Special Subject Population FAQs

When research involves vulnerable subjects, the IRB will look to ensure that the investigator provides appropriate additional safeguards to protect their wellbeing. investigators may be asked to explain their justification for selecting vulnerable subject groups in their research project. When feasible, the initial contact with vulnerable individuals should be made by or through people who have no connection with the research, in order to preserve the subjects' privacy and autonomy. If the subjects are not literate and the consent presentation is oral, investigators should ensure all requirements for obtaining documented consent are followed, including submission of a written version of the proposed consent script for review. Under certain circumstances, a witness may need to be present when vulnerable subjects document their consent.

Due in part to the legacy of research-related exploitation among these groups, if a research project will involve prisoners or children, federal law and university policy impose additional requirements. These relate to selection of subjects, risk assessment, obtaining consent, and so forth. Please contact ORCA at orca@ucsc.edu with any questions about research studies with these vulnerable groups and allow extra time for processing.

What if the research involves children/adolescents?

Federal regulations permit the UCSC IRB/ORCA to approve the following categories of research involving children:

• Research that involves no more than minimal risk to children, if adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians
• Research that involves more than minimal risk if:
  • the research offers the prospect of direct benefit for the individual subject;
  • the risk is justified by the anticipated benefit; and
  • the relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches.
• Research that involves more than minimal risk to children if:
  • the risk represents a minor increase over minimal risk;
  • the intervention or procedure presents experiences to subjects that are reasonably proportionate with those inherent in their actual or expected medical, dental, psychological, social or educational situations; and
  • the research is likely to yield generalizable knowledge about the subjects’ disorder or condition which is of vital importance for the understanding or amelioration (improvement) of the subjects’ disorder or condition.
• Research that the UCSC IRB Chair and/or IRB Chair’s designee(s) believes does not meet the previous categories, but 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, must be reviewed by HHS. 

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Definitions related to child/adolescent subjects

The following definitions are used, consistent with federal and state regulations:

• Children are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted (e.g., those under 18 years old in California).
• Assent means a child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent. The assent procedure should reflect a reasonable effort to enable the child to understand what their participation in research would involve.
• Permission means the agreement of parent(s) or guardian(s) to the participation of their child or ward in research. In general, permission should be obtained from both parents before a child is enrolled in research. However, the UCSC IRB Chair and/or IRB Chair’s designee(s) may find that the permission of one parent is sufficient on an individual or group basis for research when risks are minimal or the research will directly benefit the child. The requirement of obtaining parental or guardian permission can be waived in special circumstances.
• Guardian means an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care. 

Investigators should note that there are distinct processes and policies pertaining to conducting human subjects research with minors (e.g., those under 18 years old in California). These relate to various factors of human subjects research including guidelines for obtaining consent, justification for choosing children/adolescents for the target study population, and assessment pertaining to the risk level of the study. 

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Guidance for working with children

Providing a place where information can be disclosed in private has been seen as important in the context of qualitative research with children. However, in recent years there has been concern about the risk to both child and investigator in a one-to-one research situation.

In order to provide additional protection for investigators and underage human subjects, the UCSC IRB encourages investigators who will be working with children in a one-to-one situation to implement procedures that reduce the potential and perceived risk to the child(ren) and the investigator. These procedures should be fully described in the study submission.  Some possible protective measures an investigator might use include:

• having a third party present, or a trusted adult within sight or earshot;
• recording interviews on video;
• conducting meetings or interviews in a location that offers the possibility of passive surveillance by a third party, e.g., in a public place or in a room with a large window through which the encounter can be discreetly observed. 

If an investigator cannot include any protective methods in the research, the investigator should provide a justification why the research could not practicably be carried out with protective measures in place.

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Parental permission and assent

In general, one or both parents or a guardian must be provided with the information required for informed consent, so that they may decide whether to allow the child to participate. Children capable of assent must also express their willingness to participate. Under some conditions, with appropriate justification and approval of the IRB, waivers of parental permission and child assent are permitted depending on the nature of the research activity.

For more information about obtaining assent, see Informed Consent.

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Mandated reporting of child abuse or neglect

The California Child Abuse & Neglect Reporting Law (CANRA) requires certain individuals to report suspected child abuse or neglect. 

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Who reports child abuse or neglect?

