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NIH Investigator Manual for Human Subjects Research

Chapter 13 - Conducting Research with Special Populations


Pregnant women

Key points

  • Research involving pregnant women, human fetuses or neonates may not begin prior to IRB approval of the research.

  • When conducting research involving pregnant women, human fetuses or neonates, investigators must:
    • Ensure that the protocol and research comply both with the basic protections for human subjects and the additional requirements of 45 CFR 46 Subpart B (Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research).
    • If the research also involves pregnant children or pregnant prisoners, other subparts of 45 CFR 46 also apply (Subpart D and Subpart C, respectively).

  • If the study does not intentionally enroll pregnant women, but it is possible for a subject to become pregnant while on study (i.e., child-bearing potential), and the intent is to keep the subject on the study (because pregnancy is not an off-study criterion), then your protocol must provide sufficient justification and information for the IRB to determine that all of the regulatory requirements are met.

  • When conducting FDA-regulated research involving pregnant women, human fetuses or neonates, you must also:
    • Follow all applicable FDA requirements.
    • Note that the exception(s) from informed consent requirements for emergency research may not be applied to research that is also subject to Subpart B.

  • Exempt research may proceed so long as it meets the applicable regulatory requirements.

  • You should also be mindful of applicable state or local law, as well as Tribal law.

  • For additional information refer to NIH Policy 400, Research Involving Pregnant Women, Human Fetuses and Neonates.
What conditions must be met for enrollment of pregnant women, fetuses or neonates in trials supported or conducted by Health and Human Services (HHS)?

Pregnant women or fetuses may be involved in research if all of the following conditions are met:

  • Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses.

  • The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means.

  • Any risk is the least possible for achieving the objectives of the research.

  • If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, and her consent is obtained in accord with the informed consent provisions of Subpart A.

  • If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the required informed consent provisions, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.

  • Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate.

  • For children who are pregnant, assent and permission are obtained in accord with the provisions of Subpart D Additional Protections for Children Involved as Subjects in Research.

  • No inducements, monetary or otherwise, will be offered to terminate a pregnancy.

  • Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy.

  • Individuals engaged in the research will have no part in determining the viability of a neonate.
What should be considered when research involves pregnant women and has prospect of direct benefit?
  • Research that has the prospect of direct benefit (DB) to the pregnant woman or the fetus is generally approvable even if greater than minimal risk when the other Subpart B requirements are also met.

  • Consent of the pregnant woman alone is sufficient in this case unless the research has the prospect of DB only for the fetus.

  • If the DB is only for the fetus, the consent of both the pregnant woman and the father is required unless the father is unable to provide consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.
What should be considered when research has no prospect of direct benefit to the mother or the fetus and:
  • There is no greater than minimal risk to the fetus
    • When there is no prospect of DB to the mother or fetus, the IRB may only approve the research if the risk to the fetus is not greater than minimal, and the "purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means."
    • For such a protocol to be approved, it must justify why enrollment of pregnant women is needed to gain important biomedical knowledge related to the intent of the protocol.
    • You must provide a justification in the protocol, and the IRB must subsequently determine that the aim of gaining such knowledge cannot be achieved by enrolling only nonpregnant subjects.

  • When the research is greater than minimal risk with no prospect of direct benefit to the pregnant woman or the fetus, it cannot be approved by the IRB.
When the study does not enroll pregnant women but is greater than minimal risk, what do I need to include in the protocol about what will happen if a participant gets pregnant on study?
  • The protocol should address what will happen if participants become pregnant during the course of the study.
    • For treatment studies:
      • Indicate in your protocol if pregnancy is an off-treatment criterion.
      • If the subject's partner becomes pregnant, and the intent is to continue to collect outcome data, the IRB must review and approve a consent form which allows the partner to provide consent to have pregnancy outcome data collected.  Another option is to indicate that you intend to collect outcome data and will enroll the partners on NIH Protocol 000268, NIH Intramural Research Program's Pregnancy Registry Protocol for Subjects and their Partners.  

    • For FDA regulated research, pregnancy outcome should be collected and reported.

