150. Additional Requirements for VA Research Involving Vulnerable Populations
Updated Nov. 2, 2020
Pregnant women, children, and other vulnerable populations may be entered into Department of Veterans Affairs (VA) research if Veterans Health Administration (VHA) requirements are met as described in VHA Directive 1200.05(1) Requirements for the Protection of Human Subjects in Research (March 3, 2020).The University IRB uses review worksheets to document Department of Health and Human Services (DHHS) requirements (in Subparts B, C, and D) for additional protections and population-specific findings for VA Research involving pregnant women, fetuses, and neonates; prisoners; and children; and to evaluate protections and VA requirements for conditionally vulnerable populations.
VA Research Involving Pregnant Women, Fetuses or Neonates; and Women of Childbearing Potential
The University IRB applies DHHS requirements for Subpart B and DHHS criteria for IRB approval to VA Research involving pregnant women, fetuses, or neonates with the following additional limitations:
- Research that involves provision of in vitro fertilization services can be conducted by VA investigators while on official VA duty, at VA facilities, or at VA-approved off-site facilities.
- Research involving stem cells shall be governed by the policy set by NIH.
- Research in which the focus is either a fetus, human fetal tissue, in-utero, or ex-utero, is not allowed.
- Research involving prospective observational and retrospective record review studies for fetuses, human fetal tissue, and neonates is allowed.
- Intervention studies involving neonates or neonatal outcomes is prohibited.
- The involvement of pregnant women in greater than minimal risk VA Research requires prior written certification from the VASNHCS Facility Director attesting to the facility’s capacity to respond to obstetric emergencies.
VHA ORD Guidance on Collecting Data on Pregnancy and Outcomes of Pregnancy
The VHA Office of Research and Development (ORD) has issued Guidance on Collecting Data on Pregnancy and Outcomes of Pregnancy from VA Research Subjects and Pregnant Partners of VA Research Subjects for Safety Monitoring (March 9, 2015).
When relevant, risks to women of childbearing potential should be addressed during the consent process. The University IRB considers the VHA Office of Research and Development (ORD) Guidance on Collecting Data on Pregnancy and Outcomes of Pregnancy from VA Research Subjects and Pregnant Partners of VA Research Subjects for Safety Monitoring (March 9, 2015) for safety monitoring for pregnancy progress and outcomes when pregnancy is not the research focus. The guidance applies to the following:
- Collecting pregnancy information from or about female subjects who become pregnant while participating in VA research.
- Collecting pregnancy information from or about female partners of male subjects participating in VA research. Collecting information about the newborn infant of female subjects or female partners of male subjects in VA research. IRB considerations when collecting data on pregnancy progress and outcomes of pregnancy in VA research.
- Obtaining VA Facility Director approval for collecting data about the newborn infant.
- Obtaining VA Facility Director certification for collecting data about the female subject who becomes pregnant or the pregnant partner of a male subject in VA research.
Collecting Pregnancy Information from or about Female Subjects who become Pregnant while Participating in VA Research. In most studies conducted in the VA, pregnancy is not the focus of the research. In many research studies, particularly clinical investigations involving interventions with drugs or medical devices, the investigator or sponsor may want to obtain information about the progress of a pregnancy when a female subject becomes pregnant while participating in the research. In the majority of these studies, the female subject no longer receives the clinical intervention described in the IRB-approved protocol once the investigator is made aware of the female subject's pregnancy, but monitoring of the pregnancy for safety is requested or recommended by the sponsor of the study. If a female subject who becomes pregnant is withdrawn from the research intervention portion of the study by a VA investigator, collection of any additional data by the investigator from the female subject or obtaining identifiable private information about her after she is withdrawn would constitute human subject research activities. A subject can be withdrawn solely from receiving the research intervention, remain in the study, and the investigator would be allowed to continue data collection and other follow-up activities if the data collection and follow-up activities are described in the protocol and informed consent approved by the IRB, the HIPAA authorization, and the subject does not revoke that portion of the informed consent and HIPAA authorization. Written authorization requirements for use and disclosure of protected health information must be met as described in VHA Handbook 1605.01 ("Privacy and Release of Information") and VHA Directive 1200.05 (1). When a subject is withdrawn from all aspects of the study by the subject's or investigator's choice, the subject's participation in that study ends and additional data and identifiable private information about that subject must not be collected or obtained..
