Topics on this page: Goal 2. Objective A | Table of Related Performance Measures | Analysis of Results | Plans for the Future | Objective Progress Update Summary
Goal 2. Objective A: Accelerate the process of scientific discovery to improve health
Medical breakthroughs, fueled by scientific discovery, have made the difference between life and death for countless Americans. Nevertheless, the need for better health interventions remains. Continuing to improve the health and well-being of Americans requires ongoing investments, with goals that range from improving our understanding of fundamental biological processes to identifying the best modes of prevention and treatment. HHS investments have improved the health of many Americans, but the path from basic discovery into safe, effective patient care can be long. This is why HHS is expanding the knowledge base in biomedical and behavior sciences and investing in fundamental science and service system research to improve detection, treatment, and prevention. HHS will continue to support ethical and responsible research practices, including ensuring the protection of the humans and animals participating in health research.
The Department has identified several leverage points to accelerate movement along the pipeline from scientific discovery to more effective patient care. NIH supports basic, clinical, translational, and early-stage drug development for promising new therapies. In addition, research and dissemination activities through NIH and other HHS components will help enhance the evidence-base for preventive, screening, diagnostic, and treatment services and facilitate the use of this information by clinicians, consumers, and policymakers.
Many HHS components, including AHRQ, ASPE, ASPR, CDC, NIH, and OASH support the Department’s efforts toward scientific discovery. Below is a sample of performance measures that HHS will use to guide activities and achieve improved results for patient care. The Office of the Secretary led this Objective’s assessment as a part of the Strategic Review.
Objective 2. A Table of Related Performance Measures
Provide research training for predoctoral trainees and fellows that promotes greater retention and long-term success in research careers. (Lead Agency - NIH; Measure ID - CBRR-1.1)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | N ≥ 12% | N ≥ 12% | N ≥ 10% | N ≥ 10% | N ≥ 10% | N ≥ 10% |
| Result | Award rate to comparison group reached 12%. | Award rate to comparison group reached 11%. | Award rate to comparison group reached 11%. | Award rate to comparison group reached 10% | Dec 31, 2015 | Dec 31, 2016 |
| Status | Target Met | Target Not Met | Target Met | Target Met | Pending | Pending |
Provide research training for postdoctoral fellows that promotes greater retention and long-term success in research careers. (Lead Agency - NIH; Measure ID - CBRR-1.2)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | N ≥ 12% | N ≥ 12% | N ≥ 10% | N ≥ 10% | N ≥10% | N≥ 10% |
| Result | Award rate to comparison group reached 13% and exceeded the target by 1%. | Award rate to comparison group reached 13% and exceeded the target by 1%. | Award rate to comparison group reached 13% and exceeded the target by 3%. | Award rate to comparison group reached 14% and exceeded the target by 4%. | Dec 31, 2015 | Dec 31, 2016 |
| Status | Target Met | Target Met | Target Met | Target Exceeded | Pending | Pending |
By 2015, make freely available to researchers the results of 400 high-throughput biological assays screened against a library of 300,000 unique compounds, and the detailed information on the molecular probes that are developed through that screening process. (Lead Agency - NIH; Measure ID - CBRR-10)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | Increase depositions of bioassays in PubChem to a rate of five (5) per month. | Deposit chemical structure and biological data for 200 new small molecule probes in PubChem. | Establish 400 primary biochemical, cell-based or protein-protein interaction assays that can be miniaturized and automated as high throughput screens in the Molecular Libraries Program (MLP) Portfolio. | Increase the Molecular Libraries Program (MLP)inventory to 375 small molecule probes that can be used in biological research to interrogate basic biological processes or disease. | Make freely available to researchers the results of 400 high-throughput biological assays screened against a library of 300,000 unique compounds, and the detailed information on the molecular probes that are developed through that screening process. | Discontinued |
| Result | NIH increased the assay deposition into PubMed to a rate greater than eight HTS assays per month, resulting in a total deposit of 103 assays. | The Molecular Libraries Program deposited chemical structure and biological data for 294 new small molecule probes in PubChem since the program began. | Established 570 primary biochemical, cell-based or protein-protein interaction assays that were miniaturized and automated as high throughput screens in the Molecular Libraries Program (MLP) Portfolio. | Increased the Molecular Libraries Program (MLP)inventory to 375 small molecule probes that can be used in biological research to interrogate basic biological processes or disease. | Dec 31, 2015 | N/A |
