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Chapter XVI - Special Populations

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This chapter describes the GA IRB’s policies and procedures for the review and approval of research with (1) pregnant women and fetuses; (2) children; (3) cognitively impaired individuals; and (4) military members.

RESEARCH INVOLVING PREGNANT WOMEN, NEONATES, AND FETUSES
REGULATORY REQUIREMENTS
For research involving pregnant women, fetuses, or neonates the IRB will approve the conduct of the research only if it finds that the research meets the regulatory criteria forapproval addressed under the federal regulations at 45 CFR 46 Subpart B (45 CFR 46.204, "Research involving pregnant women or fetuses prior to delivery"; 45 CFR 46.205, "Research involving neonates"; 45 CFR 46.206, "Research involving, after delivery, the placenta, the dead fetus, or fetal material").

For research that does not meet the criteria for approval addressed under 45 CFR 46.204, "Research involving pregnant women or fetuses prior to delivery"; 45 CFR 46.205, "Research involving fetuses after delivery"; or 45 CFR 46.206, "Research involving fetuses, after delivery, the placenta, the dead fetus, or fetal material," the IRB must find that:

  • The research presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women or fetuses; AND
  • The research, if federally supported, will be submitted for review and approval by the Secretary, DHHS, in accordance with the provisions of 45 CFR 46.207, “Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women or fetuses”. If the research study is not federally-supported, the IRB will use a review by a panel of obstetrician/ gynecology experts (2 members with expertise in the area who are not currently IRB members) and an ethicist to recommend whether to approve the study as research that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women or fetuses.

PREGNANT WOMEN/FETUSES PRIOR TO DELIVERY
For research involving pregnant women or the fetus prior to delivery, the documented, written informed consent of the pregnant women or her authorized representative will be obtained in accordance with the provisions of 45 CFR 46.204; unless the IRB grants either a waiver of informed consent in accordance with 45 CFR 46.116(d) or a waiver of the requirement to document informed consent in accordance with 45 CFR 46.117(c).

NEONATES OF UNCERTAIN VIABILITY
For research involving neonates of uncertain viability, the documented, written informed consent of either parent or the authorized representative of either parent will be obtained in accordance with the provisions of 45 CFR 46.205; unless the IRB grants either a waiver of informed consent in accordance with 45 CFR 46.116(d) or a waiver of the requirement to document informed consent in accordance with 45 CFR 46.117(c).

NONVIABLE NEONATES
For research involving nonviable neonates (i.e., neonates determined to be unable, after delivery, to survive to the point of independently maintaining heartbeat and respiration), the documented, written informed consent of both parents will be obtained in accordance with the provisions of 45 CFR 46.205.

  • If either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the IRB may approve the research based on the consent of one parent. (Note: the consent of the father need not be obtained if the pregnancy resulted from rape or incest);
  • Note: the IRB may not grant approval for authorized representative (i.e., proxy) consent or a waiver of the requirement to obtain consent (i.e., 45 CFR 46.116 (c) or 45 CFR 46.116 (d)) for research involving nonviable neonates.

FETAL MATERIAL DERIVED FROM ABORTION
For research involving the dead fetus or fetal material derived from an induced abortion, the documented written informed consent of the mother must be obtained in accordance with state law.

  • The research protocol must specify that informed consent for use of the fetal tissue for research will be obtained separately from, and after, the consent is obtained for the abortion;
  • No remuneration, compensation or other consideration of any kind may be offered to a woman to consent to the use of fetal tissues for research;
  • The donor may not designate the recipient of fetal tissue.

All persons who participate in the procurement, use or transplantation of fetal tissue must be informed as to the source of the tissue (e.g., abortion, miscarriage, still birth, ectopic pregnancy). Any protocol that involves an intervention derived from fetal tissue must include the information as part of the informed consent document and/or process.

Fetal research funded by the DOD must comply with the US Code Title 42, Chapter 6A, Subchapter III, Part H, 289g.

RESEARCH WITH CHILDREN
When reviewing research with children, the IRB membership includes at least one member who is knowledgeable about or experienced in working with children.

APPLICABLE CATEGORIES OF RESEARCH
The IRB reviews all research involving children as participants and approves only research that satisfies all of the conditions of applicable federal regulatory subpart sections. The IRB assesses the potential risks and benefits for each research proposal, and the provisions for permission and assent, to determine if the activity satisfies the conditions for a category of research permitted for children, as specified in DHHS 45 CFR 46.404, 46.405, 46.406, 46.407 and 46.409 and FDA 21 CFR 50.51, 50.52, 50.53, 50.54 and 50.56.

