VA Requirements for Vulnerable

Subjects

Kevin L. Nellis, M.S., M.T. (A.S.C.P.)Program Analyst

Program for Research Integrity Development and Education (PRIDE)

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Overview

• Vulnerable Subjects

• Populations Considered Categorically Vulnerable

• Pregnant Women

• Prisoners

• Children

• Persons Who Lack Decision-Making Capacity

• Surrogate Consent

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Vulnerable Subjects

Common Rule:

When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these

[38 CFR 16.111(b)]

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IRB Must Document Deliberations

• Reasons why IRB considers population or individual to be vulnerable

• That adequate safeguards protect the rights and welfare of subjects likely to be vulnerable

• That the VA criteria are met to approve inclusion of individuals who lack decision-making capacity

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Individuals or Populations Which May Be Temporarily or Permanently Vulnerable

• Those who are susceptible to coercion or undue influence (e.g., homeless, students, patients with limited treatment options, socially or economically disadvantaged)

• Those who lack comprehension of research or potential risks (e.g., educationally disadvantaged, dementia, schizophrenia, depression)

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• Those who have increased susceptibility to harm (e.g., individuals answering questions about traumatic events such as sexual assault, or combat experiences)

• Those who are at risk for physical, psychological, economic, social, legal consequences (e.g., Individuals answering questions about drug use or HIV status)

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Individuals or Populations Which May Be Temporarily or Permanently Vulnerable

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Research Involving Pregnant WomenVA Requirements

• Adequate provisions has been made to monitor risk to subject and fetus

• Women of child bearing potential may not be entered into studies involving Category D or X drugs without a waiver from the Chief Research and Development Officer (CRADO)

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Research Involving Pregnant Women45 CFR 46, Subpart B Requirements

Prior studies must assess potential risks to pregnant women and fetuses (preclinical studies, clinical studies, studies on pregnant animals, studies on non-pregnant women), when scientifically appropriate

[45 CFR 46.204(a)]

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Research Involving Pregnant Women45 CFR 46, Subpart B Requirements

• 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

[45 CFR 46.204(b)]

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Research Involving Pregnant Women45 CFR 46, Subpart B Requirements

• Any risk is the least possible for achieving the objectives of the research

[45 CFR 46.204(c)]

• If the research holds out the prospect of direct benefit to the pregnant woman, 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 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, the pregnant woman’s informed consent is obtained in accord with the informed consent provisions of 38 CFR 16.116 [45 CFR 204(d)]

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Research Involving Pregnant Women45 CFR 46, Subpart B Requirements

Subject is fully informed regarding the reasonably foreseeable impact of the research on the fetus

[45 CFR 46.204(f)]

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Research Involving Pregnant Women45 CFR 46, Subpart B Requirements

• No inducements, monetary or otherwise, are to be offered to terminate a pregnancy [45 CFR 46.204 (h)]

• Individuals engaged in the research have no part in

• any decisions as to the timing, method, or procedures used to terminate a pregnancy [45 CFR 46.204(i)]

• determining the viability of a fetus [45 CFR 46.204 (j)]

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Research Involving Prisoners

• IRB Approval Must Comply 45 CFR 46, Subpart C

• Waiver from Chief of Research and Development Officer (CRADO)

• OHRP FAQs: http://www.hhs.gov/ohrp/policy/populations/index.html

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Research Involving PrisonersIncarceration During Study

• Investigators must notify the IRB as soon as they become aware that the subject has been incarcerated

• Investigator determines whether or not it is the best interests of the subject to remain in the study, or if the subject can be safely withdrawn from the study

• Continued participation is contingent on the IRB’s reviewing and approving such participation

• Waiver must be obtained from the CRADO

• Follow all requirements (court, penal system, local VA, Federal)

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Research Involving ChildrenVA Requirements

• VA Research must support mission of VA and enhance quality of health care delivery to veterans

• CRADO Waiver (see VHA Handbook 1200.05) must be obtained to conduct VA research involving children

• Interventions

• Interactions

• Data or specimens

• Meet requirements of 45 CFR 46, Subpart D

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Research Involving Persons Who Lack Decision-Making Capacity

