Major extramural research grants awarded to institutions, hospitals, and other research organizations, including small businesses, to support circumscribed research led by investigators, create developmental opportunities, and to provide research related resources under programs such as Research Careers, Research Centers, Research Projects, SBIR/STTRs, and Other Research.
1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. It includes: (a) mechanisms of human disease, (b), therapeutic interventions, (c) clinical trials, or (d) development of new technologies.
2) Epidemiological and behavioral studies.
3) Outcomes research and health services research
Studies falling under 45 CFR 46.101(b) (4) (Exemption 4) are not considered clinical research by this definition.
See Common Rule definition of research at 45 CFR 46.102(d)
See Common Rule definition of human subject at 45 CFR 46.102(f)
The term "prospectively assigned" refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo or other control) of the clinical trial.
An intervention is defined as a manipulation of the subject or subject's environment for the purpose of modifying one or more health-related processes and/or endpoints. Examples include, but are not limited, to: drugs/small molecules/compounds, biologics, devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); and, treatment, prevention, and diagnostic strategies.
A health-related biomedical or behavioral outcome is defined as the pre-specified effect of an intervention on the study subjects. Examples include positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and/or information retention); disease processes; health-related behavior; and, well-being or quality of life
Biomedical clinical trials of an experimental drug, treatment, device, or behavioral intervention may proceed through four phases:
Phase I. Tests a new biomedical intervention in a small group of people (e.g. 20-80) for the first time to determine efficacy and evaluate safety (e.g., determine a safe dosage range and identify side effects).
Phase II. Study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and further evaluate safety.
Phase III. Study to determine efficacy of the biomedical or behavioral intervention in large groups of people (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the interventions to be used safely.
Phase IV. Studies conducted after the intervention has been marketed. These studies are designed to monitor the effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.
Competing applications are applications for a new, renewal, or resubmission research project grants(RPG), including R01s, R21s, and related mechanisms, that require competitive peer review
Early Established Investigator (EEI)
Early Stage Investigator (ESI)
Early Stage Investigator ESI
An Early Stage Investigator is a Program Director / Principal Investigator (PD/PI) who has completed their terminal research degree or end of post-graduate clinical training, whichever date is later, within the past 10 years and who has not previously competed successfully as PD/PI for a substantial NIH independent research award. See our list of NIH grants that a PD/PI can hold and still be considered an ESI. For more information, please click here.
Funding Opportunity Announcement (FOA)
Grant or Grant Agreement
A legal instrument of financial assistance between a Federal awarding agency or pass-through entity and a non-Federal entity that, consistent with 31 U.S.C. 6302, 6304:
(1) Is used to enter into a relationship the principal purpose of which is to transfer anything of value from the Federal awarding agency or pass-through entity to the non-Federal entity to carry out a public purpose authorized by a law of the United States (see 31 U.S.C. 6101(3)); and not to acquire property or services for the Federal awarding agency or pass-through entity's direct benefit or use;
(2) Is distinguished from a cooperative agreement in that it does not provide for substantial involvement between the Federal awarding agency or pass-through entity and the non-Federal entity in carrying out the activity contemplated by the Federal award.
(3) Does not include an agreement that provides only:
(i) Direct United States Government cash assistance to an individual;
(ii) A subsidy;
(iii) A loan;
(iv) A loan guarantee; or
Grants Management Officer (GMO)
Grants Management Specialist (GMS)
Health Professional School or College
In the context of NIH's R15 program, health professional schools and colleges are accredited institutions that provide education and training leading to a health professional degree, including but not limited to: BSN, MSN, DNP, MD, DDS, DO, PharmD, DVM, OD, DPT, DC, ND, DPM, MOT, OTD, DPT, BME, MSEE, MS-SLP, CScD, SLPD, AuD, MSPO, MSAT, and MPH. Eligible health professional schools/colleges may include schools or colleges of nursing, medicine, dentistry, osteopathy, pharmacy, veterinary medicine, public health, optometry, allied health, chiropractic, naturopathy, podiatry, rehabilitation medicine, physical therapy, orthotics & prosthetics, kinesiology, biomedical engineering, occupational therapy and psychology. Accreditation must be provided by a body approved for such purpose by the Secretary of Education.
Independent Clinical Trial
An independent clinical trial is one for which the researcher proposing the study has primary or lead responsibility for conducting and executing the trial. NIH policy permits individual career development awardees and individuals appointed to institutional career development awards to be involved in a range of clinical trial activities, including leading independent clinical trials. For NRSA trainees or fellows, however, NIH policy precludes leading an independent clinical trial as part of their training experience. Instead, NRSA trainees and fellows interested in clinical trials may gain clinical trial research experience by working on a trial led by their mentor or another investigator.
In giving informed consent, people may not waive legal rights or release or appear to release an investigator or sponsor from liability for negligence. Go to 21 CFR 50.20 and 50.25
Institute or Center (IC)
The NIH organizational component responsible for a particular grant program or set of activities. The terms "NIH IC" or "awarding IC" are used throughout this document to designate a point of contact for advice and interpretation of grant requirements and to establish the focal point for requesting necessary prior approvals or changes in the terms and conditions of award.
Institutional Review Board
NIH Guide for Grants and Contracts
Notices posted in the NIH Guide for Grants and Contracts that succinctly highlight a specific topic of interest, for example a specific area of research or program. These notices direct applicants to one or more active funding opportunity announcements (often parent announcements) for submission of applications for the initiative described. Many program announcements will be issued as Notices of Special Interest going forward.
An application may be designated Not Recommended for Further Consideration (NRFC) by the Scientific Review Group 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.