The research categories are described as follows:

(45 CFRF 46.404 and 21 CFR 50.51) Research that does not involve greater than minimal risk may be approved if the IRB finds that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians.

(45 CFR 46.405 and 21 CFR 50.52) Research involving greater than minimal risk, but presenting the prospect of direct benefit to an individual participant, or a monitoring procedure that is likely to contribute to the participant’s well-being may be approved if the IRB finds that:

  • The risk is justified by the anticipated benefit to the participant;
  • The relationship of anticipated benefit to risk is at least as favorable as that presented by available alternative approaches; AND
  • Adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians.

(45 CFR 46.406 and 21 CFR 50.53) Research involving greater than minimal risk with no prospect of direct benefit to individual participants, but likely to yield generalizable knowledge about the participant’s disorder or condition may be approved if the IRB finds that:

  • The risk represents a minor increase over minimal risk;
  • The intervention or procedure presents experiences to participants that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social or educational situations;
  • The intervention or procedure 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 participant’s disorder or condition; AND
  • Adequate provisions are made for soliciting assent of the children or permission of their parents or guardians.

(45 CFR 46.407 and 21 CFR 50.54) Research that is not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health of welfare of children may be approved if the IRB and the Secretary of Health and Human Services (DHHS), after consultation with a panel of experts in pertinent disciplines and following an opportunity for public review and comment, find that the research in fact satisfies one of the above three categories; or satisfies all of the following requirements:

  • The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health and welfare of children;
  • The research will be conducted in accordance with sound ethical principles; AND
  • Adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians.

If the research study is not Federally-supported or subject to FDA regulation, the IRB Office will request review by a panel of pediatric experts to determine the applicability of approval under Section 45 CFR 46.407.

WARDS OF THE STATE
Children who are wards of the state or any other agency, institution, or entity can be included in research approved under 45 CFR 46.406 and 45 CFR 46.407 or 21 CFR 50.53 and 21 CFR 50.54 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 participants are not wards (45 CFR 46.409 or 21 CFR 50.56).

Where the proposed research involves Wards of the state or any other agency, institution, or entity; an advocate will be appointed 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 (i.e., see 45 CFR 46.409 (b) and, if applicable, 21 CFR 50.56).

  • One individual may serve as an advocate for more than one child-Ward;
  • The advocate will 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 of advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

CONSENT REQUIREMENTS
If a research study is designated as meeting the criteria for (45 CFR 46.404 or 21 CFR 50.51); or (45 CFR 46.405 or 21 CFR 50.52), the IRB will determine whether adequate provisions have been made to solicit the permission of each child’s parents or guardians, unless one parent is deceased, unknown, incompetent, or not reasonably available, or unless one parent has sole legal responsibility for the care and custody of the child. Where parent permission must be obtained, the IRB may determine that the permission of one parent is sufficient.

If a research study is designated as meeting the criteria for (45 CFR 406 or 21 CFR 50.53); or (45 CFR 46.407 or 21 CFR 50.54), the IRB requires the permission of both parents, unless one parent is deceased, unknown, incompetent, or not reasonably available, or unless one parent has sole legal responsibility for the care and custody of the child.

The permission of the child’s parent(s) must be documented by the inclusion of a signature on the consent form indicating that the child is under the age of 18 and therefore cannot provide direct consent.

WAIVER OF PARENTAL CONSENT FOR ABUSED OR NEGLECTED CHILDREN
The IRB may waive the requirement for parental consent if it determines that the research study is designated for conditions or for a participant population (e.g., neglected or abused children) for which parental or guardian permission is not a reasonable requirement to protect the participants (see 45 CFR 46.408). If the IRB grants this type of waiver based on this criterion, it must substitute an appropriate mechanism for protecting the childrenparticipants. The choice of such mechanism will depend on the nature and purposes of the proposed research activities; the risk and anticipate benefit to the children participants; and the age, maturity, status, and condition of the proposed participant population.

The IRB will not waive the requirement to obtain parent or guardian permission based on the above-stated criterion if the research study is subject to FDA regulations (21 CFR Parts 50 and 56) governing human participant protections (i.e., the research study involves an evaluation of any article regulated by the FDA).