• Individual is presumed to have decision-making capacity unless:

• Documented by a qualified practitioner* in the medical record

• Ruled incompetent by a court of law

• If there is any question whether a potential adult subject has decision-making capacity, the investigator must consult with a qualified practitioner* about the individual’s decision-making capacity before proceeding with the informed consent process

*May be a qualified member of the research team

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Research Involving Persons Who Lack Decision-Making Capacity

Individuals at high risk for temporary (e.g., head trauma) or fluctuating (e.g., schizophrenia) lack of decision-making capacity must be evaluated to determine the ability to provide informed consent

• Evaluation must be performed as described in the IRB-approved protocol

• If individual is deemed to lack decision-making capacity, a legally authorized representative (LAR) must provide informed consent

• If subject regains decision-making capacity, repeat informed consent process with subject, and obtain subject’s permission to continue

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Criteria for Enrolling Persons Who Lack Decision-Making Capacity

Risk, Harm, & Direct Benefit of Proposed Research*

Additional Requirements*

No greater than minimal risk No additional requirements

Some probability of harm Probability of direct benefit must be greater than probability of harm

Greater than minimal risk with no prospect of direct benefit to subject

Research is likely to lead to generalizable knowledge about subject’s disorder or condition that is of vital importance for understanding or amelioration of subject’s disorder or condition

*VHA Handbook 1200.05, Paragraph 49(d)(1)(a), or (b), or (c)

Criteria for Enrolling Persons Who Lack Decision-Making Capacity

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Type of Study* Additional Requirements

Example

Disorder leading to individual’s lack of decision-making capacity is being studied; whether or not the lack of decision-making itself is being evaluated

The study cannot be performed with only persons who have decision-making capability

Individual who lacks decision making capacity as the result of stroke can participate in study of cardiovascular effects of stroke

* Also need VHA Handbook 1200.05, Paragraph 49(d)(1)(a), or (b), or (c)

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Criteria for Enrolling Persons Who Lack Decision-Making Capacity

Type of Study* Additional Requirements

Example

Study is not directly related to individual’s lack of decision-making capacity

Compelling argument for including individuals who lack of decision-making capacity

Study the transmission of MRSA infection in nursing home where both individuals with, and those without, decision making capacity are affected

* Also need VHA Handbook 1200.05, Paragraph 49(d)(1)(a), or (b), or (c)

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IRB Determinations for Research Involving Persons Who Lack Decision-Making Capacity

• Ensure the study includes appropriate procedures for respecting dissent

• Consider whether or not the study needs to include procedures for obtaining assent

• Determine whether any additional safeguards need to be used (e.g., consent monitoring)

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IRB Determinations for Research Involving Persons Who Lack Decision-Making Capacity

IRB must document

• Reasons why IRB considers subject to be vulnerable

• That adequate safeguards protect subjects

• VA criteria are met to approve include individuals who lack decision-making capacity

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Surrogate Consent

Legally Authorized Representative (LAR)

• Health care agent

• Legal or special guardian

• Next of kin in this order:

• Spouse, child, parent, sibling, grandparent, grandchild

• Close friend

LAR is not synonymous with HIPAA’s “personal representative”

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Surrogate Consent

• If feasible, the investigator must explain the proposed research to the prospective research subject

• Some persons may resist participating in a research (i.e., dissent)

• Under no circumstances may a subject be forced or coerced to participate in a research study even if the LAR has provided consent

• For subjects with fluctuating decision-making capacity or those with decreasing capacity to give consent, a re-consenting process with surrogate consent may be necessary

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Key Points

• Understand who is categorically vulnerable

• Understand which individuals or populations may be vulnerable

• Understand the protections afforded to vulnerable subjects in a study

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Key Points

• IRB must document

• Reasons why IRB considers to be vulnerable

• That adequate safeguards protect subjects

• VA criteria are met to approve include individuals who lack decision-making capacity

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Key Points

• Protecting vulnerable populations is a shared responsibility among:

• Investigators

• IRB

• Legally Authorized Representative

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