ELEMENT II.4.A.

ELEMENT II.4.A.: The IRB or EC has and follows written policies and procedures for determining the risks to prospective participants who are vulnerable to coercion or undue influence and ensuring that additional protections are provided as required by applicable laws, regulations, codes, and guidance.

The IRB or EC should evaluate research to judge whether the research involves participants who are vulnerable to coercion or undue influence. When some or all of the participants are likely to be vulnerable, the IRB or EC should ensure that additional safeguards are included in the research design to protect the rights and welfare of these participants. If the IRB or EC reviews research that involves children; pregnant women, fetuses, or neonates; prisoners; or adults who lack the ability to consent, or the IRB or EC regularly reviews research that involves other vulnerable individuals (for example, students, employees, or economically or educationally disadvantaged persons, or homeless persons), the IRB or EC should have written policies and procedures regarding additional protections for these categories.

It is impractical to have specific policies for every vulnerable population that might be involved in research. Therefore, when a research study involves vulnerable populations not otherwise covered by specific policies and procedures, policies and procedures should describe in general the steps followed by the IRB or EC to evaluate such research to determine the need for additional protections.

In research involving no more than minimal risk and vulnerable populations, the IRB or EC may decide that existing protections are sufficient and no additional protections are warranted. Conversely, sometimes when research involves no more than minimal risk, additional protections for vulnerable populations might be appropriate.

If additional protections for vulnerable populations are not required under laws, regulations, codes, and guidance, then policies and procedures should describe equivalent protections. Equivalent protections ensure safeguards are in place to protect vulnerable populations, while allowing flexibility in review.

Regulatory and guidance references

DHHS: 45 CFR 46.111(b), 45 CFR 46 Subpart B, 45 CFR 46 Subpart C, 45 CFR 46 Subpart D, 45 CFR 46.111(b), 45 CFR 46.205, OHRP Guidance on Special Protections for Children as Research Subjects, OHRP Guidance on the Involvement of Prisoners in Research, May 23, 2003, 45 CFR 46 Waiver of the Applicability of Certain Provisions of Department of Health and Human Services Regulations for Protection of Human Research Subjects for Department of Health and Human Services Conducted or Supported Epidemiologic Research Involving Prisoners as Subjects (Federal Register, Vol. 68, No. 119, pp. 36929-36931, Friday, June 20, 2003)
DoD: Instruction 3216.02 7.; SECNAVINST 3900.39D, para. 6a(8), DoDD 3216.2, para. 4.4.1; SECNAVINST 3900.39D, para. 6a(6), DoDD 3216.2, para. 4.2; SECNAVINST 3900.39D, para. 6a(3);10 U.S.C. 980
DOE: 10 CFR 745, DOE Order 443.1B, Chg. 1 (April 21, 2016), DOE Notice 443.1 (January 21, 2016), and their accompanying Contractor Requirements Documents (CRDs)
EPA: 40 CFR 26.304, 40 CFR 26.404-405; EPA Order 1000.17 Change A1
FDA: 21 CFR 50.3, 21 CFR 50 Subpart D, 21 CFR 56.111(b), 21 CFR 56.111(c)
ICH-GCP: 4.8.13, 4.8.14
VA: 38 CFR 16.111(b), VHA Directive 2001-028, VHA Handbook 1200.05, 36, 45, 46, 47, 48, 49
AAHRPP Tip Sheet: Following the Guideline of the International Conference on Harmonisation – Good Clinical Practice (E6)
AAHRPP Tip Sheet: Review of Research involving Prisoners and the Role of the Prisoner Representative
AAHRPP Tip Sheet: Sufficient Information to Determine Whether the Criteria for Approval are Met