  • If the protocol indicates that the participant will remain on study, the protocol should include the following information:
    • While pregnant, neither research interventions nor research tests or procedures that are greater than minimal risk will occur (because per the regulations, research with pregnant women that is greater than minimal risk is not approvable unless there is potential for direct benefit to the pregnant woman or fetus).

    • Explain the justification in the protocol for why the biomedical knowledge to gained cannot be obtained from nonpregnant women.

    • If a participant becomes pregnant while on study and you intend the to keep the participant on-study, then a modification must be submitted to provide the justification for continued participation of the pregnant woman on the research.

    • Example:
      • In a natural history study of individuals with Lupus, the PI explains that the only way to learn about critical biological differences between pregnant and nonpregnant participants with this disease is to continue to follow pregnant women on study.
      • While pregnant, no research interventions, tests or procedures that are greater than minimal risk will be performed on the pregnant woman.
      • In this case, continued participation of a woman who becomes pregnant can be approved by the IRB under the regulations for the additional protections for pregnant women.

Prisoners

Key points

  • All non-exempt human subjects research that involves prisoners as subjects, must be conducted in compliance with applicable policies and regulations. (See 45 CFR 46 Subpart C - Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects.)

  • Sufficient information must be in the protocol for the IRB to determine that the regulations pertaining to conditions under which prisoners may be enrolled in research are met.

  • Research involving prisoners may not begin prior to approval of the research by both the IRB and the Health and Human Services (HHS) Office for Human Research Protections (OHRP).
How do the regulations define prisoner?
  • Prisoner means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing (45 CFR 46.303(c)).

  • OHRP's Prisoner Research FAQs explain that individuals are prisoners if they are in any kind of penal institution, such as a prison, jail, or juvenile offender facility, and their ability to leave the institution is restricted. Prisoners may be convicted felons or may be untried persons who are detained pending judicial action, for example, arraignment or trial.

  • OHRP's Prisoner Research FAQs provide common examples of the application of the regulatory definition of prisoner:
    • Individuals who are detained in a residential facility for court-ordered substance abuse treatment as a form of sentencing or alternative to incarceration are prisoners; however, individuals who are receiving non-residential court-ordered substance abuse treatment and are residing in the community are not prisoners.
    • Individuals with psychiatric illnesses who have been committed involuntarily to an institution as an alternative to a criminal prosecution or incarceration are prisoners; however, individuals who have been voluntarily admitted to an institution for treatment of a psychiatric illness, or who have been civilly committed to nonpenal institutions for treatment because their illness makes them a danger to themselves or others, are not prisoners.
    • Parolees who are detained in a treatment center as a condition of parole are prisoners; however, persons living in the community and sentenced to community-supervised monitoring, including parolees, are not prisoners.
    • Probationers and individuals wearing monitoring devices are generally not considered to be prisoners; however, situations of this kind frequently require an analysis of the particular circumstances of the planned subject population. Institutions may consult with OHRP when questions arise about research involving these populations.
What are the specified categories of research involving prisoners that are permitted under regulation?

Non-exempt human subjects research involving prisoners must meet one of the 4 categories specified at 45CFR 46.306. Research conducted or supported by DHHS may involve prisoners as subjects only if:

  • The institution engaged in the research must certify to the Secretary (through OHRP) that the IRB has reviewed and approved the research under 45 CFR 46.305; and

  • The Secretary (through OHRP) must determine that the proposed research falls within these categories of permissible research:
    • Study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects.
    • Study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects.
    • Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction and sexual assaults).
      • Studies in this category may proceed only after the Secretary has consulted with appropriate experts including experts in penology [which is the study of the punishment of crime and of prison management], medicine and ethics and published notice in the Federal Register of the intent to approve such research.
    • Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject.
      • In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary (through OHRP) has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research.
Can exempt research involve prisoners?
  • Exempt research involving prisoners is not allowed in research approved under the pre-2018 Common Rule.

