DEPARTMENT: Quality Management / POLICY DESCRIPTION: Recruitment of Vulnerable Subject Populations
PAGE: 1 of 5 / REPLACES POLICY DATED:
APPROVED: September 10, 2002 / RETIRED:

EFFECTIVE DATE: January 1, 2003

/ REFERENCE NUMBER: QM.IRB.007
SCOPE: All Company-affiliated facilities engaged in human subject research overseen by an Institutional Review Board (IRB).
PURPOSE: To provide guidance for IRBs regarding protecting the welfare of particularly vulnerable subjects, such as children, prisoners, pregnant women, decisionally-impaired persons, or economically or educationally disadvantaged persons. The IRB must also ensure that it has adequate representation on the Board to consider specific kinds of research involving these vulnerable populations in a satisfactory manner.
IRBs must review the regulations referenced in the reference section of this policy to understand the requirements pertaining to potentially vulnerable subject populations.
Facilities engaged in human subject research that involves potentially vulnerable subject populations must apply all federal regulations governing the conduct of vulnerable subject population research as if the research were federally-funded. Such regulations are included in the reference section of this policy.
POLICY: Local IRB policies must be developed and must include review of the following elements for research involving vulnerable subjects:
  1. Strategic issues include inclusion and exclusion criteria for selecting and recruiting participants, informed consent and willingness to volunteer; coercion and undue influence; and confidentiality of data.
  2. The IRB must carefully consider group characteristics, such as economic, social, physical, and environmental conditions, to ensure that the research incorporates additional safeguards for vulnerable subjects.
  3. The investigators must not over-select or exclude certain groups based on perceived limitations or complexities associated with those groups. For example, it is not appropriate to target prisoners as research subjects merely because they are a readily available “captive” population.
  4. IRBs must be knowledgeable about applicable state or local laws that bear on the decision- making abilities of potentially vulnerable populations. State statutes often address issues related to competency to consent for research, emancipated minors, legally authorized representatives, the age of majority for research consent, and the waiver of parental permission for research.
  5. Just as in providing medical care, research studies that plan to involve any potentially vulnerable populations must have adequate procedures in place for assessing and ensuring each subject’s capacity, understanding, and informed consent and assent. When weighing the decision of whether to approve or disapprove research involving vulnerable subjects, the IRB must look to see that such procedures are part of the research plan. In certain instances, it may be possible for researchers to enhance understanding for potentially vulnerable subjects. Examples include requiring someone not involved in the research to obtain the consent, the inclusion of a consent monitor, a subject advocate, interpreter for hearing-impaired subjects, translation of informed consent forms into languages the subjects understand, and reading the consent form to subjects slowly and ensuring their understanding paragraph by paragraph.
  6. The IRB may require additional safeguards to protect potentially vulnerable populations. For instance, the IRB may require that the investigator submit each signed informed consent form to the IRB, that someone from the IRB oversee the consent process, or that a waiting period be established between initial contact and enrollment to allow time for family discussion and questions.

PROCEDURE:
Institutions where vulnerable subjects are considered for study populations must develop specific local standard operation procedures (SOP) to assure the protection of human subjects. All relevant regulations must be incorporated into local policies.
Pregnant Women, Fetuses and Human in Vitro Fertilization:
Research involving pregnant women and fetuses should involve the least possible risk. The IRB must document specific findings to minimize the potential for risk or harm to the fetus, and additional attention must be given to the conditions for obtaining informed consent. The IRB must be familiar with the requirements of the following conditions:
  1. Research involving pregnant women;
  2. Research directed towards the fetus in utero;
  3. Research involving the fetus ex utero; and
  4. Research involving dead fetuses, fetus material, or placenta.
Research Involving Prisoners:
Research involving prisoners requires special considerations. Prisoners may have a limited ability to make truly voluntary and un-coerced decisions about whether or not to participate as research subjects. Research involving prisoners as participants should not be subjected to expedited review.
Where research involving prisoners is contemplated, the IRB composition must include the following:
  1. A majority of the Board (exclusive from the prisoner members) shall have no association with the prison(s) involved, apart from their membership on the Board; and
  2. At least one member of the Board shall be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research is reviewed by more than one Board, only one Board need satisfy this requirement.
The IRB must incorporate additional duties and requirements when reviewing research of prisoners into the local SOP.
Children Involved as Subjects in Research:
The regulations require special protections for research involving children. Under the regulations, children are persons who have not attained the legal age for consent to treatments or procedures involved in the research under the applicable jurisdiction in which the research will be conducted.
IRB records must reflect the IRB’s understanding and justification for the risks and benefits posed by approved research involving children. The proposed research must fall within one of four categories:
  1. Research not involving greater than minimal risk;
  2. Research involving greater than minimal risk, but presenting the prospect of direct benefit to the individual subjects;
  3. Research involving greater than minimal risk, but likely to yield knowledge that can be generalized about the subject’s disorder or condition;
  4. Research not otherwise approvable, which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health and welfare of children.
Each category has specific conditions which must be included in the local SOP if the institution is involved in human research where children are in the subject population.
Parental Permission:
The IRB must determine, in accordance with and to the extent that consent is required by regulation, that adequate provisions are made for soliciting the permission of each child’s parents or guardian.
Where parental permission is to be obtained, the IRB must determine whether permission of one parent is sufficient or whether permission must be obtained from both parents in order for the research to be conducted.
If the IRB determines that a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children), it may waive the consent requirements provided a mechanism for protecting the children who will participate as subjects in research is substituted, and provided further that the waiver is not inconsistent with federal, state and local law. The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity, status, and condition.
Children who are wards of the State or any other agency, institution, or entity may be included in research only if such research is:
  1. Related to their status as wards; or
  2. Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of the children involved as subjects are not wards.
The IRB must require appointment of an advocate for each child who is a ward, 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 shall be an individual who has 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.