CONSENT FOR CONTINUED PARTICIPATION
If the research study involves children (age < 18 years old) who will continue to undergo research interventions (including the collection of identifiable private information) after they become adults, the IRB research protocol should address a mechanism (e.g., addendum informed consent document with copy of originally signed consent form attached; new consent form) whereby direct consent for continued participation in the research study will be obtained from these individuals at the time they reach adult status.

CONSENT FOR CHILDREN PARTICIPATING IN NON-LOCAL RESEARCH
If the research includes enrollment of participants in other states or countries, the principal investigator is responsible for providing the IRB with sufficient information to verify the age at which participants in other jurisdictions have the ability to consent to participation in research, including any medical treatments or procedures if applicable. The IRB may, if it appears advisable, require the submission of an opinion rendered by an attorney from any applicable jurisdiction on age at which an individual can consent to participation in research.

ASSENT REQUIREMENTS
Adequate provisions must be made for soliciting the assent of the children-participants when, in the judgment of the IRB, the children-participants can provide assent. In determining whether children participants can provide assent, the IRB will take into account the ages, maturity, and psychological state of the involved children. This judgment may be made for all children to be involved in given research study, or for each child, as the IRB deems appropriate. The assent of a child-participant will not be a necessary condition for proceeding with the child’s research participation if the IRB determines:

  • That the capability of some or all the children-participants is so limited that they cannot reasonably be consulted;
  • That the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children-participants and is available only in the context of the research; OR
  • The IRB finds and documents that:
  • The research involves no more than minimal risk to the children-participants;
  • The waiver of assent will not adversely affect the rights and welfare of the children-participants;
  • The research could not practicably be carried out without the waiver; AND
  • Whenever appropriate, the children-participants will be provided with additional pertinent information after participation.

Children who are developmentally able to provide written assent will sign the consent document in addition to the parent(s). For children who are not determined to be developmentally able to sign the consent document, the investigator must certify that the purpose and nature of the research was explained in age appropriate language and that the child provided positive affirmation to participate.

RESEARCH INVOLVING DECISIONALLY IMPAIRED INDIVIDUALS
REVIEW REQUIREMENTS
Although not specifically addressed in the regulations as a vulnerable population, the GA IRB requires additional safeguards for research involving persons with decisional impairment. The IRB will approve the research only if it finds that:

  • The research bears a direct relationship to the decisionally impaired participant’s condition or circumstance;
  • The research meets one of the following criteria:
    • presenting no greater than minimal risk to the involved participants;
    • presents an increase over minimal risk to involved participants, but which offers the potential for direct individual benefit to the participant;
    • presents a minor increase over minimal risk to involved participants and which does not have the potential for direct individual benefit; provided that the knowledge sought has direct relevance for understanding or eventually alleviating the participants' disorder or condition.

In evaluating a protocol involving the enrollment of persons with decisional impairment, The GA IRB may consider requiring additional safeguards, as appropriate, for a given protocol. Such safeguards may include any of the following:

  • Use of an independent party (independent of the study investigator with appropriate expertise) to assess the capacity of the potential participant;
  • Use of standardized assessment of cognition and/or decisional capacity;
  • Use of informational or educational techniques;
  • Use of an independent person to monitor the consent process;
  • Use of waiting periods to allow for additional time to consider information about the research study;
  • Use of proxy consent;
  • Use of assent in addition to proxy consent to respect the autonomy of individuals with decisional impairment;
  • Use of a witness. The IRB will determine the following when choosing this option:
    • Whether the witness needs to be unbiased (which means the individual is not part of the study team nor a family member of the potential participant);
    • Whether the witness will observe the entire consent process or just the signature

CONSENT
In general, all adults, regardless of diagnosis or condition, should be presumed competent to consent to participation in research unless there is evidence of serious disability that would impair reasoning or judgment. In making the determination about whether it is appropriate for investigator’s to utilize proxy consent, the IRB will take into consideration the following:

  • The rationale for the need to obtain proxy consent;
  • The criteria that will be used in determining whether a potential participant has decisional impairment sufficient to require the use of proxy consent, including any use of standardized assessment tools;
  • Whether any additional methods are proposed to enhance participants’ ability to achieve decisional capacity about the proposed study (e.g., reading of the consent form may not be sufficient and use of other tools such as videos, educational materials, post-test, etc. might be considered to assist potential participants in understanding what is involved with the research);
  • Who will be approached, and in what order, to provide proxy consent.

