Protection of Vulnerable Subjects in Research

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Protection of Vulnerable Subjects in Research

• Tracy Rightmer, J.D.
• Compliance Manager
• Human Investigation Committee
• Yale University School of Medicine

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Objectives

• Discuss categories of vulnerable subjects why
  they are vulnerable
• Points to consider for protection of these
  subjects
• Struggle to balance ethical principles with the
  conduct of research and protection of the rights
  and welfare of human subjects

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Ethical Principles of Research

• Justice
• Respect of Persons
• Beneficence

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Special Protections

• Why?
• Past abuses of the rights of subjects, especially
  vulnerable subjects
• Ethical principles of justice and respect of
  persons
• What?
• Federal Regulations
• State Statutes
• Special Review by HIC
• Risk/Benefit of the study
• Researcher Sensitivity to the particular category
  of vulnerability

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Vulnerable Populations

• Cognitive or Communicative
• Decisionally impaired individuals, Children,
  Non-English speaking individuals, Fetuses and
  neonates (includes pregnant women)
• Institutional or Deferential
• Prisoners, students and employees
• Medical
• Terminally ill individuals
• Economic
• Dependent or impoverished individuals
• Social
• Minorities (includes non-English speaking
  persons)

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Categories of Vulnerable Subjects

• Cognitive or Communicative
• Decisionally impaired persons, Children, Fetuses
  and Neonates, Seriously ill persons, Non-English
  speakers, Individuals with substance abuse
  problems, Adults in ER
• Protections
• Surrogate consent from LAR, subject assent
• Pay close attention to non-verbal behavioral
  cues indicating their wishes re participation
• Delay enrollment until situation causing the
  impairment has passed or consent prior to the
  situation causing impairment
• Use translated consent forms and translator
  during IC process (not a family member) include
  provision for ongoing communication
• Carefully consider the risk/benefit ratio of the
  study and the appropriateness of the population
  being studied

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Decisionally Impaired

• Have diminished capacity for decision-making and
  may be unable to fully understand the risks of
  research
• Capacity must be assessed by trained clinician
• LAR must consent and subject assent
• Regulations governing inclusion of decisionally
  impaired subjects 45 CFR 46.102 and 45 CFR
  46.116
• Special regulations prohibit court-appointed
  guardians of mentally retarded individuals to
  give permission for participation in research
  unless very stringent terms and conditions are met

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Current Controversies

• No law in CT that confers the right to consent to
  medical procedures on the patients Next of Kin
  (NOK)
• Current practice in research surrogate consent
  of LAR or NOK
• Recent OHRP interpretation of federal regs
  indicate law authorizing NOK to consent to
  medical procedures may translate to research
  context

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Children

• Regulations 45 CFR 46.404-408 mandate favorable
  risk/benefit ratio for research with children
• Permission from parent or legal guardian assent
  from child
• Information must be presented in language
  appropriate for the age of the child
• Explicitly delineate steps of the research
• Length of each visit or procedure should be
  minimized and frequent breaks should be offered
• Preparation for procedures e.g. practice MRI

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Difficult/Sensitive Matters Involving Children or
Elderly

• In the course of research with children or other
  vulnerable subjects like the elderly, researchers
  may discover sensitive information about subjects
  that is not research related e.g., sexual
  activity, STDs, use of illegal substances and
  child or elder abuse.
• Investigators need to think about how they will
  handle such situations should they arise
• Permission/assent forms should describe plans for
  disclosure or non-disclosure of such information
  to parents, legal authorities and subjects
  themselves
• Reporting requirements apply whenever child or
  elder abuse is discovered and for certain diseases

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Categories of Vulnerable Subjects

• Institutional or Deferential
• Prisoners, students and employees
• Protections
• No inappropriate or excessive incentives to
  enroll
• Keep institution from knowing identity of
  participants
• Informed consent state clearly that participation
  is voluntary, without authority figures present,
  protections in place to prevent retaliation
• Recruitment procedures should not involve direct
  solicitation by superiors

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Categories of Vulnerable Subjects

• Medical
• Terminally ill subjects
• Protections
• Consent form states clearly the potential risks
  and benefits and characterizes the potential
  benefits appropriately
• Impartial third party perform IC and/or use
  patient advocate, consent monitor
• Potential subjects should not be approached re
  participation immediately after diagnosis or
  after theyve learned a standard treatment has
  failed

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Categories of Vulnerable Subjects

• Economic
• Dependent or impoverished subjects
• Protections
• Set economic compensation at meaningful level
  that compensates subject for his/her time, but
  not so great it becomes unduly influential
• Consider alternatives to economic compensation
• Make the risks to the subjects clear in the
  consent form

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Categories of Vulnerable Subjects

• Social
• Minorities (includes non-English speaking
  persons)
• Protections
• Keep data strictly confidential
• Consider whether study design could incorporate
  participants from all segments of society
• Consult with community and include
  representatives of this group in study design and
  oversight to reduce potential for stereotyping
  and stigmatization
• Translated ICF, and translator present for IC
  process (not family member), include provisions
  for continued communication

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Re-consent Process

• Consent is an ongoing process
• Reassess vulnerability and take steps to protect
  subjects
• Reassess capacity

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Conclusion

• Ethical research is guided by the principles of
  justice, respect for persons, and beneficence.
  Vulnerable subjects should be included but also
  deserve special protections. Think carefully
  about the populations you plan to include in your
  research and take steps to ensure their rights
  and welfare are protected.

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Further Guidance

• For the Code of Federal Regulations see
  http//www.hhs.gov/ohrp/humansubjects/guidance/45
  cfr46.htm
• For other guidance regarding human subject
  protections see http//www.hhs.gov/ohrp/
• Human Subjects Protection Training
  http//info.med.yale.edu/irbtraining/

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References

• OHRP http//www.hhs.gov/ohrp/
• University of Connecticut http//www.uconn.edu/
• University of Michigan http//www.umich.edu/