was not necessarily the sole funder of each grant. FY, fiscal year; IC, Institute or Center; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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statistical modeling to identify research topics in the set of 8,470 NIH research abstracts related to autoimmune disease grants funded between 2008 and 2020. Topic modeling using LDA is a method of fitting a pre-determined number of topics to a set of texts.
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All ICs in this table are administrative ICs. FY, fiscal year; IC, Institute or Center; 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 of Neurological Disorders and Stroke; OD, Office of the Director.
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In Figure 6-21, immune response (innate immunity) may be disproportionately high because of its relevance to various aspects of autoimmune disease research as well as a lack of a concrete definition for innate immunity.
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382 FIGURE 6-20 LDA-generated topics for NIH autoimmune disease grants, FY 2008–2020: Disease focused topics. NOTE: IBD, inflammatory bowel disease; LDA, latent dirichlet allocation; SLE, systemic lupus erythematosus.
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In other words, this method cannot be used to actively search for specific research topics. RCDC Spending Categories The second approach the committee used to evaluate the NIH research portfolio was to determine which other NIH RCDC spending categories co-occur with the autoimmune disease spending category.
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384 FIGURE 6-21 LDA-generated topics for NIH autoimmune disease grants, FY 2008–2020: Immune response related topics. NOTE: FY, fiscal year; LDA, latent dirichlet allocation.
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SOURCE: NIH, 2021f. FIGURE 6-23 LDA-generated topics for NIH autoimmune disease grants, FY 2008–2020: Administrative topics.
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386 ENHANCING NIH RESEARCH ON AUTOIMMUNE DISEASE TABLE 6-9 Percent of Autoimmune Disease Grants Co-occurring with other RCDC Spending Categories (N=8,470) Co-Occurring with Autoimmune Disease RCDC Spending Category Spending Category Genetics 2,718 32.1% Biotechnology 1,978 23.4% Prevention 1,938 22.9% Pediatric 1,349 15.9% Women's Health 1,095 12.9% Infectious Disease 1,007 11.9% Aging 688 8.1% Cancer 660 7.8% Minority Health 590 7.0% Cardiovascular 490 5.8% Immunotherapy 388 4.6% Eye Disease and Disorders of Vision 327 3.9% Microbiome 298 3.5% Biomedical Imaging 176 2.1% Precision Medicine 157 1.9% Pain Research 143 1.7% Health Services 132 1.6% Estrogen 71 0.8% Chronic Pain 56 0.7% Acquired Cognitive Impairment 49 0.6% Depression 42 0.5% Cerebrovascular 41 0.5% Fibromyalgia 14 0.2% Burden of Illness 12 0.1% Caregiving Research 2 0.0% SOURCE: NIH, 2021f.
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Alternatively, depression as both an RCDC category and a PICO Portal research characteristic tag both occurred infrequently in autoimmune disease grants (0.5 percent)
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. NOTE: Percentages in the figure sum to more than 100 percent because grants could be tagged with more than one research characteristic.
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nih.gov/StudySections, accessed November 24, 2021. The committee entered the name of each of the select autoimmune diseases of committee interest into the study section search field to identify the names of its associated chartered study sections.
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Table 6-1015 provides a snapshot of data generated by the RePORTER Matchmaker tool. The table shows study sections -- the names of which appear in the far left column -- that reviewed funded grants focusing on the autoimmune diseases of interest to the committee; the table reflects a 2-year period.16,17 The table identifies those study sections that reviewed the most funded grants for each disease of focus according to a bar graph RePORTER automatically generates to provide this information; the number of grants are indicated in the corresponding cells.