Required written materials

Essential requirements for IRB or EC review:
1. Policies and procedures describe the process to evaluate risks to vulnerable participants and ensure additional protections are provided:
  1. Applications include whether some or all of the participants are likely to be vulnerable to coercion or undue influence.
  2. When some or all of the participants are likely to be vulnerable, applications include a description of additional safeguards included in the protocol to protect their rights and welfare.
  3. In order to approve research where some or all of the participants are likely to be vulnerable, policies and procedures have the IRB or EC determine whether additional safeguards have been included in the protocol to protect their rights and welfare.
  4. If research involves pregnant women, fetuses, or neonates, policies and procedures have the IRB or EC follow Subpart B of the DHHS regulations or equivalent protections as allowed by law.
    1. If the organization chooses not to apply Subpart B to all research regardless of funding, policies and procedures include equivalent protections for participants in non-funded research.
  5. If research involves prisoners as participants, policies and procedures have the IRB follow Subpart C of the DHHS or equivalent protections as allowed by law.
    1. If the organization chooses not to apply Subpart C to all research regardless of funding, procedures include equivalent protections for participants in non-funded research.
    2. If the convened IRB or EC reviews research that involves prisoners, policies and procedures indicate that one or more individuals who are prisoners or prisoner representatives have to be present at the meeting.
  6. If research involves children as participants, policies and procedures have the IRB or EC follow Subpart D of the DHHS or equivalent protections as allowed by law.
    1. If the organization chooses not to apply Subpart D to all research regardless of funding, procedures include equivalent protections for participants in non-funded research.
  7. If research involves adults unable to consent, policies and procedures have the IRB or EC consider specific criteria for approval of such research that provides additional safeguards to protect their rights and welfare.
  8. If the IRB or EC regularly reviews research that involves other vulnerable populations, policies and procedures describe the steps the IRB or EC follows to evaluate whether additional safeguards are included in research to protect the rights and welfare of these participants.
When following DHHS regulations:
1. Policies and procedures have the IRB or EC follow the requirements specified in Subpart B for research involving pregnant women, fetuses, or neonates; Subpart C for research involving prisoners; and Subpart D for research involving children.
When following DoD requirements:
1. Research involving pregnant women, prisoners, and children are subject to the DHHS Subparts B, C. and D.
2. For purposes of applying Subpart B, the phrase “biomedical knowledge” must be replaced with “generalizable knowledge.”
3. The applicability of Subpart B is limited to research involving pregnant women as participants in research that is more than minimal risk and included interventions or invasive procedures to the woman or the fetus or involving fetuses or neonates as participants.
4. Fetal research must comply with the US Code Title 42, Chapter 6A, Subchapter III, Part H, 289g.
5. Research involving prisoners cannot be reviewed by the expedited procedure.
6. When the IRB reviews research involving prisoners, at least one prisoner representative must be present for quorum. The prisoner representative may be a prisoner, an employee of the prison, or an individual not affiliated with the prison.
7. In addition to allowable categories of research on prisoners in Subpart C, epidemiological research is also allowable when:
  1. The research describes the prevalence or incidence of a disease by identifying all cases or studies potential risk factor association for a disease.
  2. The research presents no more than minimal risk.
  3. The research presents no more than an inconvenience to the participant.
8. When a previously enrolled human participant becomes a prisoner, if the researcher asserts to the IRB that it is in the best interest of the prisoner-participant to continue to participate in the research while a prisoner, the IRB chair may determine that the prisoner-participant may continue to participate until the convened IRB can review this request to approve a change in the ,research protocol and until the organizational official and DoD Component office review the IRB’s approval to change the research protocol. Otherwise, the IRB chair must require that all research interactions and interventions with the prisoner-subject (including obtaining identifiable private information) cease until the convened IRB can review this request to approve a change in the research protocol. The convened IRB, upon receipt of notification that a previously enrolled human participant has become a prisoner, must promptly re-review the research protocol to ensure that the rights and wellbeing of the human subject, now a prisoner, are not in jeopardy. The IRB should consult with a subject matter expert having the expertise of a prisoner representative if the IRB reviewing the research protocol does not have a prisoner representative. If the prisoner-participant can continue to consent to participate and is capable of meeting the research protocol requirements, the terms of the prisoner-participant’s confinement does not inhibit the ethical conduct of the research, and there are no other significant issues preventing the research involving human participants from continuing as approved, the convened IRB may approve a change in the study to allow this prisoner-participant to continue to participate in the research. This approval is limited to the individual prisoner-participant and does not allow recruitment of prisoners as participants.
9. Research involving a detainee as a human participant is prohibited.
  1. This prohibition does not apply to research involving investigational drugs and devices when the same products would be offered to US military personnel in the same location for the same condition.
10. The exemption for research involving survey or interview procedures or observation of public behavior, 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.