Under CANRA, legally mandated reporters include, but are not limited to:

• Clergy members (i.e., a priest, minister, rabbi, religious practitioner, or similar functionary of a church, temple, or recognized denomination or organization)
• Any custodian of records of a clergy member
• Child care providers (e.g., an administrator of a public or private day camp; an administrator or employee of public or private youth center, recreation program, or organization; a licensee, administrator, or employee of licensed community care or child day care facility; an employee of a child care institution (foster parents, group home personnel, personnel of residential care facilities))
• Educators (e.g., teachers; instructional aides; teacher’s aides or assistants employed by any public or private school; classified employees of any public school; administrative officers or supervisors of child welfare and attendance, or certificated pupil personnel employees of any public or private school; any employee of a County Office of Education or the State Department of Education whose duties require direct contact and supervision of children; Head Start Program teachers)
• Law enforcement (i.e., any employee of any police department, county sheriff’s department, county probation department, or county welfare department; peace officers; firefighters (except for volunteer firefighters); and animal control officers or humane society officers) 
• Medical professionals (e.g., nurses, paramedics, EMT’s, physicians, dentists, chiropractors, alternative health practitioners, physical therapists)
• Mental health professionals (e.g., clinical social workers, trainees and interns; marriage, family and child counselors, trainees and interns; school counselors; psychologists, psychological assistants, and interns; alcohol and drug counselors)
• Commercial film and photographic print processors

A complete list of mandated reporters is provided in the California Penal Code (PC) section 11165.7.

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What about investigators?

Investigators are not specifically identified as mandated reporters under CANRA. There is debate around whether or not investigators should be compelled by other means to report suspected abuse, but the UCSC IRB does not currently have such a policy. Note that if an investigator is mandated by nature of also being a physician or teacher, for example, they would still be required to report and this issue would need to be addressed in the study submission, e.g., disclosure of the reporting requirement to subjects during the informed consent process and discussion of associated risks.

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What if the research involves people with limited decision-making capacity?

The decisional capacity of potential research subjects should be evaluated if there is reason to believe that they may not be capable of making voluntary and informed decisions about research participation. Whenever possible, investigators should attempt to obtain informed consent directly from the research subject; however, if a subject’s decisional capacity is limited, surrogate consent may be warranted.

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What is "decisional capacity"?

Decisional capacity or decision-making capacity refers to a subject’s ability to make a meaningful decision about whether or not to participate in research. It is generally includes the following elements:

1. Understanding, which includes the ability to comprehend information about the purpose and procedures of the study, as well as the potential risks and benefits of participating;
2. Appreciation, consisting of the ability to appreciate the significance of the disclosed information and the potential risks and benefits for one’s own situation;
3. Reasoning, or the ability to process the risks and benefits of participating versus not participating; and
4. The ability to express a decision or choice about whether or not to participate.

Decisional capacity should be considered situational and specific to the particular research study, and should not be confused with the legal concept of competence. Someone who is legally deemed incompetent may be able to make informed decisions about participation in a particular study and someone with full cognitive functioning may have their decision-making capacity diminished by pain or duress.

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When is a capacity assessment required?

Capacity assessments are needed for research involving subjects who may not possess full decision-making capacity, unless the investigator can justify why such assessments would be unnecessary for a particular group. The likelihood that a capacity assessment will be warranted increases with the potential risks to subjects. For research that poses greater than minimal risk to subjects, the IRB requires investigators to use appropriate means of assessing the prospective subjects' capacity to consent. For research that poses minimal risk, the IRB may require this assessment if it believes that it is an appropriate method to safeguard the subjects’ welfare. For more information, see Decision Making Capacity Guidelines. 

If capacity assessments are needed, the study should describe who will conduct the assessment, the method by which prospective subjects’ decisional capacity will be evaluated, the criteria for identifying those with limited decisional capacity, and how these determinations will be documented.

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Who can assess decisional capacity?

In general, the capacity assessor should be an investigator or consultant familiar with dementias or cognitive impairment and qualified to assess and monitor subjects' capacity and consent on an ongoing basis. The IRB will consider the qualifications of the proposed individual(s) and whether they are sufficiently independent of the research team and/or institution.

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How is decisional capacity assessed?

There are a variety of methods that can be used to assess capacity.  In some cases, standardized cognitive assessments may be warranted; in other cases, less formal procedures may be used, such as having the individual recall and summarize their understanding of the study, including risks and benefits. Methods include repetitive teaching, audiovisual presentations, follow-up questions to assess subject understanding, audio/video-recording of consent interviews, or involvement and/or concurrent consent of a trusted family member or friend in the disclosure and decision-making process. Sample assessments can be found at the bottom of Decision Making Capacity Guidelines. 

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What is surrogate consent?

If capacity assessment determines that an individual is unable to give thoroughly informed consent, surrogate consent must be obtained from the subject's legally authorized representative such as a parent, guardian, or conservator. For more information, see Informed Consent.

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What if the research involves pregnant women?

For research involving the participation of pregnant women as subjects, regulations require the following:

• Any risk is the least possible for achieving the objectives of the research;
• Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate.