  • Under the 2018 Common Rule, research involving prisoners cannot be deemed exempt except for research aimed at involving a broader subject population that only incidentally includes prisoners. Examples of exempt research that only incidentally includes prisoners include:
    • Exempt secondary research use of information or biospecimens from subjects who are prisoners, if that analysis is not seeking to examine prisoners as a population and only incidentally includes prisoners in the broader study.
    • An exempt study that recruited subjects from a local community center to participate in a comparison of HIV educational materials even if some of the subjects became prisoners after enrollment.
What are my responsibilities as an investigator when anticipating the enrollment and participation of prisoners on my research protocol?
  • When anticipating the participation of prisoners on your research protocol, clearly indicate this intent in the protocol and any safeguards for prisoner-subjects must be clearly described.

  • You should also be mindful of applicable state or local law, as well as Tribal law.
What are my responsibilities as an investigator when a subject becomes a prisoner after enrollment on my research protocol not previously reviewed and approved by the IRB for prisoner participation?
  • If a subject becomes incarcerated and the IRB and OHRP have not previously approved prisoner participation on your research protocol, you must notify IRBO as soon as possible by submitting a Reportable New Information form in the eIRB system.

  • All research interactions, interventions with, and obtaining identifiable private information about the now-incarcerated prisoner-subject, must be halted until IRB and OHRP approval are obtained.

  • If it is in the best interest of the subject to remain on study while incarcerated, you must promptly notify IRBO and obtain permission from the IRB Chair to continue activities needed to ensure the safety and welfare of the now prisoner-subject until IRB and OHRP approval are obtained.
    • Submit a modification in the NIH electronic IRB system for review by the convened IRB requesting permission for the prisoner-subject to remain on study and include any additional safeguards and changes to procedures (if any) needed for the now-prisoner-subject to remain on the research.

  • No research activities involving the prisoner-subject may take place prior to IRB approval and receipt of a letter of authorization from OHRP, except for those necessary for the welfare or safety of the prisoner-subject.

  • If the IRB disapproves continued participation of the prisoner-subject, the subject must be taken off study.

  • For additional information, refer to OHRP Guidance–Prisoner Involvement in Research (May 23, 2003).
Can informed consent be waived or altered in research involving prisoners?
  • Informed consent can be waived or altered in research involving prisoners only in accordance with applicable regulations. However, even if informed consent is waived or altered, subjects must be clearly informed in advance that participation in the research will have no effect on their parole, if such notification is relevant.

  • Prisoners cannot be involved in emergency research where the requirement for informed consent has been waived by the Secretary under the authority of 45 CFR 46.101. (See also 61 Fed. Reg. 51531.)
Where can I find additional information about conducting human subjects research with prisoners?

Children

Key points

  • Research involving children may not begin prior to IRB approval of your research protocol.

  • Children cannot provide legally effective informed consent for participation in research.

  • No child may be enrolled, screened, or have research procedures initiated, unless parental permission and child assent is obtained unless waived by the IRB.

  • Provide a plan in your protocol for obtaining parental permission as well as assent from the child, or you must provide a justification for requesting a waiver of parental permission and/or assent.

  • For research taking place at an NIH site, when parents share joint legal custody for medical decision-making of a child (e.g., by a custody agreement or court order), both parents must give their permission regardless of the risk level of the research. Exceptions may include if one parent has since died, become incompetent, or is not reasonably available.

  • See NIH Policy 402, Research Involving Children.
How do the human subjects research regulations define children?
  • The human subjects research regulations define children 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 (45 CFR 46.402(a)).

  • The OHRP Research with Children FAQs further note that in the United States laws regarding who is legally considered a child may vary from state to state; in a large majority of states eighteen years of age is the legal age of adulthood, but this is not true in every state, locality, or territory. Also, there may be exceptions to who is considered a child and additional laws may be in place that define emancipated minors.

  • The definition of children also takes into account the particular treatments or procedures involved in the proposed research; for example, in some places individuals who are sixteen years of age may legally consent to certain medical treatments, and so if the involvement of human subjects in a proposed research activity consists of these treatments, then they may be considered as adults for that purpose. If a proposed activity includes something for which the subject has not yet reached the legal age of consent, however, that person must be considered a child.
What should I know about enrolling a child who is legally emancipated?
  • Children who are legally emancipated are considered adults and the requirements of NIH Policy 402, Research Involving Children do not apply.

