VA Requirements for Vulnerable Subjects

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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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Individuals or Populations Which May Be
Temporarily or Permanently Vulnerable

• 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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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 womans 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/populati
  ons/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
  IRBs 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 individuals
  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 subjects 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 subjects disorder or condition that is of vital importance for understanding or amelioration of subjects disorder or condition
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
Disorder leading to individuals 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 individuals 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 HIPAAs 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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QUESTIONS
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