11. Policies and procedures prohibit research involving prisoners of war.
12. The IRB or EC is aware of the definition of “prisoner of war” for the DoD component granting the addendum.
When following DOE requirements:
1. Policies must indicate that employees and contractors are considered vulnerable participants.
2. Policies must include direction for the IRB to consider if additional protections are required for research involving employees and contractors.
When following EPA regulations:
1. Policies and procedures include that for research conducted or supported by the EPA, research involving intentional exposure of pregnant women or children to any substance is prohibited and not approved by the IRB or EC.
2. Policies and procedures include that for research intended for submission to the EPA, research involving intentional exposure of pregnant women or children to any substance is prohibited and not approved by the IRB or EC.
3. Policies and procedures have the IRB review observational research involving pregnant women and fetuses using 40 CFR 26 and 45 CFR 46 Subpart B.
4. Policies and procedures allow the IRB to review and approve observational research involving children that does not involve greater than minimal risk only if the IRB finds that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in 26.406.
5. Policies and procedures allow the IRB to review and approve observational research involving children that involves greater than minimal risk but presenting the prospect of direct benefit to the individual participants if the IRB finds and documents that:
  1. The intervention or procedure holds out the prospect of direct benefit to the individual participant or is likely to contribute to the participant's well-being.
  2. The risk is justified by the anticipated benefit to the participants.
  3. The relation of the anticipated benefit to the risk is at least as favorable to the participants as that presented by available alternative approaches.
  4. Adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians, as set forth in 26.406.
When following FDA regulations:
1. Policies and procedures have the IRB or EC follow the requirements specified in Subpart D for research involving children.
When following the ICH-GCP (E6) guideline:
1. When adults are unable to consent, policies and procedures have the IRB or EC determine:
  1. A non-therapeutic clinical trial (i.e., a trial in which there is no anticipated direct clinical benefit to the participant) should be conducted in participants who personally give consent and who sign and date the written consent document.
  2. Non-therapeutic clinical trials may be conducted in participants with consent of a legally acceptable representative provided the following conditions are fulfilled:
    1. The objectives of the clinical trial cannot be met by means of a trial in participants who can give consent personally
    2. The foreseeable risks to the participants are low
    3. The negative impact on the participant’s well-being is minimized and low
    4. The clinical trial is not prohibited by law; and
    5. The opinion of the IRB or EC is expressly sought on the inclusion of such participants, and the written opinion covers this aspect. Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended. Participants in these trials should be particularly closely monitored and should be withdrawn if they appear to be unduly distressed.
When following VA requirements:
1. Policies and procedures have the IRB find and document in the minutes or IRB records specific findings in accordance with VA requirements.
2. Policies and procedures indicate:
  1. Research involving stem cells shall be governed by the policy set by NIH.
  2. Research involving the provision of in vitro fertilization services is not allowed.
  3. Research in which the focus is either a fetus, human fetal tissue, in-utero, or ex-utero, is not allowed.
  4. Interventional research involving neonates is not allowed. Prospective observational or retrospective record review studies that involve neonates or neonatal outcomes are permitted.
  5. Research involving pregnant women as participants is not allowed unless the IRB determines the requirements in 45 CRR 46.204 are met, and the facility director certifies the facility has sufficient expertise in women's health to conduct the proposed research.
  6. Research involving prisoners as participants is not allowed unless a waiver has been granted by the chief research and development officer.
  7. Research involving children as participants is not allowed unless a waiver has been granted by the facility director. Research involving children may not pose greater than minimal risk to the child.
  8. Biological specimens and data obtained from children is considered research involving children even if de-identified.
  9. International research is not initiated unless permission is obtained from the facility director.
  10. Research involving adults who are unable to consent may occur only when the IRB determines the proposed research:
    1. Does not present greater than minimal risk, or
    2. Presents a greater probability of direct benefit to the participant than harm to the participant, or
    3. Poses greater than minimal risk and no prospect of direct benefit to individual participants, but is likely to yield generalizable knowledge about the participant’s disorder or condition that is of vital importance to understanding or amelioration of the participant’s disorder or condition.
    4. In addition, the IRB determines the research cannot be performed solely on adults who can consent, and the focus of the research is the disorder leading to the lack of decision-making capacity, or
    5. Where the participant of the research is not directly related to the participant’s lack of decision-making capacity, the researcher has presented a compelling reason for including adults unable to consent.

Common types of materials that may be used to meet the element

Application form
Reviewer checklist

Outcomes

IRB or EC members determine whether additional safeguards are required in research that involves vulnerable individuals in order to protect their rights and welfare.
The IRB or EC documents required determinations and provides protocol-specific findings justifying the determinations.

Proceed To: ELEMENT II.4.B.

Resources: For Accreditation - Evaluation Instrument

Evaluation Instrument for Accreditation

Table of Contents

ELEMENT II.4.A.