| Status | Target Exceeded | Target Exceeded | Target Exceeded | Target Met | Pending |
By 2020, identify two molecular-targeted therapies for disorders of the immune system in children. (Lead Agency - NIH; Measure ID - SRO-3.9)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | Complete phenotypic characterization of a patient cohort. | Complete genetic, biochemical, or cellular studies aimed at identifying a molecular pathway underlying the diseasein the patient cohort. | Identify at least one molecular pathway suitable for targeting in the patient cohort by performing detailed genetic mapping and confirmatory analyses for markers and pathways identified through genome-wide association. | Design a clinicaltrial testing an agent for a disorder of the immune system in children (e.g., Still's disease). | Complete a clinical pilot study in a cohort of pediatric patients with a disorder of the immune system. | Identify at least one molecular pathway based on genetic analysis suitable for therapeutic targeting in a pediatric cohort of patients with an immune-mediated disease. |
| Result | NIH researchers completed recruitment of a cohort of well-characterized patients with systemic-onset juvenile idiopathic arthritis through an international consortium of investigators. | A genome-wide association study has been performed on the cohort of 982 systemic-onset juvenile idiopathic arthritis patients and over 7000 healthy controls for 1.4 million genetic markers. | Researchers have identified a genetic variant that confers an increased risk of developing systemic juvenile idiopathic arthritis (sJIA) and that indicates the CD4+ T cell activation pathway as a therapeutic target. | Researchers have designed a compassionate use study to evaluate a novel class of drugs Janus Kinase (JAK) inhibitors in pediatric patients with the immune disorder, Chronic Atypical Neutrophilic Dermatosis with lipodystrophy and elevated temperature (CANDLE). | Dec 31, 2015 | Dec 31, 2016 |
| Status | Target Met | Target Met | Target Met | Target Met | Pending | Pending |
By 2015, identify and characterize two molecular pathways of potential clinical significance that may serve as the basis for discovering new medications for preventing and treating asthma exacerbations. (Lead Agency - NIH; Measure ID - SRO-6.4)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | Characterize cellular and molecular inflammation in the distal lung that may contribute to severe disease with frequent exacerbations. | Investigate the role of mucus gel formation in healthy controls and asthma patients. | Conduct investigations to elucidate the dynamic, pathophysiologic phenotypes of severe asthma. | Investigate the disease processes involved in asthma exacerbations and/or severe asthma using state-of-the-art pulmonary imaging techniques. | Identify and characterize two molecular pathways of potential clinical significance that may serve as the basis for discovering new medications for preventing and treating asthma exacerbations. | Discontinued |
| Result | Scientists characterized the molecular pathways in fibroblasts (the principal active cells of connective tissue) from two regions of the lung. Their findings suggest that fibroblasts from the distal lung may be the more important fibroblast cell type in processes that contribute to disease progression and severity in asthma. | Researchers investigated two proteins associated with mucus formation, CLCA1 and TMEM16A that may serve as potential targets for treating asthma. | The Severe Asthma Research Program is conducting investigations. | The Severe Asthma Research Program (SARP) is using state of the art imaging techniques to help define disease phenotypes and endotypes, which will enable the development of tailored interventions for the appropriate patient populations. | Dec 31, 2015 | N/A |
| Status | Target Met | Target Met | Target Met | Target Met | Pending |
By 2015, establish and evaluate a process to prioritize compounds that have not yet been adequately tested for more in-depth toxicological evaluation. (Lead Agency - NIH; Measure ID - SRO-5.13)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | Identify an additional 3,000 compounds to the library for testing, complete compound analytical analysis, and test 50 compounds in mid-throughput assays. | Test 10,000 compound main library in 50 qHTS and test 50 compounds in mid-throughput assays. |
Test 10,000 compound main library in 25 qHTS and test 180 compounds in densely sequenced human lymphoblastoid cell lines to assess genetic diversity in response to toxicants. | Test 10,000 compound main library in an additional 15 qHTS and test 20 subsets of possible high risk chemicals in high-content screens. | A formal process of prioritizing compounds for more extensive toxicological testing will be evaluated and used | Discontinued |
