Extramural and Intramural Research Programs
As noted, NIH supports research and research training through extramural activities and conducts research and research training through intramural activities. This section provides overviews of the extramural and intramural programs.
More than $8 of every $10 appropriated to NIH is awarded by the ICs to the extramural biomedical and behavioral research community through grants and contracts. The extramural research community is composed of scientists, clinicians, and other research personnel affiliated with more than 2,600 organizations, including universities, medical schools, hospitals, and other research facilities located in all 50 states, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, and abroad. In FY 2011, NIH funded more than 35,000 principal investigators through research grants, with many thousands more personnel supported by the projects. With NIH support, these investigators, with their research teams, conduct the vast majority of research that leads to improvements in the prevention, detection, diagnosis, and treatment of disease and disability.
The NIH Deputy Director for Extramural Research provides leadership and coordinates policy, guidance, and oversight for IC grant and programmatic management operations and is a conduit for extramural policy issues with the biomedical research community beyond NIH. OER is where grants policy, program coordination, compliance, and services converge to support and sustain the NIH extramural research program.
A primary service OER provides for the NIH grants program is the electronic Research Administration (eRA) system. eRA supports the grant administration functions for grantees and federal staff from the submission of applications to the close out of awards. eRA also provides services to other operating divisions of the Department of Health and Human Services (HHS), as well as other federal agencies, and supports more than 100,000 investigators worldwide.
NIH announces the availability of funds for grant programs by issuing funding opportunity announcements (FOAs)14 in the NIH Guide for Grants and Contracts15 and on https://Grants.gov. The majority of NIH grants funding is for projects that are investigator-initiated and submitted through omnibus parent announcements that span the breadth of the NIH mission. NIH uses program announcements (PAs), requests for applications (RFAs), and other types of FOAs, to solicit applications for funding in targeted areas of research identified through strategic planning. Because many FOAs are trans-NIH opportunities, their preparation can involve considerable collaboration. In 2010, based on input from more than 1,000 stakeholders, OER implemented a shorter FOA format that eliminates redundancy, limits the amount of administrative detail, and directs applicants to the most up-to-date source of information.
The main types of grant funding provided by NIH are Research Grants (R series), Career Development Awards (K series), Research Training and Fellowships (T and F series), and Program Projects/Centers Grants (P series). Activity codes that incorporate the funding series differentiate the wide variety of research and research-related awards made by NIH. The most commonly used activity code is the R01, which designates a grant for a discrete, specified research project that is generally awarded for 3–5 years. Receipt of an R01 traditionally is the mark of a scientist achieving scientific independence, and a faculty member’s track record with R01 awards often is a significant factor in university promotion and tenure decisions. Examples of other activity codes are:
ICs vary in the extent to which they use various activity codes.
Other funding mechanisms are often applied to more unique applications. For example, NIEHS supports P42 grants, which are part of the Superfund Research Program, a network of university grants designed to seek solutions to the complex health and environmental issues associated with the nation's worst hazardous waste sites. The research conducted by the Superfund Research Program is funded and administered by the NIEHS in coordination with the U.S. Environmental Protection Agency (EPA), the federal entity charged with cleaning up these sites, and the HHS Agency for Toxic Substances and Disease Registry
14An FOA is a publicly available document by which a federal agency makes known its intentions to award grants or cooperative agreements. FOAs may be known as PAs, RFAs, solicitations, or parent announcements.
15 For more information, see https://grants.nih.gov/grants/guide/.
The Research and Development Contracts mechanism is another means by which NIH supports research and research-related activities. A research contract is typically used to acquire goods or services for the direct benefit or use of the government. For example, contracts may be used to support research in areas of significant scientific interest, to further scientific knowledge, or to achieve a specific research goal. A research contract differs from a grant in a number of respects that are designed to comply with provisions of the Federal Acquisition Regulation. These differences include the manner used to solicit and negotiate the requirement, the level of NIH participation during contract performance, and the control of study results. Research contracts are awarded to universities, non-profit organizations, and profit making organizations. Contract opportunities are announced in the NIH Guide for Grants and Contracts and also on the federal-wide Web site FedBizOpps.gov.
All NIH grant, fellowship, and cooperative agreement applications and contract proposals for research and development funding undergo evaluation through peer review, in which external expert panels determine which applications or proposals are the most scientifically and technically meritorious (the first tier of peer review) and are most programmatically relevant and therefore should be considered for funding (the second tier of peer review). The NIH peer review process is designed to be fair, equitable, timely, and free of bias. The NIH two-tiered peer review system is mandated by statute (section 492 of the Public Health Service Act) and by federal regulations governing “Scientific Peer Review of Research Grant Applications and Research and Development Contract Projects” (42 CFR Part 52h).16
The Center for Scientific Review is the portal for receipt and referral of NIH grant applications and is the locus for the first level of review for most applications. Applications relevant to the NIH mission receive two assignments. One assignment is to an IC that has a mission encompassing the aims and objectives of the application and potential interest in funding the application. The other assignment is to the Scientific Review Group (SRG) that will conduct the first level of review, including evaluation of scientific and technical merit. If the application is in response to an RFA, the SRG most often will be convened by the IC(s) responsible for the initiative. NIH uses established referral criteria to determine the appropriate SRG to carry out review and the IC(s) most suitable to potentially fund the project.
