IRB Responsibilities Related to Review of VA Research
IRB Member Fact Sheet--Version Date: 3.12.2013
The VA regulations generally parallel those issued by Department of Health & Human Services (DHHS) but there are some important interpretations and restrictions specified by the VA in its guidance. Major differences relate to tissue banking, enrollment of incompetent subjects, and restriction of the types of research that can be conducted under the auspices of the VA.
The University of Wisconsin-Madison has a Memorandum of Understanding with the William S. Middleton Memorial Veteran’s Hospital (Madison VA) for the Health Sciences IRB and Health Sciences IRB and Minimal Risk IRB to serve as IRBs on behalf of the Madison VA. The Health Sciences IRB and Minimal Risk IRB are thus referred to by the VA as affiliate IRBs. Some VA institutions have their own IRBs.
The VA follows FDA regulations and the Common Rule (38 CFR 16), which is identical to the DHHS regulations (45 CFR 46), except for the subparts B-D that apply to pregnant women, fetuses, embryos, prisoners, and children. The authority and responsibilities of IRBs who review VA-regulated research are also detailed in VHA Handbook 1200.5, “Requirements for the Protection of Human Subjects Research” and 1058.03, “Assurance of Protection for Human Subjects in Research”. The VA also has issued directives that outline additional requirements for the protection of human subjects.
The following are considered to represent VA research:
Requirement for Separate VA and UW-Madison IRB Applications
- There are key personnel engaged in human subjects research for this project or study under their Madison VA (Wm. S. Middleton VA Hospital) appointment.
- The study or project enrolls, uses specimens obtained from, or involves the use of medical records of Madison VA (Wm. S. Middleton VA Hospital) patients.
- The study or project uses Madison VA (Wm. S. Middleton VA Hospital) facilities (i.e., space that is not rented by the University).
- The project or study is supported by VA funds.
Study teams planning to conduct studies jointly with VA AND UW-Madison are required to submit separate IRB applications for the VA and UW-Madison components when they are distinct (e.g., study procedures for UW subjects only occur at the UW and those for VA subjects only occur at the VA).
VA Research & Development (R&D) Committee
All research, including human subjects research determined exempt from IRB review, quality improvement, or related development programs conducted at the VA must be reviewed and approved by the VA R&D Committee. From the perspective of the VA, the UW-Madison IRBs are subcommittees of the VA R&D committee. The VA R&D Committee is not an ethics board, but rather reviews research to:
- Determine if research fits the mission of the VA and whether it may benefit veterans
- Consider safety and ethical issues in light of the IRB’s recommendations
- Conduct a scientific review of the research, including the quality of the study, study design, and the feasibility of the study
- Determine if the use of VA facilities is appropriate, the study budget is adequate, and the personnel conducting the study are appropriate
VA regulations require IRBs reviewing VA research to ensure that in addition to the composition requirements outlined in the Common Rule that each committee includes:
At least one VA member of the IRB is responsible for making regular reports on IRB activities to the VA Research and Development Committee.
- A licensed physician for the review of FDA-regulated products
- Two voting members with VA appointments at a certain level, one of whom must have scientific expertise
Additional Criteria for IRB Approval
As noted in the Criteria for IRB Approval: 45 CFR 46.111 (DHHS), 21 CFR 56.111 (FDA), and 38 CFR 16.111 (VA) , the Common Rule outlines specific criteria that must be met in order for an IRB to approve a research study. In addition to these, the VA requires additional criteria to be assessed:
The Madison VA Research Office evaluates the investigators’ conflict of interest obligations under the VA regulations and their educational requirements on behalf of the Health Sciences IRBs.
- Any conflict of interest must be evaluated and managed;
- The IRB must ensure protocols with treatment or services that constitute “usual care” include a narrative section that clearly differentiates the research interventions from usual care, whether usual care is delivered to only some or to all research subjects
- If non-Veterans will be included, whether adequate justification has been provided
- The investigator must meet particular educational requirements and certifications.
Restrictions on VA Research
The Madison VA does not allow research involving the following populations or procedures:
In conjunction with the VA R&D Committee, it is the responsibility of the IRB to ensure that human subjects research that falls under the Madison VA purview does not involve any of the restricted populations or procedures.
- Pregnant women
- In vitro fertilization
- Embryos, embryonic tissue, fetuses, or fetal tissue
- Children or neonates
- Planned emergency research
- International research
Flagging Medical Records
The IRB determines if patient electronic records must be flagged. Flagging is only needed in certain situations, such as:
- Any invasive research procedure (e.g., muscle biopsy or bronchoscopy);
- Interventions that will be used in the medical care of the subject, or that could interfere with other care the subject is receiving or may receive (e.g., administration of a medication, treatment, or use of an investigational device);
- Clinical services that will be used in the medical care of the subject (e.g., orders for laboratory tests or x-rays ordered as a part of the study), or that could interfere with other care the subject is receiving or may receive; or
- The use of a survey or questionnaire that may provoke undue stress or anxiety unless the IRB determines that mandatory flagging is not in the best interests of the subject (e.g., an interview study of victims of sexual assault).
A research study does not need to be flagged for research, for example, when:
VA Consent Form Requirements
- Participation in the study involves a single encounter
- The study involves a questionnaire that is not sensitive or use of previously collected biological specimens
- The identification of the patient as a subject in a particular study would place the subject at greater than minimal risk.
