Clinical Research

Of NIH’s more than $17B investment, clinical trials (~$7B) reflect the point at which the public is most directly engaged in NIH’s clinical research activities, either as dedicated volunteer research participants or users of the resulting data and health interventions. Successful management and oversight of the clinical trial enterprise remains essential to NIH’s mission to translate basic biomedical discoveries into improved health outcomes. OSP works to ensure that NIH’s clinical trial policies enhance the design, conduct and oversight of clinical trials.

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Clinical Trials

NIH Definition of 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.

Clinical Trial E-Protocol Tool

Clinical Trial E-Protocol Tool and Template Documents

The electronic protocol writing tool aims to facilitate the development of two types of clinical trials involving human participants.  The first type of trials are Phase 2 and 3 clinical trial protocols that require a Food and Drug Administration (FDA) Investigational New Drug (IND) or Investigational Device Exemption (IDE) application.

NIH developed a second protocol template to help behavioral and social science researchers prepare research protocols for human studies measuring a social or behavioral outcome or testing a behavioral or social science-based intervention.

Both templates found in the electronic protocol tool meet the standards outlined in the International Council on Harmonisation (ICH) Guidance for Industry, E6 Good Clinical Practice: Consolidated Guidance (ICH-E6). These are international standards of good clinical practice that apply to all clinical trials, and their goals are to ensure research integrity and protect human subjects. In addition, use of the electronic protocol tool allows researchers to interface directly with

Take me to the Web-based e-Protocol Writing Tool

Informed Consent

As a steward of the nation’s biomedical research enterprise, NIH is dedicated to ensuring that data and biospecimens are shared for research ethically, securely, and with respect for the privacy, autonomy, and well-being of research participants and the communities to which they belong. Responsible sharing of data and biospecimens derived from human participants relies on robust informed consent practices that uphold the principles of autonomy and trust in biomedical research. Fundamental to these practices are clear, efficient, and transparent communication strategies for conveying potential risks and benefits of sharing, enabling individuals to make informed decisions to participate in research, retain autonomy in decision making, and understand potential uses and contributions of their data and specimens.

OSP works to ensure robust informed consent practices are understood and in place across NIH, with the goal of protecting research participants altruistically donating data and specimens to advance the scientific enterprise.


Informed Consent for Secondary Research with Data and Biospecimens: Points to Consider and Sample Language for Future Use and/or Sharing
Informed Consent for Research Using Digital Health Technologies: Points to Consider & Sample Language

NIH Single IRB (sIRB) Policy

The NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research establishes the expectation that all sites participating in multi-site studies involving non-exempt human subjects research funded by the National Institutes of Health (NIH) will use a single Institutional Review Board (sIRB) for all U.S. sites to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects. If you have any questions about this policy, please contact us here.

Data and Safety Monitoring

Clinical trials must be conducted with a high standard of quality that assures the research question is answered in a reliable, valid, and unbiased manner, and that the rights and welfare of human subjects are protected.

In 1998, NIH issued a policy and further guidance was published in 2000. The NIH Data and Safety Monitoring policy states that each NIH Institute and Center (IC) should have a system for appropriate oversight and monitoring of clinical trials in order to ensure the safety of participants and the validity and integrity of the data. The 1998 and 2000 policies provide guidance on when monitoring should be conducted by a Data and Safety Monitoring Board (DSMB). The NIH requirement for data and safety monitoring –at a level commensurate with the risks, size and complexity of the trial–is separate and distinct from the requirement for protocol review and approval by an Institutional Review Board (IRB).

Relevant Documents and Resources

Protections for Participants in Research (Human Subjects Research Protections)

Participants in NIH-funded clinical research studies receive a robust set of protections in accordance with standards established by the U.S. Department of Health and Human Services (HHS) in 45 Code of Federal Regulations (CFR) part 46 (“the Common Rule”), and, when applicable, Food and Drug Administration (FDA) Regulations for 21 CFR Part 50 and 56. Additional protections for research participants are also established under Section 2012 and 2013 of the 21st Century Cures Act, the NIH Certificates of Confidentiality policy, the Privacy Act, and the HIPAA Privacy Rule. Protections provided by the Common Rule ensure the safety, rights, and welfare of participants in research (what the Common Rule calls “human subjects”) under a framework that prioritizes the ethical principles enshrined in the Belmont Report (i.e., respect for persons, beneficence, and justice). These protections include oversight of research by Institutional Review Boards (IRBs), as well as requirements for informed consent, confidentiality, and privacy.

OSP serves as a resource for and advisor to the NIH research community with respect to the implementation of regulations, laws, and policies impacting the protection of participants in NIH research. OSP advises on harmonization and optimization, works with NIH Institute, Center, and Office (ICO) partners to identify and resolve policy issues, and recommends and develops new policies as needed. OSP works closely with colleagues across NIH and HHS, including NIH ICOs as well as FDA, the Department of Defense (DOD), the Department of Veteran’s Affairs (VA), the HHS Office for Human Research Protections (OHRP), and the HHS Secretary’s Advisory Committee on Human Research Protections (SACHRP).

Relevant Documents and Resources

Privacy and Confidentiality in Research

Privacy and confidentiality are essential components of a robust research enterprise. NIH takes seriously the obligation to ensure privacy and confidentiality for individuals who have altruistically provided data and samples for research. Some of the obligations for these protections are outlined in the Common Rule, which describes a framework for protecting the privacy and confidentiality of sensitive, private information. Additional protections are provided by Section 2012 and 2013 of the 21st Century Cures Act and the NIH Certificates of Confidentiality Policy, which ensure appropriate protections for research when identifiable, sensitive information is collected or used. The Privacy Act and HIPAA Privacy Rule outline further protections for when individual data subject to these laws can be released.

OSP serves as a resource and advisor to the NIH research community on privacy and confidentiality regulations, laws, and policies. OSP advises NIH ICOs on these protections and works with ICOs to identify and resolve any policy issues.

Relevant Documents and Resources

Return of Research Results

NIH has long supported a movement in the research enterprise to engage participants as partners in research by informing research priorities and advising on clinical study designs to ensure that outcomes are meaningful to them. Research participants, for their part, have indicated the desire to have information returned to them about the studies in which they participate, including individual-level research results. In 2018, NIH co-sponsored a study by the National Academies of Sciences, Engineering, and Medicine (NASEM) to examine Returning Individual Research Results to Participants, specifically reviewing the current evidence on the benefits, harms, and costs of returning individual research results while considering the ethical, societal, regulatory, and operational issues related to the return of individual-specific research results generated from research on human biospecimens. In recognition of the evolving nature of research and the relationship between research participants and investigators, as well as the responsibility to uphold participant preferences, various programs and initiatives across NIH are moving towards creating a more participatory model of enabling greater return of individual-level research results.

OSP serves as a resource for and advisor to the NIH research community with regard to identifying and resolving policy issues and promoting best practices for the appropriate return of individual research results to participants.

The below list of programs and initiatives is non-exhaustive and highlights select examples that include either a focus on returning research results from particular studies or promoting the development of tools and best practices to enable return of results.