| Result | The 10K library was completed. Performance on mid-throughput assays surpassed the target. Analytical or chemical analysis is in progress, but not yet completed. | The library containing 10,000 compounds was screened in 65 quantitative high throughput screens (qHTS) or assays. Fifty compounds were screened in approximately 600 mid-throughput assays. | The 10,000 compound library was screened in 33 qHTS assays and data was analyzed on 179 compounds screened for cytotoxicity across 1086 human lymphoblastoid cell lines representing 9 racial groups to assess genetic diversity in response to toxicants. | The 10,000 compound library was screened in 42 qHTS assays and 22 subsets of possible high risk chemicals were screened in high content screens using cells (e.g., cardiomyocytes, neuronal cells) and alternative organisms (zebrafish, Caenorhabditis elegans) | Dec 31, 2015 | N/A |
| Status | Target Not Met | Target Met | Target Met | Target Met | Pending |
By 2018, (a) identify genetic factors that enhance or reduce the risk of development and progression of chronic obstructive pulmonary disease (COPD) and (b) validate new genetic and clinical criteria that may be added to COPD classification and contribute to better and/or earlier diagnosis or prognosis of the disease. (Lead Agency - NIH; Measure ID - SRO-5.2)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | N/A | N/A | N/A | Complete Genome-wide Association analysis of the original 10,000 subjects to discover 3 statistically significant genetic risk factors for COPD. | Using analysis of genetic and clinical data from the original 10,000 subjects, identify 1-3 COPD sub-classes that can then be tested for prognostic potential. | Analyze longitudinal for the first 1000 five year follow-up visits to identify 1-3 predictors of lung function decline. |
| Result | N/A | N/A | N/A | A meta-analysis was published in FY 2014 using COPDGene as well as other studies to identify three known loci and three new loci marking genetic risk factors. | Dec 31, 2015 | Dec 31, 2016 |
| Status | Target Met | Pending | Pending |
By 2018, complete pre-commercial development of a point-of-care technology targeted for use in primary care setting. (Lead Agency - NIH; Measure ID - SRO-5.5)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | N/A | N/A | N/A | Identify 6 enabling technologies with potential clinical use in primary care setting. | Establish feasibility of use of 3 to 4 identified technologies through preliminary testing. |
Complete pilot clinical studies on 1 to 2 prototype devices. |
| Result | N/A | N/A | N/A | Six technologieswere identifiedthat have potential for clinically focused solutionsto improve primary care. | Dec 31, 2015 | Dec 31, 2016 |
| Status | Target Met | Pending | Pending |
By 2017, identify circuits within the brain that mediate reward for 1) drugs, 2) non-drug rewards such as food or palatable substances, and 3) aversion to drug effects, and 4) determine the degree of overlap between these circuits. (Lead Agency - NIH; Measure ID - SRO-8.2)
| FY 2011 | FY 2012 | FY 2013 | FY 2014 | FY 2015 | FY 2016 | |
|---|---|---|---|---|---|---|
| Target | N/A | N/A | N/A | Identify drug-activated reward circuits | Identify non-drug activated reward circuits and compare with drug-activated reward circuits | Support research to compare and contrast rewarding versus aversive pathways in response to substances of abuse |
| Result | N/A | N/A | N/A | Classical and pharmacological dissection of the central drug reward system was confirmed, extended to demonstrate projections which had two or more transmitters with functional significance for drug reward, and identified the rostromedial tegmentem as a GABAergic nucleus which could functionally inhibit the dopaminergic pathway. | Dec 31, 2015 | Dec 31, 2016 |
| Status | Target Met | Pending | Pending |
Analysis of Results
HHS recognizes that a high-quality workforce is crucial to the effective delivery of health and human services. The Department has a number of activities that focus on addressing current workforce issues and the strategic development of workforce capacity. For example, HHS seeks to ensure that our country not only maintains, but enhances its capacity for innovative health-related research. A critical part of the NIH mission is the education and training of the next generation of biomedical, behavioral, and clinical scientists. In FY 2014, NIH pre-doctoral Ruth L. Kirschstein National Research Service Award (NRSA) trainees and fellows were 10 percent more likely to remain active in biomedical research than non-NIH trainees and fellows; this result matched the annual target of 10 percent. Each year’s target represents the proportion of NIH trainees and fellows who go on to apply for and receive subsequent NIH support in comparison to non-NIH trainees and fellows. Subsequent support is an indicator of retention success in the research arena, and reflects the impact of NIH-funded training on the ability of trainees and fellows to be competitive and sustain a research career with independent funding. Annual targets were adjusted for FY 2013 and beyond in light of the general decline in NIH grant success rates over the past ten years. Despite this trend, former trainees and fellows have continued to outperform individuals who did not receive NRSA support.