 Although it is not common that these would pertain to UCSC research, regulations also require the following:

• Preclinical studies, including studies on pregnant animals and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;
• The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;
• If the research holds out the prospect of direct benefit to the pregnant subject, the prospect of a direct benefit both to the pregnant subject and the fetus, or no prospect of benefit for the subject nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, their consent is obtained in accord with informed consent provisions;
• If the research holds out the prospect of direct benefit solely to the fetus, then the consent of the pregnant subject and the father (if applicable) is obtained in accord with informed consent provisions, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.
• For children who are pregnant, assent and permission are obtained in accord with federal regulations regarding children in research;
• No inducements, monetary or otherwise, will be offered to terminate a pregnancy;
• Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy;
• Individuals engaged in the research will have no part in determining the viability of a neonate.

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What if the research involves fetuses or fetal tissue?

The University of California is compliant with California state law that permits research using human embryonic stem cells if that research is reviewed and approved by a federally registered IRB.

Research conducted by UCSC investigators that is funded by federal agencies other than the Department of Veterans Affairs (VA) must comply with provisions of the NIH Revitalization Act of 1993 (Public Law 103-43) with respect to use of fetal tissue. The VA prohibits research involving a fetus, in-utero or ex-utero (including human fetal tissue) or in vitro fertilization by VA investigators.

Provisions of that act include the following:

• Human fetal tissue means tissue or cells obtained from a dead embryo or fetus after a spontaneous or induced abortion, or after a stillbirth.
• Human fetal tissue may be used regardless of whether the tissue is obtained pursuant to a spontaneous or induced abortion or pursuant to a stillbirth.
• The subject donating the human fetal tissue must sign a statement declaring that the tissue is being donated for therapeutic transplantation research, the donation is being made without any restriction regarding the identity of individuals who may be the recipients of transplantations of the tissue, and the donation is being made without the donor having been informed of the identity of those individuals who may be the recipients.
• The attending physician must sign a statement declaring that the tissue has been obtained in accord with the donor's signed statement and that full disclosure has been made to the donor of: (1) The attending physician's interest, if any, in the research to be conducted with the tissue, and (2) any known medical risks to the donor or risks to the donor’s privacy that might be associated with the donation of the tissue and are in addition to the risks associated with the woman's medical care. In the case of tissue obtained pursuant to an induced abortion, the attending physician's statement must also declare that the consent of the donor for the abortion was obtained prior to requesting or obtaining consent for donation, the abortion was conducted in accordance with applicable state law, and no alteration of the timing, method, or procedures used to terminate the pregnancy was made solely for the purposes of obtaining the tissue.
• The individual with the principal responsibility for conducting the research must sign a statement declaring that the individual is aware that the tissue is human fetal tissue donated for research purposes and may have been obtained pursuant to spontaneous or induced abortion or pursuant to a stillbirth; that the principally responsible investigator has provided such information to other individuals with responsibilities regarding the research; that the principally responsible investigator will require, prior to obtaining the consent of a person to be the recipient of a transplantation of the tissue, written acknowledgement of receipt of the foregoing information by such recipient; and that the principally responsible investigator has had no part in any decisions as to the timing, method, or procedure used to terminate the pregnancy made solely for the purposes of the research.
• Research involving the transplantation of human fetal tissue for therapeutic purposes must be conducted in accord with applicable State law and the Secretary may not provide support for such research unless the applicant for assistance agrees to conduct the research. The conduct of such research by the Secretary must be in accord with applicable state and local law.
• The provisions of section 498B of the Public Health Service Act (42 U.S.C. 298g-2), added by Public Law 1-3-43, the NIH Revitalization Act of 1993 are summarized as follows:
  • It shall be unlawful for any person to knowingly acquire, receive, or otherwise transfer any human fetal tissue for valuable consideration if the transfer affects interstate commerce. (Valuable consideration does not include reasonable payment associated with the transportation, implantation, processing, preservation, quality control, or storage of human fetal tissue.)
  • It shall be unlawful for any person to solicit or knowingly acquire, receive, or accept a donation of human fetal tissue for the purposes of transplantation of such tissue into another person if the donation effects interstate commerce, the tissue will be obtained pursuant to an induced abortion, and: (1) The donation will be or is made pursuant to a promise to the donating individual that the donated tissue will be transplanted into a recipient specified by such individual; (2) the donated tissue will be transplanted into a relative of the donating individual; or (3) the person who solicits or knowingly acquires, receives, or accepts the donation has provided valuable consideration for the costs associated with such abortion. (Valuable consideration does not include reasonable payments associated with the transplantation, processing, preservation, quality control or storage of human fetal tissue.)
• The IRB, in reviewing research involving fetal tissue that is sponsored by federal agencies, will ensure that all requirements outlined in this section of the guidelines be met. Copies of all the required signed consent documents must be included with the application.