The following are specific procedures that must be followed if proxy consent is utilized:

  • Persons with decision impairment may also have been adjudicated legally incapacitated by a court decision. If such persons are considered for enrollment in a research protocol, the only party who may provide proxy consent is the courtappointed guardian. The guardian may only provide proxy consent if the court order, appointing them guardian, specifically states that they have the authority to enroll the incapacitated person into a research protocol. For this category of participants, a copy of the court order appointing the guardian and granting the guardian authority to enroll the person into a research study should be attached to the informed consent document;
  • Persons may also, through a health care proxy appointed by a power of attorney, designate a person to make decisions for them if they are subsequently incapacitated. This person may give proxy consent for enrollment of a participant in research;
  • If a potential participant has neither a guardian, nor a health care proxy designated, the investigator may obtain the informed consent of the participant’s legally authorized representative. Where neither a court-appointed guardian, nor a health care proxy exists, investigators may seek informed consent from the following individuals, in the order listed below:
    • Spouse;
    • natural or adoptive parent;
    • adult child;
    • adult brother or sister;
    • any other available adult relative related through blood or marriage known and documented to have made decisions for the participant in prior health care settings.

When a person is giving proxy consent, the proxy should be informed that, where possible, s/he should base the decision on substituted judgment, reflecting the views that the participant expressed while decisionally capable. The proxy should be fully informed on the risks, benefits and alternatives to the research. If the values of the participant are not known with respect to a proposed research study, the proxy should act in the best interest of the participant.

If a person with decisional impairment is capable of exercising some judgment concerning the nature of the research and participation in it, the investigator should obtain the participant’s assent in addition to the consent of his/her legally authorized representative.

The verbal objection of an adult with decisional impairment to participation in the research should be binding. If the participant, at any time, objects to continuing in the research study, such objection should be respected.

Where the condition causing the participant’s decisional impairment is of an intermittent or temporary nature, the informed consent process should include a mechanism for obtaining the participant’s subsequent direct informed consent to participate in the research. If a participant regains decision making capacity and declines to continue in the research, the decision must be respected.

DOCUMENTATION OF CONSENT AND ASSENT: INFORMED CONSENT DOCUMENT
Adult participants, not deemed to have decisional impairment, should read and sign the informed consent document in the standard manner.

DOCUMENTATION OF CONSENT AND ASSENT: RESEARCH RECORD
In studies in which some or all participants may have decisional impairment, it is recommended that at the time of obtaining consent the following be documented in a note to file for the participant’s research record:

  • Whether the participant demonstrated the ability to understand the nature of the research procedures, the potential risks and benefits, the voluntary nature of the participation and to make a personal judgment about participation;
  • Use of any supplemental methods to enhance or evaluate decisional capacity;
  • A summary of the matters discussed with the participant’s legally authorized representative.

RESEARCH INVOLVING MILITARY PERSONNEL
Military personnel may be under unique constraints compared to other research participants, affecting their ability to make a truly voluntary and un-coerced decision whether or not to participate as participants in research. To safeguard their interests and to protect military personnel from research harms, special ethical and regulatory considerations apply for reviewing research involving military personnel.

The GA IRB may approve research involving military personnel only if the following special provisions are met:

  • The GA IRB must find that research involving military personnel as participants addresses additional considerations for military personnel as determined by DOD, Army, and any localregulations;
  • For research involving military personnel, the GA IRB will apply the definition of minimal risk. Per 32 CFR 219.i, i.e., “. . . the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” “Daily life” in the definition of minimal risk is interpreted in terms of the daily life of the age-matched general population, not the study target population (e.g. Special Forces Soldiers);
  • The GA IRB will consider the following criteria during review of protocols that target enrollment of military personnel:
    • The risks involved in the research are commensurate with risks that would be encountered by age-matched non-military volunteers;
    • Any possible advantages accruing to the military member through his or her participation in the research, when compared to duty assignments, favorable acknowledgments, general living conditions, medical care, and other conditions, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages is impaired;
    • Procedures for the selection of participants are fair and immune from arbitrary intervention by personnel in the military members’ chain of command;
    • The research procedures or outcomes will not adversely affect military members’ deployability during or after study completion; AND
    • Where the GA IRB finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care;
    • When a military member is also a member of another special population (e.g., a minor, pregnant woman, or a person with cognitive impairment), the additional policies in this chapter will also apply.

As appropriate, the additional considerations for including military personnel as research participants that will be considered by the GA IRB include those regarding the requirement for an ombudsman, reducing undue influence by the chain of command, confidentiality and payment for study participation.

RESEARCH INVOLVING PRISONERS
GA IRB will not review protocols involving prisoners.

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