As noted above, the first level of review is conducted by SRGs that evaluate and give expert advice on the overall scientific and technical merit of the research proposed in the application, as well as the protection of human subjects, vertebrate animal welfare, and the budget and period of support requested. SRGs conducting the first level of review are composed primarily of non-federal experts qualified by training or experience in particular scientific or technical fields, or as authorities knowledgeable in the various disciplines and fields related to the applications under review. No more than one-fourth of the members of any SRG may be federal employees. SRGs may also include public members with perspective on the public health impact of the research being considered.
The second level of peer review is performed by the National Advisory Councils of each IC, which are composed of scientific and public members chosen for their expertise, interest, or activity in matters related to a specific area of science, health, and/or disease. The vast majority of SRG -reviewed applications assigned to an IC go to the respective Council,17 which then recommends which applications should be considered for funding. Identifying applications that further specific program priorities and potential public health impact is a particularly important function of this second level of peer review. Advisory Councils recommend projects for funding but do not make funding decisions.
Applications that are scientifically meritorious, based on SRG review, and favorably recommended by an IC’s National Advisory Council are considered for funding. The score given to an application during the initial peer review process is important, but it is not the sole factor determining an IC’s funding decision. Other considerations are portfolio balance, requirements specified in congressional appropriations, programmatic relevance, IC priorities, and availability of funds.
Many ICs establish a “payline,” which is a percentile-based18 funding cutoff point that is determined at the beginning of the fiscal year by balancing the projected number of applications assigned to an IC with the amount of funds expected by NIH and the IC to be available for such projects. Applications that score within the payline are most likely to be funded. However, Advisory Councils consider, evaluate, and make recommendations on specific applications that score both within and beyond the payline.
In addition to setting paylines, many ICs establish procedures for funding applications that scored beyond the payline. Terms used for this category of awards vary by IC, but include “select pay,” “exception pools,” “high program-priority,” and “special emphasis.” What is consistent is the use of these funds, with strong justification, to support highly innovative or high program-priority applications that score beyond the payline.
Prior to issuing an award, NIH ensures that the planned research meets all requirements for safe and responsible conduct. This includes making sure that the research has undergone all necessary reviews and has obtained required approvals from boards and committees charged with protection of human subjects; inclusion of minorities, women, and children; humane animal care and use; biosafety; and other matters, as appropriate. NIH also ensures that the institution where the research takes place has necessary and appropriate policies in place for avoidance of financial conflicts of interest in research.
NIH policies extend into the post-award phase of research as well, so that NIH can monitor research progress and provide oversight to ensure responsible conduct of research. Scientific monitoring includes reviewing yearly progress and financial reports submitted by grantees, the publications generated by the research, and any invention reports.19 NIH also monitors compliance with federal laws and policies pertaining to protection of human subjects, the care and use of vertebrate animals used in research, data sharing, the NIH Public Access Policy, and other matters. In addition, oversight of clinical research may involve data and safety monitoring and monitoring of inclusion of participants by sex/gender, race, and ethnicity in clinical research.
16 For more information, see https://grants.nih.gov/grants/peer_review_process.htm.
17 An application may be designated “Not Recommended for Further Consideration” (NRFC) at the first level of peer review if it lacks significant and substantial merit; presents serious ethical problems in the protection of human subjects from research risks; or presents serious ethical problems in the use of vertebrate animals, biohazards, and/or Select Agents. Applications designated as NRFC do not proceed to the second level of peer review (National Advisory Council/Board) because they cannot be funded.
18 Percentile represents the relative position or rank (from 1 to 100) of each overall impact/priority score.
19 For more information, see https://grants.nih.gov/grants/funding/sbir_sttr_invention_letter.htm, https://grants.nih.gov/grants/guide/notice-files/not95-003.html, and https://s-edison.info.nih.gov/iEdison/timeline.jsp.
