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: VHA Directive 1200.05(3), 19, 20, 21
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 organizations must comply with all requirements in Subparts B, C, and D, with the qualifications below:
1. Research involving pregnant women, prisoners, and children are subject to the DHHS Subparts B, C, and D, except where modified by DoDI 3216.02.
2. For purposes of applying Subpart B, the phrase “biomedical knowledge” is replaced with “generalizable knowledge.”
3. For human participant research that would not otherwise be approved but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women, fetuses, or neonates, written approval from the DOHRP must be obtained through the COHPR prior to research starting.
4. In addition to the categories of permissible human participant research involving prisoners identified in DHHS regulations Subpart C, two additional categories are permissible:
  1. Epidemiological research is permitted under the following conditions:
  2. Human participant research involving prisoners that would otherwise meet exemption criteria may be conducted, but must first be approved by an IRB and meet the requirements of Subpart C and DoDI 3216.02.
5. DoD organizations conducting research involving prisoners must demonstrate to the senior designated official that the IRB has fulfilled its duties in accordance with Subpart C.
6. When a previously enrolled human participant becomes a prisoner, and the protocol has not been reviewed and approved by the IRB in accordance with Subpart C, the researcher must promptly notify the IRB.
7. Research involving a detainee or a prisoner of war as a human participant is prohibited.
8. Service members and DoD-affiliated personnel are considered to be vulnerable to coercion and undue influence by the DoD due to the nature of the command structure of the organization. Therefore, additional protections for DoD-affiliated personnel are required, as follows (DoDI 3216.02 section 3.9 (f)):
9. Research involving large-scale genomic data from DoD-affiliated personal is subject to additional requirements (DoDI 3216.02 section 3.10):
10. DoD organizations must demonstrate to the senior designated official that the IRB has fulfilled its duties in accordance with DHHS Subpart D, 45 CFR 46. 407 and 21 CFR 50.54.
When following DOE requirements:
1. DOE and DOE site employees are considered vulnerable subjects when participating in research and additional care must be taken to ensure their participation is truly voluntary (e.g., by ensuring they do not report to members of the research team) and that data collected about them is kept confidential.
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. For research involving pregnant women, fetuses, and neonates, policies and procedures indicate:
  1. Research that involves provision of in vitro fertilization services is permitted and can be conducted by VA researchers while on official VA duty, or at VA facilities, or at VA-approved off-site facilities.
    1. This includes prospective and retrospective research involving provision of or the enhancement of FDA-approved methods of in vitro fertilization for studies involving consenting participants, both male and female, undergoing or who have undergone in vitro fertilization for the treatment of certain forms of human infertility. In vitro fertilization is any fertilization of human ova that occurs outside the body of a female, either through a mixture of donor human sperm and ova or by any other means.
  2. Prospective and retrospective studies that enroll or include pregnant participants who conceived through in vitro fertilization or other artificial reproductive technologies are permitted.
  3. Research that uses human fetal tissue or that focuses on either a fetus, or human fetal tissue, in-utero or ex-utero cannot be conducted by VA researchers while on official VA duty, at VA facilities, or at VA-approved off-site facilities. Use of stem cells shall be governed by the policy set by NIH for recipients of NIH research funding. (1200.05(3)(19)
  4. Research involving the creation of a human embryo or embryos solely for research purposes or research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.208(a)(2) and Section 498B of the Public Health Service Act (42 U.S.C. 289g(b)) cannot be conducted by VA researchers, at VA facilities, or at VA-approved off-site facilities.
  5. Women who are known to be pregnant and their fetuses may be involved in research if all the following requirements are met and the VA medical facility Director certifies that the VA medical facility has sufficient expertise in women’s or reproductive health to conduct the proposed research if the research includes interventional studies or invasive monitoring of pregnant women as participants.
  6. VA researchers cannot conduct interventions in research that include neonates while on official VA duty, at VA facilities, or at VA-approved off-site facilities. VA researchers may conduct research involving noninvasive monitoring of neonates if the research is determined by the IRB to be minimal risk. Prospective observational and retrospective record review studies that involve neonates or neonatal outcomes are permitted.
    1. The reviewing IRB must have the appropriate expertise to evaluate any VA research involving neonates and must comply with the requirements of 45 CFR 46.205. The VA medical facility Director must certify that the medical facility has sufficient expertise in neonatal health to conduct the proposed research.
3. For research involving prisoners, policies and procedures indicate:
  1. Research involving prisoners cannot be conducted by VA researchers while on official VA duty, at VA facilities, or at VA-approved off-site facilities unless a waiver has been granted by the VA Chief Research and Development Officer (CRADO). (VHA Directive 1200.05 Section 20)
  2. Waiver requests, along with supporting documentation from the IRB, must be submitted to the CRADO by the VA medical facility Director stating support for the conduct of the VA study involving prisoners.
  3. If such a waiver is granted, the research must comply with the requirements of 45 CFR 46.301 - 46.306.
4. For research involving children, policies and procedures indicate:
  1. Research involving children as participants is not allowed unless a waiver has been granted by the VA medical facility director.
  2. Research involving children may not pose greater than minimal risk to the child. (VHA Directive 1200.05 Section 21)
  3. Biological specimens and data obtained from children is considered research involving children even if deidentified.
5. For VA facilities:
  1. The R&D Committee must ensure and document that research proposals (especially those involving vulnerable populations such as pregnant women, neonates, children, and prisoners) support the mission of VHA and enhance the quality of health care for Veterans.

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.