Standard Operating Procedures - Chapter 16

POTENTIALLY VULNERABLE PARTICIPANT GROUPS

Certain groups of human participants are considered particularly vulnerable in a research setting. Federal regulations for protecting human participants in research include specific protections for children, pregnant women, human fetuses, neonates and prisoners. In reviewing these research studies, the IRB ascertains that the inclusion of the vulnerable population is adequately justified and that safeguards are implemented to minimize risks unique to each population.

Each research study is evaluated for possible vulnerable populations. If a population is identified for which specific IRB policies and procedures do not exist, e.g. economically disadvantaged, terminally ill or employees, the IRB addresses the recruitment process and the consent process to determine if additional safeguards are required.

Approval for research studies involving vulnerable populations is considered if one of the following conditions is met: (1) the research does not involve more than minimal risk to the participant; (2) the research is likely to benefit the participant directly, even though the risks are considered to be more than minimal; or (3) the research involves greater than minimal risk with no prospect of direct benefit to individual participants, but is likely to yield generalizable knowledge about the participant's disorder or condition.

16.1	Research Involving Children
16.2	Research Involving Prisoners
16.3	Research Involving Pregnant Women, Fetuses, In Vitro Fertilization, Neonates

16.1 Research Involving Children

UMASS adheres to the regulatory requirements for research with children, as outlined in 45 CFR 46 Subpart D, “Additional DHHS Protections for Children Involved as Participants in Research.” The IRB assesses the potential risks and benefits for each research proposal, and the provisions for permission and assent, to determine if an activity satisfies the conditions for a category of research permitted in children, as specified in Subpart D, sections §46.404, §46.405, §46.406 §46.407 and §46.409. The research categories are described below.

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 46.404).

The IRB generally finds that permission of one parent or guardian is sufficient.

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 (45 CFR 46.405):

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.

The IRB generally finds that permission of one parent or guardian is sufficient.

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 (45 CFR 46.406):

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 and permission of their parents or guardians.

The IRB generally finds that permission of both parents is required, unless one parent is deceased, unknown, incompetent, or not reasonably available, or unless only one parent has legal responsibility for the care and custody of the child.

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 only if such research is: (1) related to their status as wards; or (2) conducted in schools, camps, hospitals, institutions, or similar setting in which the majority of children involved as participants are not wards (45 CFR 46.409).

Assent is defined as “a child’s affirmative agreement to participate in research.” Passive resignation to submit to an intervention or procedure is not considered assent. Federal regulations do not specify any of the elements of assent and do not provide an age at which assent ought to be possible. In determining whether children are capable of assenting, the IRB takes into account the ages, maturity, and psychological state of the children involved. The IRB determines whether all or some of the children are capable of assenting. In general, capacity to assent is assumed to begin at about age seven and continues up to age 17.

Investigators must obtain informed consent to continue in the research from participants who were enrolled in research as minors but have now reached the age of majority. This consent to continue in the research must be documented by having participants sign a consent form for continued participation at the next visit after becoming the official, legal consent authority for themselves. If participants are undergoing any research procedures or interventions, a current, approved version of the consent form must be used. If, however, all research procedures and interventions have been completed and the participant is in long-term follow-up involving data collection only, an addendum to consent for continued data collection may be used following IRB review and approval.

16.2 Research Involving Prisoners

The UMASS IRBs comply with the requirements of 45 CFR 46, Subpart C, “Additional DHHS Protections Pertaining to Biomedical and Behavioral Research Involving Prisonersas Participants.” The term “prisoner” refers to any individual: (1) involuntarily confined or detained in a penal institution; (2) sentenced under a criminal or civil statue; (3) detained in other facilities by virtue of statues or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution; and (4) detained pending arraignment, trial or sentencing. The same regulations that apply to prisoner enrollment in human participant research studies also apply to participants already enrolled in a study who suddenly become incarcerated. Moreover, federal regulations do not differentiate between detention, jail or prison. People incarcerated in any of these places are considered prisoners.

The principal investigator indicates in the application and provides justification to theIRB if the enrollment of prisoners is anticipated. If the study is not initially approved to recruit prisoners, then the investigator may not enroll a prisoner. For ongoing research studies, investigators notify the IRB immediately upon becoming aware of a current participant’s incarceration, and all interactions and interventions cease until requirements of Subpart C have been satisfied for the research. EXCEPTION: The principal investigator may assert to the IRB that it is in best interest of the participant to remain in the research while incarcerated and the IRB Chair may determine that the participant may continue while the requirements of Subpart C are satisfied.

For review of research with prisoners:

The IRB membership includes an individual with appropriate background and experience to serve as a prisoner representative, by nature of having experience or a close working knowledge, understanding and appreciation of prison conditions from the perspective of the prisoner. In addition, the majority of the IRB membership (exclusive of prisoner members) has no association with the prison(s) involved, apart from their membership on the board.
When the IRB reviews research involving prisoners, the prisoner or prisoner representative is present as a voting member.
The prisoner representative is present during the review of initial applications, continuing reviews, modifications, adverse events, and other reviews that may be applicable.
An expedited review process can be used if appropriate to the research and only minimal risk as defined for the prisoner population is evident. If the expedited review process is used to review research involving prisoners, the prisoner representative of the IRB must be one of the designated reviewers.
Exempt review does not apply to research with prisoners.
Only research studies meeting one of four categories described below may be approved to include prisoners as research participants:

Category A: Studies of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the participants;
Category B: Studies of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the participants;
Category C: Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) provided that the study may proceed only after the Secretary of the Department of Health & Human Services (DHHS) has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research; or
Category D: Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the participant. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary of DHHS has consulted with appropriate experts, including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research.

In addition to the other responsibilities described in the section for the use of prisoners, the IRB can only approve research studies if it finds that:

1. any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;

2. the risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;

3. procedures for the selection of participants within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Board justification in writing for following some other procedures, control participants must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research study;

4. the information is presented in a language and reading level that is understandable to the participant population;

5. adequate assurance exists that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and

6. where the Board 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, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact.

If a study utilizing prisoners as research participants is federally funded, the HPO must send a letter to the Office for Human Research Protections (OHRP) indicating it has approved a study that will include prisoners, the category the study fits into as well as how the study satisfies the six criteria listed above. A research study is not permitted to commence for DHHS supported research until written approval is received from OHRP on behalf of the DHHS Secretary.

16.3 Research Involving Pregnant Women, Fetuses, In Vitro Fertilization, Neonates

UMASS adheres to the regulatory requirements of 45 CFR 46 Subpart B, “Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research.” Pregnant women or fetuses may be involved in research only if the conditions outlined in the regulations are met including scientific appropriateness, acceptability of potential risks and benefits, compliance with the additional informed consent provisions, absence of any inducements (monetary or otherwise) to terminate a pregnancy, and confirmation of the independence of the researchers from the decisions related to pregnancy termination and/or any decisions related to the determination of viability of a neonate.