Protection of Vulnerable Subjects in Research

1. Protection of Vulnerable Subjects in Research Tracy Rightmer, J.D. Compliance Manager Human Investigation Committee Yale University School of Medicine

2. 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

3. Ethical Principles of Research • Justice • Respect of Persons • Beneficence

4. 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

5. 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)

6. 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

7. 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

8. Current Controversies • No law in CT that confers the right to consent to medical procedures on the patient’s 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

9. 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

10. 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

11. 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

12. 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 they’ve learned a standard treatment has failed

13. 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

14. 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

15. Re-consent Process • Consent is an ongoing process • Reassess vulnerability and take steps to protect subjects • Reassess capacity

16. 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.

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

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