Protection of Vulnerable
Subjects in Research
Tracy Rightmer, J.D.
Compliance Manager
Human Investigation Committee
Yale University School of Medicine
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
Ethical Principles of
Research

Justice

Respect of Persons

Beneficence
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
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)
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
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
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
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
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
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
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
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
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
Re-consent Process
 Consent
is an ongoing process
 Reassess vulnerability and take
steps to protect subjects
 Reassess capacity
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.
Further Guidance



For the Code of Federal Regulations
see:
http://www.hhs.gov/ohrp/humansubje
cts/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/
References



OHRP
http://www.hhs.gov/ohrp/
University of Connecticut
http://www.uconn.edu/
University of Michigan
http://www.umich.edu/