Children are considered a vulnerable research population because their intellectual and emotional capacities are limited and therefore, they are legally incompetent to give valid informed consent. Investigator's interested in enrolling children are required to address specific additional questions when completing the electronic IRB Application or when requesting an amendment to an IRB-approved study. When reviewing research involving children as subjects, the IRB considers the risks and discomforts inherent in the proposed research and assesses their justification in light of the expected benefits to the child-subject or to society as a whole.
Federal Regulations regarding "Children" (both 45 CFR 46 and 21 CFR 50) state, "'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." Thus, who qualifies as a 'child' depends on local laws for consent. In California, 18 is the usual age when people can consent to treatments or procedures, but there are important exceptions, such as when seeking medical care related to the prevention or treatment of pregnancy (see below for further clarifications).
Prisoners are considered a vulnerable research population because the very fact of incarceration may make it difficult for them to give truly voluntary informed consent. Investigators interested in enrolling prisoners as research subjects must complete Appendix C when completing the electronic IRB Application or when requesting a amendment to an IRB-approved study.
Definition of a Prisoner (45 CFR 46.303 (HHS – Subpart C)
“Prisoner” means 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 (45 CFR 46.303(c)).
Individuals are prisoners if they are in any kind of penal institution, such as a prison, jail, or juvenile offender facility, and their ability to leave the institution is restricted. Prisoners may be convicted felons or may be untried persons who are detained pending judicial action, for example, arraignment or trial.
- Individuals who are detained in a residential facility for court-ordered substance abuse treatment as a form of sentencing or alternative to incarceration
- Individuals with psychiatric illnesses who have been committed involuntarily to an institution as an alternative to a criminal prosecution or incarceration
- Parolees who are detained in a treatment center as a condition of parole
- Individuals who are receiving non-residential court-ordered substance abuse treatment and are residing in the community
- Individuals who have been voluntarily admitted to an institution for treatment of a psychiatric illness, or who have been civilly committed to non-penal institutions for treatment because their illness makes them a danger to themselves or others
- Persons living in the community and sentenced to community-supervised monitoring, including parolees
- Probationers and individuals wearing monitoring devices, however, situations of this kind frequently require an analysis of the particular circumstances of the planned subject population. Institutions may consult with OHRP when questions arise about research involving these populations.
For research involving prisoners, the definition of minimal risk is as follows:
“Minimal risk” as it relates to prisoners is defined as the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons (45 CFR 46.303(d)).
Important Note: The criteria for involving prisoners in research apply whenever any human subject in a research protocol becomes a prisoner at any time during a study. If a subject becomes a prisoner after enrollment in research, the investigator must notify the IRB right away. See also FAQs about Prisoner Research.
To protect this study population, federal regulations stipulate that the only studies that may use prisoners are those with an independent and valid reason for involving them. Specifically:
- 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 subjects.
- 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 subjects.
- Research on conditions particularly affecting prisoners as a class (e.g., 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 consultation with, and approval by the HHS Secretary.
- 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, and approval by the HHS Secretary.
- Studies of epidemiologic research that describe the prevalence or incidence of a disease by identifying all cases or studies of the potential risk factor associations for a disease, where prisoners are not the particular focus of the research.
While pregnant women may be involved in several categories of research, studies involving the human fetus raise special concerns. Research involving pregnant women, fetuses and human in vitro fertilization are subject to special federal regulations that guide IRB deliberations on such studies. Investigators interested in studying pregnant women, fetuses and/or neonates are required to complete Appendix B when completing the electronic IRB Application or when requesting a amendment to an IRB-approved study.
Additional protections are in place for all research involving pregnant women, human fetuses, neonates of uncertain viability, or nonviable neonates.
- Fetus means the product of conception from implantation until delivery.
- Neonate means a newborn.
- Pregnancy encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.
- Viable, as it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration. If a neonate is viable then it may be included in research only to the extent permitted and in accordance with the requirements for research involving children.
Research studies involving pregnant women or fetuses can be approved by the IRB if the following requirements of federal regulations are satisfied
- Preclinical studies have been conducted, including studies on pregnant animals; clinical studies, that include nonpregnant women and provide data for assessing potential risks to pregnant women and fetuses
- Risk to the fetus is caused solely by interventions or procedures that hold the prospect of direct benefit for the woman or the fetus or,
- If no benefit, the risk to the fetus is not greater than minimal and the research develops important biomedical knowledge not obtainable by any other means.
- Any risk is the least possible for achieving the objectives of the research.
- Individuals engaged in the research will have no part in: 1) any decisions as to the timing, method, or procedures used to terminate a pregnancy, and 2) determining the viability of the fetus at the termination of the pregnancy; and
- No inducements, monetary or otherwise, will be offered to terminate the pregnancy.