Assent of the Child:

Provisions must also be made to obtain the child’s assent when the IRB has determined that the child is capable of giving assent. The IRB should consider the age, maturity, and psychological state of the child involved. The IRB may determine that the assent of the child is not necessary if and only if all three of the following conditions are satisfied:
  1. The research offers the child the possibility of direct benefit;
  2. The benefit is important to the health or well being of the child; and
  3. The benefit is available only in the context of the research.
IRBs must take great care in approving research where the child is suffering from a life-threatening illness with little real chance of therapeutic benefit from the research. IRBs must also be cautious in allowing parents to overrule a child’s dissent where experimental therapy has little or no reasonable expectation of benefit. The justification for exposing a child to extreme discomfort, with little possibility for benefit, may be tenuous at best.
If it is deemed appropriate that the child’s assent should be solicited, the IRB must ensure that the assent form is tailored for the child, with respect to his or her level of understanding. For young children, especially, the assent form should be designed as a one-page document, with simple, age-appropriate language, and presented in a manner understandable to the child.
Research Involving Decisionally-Impaired Subjects:
Decisionally-impaired individuals are those who have a diminished capacity for judgment and reasoning due to psychiatric, organic, developmental, or other disorder that affects cognitive or emotional functions. Other individuals who may be considered decisionally-impaired, with limited decision making ability, are individuals under the influence or dependent on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps.
There are no regulations specific to research involving decisionally-impaired persons. As with all subjects the IRBs must carefully consider selection issues, privacy and confidentiality, coercion and undue influence, and risk-benefit analysis. Additional safeguards should be considered by the IRB to protect these subjects.
Specific DHHS regulations defining various requirements are included in the references at the end of this policy. The IRB must review and understand the regulations and their role prior to reviewing and approving protocols that involve vulnerable subject populations.
Numerous articles to assist an IRB in the efforts to protect human research subjects with decisional impairment are found in recent publications. Access to these documents may be found at and
REFERENCES:
FDA

Protection of Children, 21 CFR 56.109(h), April 2002

DHHS
Basic policy for Protection of Human Research Subjects, June 18, 1991, Subpart A 46.101–124;
Additional Protections for Pregnant Women, Human Fetuses and Neonates involved in research, November 13, 2001, Subpart B 46.201-207;
Additional Protection Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects, November 16, 1978, Subpart C 46.301-306;
Additional Protection for Children Involved as Subjects in Research, June 18,1991, Subpart D
46.401-409
Terms of Assurance,
OHRP Guidance – July 11, 2002
VA-ORCA Best Practice Guidelines
NCQA Accreditation Standards
Policies
IRB Guidance Policy, QM.IRB.001
IRB Protocol - Initial and Continuing Review Policy, QM.IRB.002
Informed Consent IRB Review Policy, QM.IRB.003
Development of Local Standard Operating Procedures for IRB Policy, QM.IRB.004
Adverse Event Review Policy, QM.IRB.005
Use of Non-local, Cooperative and Multi-Institutional IRBs Policy, QM.IRB.006

10/2002