HRPP policies & procedures manual

1103: National Institutes of Health

1. Purpose

The purpose of this policy is to define the procedures as they apply to human research that is funded by National Institutes of Health. Research supported by National Institutes of Health requires compliance with additional federal regulations, directives and instructions.

2. Definitions

Clinical research

Research with human subjects that is:

  • 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:
    1. mechanisms of human disease
    2. therapeutic interventions
    3. clinical trials, or
    4. development of new technologies
  • Epidemiological and behavioral studies
  • Outcomes research and health services research

Studies falling under 45 CFR 46.104(4) (Exemption 4) are not considered clinical research by this definition.

Clinical trial

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. 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.

Use the following four questions to determine the difference between a clinical study and a clinical trial:

  1. Does the study involve human participants?
  2. Are the participants prospectively assigned to an intervention?
  3. Is the study designed to evaluate the effect of the intervention on the participants?
  4. Is the effect being evaluated a health-related biomedical or behavioral outcome?

Note that If the answers to the 4 questions are yes, your study meets the NIH definition of a clinical trial, even if…

  • You are studying healthy participants
  • Your study does not have a comparison group (e.g., placebo or control)
  • Your study is only designed to assess the pharmacokinetics, safety, and/or maximum tolerated dose of an investigational drug
  • Your study is utilizing a behavioral intervention

Studies intended solely to refine measures are not considered clinical trials.

Studies that involve secondary research with biological specimens or health information are not clinical trials.

3. Specific policies


If the study is a clinical trial and is funded in whole or in part by NIH, there are obligations and requirements per NIH policy to register the trial and provide summary results on

3.2 Other NIH policies

3.2.1 Certificates of confidentiality (COC)

Certificates of confidentiality protect the privacy of the subjects by prohibiting disclosure of identifiable, sensitive research information to anyone not connected to the research except when the subject consents or in a few other specific situations.

All CoCs issued in the past or in the future, regardless of funding sources, must comply with the requirements of the CoC policy, especially the new disclosure requirements and restrictions.

The new disclosure requirements prohibit disclosure of the name of research subjects or any identifiable research information, document, or biospecimen to anyone not connected with the research except under very specific circumstances as detailed in the CoC policy.

Effective October 1, 2017, CoCs will be issued automatically for any NIH-funded project using identifiable, sensitive information that was on-going on/after December 13, 2016.

The CoC will be issued as a term and condition of award.

There will be no physical certificate issued.

Read the CoC policy to learn more.

3.4 Requirements of researchers

Researchers are required to follow the NIH guidance on clinical trials.

4. Applicable regulations and guidelines

34 CFR 98

32 CFR 219

5. Forms


6. Procedures employed to implement this policy & assignment of responsibility

ORA director, chairpersons of IRBs, IRB members, IRB coordinator, and institutional officialEnsure compliance with federal regulations, policy and procedures to guarantee the protection of human subjects participating in research.
Institutional official and ORA directorEvaluate on an ongoing basis the HRPP program for adherence and compliance with federal, state, and local policy and regulations.