  • You MUST consult OHSRP who will contact OGC for guidance before considering a minor to be emancipated.
What is a ward and do special regulations apply to conducting human subjects research with children who are wards (of the state or other agency, institution, or entity)?
  • A child who is a ward is one who is placed under the protection of, and in the legal custody of, the State or other agency, institution, or entity (including guardians), consistent with applicable State or local law. Specific research regulations apply if a protocol will enroll wards.
  • Children who are wards of the state or any other agency, institution, or entity can be included in research approved under § 46.406 or § 46.407 (see description of these categories in the following question) only if such research is:
    • Related to their status as wards; or
    • Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.

  • If the IRB approved such research, appointment of an advocate for each child who is a ward is required, in addition to any other individual acting on behalf of the child as guardian or in loco parentis. One individual may serve as advocate for more than one child. The advocate should be someone with the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child's participation in the research and who is not associated in any way (except in the role as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

  • Contact IRBO if you plan to enroll wards of the state.
What are the categories of research involving children and who can approve this research?

Three of the categories of research involving children can be approved by the IRB. A fourth category of research (§ 46.407) requires additional review by the Secretary of HHS.
The table below summarizes the categories of research with children described in the regulations.

Type of Research
(HHS regulations/FDA regulations)

Risk/Benefit

Who can be enrolled?

Parental Permission/Assent

Category 1 (46.404/50.51) Not involving greater than minimal risk.
Examples:

  • Chart review
  • Questionnaires
  • Non-contrast MRI

N/A or None

Healthy or affected child

  • Assent of the children and the permission of their parents or guardians required unless waived by the IRB.
  • The IRB may find that the permission of one parent is sufficient. *

Category 2 (46.405/50.52)
More than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit (DB) for the individual subject, or by a monitoring procedure that is likely to contribute to the subject's well-being.
Example:

  • Administration of investigational drug to treat minor subjects' condition
  • The risk involved is justified by the anticipated benefit to the subjects.
  • The relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by alternative approaches.

Minors with the condition under study.

  • Assent of the children and the permission of their parents or guardians required unless waived by the IRB.
  • The IRB may find that the permission of one parent is sufficient. *

Category 3 (46.406/50.53)
More than minimal risk to children is presented by an intervention/procedure that does not hold out the prospect of DB for the individual subject, or by a monitoring procedure which is not likely to contribute to the well-being of the subject but is likely to yield generalizable knowledge about the participant's disorder or condition which is of vital importance for the understanding or amelioration of the subjects' disorder or condition.
Example:

  • CT scan or MRI with contrast
  • The risk represents only a minor increase over minimal risk.
  • The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in the participant's actual or expected medical, dental, psychological, social or educational situations.

Children with/at risk for the condition under study.
MAY NOT ENROLL HEALTHY CHILDREN

  • Assent of the children and the permission of their parents or guardians required unless waived by the IRB.
  • Both parents must give their permission unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.

Category 4 (46.407/50.54)
Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.
AND
The Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, education, ethics, law) and following opportunity for public review and comment, has determined either:

  1. That the research in fact satisfies the conditions of § 46.404, § 46.405, or § 46.406, as applicable, or
  2. The following:
    1. The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children.
    2. The research will be conducted in accordance with sound ethical principles.
      Majority reviewed under 46.407 to date have been for interventions that are > minimal risk to children lacking a disorder or a condition (healthy controls), or more than minor increase over minimal with no prospect of direct benefit (PDB).
      Examples:
  • Metabolic studies in normal children


Healthy or affected child

  • Assent of the children and the permission of their parents or guardians required unless waived by the IRB.
  • Both parents must give their permission unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.

* For research taking place at an NIH site when parents share joint legal custody for medical decision-making of a child (e.g., by a custody agreement or court order), both parents must give their permission regardless of the risk level of the research. Exceptions may include if one parent has since died, become incompetent, or is not reasonably available.

What are my responsibilities when enrolling a child on my research protocol?
  • It is your responsibility to determine if it is scientifically and ethically appropriate to enroll children in your protocol, and this rationale much be documented in the protocol.