Collecting Pregnancy Information from or about Female Partners of Male Subjects Participating in VA Research.
Most studies conducted in VA involve recruitment of male subjects. In research studies, particularly clinical investigations, the investigator may want to obtain information about the progress of a pregnancy if the female partner of a male Veteran subject becomes pregnant during the interval when the male subject is participating in a VA research study.
VA applies the Common Rule to all human subject research which is approved as VA research. Collection of data in the research through intervention or interaction with the female partner or obtaining identifiable private information about the female partner constitutes human subjects research. The female partner becomes a human subject according to the Common Rule and is given protections as a human subject as required in 38 CFR 16 and VHA Directive 1200.05 (1). In such cases, the IRB-approved protocol must include provisions for collecting information from the pregnant female partner of the male subject enrolled into the research. Informed consent as approved by the IRB must be obtained by the investigator from the female partner prior to the collection of any data by the investigator from the female partner or obtaining identifiable private information about her unless the IRB has waived informed consent in accordance with criteria described in 38 CFR 16.116. Written authorization for use and disclosure of protected health information must be obtained from the female partner as described in VHA Handbook 1605.01: Privacy and Release of Information. Collecting Information About the Newborn Infant in VA Research. When a VA investigator conducting human subjects, research collects identifiable private information about the newborn infant of subject enrolled in VA research, the infant is a human subject, and the investigator is conducting VA research involving children. The IRB-approved protocol must include provisions for collecting information about the newborn infant. Informed consent as approved by the IRB and obtained from the adult subject(s) must contain sufficient information about the data to be obtained for the newborn. Written authorization for use and disclosure of protected health information must be obtained as described in VHA Handbook 1605.01: Privacy and Release of Information. The VA facility director must approve participation of children in the research prior to collection of data about the newborn infant following IRB review and approval in accordance with VHA Directive 1200.05(1) requirements. IRB Considerations When Collecting Data on Pregnancy Progress and Outcomes of Pregnancy in VA Research
When VA research involves collecting data from or about pregnancy and pregnancy outcomes, the IRB must still ensure that subjects' ethical rights are protected. VHA follows 45 CFR 46.204 requirements for including pregnant women in VA research. IRBs are not expected or required to review studies using the criteria described in 45 CFR 46.204 simply because the study involves women of child-bearing potential. However, once the reviewing IRB is made aware that information about a subject's pregnancy is being obtained in a VA study, the reviewing IRB must ensure that:
- the IRB-approved protocol addresses the data collection procedures for obtaining data about the progress of the pregnancy and pregnancy outcomes (live birth with or without birth defects, stillborn, or aborted fetus);
- informed consent has been obtained from the adult subject to obtain information about the progress of the pregnancy and pregnancy outcomes unless the IRB has waived informed consent in accordance with criteria described in 38 CFR 16.116;
- the data collection involving the pregnant female subject described in the IRB approved protocol meets the conditions described in 45 CFR 46.204; and
- the data collection involving the newborn infant described in the IRB-approved protocol meets 45 CFR 46 Subpart D requirements for research activities not involving greater than minimal risk (45 CFR 46.404).
Obtaining VA Facility Director approval for collecting data about the newborn infant
When identifiable private information or de-identifiable information is collected about a newborn infant in VA research, the newborn infant is a research subject who is also a child. Following IRB, other applicable subcommittees, and R&D Committee approvals, the VA Facility Director must approve this activity which constitutes VA research involving children as research subjects. This VA Facility Director approval should be in the investigator’s study files and, in the R&D file in the Research Office.
VA Facility Director approval for VA research involving children does not have to be obtained until the research involves children. There is no ORD requirement to obtain VA Facility Director approval for research involving children in VA research if a protocol includes women of child-bearing potential unless an event occurs in which data about the newborn infant from a female subject or the pregnant partner of a male VA subject will be collected in VA research.
If the research activities involving the newborn infant consist of data collection through review of records (no intervention or interaction with the infant), considerations that the VA Medical Center Director may evaluate during the approval process such as procuring liability insurance to allow collection or data or considering whether the VA Facility is able to respond to pediatric emergencies is not applicable because the research activity consists of data collection in the absence of interventions or interactions.