Consent Signature Requirements
The mother's consent is required when the research holds:
- the prospect of direct benefit to the pregnant woman, or
- the prospect of a direct benefit both to the pregnant woman and the fetus, or
- no prospect of benefit for the woman nor the fetus but 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;
Consent from the mother *and* father is required (unless the father is absent, incompetent, unknown or the pregnancy resulted from rape/incest) when the research holds out the prospect of direct benefit solely to the fetus.
Consent Decision Chart for Pregnant Women and Fetuses
|Direct benefit to mother only||Direct benefit to mother and fetus||Direct benefit to fetus only||No direct benefit or societal benefits only|
|Risk is more than minimal||Mother's consent||Mother's consent||Mother and father's consent||NOT APPROVABLE BY IRB|
|Risk is no more than minimal||Mother's consent||Mother's consent||Mother and father'sconsent||NOT APPROVABLE BY IRB|
Investigators proposing to conduct research using neonates (viable, uncertain viability, or nonviable) or research using the placenta, dead fetuses or fetal material, or pregnant women, fetus and neonate research not otherwise described above, are encouraged to consult with the Research Protections staff for additional guidance prior to submitting an IRB application.
UCI students and employees that are asked to volunteer as human subjects in a researcher's study may feel some pressure to agree to participate, especially if the requesting researcher is their supervisor or instructor, or someone who might be in a position to influence their future. Students and employees may volunteer to participate out of a belief that doing so will place them in good favor with faculty (e.g., that participating will result in receiving better grades, recommendations, employment, or the like), or that failure to participate will negatively affect their relationship with the investigator or faculty generally (i.e., by seeming "uncooperative").
- To protect against even the appearance of coercion or undue influence, when UCI investigators wish to recruit UCI students (undergraduate, graduate, and medical students), staff (administrative, clerical, nursing, lab, "house" staff, etc.), or faculty as human subjects, they must first request approval for inclusion of one or more of these populations on the IRB Application, or by requesting an amendment to an IRB- approved study.
- Researchers who include students and subordinates in research are urged to exercise great caution to avoid even the appearance of pressuring or coercing potential subjects into enrollment or continued participation. In addition, researchers should guard against the potential for compromised objectivity and/or confidentiality when including students or subordinates in a study.
Additional Guidelines for the Recruitment of Students
- The Lead Researcher must provide assurance in the protocol narrative that a student's experimental results, performance, or any confidential data will not be given to whomever is grading the student, except for stating whether the student participated or not unless the approved study design provides for this.
- It is unacceptable to require participation in research for course credit. However, instructors who wish to involve students in simulations of human experimentation and course-assigned data collection for educational purposes only (as opposed to research purposes) may require such participation as part of the class requirements.
- UCI students may earn extra course credit through the Social Science Lab if an instructor includes this option in the course syllabus. When students participate in research studies for extra class credit, they must be provided alternative ways to earn extra credit that require equal or less time and effort. The IRB may require the investigator to include the available alternatives to participation in the informed consent document.
- Researchers interested in accessing student records for research purposes are directed to the UCI Registrar website on Privacy and Student Records. The disclosure of information from student records is governed in large measure by the Federal Family Educational Rights and Privacy Act of 1974, by the State of California Education Code, and by University policy and procedures implementing these laws. Generally, documentation of informed consent is required to access private student information.
All adults (including those with cognitive impairments) are presumed competent to consent unless legally judged to be incompetent. Cognitively impaired persons are considered a vulnerable research population because their mental disability may compromise their capacity to make a reasoned decision about participation in a study. Investigators interested in studying individuals with cognitive impairment are required to address additional consideration as part of the IRB review process in Kuali Research (KR) Protocols.
People with Alzheimer's disease, dementia, mental illness and developmental disabilities may be considered cognitively impaired and may not be able to provide informed consent for participation in research. In certain circumstances, when it is determined that a potential research participant is cognitively impaired, federal regulations and state statute permit researchers to obtain consent from a legally-authorized representative (surrogate consent).
To have the option to obtain consent from a subject's legally-authorized representative, the investigator must request that the IRB allow for the use of surrogate consent.
Resources for Researchers & Families
- OHRP 45 CFR 46 Subpart B (Pregnant Women, Fetuses, Neonates)
- OHRP 45 CFR 46 Subpart C (Prisoners)
- OHRP 45 CFR 46 Subpart D (Children)
- FDA 21 CFR 50 Subpart D (Children)
- Understanding Confidentiality and Minor Consent in California
- OHRP FAQ's on Research with Children
- Children and Clinical Studies - A Resource for Researchers and Families
- Ethical Considerations for Clinical Investigations of Medical Products Involving Children