Approximately 11 percent of NIH funds support research and training activities carried out by NIH scientists in NIH laboratories on its campuses in the Bethesda (including the NIH Clinical Center), Rockville, Frederick, and Baltimore areas in Maryland; Research Triangle Park, North Carolina; Detroit, Michigan; Phoenix, Arizona; and the Rocky Mountain Laboratories in Hamilton, Montana. Approximately 1,200 principal investigators lead intramural research projects that involve more than 6,000 trainees ranging from high school students to postdoctoral and clinical fellows. OIR is responsible for trans-NIH oversight and coordination of intramural research, human subject protections, animal welfare, training, policy development, laboratory safety, and technology transfer conducted within NIH laboratories and clinics. OIR is led by the NIH Deputy Director for Intramural Research, and each IC intramural research program is led by an IC Scientific Director. OIR oversight is carried out in conjunction with the IC Scientific Directors. A summary of policies governing intramural research can be found in the Intramural Research Sourcebook.20
The NIH intramural research programs conduct basic, translational, and clinical research. Organizationally, the individual laboratories and clinics report to their respective IC and are responsible for conducting original research consistent with the goals of the IC. Most ICs have an intramural program. As with the extramural program, intramural research proposals are generated by scientists. In the intramural research program, however, program directions and research priorities are not shaped primarily through grant awards21 but rather through professional hiring and promotion decisions, external reviews, and the allocation of resources to laboratories and branches.
Each intramural research program has a promotion and tenure committee that evaluates all recommendations for professional appointment or promotion, and tenured and tenure-track scientists undergo formal internal reviews annually. Resource allocations and promotions are determined based on these reviews. In addition, at least every four years, an external expert Board of Scientific Counselors reviews the work of each tenured/tenure-track scientist and makes recommendations regarding continuation or modification of projects and adjustment of resources (e.g., budget, space, and personnel). Moreover, IC Scientific Directors are evaluated by an external committee every five years, and each IC intramural research program is reviewed, in its entirety, by a “blue ribbon” panel approximately every 10 years. These panels assess and make recommendations concerning the impact of the research program, program balance, and other significant matters that play a role in the success of the program.
Two offices manage research training for OIR. The Office of Intramural Training and Education is charged with helping trainees in the intramural research program, including graduate students in partnership with universities in the U.S. and abroad, to develop scientific and professional skills needed to become leaders in the biomedical research community. The Office of Clinical Research Training and Medical Education deals with all aspects of clinical training.
NIH also provides primary administrative and research capacity for the National Toxicology Program, a federal interagency research program headquartered at the NIEHS, whose goal is to safeguard the public by identifying which of the many thousands of chemicals and other substances that humans are exposed to in the environment are toxic and may affect human health. Current National Toxicology Program initiatives examine the effects of cell phone radiation, endocrine disruptors, and nanomaterials, as well as developing new approaches to advance high throughput (high speed and high quantity) screening of chemicals, and to reduce the number of animals used in research.
20 For more information, see https://sourcebook.od.nih.gov/.
21 The exception is that intramural investigators are eligible to compete for most NIH Roadmap initiatives to allow qualified intramural researchers to contribute to the goals of Roadmap programs.
The Clinical Center is the nation’s largest hospital devoted entirely to clinical research and patient care. Research at the Clinical Center is conducted with access to cutting-edge technologies in an environment of compassionate care. This world-class national resource promotes translational research—the transformation of scientific observations and laboratory discoveries into applications for diagnosing, treating, and preventing disease that benefit patient health and medical care. Composed of two facilities—the Mark O. Hatfield Clinical Research Center (2005) and the original Warren Grant Magnuson Clinical Center (1953)—the center houses 240 inpatient beds, 82 day-hospital stations, an ambulatory care research facility, 12 operating rooms, critical care facilities, advanced radiology and imaging capabilities, and research laboratories. The unique design of the facility locates patient care units in proximity to laboratories conducting related research. This design facilitates interaction and collaboration among intramural clinicians and researchers to enhance patient care.
More than 1,500 studies are in progress at the Clinical Center, bringing 10,000 new research participants per year from all 50 states and throughout the world. The center has more than 95,000 outpatient visits a year and 6,000 inpatient admissions. Approximately 1,200 credentialed physicians, dentists, and Ph.D. researchers, 620 nurses, and 450 allied health care professionals, such as pharmacists, dietitians, and medical technologists, work at the center. As a research facility, the Clinical Center enrolls healthy volunteers and patients with common and rare conditions. Those with mysterious conditions that have long eluded diagnosis are also seen through the Undiagnosed Diseases Program, a clinical research program in collaboration with the NIH Office of Rare Diseases and NHGRI.
In 2011, the Clinical Center received the Albert and Mary Lasker Foundation’s Lasker~Bloomberg Public Service Award, “for serving since its inception as a model research hospital—providing innovative therapy and high-quality patient care, treating rare and severe diseases, and producing outstanding physician-scientists whose collective work has set a standard of excellence in biomedical research.”
In addition to the Clinical Center on the main campus, NIH supports satellite clinical research facilities through various ICs. For example, the NIEHS Clinical Research Unit, located on the institute’s North Carolina campus, is focused on studying the interactions of genetics and environmental exposures in the development of disease, conducting pharmacokinetic studies on environmental chemicals, as well as identifying populations at increased risk, with the goal of developing novel preventive and therapeutic strategies to address human disease.