  • When your research involves children, you must provide a plan in your protocol for obtaining parental permission as well as assent from the child, as applicable, or provide a justification for requesting a waiver of parental permission and/or assent.

  • Do not initiate or conduct research involving children unless IRB approval has been obtained.

  • Ensure that you will comply with the requirements for obtaining and documenting parental permission and assent as described in the protocol.

  • No child may be enrolled, screened, or have research procedures initiated, unless parental permission and child assent are obtained consistent with the Common Rule and, as applicable, FDA regulations.
What are my responsibilities for obtaining parental permission and assent from a minor subject when I will be enrolling children in my study?

Please refer to an earlier section of this manual that describes details about the consent process when minors are being enrolled (e.g., the assent process, documentation of assent, process regarding consent when minor participants on my study reach adulthood, and waiver of parental permission or requirement for assent by the IRB.)

Can children be enrolled in exempt research?
  • The research exemptions are complex, and not all exemptions can be applied to research involving children.

  • Consult with the OHSRP Office of IRB Operations (IRBO) before submitting an exempt research protocol involving children in the electronic IRB system.

  • Note that exempt category 3 for benign behavioral interventions that was added with the 2018 Common Rule revisions cannot involve children. Such interventions constitute non-exempt research and must be reviewed by the IRB accordingly.

Adults who lack capacity to consent to research

Key points

What must be incorporated in my research study to allow for enrollment of adults who lack capacity to consent to research?

When your research study will, or may, include subjects without capacity, you must describe the following in your protocol:

  • Indicate that subjects without capacity are eligible to participate in the research.
    • If these subjects originally have capacity to consent, and may subsequently lose capacity to consent, then describe the conditions under which these subjects will be able to continue to participate in the research.

  • Describe the compelling justification for including the participation of these subjects in your research study, any safeguards that will be put in place, and the procedures to be followed.

  • Explain the plan for assessing the initial and ongoing capacity of the subjects and identifying the Legally Authorized Representative (LAR).

  • Delineate in your protocol the process for obtaining initial consent from the LAR and/or reconsent from the LAR.
What are the categories of research for adults who lack capacity to consent to research participation?
  • The research is minimal risk (Category A)

  • The research is greater than minimal risk, and offers a prospect of direct benefit to the participant (Category B)

  • The research is no more than a minor increase over minimal risk with no prospect of direct benefit, and does not adversely affect the rights, safety, or welfare of the participants (Category C)

  • The research does not meet the above conditions but has undergone additional institutional review and approval by the NIH Institutional Official (IO) (Category D)
What are my responsibilities as an investigator before enrolling a subject who may lack capacity to consent to my research protocol?
  • Ensure that a capacity assessment of the potential subject is conducted.

  • At the Clinical Center, the Ability to Consent Assessment Team (ACAT) can provide such assessments. ACAT is a group of NIH health care staff, including members from Psychiatry (which includes the National Institute of Mental Health (NIMH) Human Subjects Protection Unit (HSPU)) and Bioethics, which is trained and available to determine whether a patient has capacity to consent to clinical care or hospital re-admission, and/or has the capacity to assign a DPA for health care. ACAT services can be accessed by contacting the Bioethics Consultation Service. (See Clinical Center Bioethics Consultation webpage.)

  • If it is determined that the potential adult subject lacks decision-making capacity to provide informed consent to research participation, and consent is required for a subject to participate or to continue to participate in the research, then informed consent must be obtained from the legally authorized representative (LAR) to be considered legally effective.

  • Confirm the validity of the Legally Authorized Representative (LAR). The LAR is someone who:
    • Is permitted consistent with the risk/benefit category made by the NIH IRB
    • Is permitted consistent with the hierarchy described earlier in this manual
    • Has the capacity to consent to the research
    • Is able to represent the wishes or best interests of the subject

  • Ensure that the LAR will be available, ideally present, at the time of consent.

  • Be aware that for any subject with a guardianship order who will be seen at an NIH site, you must provide a copy of the court order to the NIH Office of General Counsel (OGC) for review.