The VA requires the use of a specific consent form template for research studies under its purview (i.e., VA research consent form 10-1086). Additional requirements for VA consent forms include:
Research Involving Tissue Banking or Re-Use of Specimens
- VA-specific compensation for injury language. When a study occurs at both the VA and the UW, compensation for injury language for both institutions must be included.
- Consent forms must be stamped with the IRB expiration date on each page.
- The consent form also must include the VA Patient Representative rather than or in addition to the UW Hospital patient relations representative as well as a contact who can verify the study is a valid VA study.
- Consent forms for research studies involving tissue banking must contain VA-specific language.
Since November 2000, the VA does not permit researchers to bank human tissues for research purposes unless the specimens are stored in VA-sponsored or VA-approved tissue banks. Researchers seeking approval for tissue banks not housed at a VA facility must seek approval through the VA Central Office. The VA defines "banked" specimens as those collected and stored for future research purposes.
The VA requires that the reuse of specimens must be consistent with the consent under which they were collected, and the reuse must only occur through a VA-approved protocol. If a protocol requires that the specimens be analyzed or used at a non-VA institution, a written understanding between the VA investigator and the non-VA institution must specify the analysis/use as defined in the protocol. The agreement must also specify that any remaining quantities of the specimens shall be either destroyed or returned to the VA. If the remaining quantity is destroyed, that institution must certify the destruction of the specimens in writing. The remaining quantity may not be retained and/or stored by the non-VA institution.
Payment for Subjects
VA policy prohibits paying human subjects to participate in research when the research is an integral part of a patient's medical care and when it makes no special demands on the patient beyond those of usual medical care. Payment may be permitted, with approval of the IRB and the R&D Committee, in the following circumstances:
In their IRB application, investigators who wish to pay research subjects must:
- No direct subject benefit: When the study to be performed is not directly intended to enhance the diagnosis or treatment of the medical condition for which the volunteer subject is being treated, and when the standard of practice at the UW is to pay subjects in this situation.
- Others being paid: In multi-institutional studies, when human subjects at a collaborating non-VA institution, such as the UW, are to be paid for the same participation in the same study.
- Comparative situations: In other comparable situations in which, in the opinion of the IRB and R&D Committee, payment of subjects is appropriate.
- Transportation expenses: When transportation expenses are incurred by the subject, that would not be incurred in the normal course of receiving treatment, and that are not reimbursed by any other mechanism.
The IRB must review VA proposals that include subject payment to assure they conform to VA policies. This review includes consideration of the schedule of payments to avoid any coercion that might result from withholding all or most payment until the end of a long trial.
- Substantiate that proposed payments are reasonable and commensurate with the expected contributions of the subject.
- Describe the terms of the subject participation agreement and the amount of payment in the informed consent form.
- Demonstrate that subject payments do not constitute (or appear to constitute) undue pressure, influence, or coercion on the prospective research subjects to volunteer for or continue to participate in the research study.
Subjects with Impaired Decision-Making Capacity, Incompetent Subjects, and Surrogate Consent
VA investigators who plan to include incompetent subjects in their research must meet additional requirements. Competence is a legal term that refers to individuals’ legal and moral status that entitles them to make their own decisions, such as about health care. A court has the power to declare individuals incompetent and appoint guardians for them. In contrast, impaired decision-making capacity (also lack of capacity or decisionally impaired) is not a legal term but rather describes a situation when a person does not possess the ability to give informed consent due to medical reasons (e.g., shock, coma, sedation, onset of Alzheimer’s Disease) and can be variable.
Research involving incompetent subjects who may not be able to make decisions on their own behalf can only be approved under the VA regulations when it meets all of the following conditions:
1) The proposed research entails
- No greater than minimal risk to the subject as determined by the IRB; OR
- If the research presents some probability of harm, there must be at least a greater probability of direct benefit to the subject; OR
- Greater than minimal risk and no prospect of direct benefit to individual subjects, but is likely to yield generalizable knowledge about the subject’s disorder or condition that is of vital importance for the understanding or amelioration of the subject’s disorder or condition.
2) The disorder (e.g., Alzheimer’s) leading to the individual’s lack of decision-making capacity is being studied, whether or not the lack of decision-making itself is being evaluated (e.g., an individual who lacks decision-making capacity as the result of a stroke can participate in a study of cardiovascular effects of a stroke), but only if the study cannot be performed with only persons who have decision-making capability.
3) The subject of the study is not directly related to the individual’s lack of decision-making capacity, but the investigator can make a compelling argument for including individuals who lack decision-making capacity in the study (e.g., transmission of methicillin-resistant Staphylococcus aureus (MRSA) infections in a nursing home where both individuals with, and those without, decision-making capacity are affected).The IRB must document that research involving subjects with impaired decision-making capacity meet the above criteria. For subjects with fluctuating decision making capacity or those with decreasing capacity to consent, a re-consenting process with surrogate consent may be necessary.
Destruction of Research Data
VA policy (VHA Records Control Schedule 10-1) prohibits the destruction of data collected during the course of a VA research study, including screening data. Protocols, consent forms, phone screening scripts, and any other relevant documents should state that all data collected will be maintained indefinitely..
For more information about VA regulations see the US Department of Veteran’s Affairs website at: http://www.research.va.gov/programs/pride/policy/default.cfm or contact the VA Research Office at 280-7007