Vulnerable and Other Populations Requiring Additional Protections

The Code of Federal Regulations outlines specific requirements to enhance protections for three groups. Click on the links below to learn more about what is required for each of the populations.

Pregnant women, human fetuses, and neonates
Children
Prisoners

It is important for researchers to keep in mind that risks may vary for particular groups, depending on the nature of the research being conducted. In addition to the groups specified in 45 CFR 46, consider what protections or additional steps may be needed to minimize risk for your study population, such as outlining procedures for consenting individuals with diminished decision-making capacity, or specifying a plan to address incidental findings from your research. Points to consider regarding consent of individuals with reduced decision-making capacity can be found here.

Please note that the existence of additional protections should not discourage research with vulnerable populations or those requiring special considerations. NIH policies state that studies should not be designed to exclude women, minorities, and individuals based on age unless there is a scientific or ethical reason not to include them. Please visit the Inclusion of Women and Minorities in Clinical Research website and the Inclusion Across the Lifespan website for more information about these policies.

Within the application/proposal for funding, the Human Subjects and Clinical Trials Information Form Section 2 requires an explanation of the target population, including an explanation of the proposed study population in light of NIH policies regarding the inclusion of women and minorities, and individuals across the lifespan. Justification for the inclusion/exclusion of specific groups can be stated here. In addition, Section 3 of the Human Subjects and Clinical Trials Information Form requires the risks to subjects, protections, benefits and importance of the knowledge to be gained from the project to be discussed. These sections can be used to address participation and protections for vulnerable populations, such as children and prisoners, and groups that may be at increased risk and/or require additional protections, such as pregnant women. For more information, please see the application guide and the Human Subjects Pre-Award and Post-Award Processes website.

Pregnant women, human fetuses, and neonates

Because research may pose additional and/or unknown risks to pregnant women, human fetuses and neonates, the regulations require additional safeguards in research. These safeguards can be found in 45 CFR 46, Subpart B

. Additional information about research with pregnant and lactating women is available from the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC)

Children

NIH policy (NOT-OD-18-116) requires individuals of all ages, including children, to be included in NIH-supported research unless there is a scientific or ethical reason not to include them. There are also specific requirements that apply to research involving children in 45 CFR 46 Subpart D .

NIH defines a child as an individual under the age of 18. Note that children is defined in 45 CFR 46 as “persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.”

Important points from 45 CFR 46 regarding research with children:

Exemption 2 does not apply to research with children except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.
Research with children may require assent from the child in addition to permission from a parent(s).
Research involving greater than minimal risk is permitted with children only under specific conditions, and requirements depend on the prospect or absence of direct benefit to the individual participants.
When children are wards of the State or other agency/institution/entity, an advocate may be required in addition to an individual acting on behalf of the child as a guardian or in loco parentis.

Please review 45 CFR 46 Subpart D for full details, as the information above does not highlight all of the requirements.

Additional note: in situations where children are also prisoners, 45 CFR 46 Subpart C requirements also apply.

Prisoners

Because prisoners may not be free to make a truly voluntary and uncoerced decision regarding whether or not to participate in research, the regulations require additional safeguards for the protection of prisoners. These safeguards are found in 45 CFR 46, Subpart C . Subpart C applies to all research that includes any individual who is or becomes a prisoner while participating in a research study.

Under 46.305(c), the awardee institution must certify to OHRP that the IRB has made all of the findings required under 46.305(a). NIH conducted or supported research involving prisoners as subjects may not proceed until OHRP issues its approval in writing to the institution and to the NIH.

Roles and responsibilities of the investigator, institution, and IRB are outlined in Subpart C of 45 CFR 46 .

Roles and Responsibilities of NIH Staff in Reviewing and Funding Research Involving Prisoners

The Scientific Review Group (SRG) conducts a review of the proposed research. Reviewers may choose to comment on the additional protections for prisoners in their critiques. Unacceptable risks and/or inadequate protections for participants who are prisoners must be identified as Unacceptable Human Subjects Protections in the Summary Statement.
When appropriate, Program Staff communicates with the PI and provides information and resources describing:
- The responsibilities of the PI when conducting research involving prisoners
- The proper process for IRB review and approval
- The need for documented approval from OHRP prior to the initiation of any research involving prisoners
- Program Staff communicates with Grants Management Staff after OHRP issues its approval, in writing, of the proposed research.

If an award is made prior to documentation of OHRP approval, Grants Management Staff must restrict research involving prisoners on the Notice of Award. Restrictions are lifted by Grants Management Staff in a revised Notice of Award after Program Staff has notified them that OHRP has provided documentation of approval for the proposed research.

For additional information about the Peer Review and Pre-award processes, visit the Peer Review and Pre-Award and Award Process websites.

Resources:

OHRP Guidance Website: Vulnerable Populations