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What if the research involves prisoners?

Additional provisions apply to any research with incarcerated individuals as subjects. This includes situations where a subject becomes a prisoner after the research has started.

If the study is aimed at a broader subject population and prisoners are only incidentally involved, the research would not be considered to involve prisoners.

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Who is considered a prisoner?

"Prisoner" is defined by HHS regulations at 45 CFR 46.303(c) as "any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing."

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Is an adolescent (e.g., age 13-18) detained in a juvenile detention facility considered a prisoner?

Yes. In addition to the regulations involving prisoners, the regulations involving minors would also apply.

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What special responsibilities does the IRB hold when reviewing prisoner research?

When an IRB is reviewing a study in which a prisoner is a subject, the IRB must make, in addition to other requirements under 45 CFR 46, subpart A, seven additional findings under 45 CFR 46.305(a), as follows:

1. The research under review represents one of the categories of research permissible under 45 CFR 46.306(a)(2); (outlined below)
2. Any possible advantages accruing to the prisoner through their 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 their ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;
3. The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;
4. Procedures for the selection of subjects 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 IRB justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;
5. The information is presented in language which is understandable to the subject population;
6. 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 their parole; and
7. Where the IRB finds there may be a need for follow-up examination or care of subjects 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 subjects of this fact.

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Do the additional requirements for prisoners apply only where the research targets prisoners as subjects?

No, the requirements apply whenever any subject in a research study becomes a prisoner at any time during the study. 

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What should an investigator do if a subject becomes a prisoner after enrollment in research? 

When a previously enrolled research subject becomes a prisoner and the relevant research study was NOT reviewed and approved by the IRB in accordance with the requirements of HHS regulations at 45 CFR 46, subpart C, the PI should promptly notify the IRB of this event. All research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated prisoner-subject must cease until the requirements have been satisfied with respect to the relevant study. Note: In special circumstances in which the PI demonstrates that it is in the best interest of the subject to remain in the research study while incarcerated, the IRB Chair may determine that the subject may continue to participate in the research until the requirements of subpart C are satisfied. Upon receipt of notification that a previously enrolled subject has become a prisoner, the IRB will promptly re-review the study in accordance with the requirements of subpart C if the PI wishes to have the prisoner-subject continue to participate in the research.

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Special composition of IRB for research involving prisoners

In addition to satisfying the requirements of 45 CFR 46.116 and 46.117, when an IRB reviews a study involving prisoners as subjects that is conducted or supported by HHS, the composition of the IRB must satisfy the following requirements of HHS regulations at 45 CFR 46.304(a) and (b):

• A majority of the IRB (exclusive of prisoner members) shall have no association with the prison(s) involved, apart from their membership on the IRB.
• At least one member of the IRB must be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one IRB, only one IRB needs to satisfy this requirement.
• In the absence of choosing someone who is a prisoner or has been a prisoner, the IRB should choose a prisoner representative who has a close working knowledge, understanding and appreciation of prison conditions from the perspective of the prisoner.
• In addition, the IRB must notify OHRP of any change in the IRB roster occasioned by the addition of a prisoner or a prisoner representative, as required by HHS regulations at 45 CFR 46.103(b)(3). IRBs should be alert to the impact of roster changes on quorum requirements under HHS regulations at 45 CFR 46.108(b).
• If a study involving prisoners as subjects is to be reviewed by more than one IRB, only one IRB must satisfy the requirement that at least one member of the IRB be a prisoner or a prisoner representative.
• For research involving prisoners as subjects, the IRB must meet the special composition requirements of 45 CFR 46.304 for all types of review of the study, including initial review, continuing review, review of study modifications, and review of reports of unanticipated problems involving risks to subjects.

For research involving prisoners, two actions must occur:

1. The institution engaged in the research must certify that the IRB designated under its assurance of compliance has reviewed and approved the research in accordance with guidelines for conducting research with prisoners.
2. It must be determined that proposed research falls within the categories of research permissible. The categories of permissible research are the following:

• Study 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 subjects; (note that the definition of minimal risk for prisoner research at 45 CFR 46.303(d) differs from the definition of minimal risk for other research, contained in 45 CFR 46, subpart A, 45 CFR 46.102(i))
• Study 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 subjects;
• 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 consolation with appropriate experts including experts in penology, medicine, and ethics; or
• Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well- being of the subject. 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 consultation with appropriate experts including experts in penology, medicine, and ethics.

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Can research involving prisoners be exempt from IRB review?

No, the exemptions do not apply to research involving prisoners.

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