Informed consent requirements presume that the person being considered as a potential subject is autonomous: he or she has the legal capacity and emotional and mental capability to consider the proposition and is not feeling coerced or unfairly induced to agree. This is not always the case. There are many potential subjects whose ability to exercise their free will is limited in some way. Informed consent procedures used in any protocol should be sufficient to compensate for the individual's limits of understanding.
IRB members should consider whether there is any reason for the protocol to include subjects in any special subject population and, if so, if the protocol provides any special consent process.
When special populations are involved, the duty of the IRB is increased. It is suggested that provision should be made to have the informed consent process monitored either by an IRB member or by an appropriate subject advocate. It is also suggested that the IRB should consider more frequent continuing review or periodic reports.
Five subject populations have been designated by various regulators as "special subject populations" because, as a group, all members show limits to their ability to give their own consent. These populations are: pregnant women, fetuses, children, prisoners, and the mentally or emotionally disabled. Regulations have been developed for only a few of these groups. Generally, common sense and a conservative application of the usual criteria for approval will accomplish the spirit of the regulation.
The regulations often depend on a "legally authorized representative." This is an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject.1. Children
Review of studies involving children requires the IRB to determine whether the procedures will involve direct benefit and whether the risk is or is not greater than "minimal risk".
a. If the risk is not greater than minimal risk, no special action need be considered.
b. If the risk is greater than minimal risk but there is the prospect of direct benefit to the child, then
- The benefit/risk relation of the proposed procedure has to be better than that for other alternatives, and
- There must be adequate provision for the solicitation of the child's assent and the parent's permission.
c. If the risk is greater than minimal risk and there is no direct benefit to the child, then
- The risk must be a "minor increase over minimal risk" ,
- The experience must be commensurate with something in the child's experience,
- The intervention or procedure is likely to yield generalizable knowledge about the participant’s disorder or condition, and
- There must be adequate provision for solicitation of the child's assent and the parent's permission.
d. If the risk is greater than minimal risk and the risk is more than a minor increase over minimal risk, the IRB may still approve the protocol only if the
- IRB finds that the research presents a reasonable opportunity to further the understanding, prevention. or alleviation of a serious problem affecting the health or welfare of children, and
- Secretary of the DHHS, after consultation with a panel of experts in pertinent disciplines, also approves the proposed study.
45 CFR 46.401-409 Subpart D
In as much as prisoners may be under constraints because of their incarceration that could affect their ability to make a truly voluntary and uncoerced decision additional safeguards will be provided.
Review of such a study requires the IRB to add, as a consultant, an ad hoc representative of the prisoner community.
Regardless of any regulations, NGHS will not accept biomedical protocols targeting incarcerated prisoners nor any protocols using prisoners as healthy volunteers in any medical study.
Non-medical studies will be considered if the study is of a condition pertaining to prisoners and cannot be otherwise performed.
2. Individual prisoners may be included in approved protocols if
- a. They meet the criteria of that protocol,
- b. Arrangements can be made for appropriate follow-up care,
- c. The constraints on informed consent are no greater than they would be for routine medical care, and
- d. Enrollment of patient prisoners is limited to one. Should more than one be contemplated, the IRB must be informed so that a prisoner advocate may be consulted.
45 CFR 46.301-306 Subpart C
Both DHHS and FDA are currently supporting equal access of women to clinical trials. Wholesale exclusion of women must be justified.
In addition to the requirements for the review and approval of proposed research, the members must also determine that:
- Appropriate studies on animals and non-pregnant individuals have preceded the request.
- Unless the study purpose is to meet the health needs of the mother or her fetus, the risk to the fetus is minimal and is the least possible risk for achieving the study objectives.
- No investigator has any part in any decision as to timing, method, or procedure used for termination of the pregnancy or determining viability of the fetus at the termination of pregnancy.
- There may be no procedural changes that cause greater than minimal risk to the fetus or the pregnant woman introduced into the procedure for pregnancy termination solely in the interest of the study.
- No inducements, monetary or otherwise, may be offered to terminate pregnancy for purposes of the study.
- The father's consent should be gained if he is reasonably available unless the study is to meet the health needs of the mother, or the pregnancy resulted from rape.
Should a protocol reviewed by the IRB concern a "fetus ex-utero or a nonviable fetus", further direction will be given.
45 CFR 46.201-211 Subpart B