NIH also routinely monitors the career outcomes of former postdoctoral fellows. In FY 2014, NIH postdoctoral fellows were 14 percent more likely to remain active in biomedical research than non-NIH fellows; this result exceeded the annual target of 10 percent. Despite the general decline in NIH grant success rates, former postdoctoral fellows have been more likely to receive subsequent NIH research grants than individuals who did not receive NRSA support.
Accelerating the process of scientific discovery for the purpose of improving health outcomes is important to Americans’ well-being and health. The Molecular Libraries Program (MLP) made progress and met the FY 2014 target by increasing the inventory to 375 small molecule probes that can be used in biological research to interrogate basic biological processes or disease. By disseminating results in PubChem, the NIH enables one of the largest sets of publicly available chemical biology information to be used by researchers in the public and private sectors.
Advances in technology and reductions in cost have made it possible to identify the causes of certain genetically complex diseases. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) is a novel rare pediatric autoinflammatory syndrome that is predominately characterized by inflammation, attacks of fever, skin lesions, and fat loss. NIH researchers, along with an international team of collaborators, identified in a group of affected patients mutations in a gene causing cells to be unable to recycle or remove waste products. During FY 2014, researchers designed a compassionate use study to evaluate a novel class of drugs Janus Kinase (JAK) inhibitors in pediatric patients with CANDLE.
Asthma attacks are a significant cause of morbidity in patients with asthma and represent a substantial public health burden. The Severe Asthma Research Program (SARP) unites transdisciplinary teams in a collaborative platform to foster an understanding of severe asthma and its phenotypes at genetic, molecular, cellular, and clinical levels over time. HHS is tracking SARP and other severe asthma research through a series of annual milestones. In FY 2014 NIH achieved its milestone, using state of the art imaging techniques to help define disease phenotypes and endotypes, which will enable the development of tailored interventions for the appropriate patient populations.
In addition to the cataloging of data about naturally occurring biological chemicals, NIH manages a program to investigate and catalog the potential health effects of many of the estimated 125,000 man-made chemicals in use commercially. NIH and the EPA began the program, titled Tox21, in early 2008 to collaborate on the research, development, validation, and translation of new and innovative test methods that characterize how chemicals interact with cellular pathways, determining chemical toxicity, as well as danger to human health. This is important for the development of prevention and mitigation strategies. Tox21 has a library of over 10,000 compounds. NIH exceeded expectations in FY 2014 by screening in 42 qHTS assays and 22 subsets of possible high risk chemicals in high content screens using cells (e.g., cardiomyocytes, neuronal cells) and alternative organisms (zebrafish, Caenorhabditis elegans).
COPD is characterized by airway obstruction and/or emphysema. COPD is known to have both environmental (e.g., tobacco smoke) and genetic risk components. Current and former smokers are at highest risk, although only a minority of smokers ever develops COPD. Why some smokers develop COPD while others do not is unknown, as is why some non-smokers develop COPD. The COPDGene study, in which 10,000 current and former smokers with or without COPD were studied to identify clinical and genetic markers of the disease, was begun in 2008 to address some of these questions. A meta-analysis was published this year using COPDGene as well as other studies to identify three known loci and three new loci marking genetic risk factors for COPD.
As the number of primary care providers diminishes and the need for primary care increases, there is an urgent need to increase the capacity of providers to care for more patients without a decrease in the quality of care and without unduly burdening the providers. Primary care providers are also being tasked with providing increasingly complex care as the population ages and the burden of chronic disease grows. Point-of-care technologies have emerged as scientific knowledge has grown. An early example of a point-of-care technology is the home pregnancy test. More recent tests for diagnosing strep throat at the point-of-care have become available. Emerging microfluidic, nanotechnology, and sensor miniaturization technologies are making it possible to develop a new generation of point-of-care test systems designed to improve the efficiencies of primary care practices. NIH is supporting efforts to define and prioritize unmet clinical needs in primary care where technology-enabled solutions could be of benefit. In fiscal year 2014 NIH met its target by identifying and funding six promising point-of-care technology projects that aim to provide rapid testing in a clinic or doctor's office to enable the diagnosis of disease or illness where treatment can begin at the time of diagnosis.