Obtaining VA Facility Director Certification for Collecting Data about the Female Subject who Becomes Pregnant or the Pregnant Partner of a Male Subject in VA Research
When identifiable private information is collected about or from the female subject who becomes pregnant or the pregnant partner of a male subject, VA research involving pregnant women is being conducted. Following IRB, other applicable subcommittee, and R&D Committee approval, the VA Facility Director is required to certify that the Medical Facility has enough expertise in women’s health to conduct this activity. This VA Facility Director approval should be in the investigator’s study files and, in the R&D file in the Research Office.
If the research activities with collecting pregnancy progress and pregnancy outcome data involves minimal risk activities (e.g., no obstetric interventions being done at the VA Facility to collect data), considerations that the VA Medical Center Director may evaluate as part of the certification process such as ensuring that the VA facility is able to respond to obstetric emergencies is not applicable because the research activity is not associated with obstetric emergencies.
VA Research Involving Prisoners
The University IRB applies DHHS requirements for Subpart C and DHHS criteria for IRB approval to VA Research involving prisoners with the following additional requirements and prohibitions:
Research involving prisoners cannot be conducted by VA investigators while on official VA duty, at VA facilities, or at VA-approved off-site facilities unless a waiver has been granted by the CRADO. Waiver requests must be submitted electronically to the CRADO by the VA medical facility Director with the following documents:
- A letter from the VA medical facility Director supporting the conduct of the VA study involving prisoners;
- Rationale for conducting the research involving prisoners to include additional ethical protections taken by the proposed research for prisoners to make voluntary and uncoerced decisions whether or not to participate as subjects in research;
- Documentation of the VA investigator’s qualifications to conduct the research involving prisoners, such as a biosketch and a list of all research team members;
- Location of institutions where the research is proposed to be conducted;
- A copy of the IRB approval letter specifically documenting its review;
- A copy of the IRB minutes approving the research with documentation that at least one member of the IRB included a prisoner or a prisoner representative for the review of the research;
- A copy of the IRB-approved research study;
- A copy of the IRB-approved informed consent document; and
- A copy of the written HIPAA authorization.
If such a waiver is granted, the research must comply with the requirements of 45 CFR 46.301 - 46.306.
Incarceration of a Participant in VA Research
See IRB Policy Manual for information about unexpected incarceration of a research participant.
For VA research, if a participant becomes incarcerated during the course of a study and continued participation is in the individual’s best interest, the requirement for a waiver from the CRADO will apply.
VA Research Involving Children
Research involving biological specimens or data obtained from children is considered to be research involving children even if de-identified. Research involving children does not include neonates.
Research involving children must be reviewed carefully by the IRB for its relevance to VA and must not present greater than minimal risk to the children. The VA medical facility Director must approve participation in the proposed research that includes children. The IRB must have the appropriate expertise to evaluate any VA research involving children and must comply with the requirements of 45 CFR 46.401 - 46.404 and 46.408.
The University IRB applies DHHS requirements for Subpart D and DHHS criteria for IRB approval to VA Research involving children, including research involving biological specimens or data obtained from children (whether identified or de-identified), with the following additional requirements:
- PIs must obtain written approval from the VASNHCS Facility Director, including certification of the facility’s capacity to respond to pediatric emergencies (for interventional research).
- The IRB must determine risk is no more than minimal.
- IRB meeting minutes document IRB risk determinations and consent waivers (if applicable).
- Review worksheets document determinations related to informed consent, permission, and assent; investigators’ qualifications to conduct research involving children; and additional safeguards incorporated into the protocol, if any.
Conditionally Vulnerable Populations in VA Research
Individuals or populations that may be considered permanently or temporarily vulnerable due to conditions or circumstances include persons who
- are susceptible to coercion or undue influence (e.g., homeless or institutionalized persons, students or employees, patients with limited or no treatment options, persons who are socially or economically disadvantaged);
- may not be able to comprehend what they may experience during the research and the risks of participation (e.g., those who are educationally disadvantaged; or who have cognitive impairment, dementia, schizophrenia, or depression);
- have increased susceptibility to harm from the procedures of the specific study under review (e.g., individuals answering study survey questions about sexual assault); or
- are at risk for economic, social, or legal consequences from the study (e.g., participants who answer survey questions about their drug use or HIV status).