  • It is expected that the LAR will accompany a subject during any admission/visit to the Clinical Center and further be available, ideally present, at the Clinical Center for additional conversations with the health care team during the subject's stay.

  • Document this process in the participant's medical (e.g., CRIS) and/or research record.
What should I do if my research study was not previously approved by the IRB for the participation of subjects without capacity, and a subject who was previously able to provide consent subsequently loses capacity to provide ongoing consent?

If the research has not been approved by the IRB for the participation of subjects without capacity, and a subject who was previously able to provide consent for themselves subsequently loses the capacity to provide ongoing consent, and the research involves continued interactions or interventions with the subject (excluding only data or specimen analysis), and if the subject is to remain on the research, then the following actions must be taken:

    • Identify and engage with the LAR, so the LAR can advocate on behalf of the subject.

    • Assess whether the loss of capacity is temporary or permanent.
      • When the loss of capacity is temporary (e.g., they are expected to regain capacity):
        • No modification of the protocol needs to be submitted to the IRB.
        • Reconsent of the subject by the LAR is not needed for the subject's continued participation in the research.
      • When the loss of capacity is permanent:
        • Modify the protocol and obtain IRB approval for the inclusion of subjects without capacity.
        • Note that the subject may remain on the research until the IRB has made the determination whether the protocol can include subjects without capacity on the research.
        • If the IRB determines that the subject without capacity can remain on the research, then reconsent by the LAR is required.
        • If the IRB determines that subjects without capacity may not be included on the research, then the subject must be withdrawn from the research study.
What resources are available at the Clinical Center to help guide me when enrolling potential subjects who may not have the capacity to consent?
  • Bioethics Consultation Service: You can contact the Department of Bioethics for consultation. The Bioethics Consultation Service is made up of members of the NIH Department of Bioethics and the Clinical Center Ethics Committee. The members of the Bioethics Consultation Service have been trained in medical ethics and advising patients.

  • Human Subjects Protection Unit (HSPU): The Human Subjects Protection Unit (HSPU) is made up of clinicians who function as Clinical Research Advocates (CRAs) to assess, develop and implement human subjects' protections for potentially vulnerable participants enrolling in research. HSPU functions include assessing and monitoring NIMH participants, consulting with researchers and the NIH IRB and training researchers to obtain informed consent. The HSPU CRAs are also on the ACAT, which provides these services throughout the NIH Clinical Center upon request.
    • The HSPU can provide per protocol requirement or research request, a capacity assessment. For capacity assessment, protocol-specific assessment tools are developed and administered to determine a potential participant's ability to provide informed consent. Capacity assessments may be mandated by the NIH IRB or requested by the researcher.

NIH Staff

Key points

What must be done prior to enrolling NIH staff member on my research study?
  • For research that offers the prospect of direct benefit to the subject (e.g., studies of potential therapeutic intervention for a condition from which the subject suffers), you are not required to obtain IRB approval for enrollment of NIH staff or the immediate family members of the study team.

  • The NIH staff member must still be provided with the FAQs for Staff who are Considering Participation in NIH Research when the research offers no prospect of direct benefit and NIH staff, or immediate family of a study team member wants to participate. In this case, the IRB must approve inclusion of this population prior to enrollment, and the protocol must describe:
    • Whether staff or family members will be included in the research
    • The safeguards for this subject population (e.g., recruitment methods, consent monitoring, eligibility assessment)
    • Recruitment plan, including:
      • Solicitation of subordinates should not be direct, either orally or through individual mailings or email distribution.
      • Recruitment materials may be displayed only where public announcements are permitted.

  • Prior to enrollment the NIH investigator must request NIH staff member to review the Leave Policy for NIH Employees Participating in NIH Medical Research Studies (NIH Policy Manual 2300-630-3). NIH login required

  • If investigators at an NIH site will enroll NIH staff members on a protocol that is being reviewed by an external non-NIH IRB, information about NIH Policy 404, Research Involving NIH Staff as Subjects, will be included as local context information that is provided to that IRB.


Chapter 14 - FDA Regulated Research