Decades of neuroscience research have shown how substances of abuse impact the brain in many ways, with effects on reward pathways, motor function, cognitive abilities, etc., yet we still know very little about the specific brain circuits that signal rewarding effects in response to drugs vs other natural rewards (e.g., food, sweets, water). We also know that substances of abuse can have both rewarding and aversive effects, but the brain circuitry that signals one response vs. the other remains unclear. Recent advances in the development of tools to probe the central nervous system such as multi-array recording electrodes, in vivo fast scan electrochemical voltammetry, and optogenetics, stand to increase dramatically our understanding of this brain circuitry. These data will generate new scientific knowledge that may help to define the basis of individual differences in the responsiveness to reward/aversion-producing substances, including substances of abuse and may help to identify novel targets for the development of anti-addiction medications. Using genetically-defined reporter proteins has led to an explosion in the precise identification of neurons that are involved in the processing of reward by the brain. In FY 2014, NIH researchers confirmed classical and pharmacological dissection of the central drug reward system, extended to demonstrate projections which had two or more transmitters with functional significance for drug reward, and identified a drug-activated reward pathway in the brain.
Plans for the Future
NIH expects to maintain the retention targets of both pre- and post-doctoral trainees and fellows in FY 2015 and 2016, despite the challenges described above. It is taking a number of steps to bring this about, including encouraging the routine use of individual development plans to guide the career development of graduate students and post-doctorates supported by NIH, and establishing a new office to address biomedical workforce issues. To assess its performance, NIH routinely monitors degree completion by its pre-doctoral Kirschstein-NRSA trainees and fellows and tracks the extent to which the graduate students and post-doctorates it supports are subsequently involved in research, using data from the national Survey of Earned Doctorates and the NIH IMPAC II administrative database.
For its various milestone-based research goals, NIH expects to achieve each during the next few years. This includes: making more chemical biology information available to researchers; further examining immune disorders; examining more compounds for toxicological effects; exploring molecular pathways that may lead to promising avenues for preventing and treating asthma; studying the genetic factors leading to COPD to enhance risk evaluation and diagnosis, exploring new point-of-care technologies; and understanding drug effects on the brain.
Objective Progress Update Summary
HHS demonstrated progress toward this objective as shown by the representative performance measures described in the HHS Annual Performance Plan and Report. Further evidence of progress is described below.
- The NIH performance measures reflect the Agency’s overall goals to advance basic biomedical and behavioral science, support translational research, and enhance the development of human capital, and strengthen the scientific workforce. NIH has proposed 45 new measures to replace those that ended or will be ending soon. A multi-level review process, supported by two trans-NIH committees, was used to develop, refine, and select measures that best align with the Agency’s performance priorities. All of these new measures are available publicly in the Fiscal Year 2016 NIH Congressional Budget Justification.
- ASPR has joined with select state and local partners to conduct innovative pilots to better understand whether limited federal data can inform and support state and local health department emergency planning for, and outreach and assistance to, individuals that rely upon life-saving and maintaining medical equipment and healthcare services prior to, during, and after an emergency or disaster.
- ASPR has conducted proof of concept research studies to characterize and assess disaster induced healthcare system stress and potential adverse outcomes on at-risk populations that rely upon life-maintaining healthcare services.
- In 2013, CDC released the results of its Dialysis Bloodstream Infection Prevention Collaborative showing a 32 percent decrease in overall bloodstream infections and a 54 percent decrease in vascular access-related bloodstream infections after CDC prevention guidelines were used. Vascular access-related bloodstream infections are those related to devices used to access the bloodstream for hemodialysis. With approximately 37,000 bloodstream infections occurring each year among dialysis patients with central lines, at an estimated cost of $23,000 per hospitalization, wider implementation of the practices in this study could help save lives and reduce excess health care spending.
- The Office for Human Research Protections worked with other HHS agencies to revise the regulations for the protection of human subjects in research. Those revisions, when implemented, will reduce the administrative burden and delays to the progress of research without lessening the protection of human subjects in research, accelerating the process of scientific discovery to improve patient care.