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Celiac Sjögren's Psoria- Crohn's Hashimoto's SLE APS RA IBD Dis- PBC MS T1D Disease sis Disease Thyroiditis ease Gastrointestinal Muco 25 1 13 sal Pathobiology Hypersensitivity, Autoimmune and Immune- 11 6 6 9 Mediated Diseases Arthritis, Connective 8 6 3 Tissue and Skin Oral, Dental and Cra- 2 7 4 niofacial Science Cellular and Molecular 3 1 4 3 Immunology B Clinical Neuroimmunology and Brain 11 Tumor Innate Immunity 4 3 3 and Inflammation Cellular and Molecular 8 Biology of Glia continued 391
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TABLE 6-10 Continued 392 Celiac Sjögren's Psoria- Crohn's Hashimoto's SLE APS RA IBD Dis- PBC MS T1D Disease sis Disease Thyroiditis ease Clinical and Integrative 8 Diabetes and Obesity Cellular Aspects of 6 Diabetes and Obesity Hepatobiliary Patho 6 physiology Skeletal Biology and 3 Developmental Disease Diseases and Pathol ogy 2 of the Visual System Molecular and Cellular 2 Endocrinology Atherosclerosis and Inflammation of the 1 Cardiovascular System Cellular Signaling and Regulatory Sys- 1 tems
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Table reflects data available as of October 5, 2021. NOTE: APS, antiphospholipid syndrome; IBD, inflammatory bowel disease; MS, multiple sclerosis; PBC, primary biliary cholangitis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; T1D, type 1 diabetes SOURCE: NIH, 2021f.
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Clinical trials were fewer for the remaining autoimmune diseases. 18Grants with an RCDC code for "Autoimmune Disease" obtained from NIH RePORTER for Fiscal Year 2008 (October 1, 2008–September 30, 2008)
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. NOTE: Percentages in the figure sum to more than 100 percent because clinical trials can be associated with more than one autoimmune disease.
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Figure 6-2720 shows publications by disease category per year. Of the autoimmune diseases examined, the four diseases associated with the greatest number of publications over the 2008–2020 period were other autoimmune disease TABLE 6-11 Phase 4 Clinical Trials, Autoimmune Disease Prevention or Treatment Condition or Primary Official Title Disease Purpose RHYTHM (RHeumatoid Arthritis studY of THe Myocardium)
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, and JIF is a measure of journal quality exclusively. In the context of evaluating NIH's autoimmune disease portfolio, the committee focused on publications resulting from NIH-funded autoimmune disease research and the quality of the journals in which they are published.
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. NOTE: Percentages in the figure sum to more than 100 percent because publications can be associated with more than one autoimmune disease.
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FIGURE 6-28 Number of autoimmune disease publications by disease and year, 2008–2020 (N=159,416)
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. Patents granted as a result of NIH-funded autoimmune disease research aim to encourage and protect biomedical innovation and may serve as a proxy for knowledge generation and translational value in the field (Kalutkiewicz and Ehman, 2014)
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JIF, Journal Impact Factor. SOURCES: Clarivate, 2021; NIH, 2015, 2021f; NLM, 2021b.
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26 Autoimmune Disease Research Highlights were collected from NIH biennial and trien nial reports to Congress, and NIH websites.
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. NOTE: Percentages in the figure sum to more than 100 percent because patents can be associated with more than one autoimmune disease.
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. NOTE: Percentages in the figure sum to more than 100 percent because patents can be associated with more than one autoimmune disease.
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This finding paves the way for Research on Interferons Could "precision-based medicine," a customized treatment Identify Individuals with approach which tailors health care based on a person's Sjögren's Disease Most Likely genes to those patients most likely to respond to certain to Respond to Treatment therapies, such as anti-IFN treatments. In addition, it could improve the selection of for clinical trials.
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Better outcomes such as improvement in bone marrow and "resetting" of the immune system are associated with such factors for patients as younger age, fewer prior immunotheraStem Cell Transplants Leads pies and not having reached high disability levels. For to Positive Outcomes for Mul researchers, such results justify a future clinical trial tiple Sclerosis Patients on stem cell transplants for treating MS including an evaluation of safety and efficacy against approved therapies of high efficacy.
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. Rheumatoid arthritis Research has found that women with lung diseases such as asthma or chronic obstructive pulmonary disease (COPD)
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NIH may need to reconsider the current strong focus on investigator-initiated research in order to target areas of high priority and effectively address the long-term, complex, and heterogeneous nature of autoimmune diseases. Regarding the activities conducted under funded autoimmune disease research grants, the multiple methods the committee used yielded
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The outputs of NIH's investment in autoimmune disease research can be measured in a variety of ways, including clinical trials (the translation of research knowledge into interventions) , publications, and the number of patents associated with autoimmune disease research grants (an important indicator of innovation)
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2021. Autoimmune disease research supported by extramural NIAID.
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https://clinical trials.gov/ct2/about-studies/glossary (accessed December 14, 2021)
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