1 informed consent bernard lo, m.d. august 13, 2009
TRANSCRIPT
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Informed consent
Bernard Lo, M.D.
August 13, 2009
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Anyone doing project using
Existing data? Medical records Previous research dataset
Existing biological materials?
Using genomic analyses?
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Questions for audience
After signing consent forms, do most
participants understand key features of
study?
Do IRB modifications improve
consent?
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Outline for today
What does informed and voluntary
consent require?
How can consent be improved?
What are exceptions to consent? Why are some exceptions problematic?
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Why is consent needed?
Compared to clinical care Risks and benefits uncertain Risk/benefit balance less favorable Purpose is not to benefit participants
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Rationale for informed consent
Respect for values and choices of
subjects
Deter research with unacceptable risks
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Federal requirements for research
Review by IRB
Risks / benefits acceptable Risks must be minimized
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Federal requirements for research
Informed and voluntary consent Concerns about undue inducement if
payment Exceptions to consent
• Not capable of consent (children, adults who lack decision-making capacity)
• Impracticable to obtain consent
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1. HIV prevention trial
RCT of diaphragm + gel vs. diaphragm
+ placebo in women in Africa at risk for
HIV infection Both arms receive free condoms
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What must researchers disclose?
Nature and purpose of research
Research procedures, risks, benefits Unforeseeable risks
Participation voluntary, may
discontinue
IRB template
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Why is informed consent difficult?
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Why is informed consent difficult?
Participants commonly misunderstand Not understand how RCT differs from
clinical care Believe that study interventions are
• Standard therapy
• Best treatment for condition
• No additional risks
• For their personal benefit
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Why is informed consent difficult?
Participants commonly misunderstand Basic features of trial design
• May be in control group• Randomization• Therapeutic options restricted by study design
rather than individualized for them
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Why is informed consent difficult?
Vulnerable participants Low health literacy, low literacy Poverty, few options
Cultural context No informed consent in clinical care No acknowledgement of medical
uncertainty
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How can informed consent be enhanced?
Empirical studies Spend more time talking to participants Questions and feedback Shorter, simpler consent forms Multimedia -- mixed evidence
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How can informed consent be enhanced?
Practical suggestions Take point of view of participant Use simple language that 8th grader can
understand Explain how RCT differs from clinical care Invite questions
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How can informed consent be enhanced?
Focus on comprehension by
participant, not consent forms Administer questionnaire to ensure
appreciation of key aspects of study
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What should participants comprehend?
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What should participants comprehend?
Could still get HIV
Don’t know whether intervention works
May not get active intervention
Keep using condoms every time
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What should participants comprehend?
May refuse to participate
May withdraw from study
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Questions?
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Why is voluntary consent difficult?
Hard to say no to persons in power Defer to husband or father Relationship to investigator
• Student
• Employee
Undue monetary influence
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Voluntary and free consent
Historical concerns Prisoners, institutionalized persons Excluded from research
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Voluntary and free consent
Undue influence
Coercion = threat Threat to discharge from clinic Unspoken concerns in students, employees,
patients of investigator
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Research participants who may lack decision-making capacity
Persons receiving CPR, ICU care
Severe dementia
Severe psychiatric illness
Children
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Research participants who may lack decision-making capacity
Not appreciate risks
Not able to refuse
Might be subjected to risks that
competent persons would refuse
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Options if lack decision-making capacity
Exclude from trials But lack evidence safety and effectiveness
of treatments
Additional protections
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Research participants who may lack decision-making capacity
Formal assessment of decision-making
capacity
Permission from surrogate
Assent of participant
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Additional protections for vulnerable partcipants
Closer monitoring for adverse effects
Subject advocate who can withdraw
participant from study
IRB include persons familiar with the
condition that impairs capacity
Research advance directives
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Questions for audience
Without consent, may researcher
Use EMR to study whether patients
have worse outcomes if admitted over
weekend?
Use leftover cancer tissue to identify
prognostic markers?
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Ethical rationale for exception from consent
Very low risk No physical risks Confidentiality the main risk Cannot be breached if not identifiable
Benefits of research >> risks
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Ethical rationale for exception from consent
Impracticable to get consent Could not carry out important study
No one would or should object if asked Leftover tubes of blood Cancer tisssue
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IRB approval for exception to consent
1. Not human subjects research No IRB review Self-certification form
2. Exempt from human subjects
regulations Exempt form reviewed at CHR
3. Qualifies for waiver
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What is human subjects research?
Interact with person OR
Use identifiable private information Not human subjects research if data and
materials cannot be identified Examples of tissue from cancer surgery
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What is human subjects research?
Data and materials are coded but
researcher cannot access keys to code
None of 18 HIPAA identifiers Code may be retained by database or
biobank
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2. Exempt from federal regulations
Most survey and interview research Unless subjects can be identified and
responses could put respondents at risk• Not if ask about illegal activities, sensitive or
private topics
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2. Exempt from federal regulations
Existing data or materials Publicly available Existing data or specimens if researcher
records information in manner than subjects cannot be identified
• Can look at medical records
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3. Waiver of consent
Minimal risk
Not adversely affect rights and welfare
Could not be practicably carried out
IRB may allow identifiable data to be
used without consent Use identifiers to link different databases
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Questions?
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Questions for audience
May research be carried out on de-
identified materials without consent?
Whole genomic sequence?
Derive new hESC line from
“abandoned” frozen embryos?
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How are embryos different from other tissue?
Some believe embryos are persons
Emotional and symbolic significance
Some may prefer to discard rather than
donate for research
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Exception to consent not justified
Some donors known to object Even if no physical risk, not identifiable Materials considered sensitive, have
symbolic value Object to certain types of research
Respect minority of donors who have
strong objections
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Use of reproductive materials without consent
Legally permissible
Ethically problematic
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Concerns about whole genome sequencing
Subject may consider information very
personal, may not want others to know Even if identity not explicitly known
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Concerns about whole genome sequencing
De-identified sample may be re-
identified Genomic sequence widely shared Confidentiality may be breached
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Re-identification in whole genomic sequencing
Reference samples in forensic
databases DOJ has 7.3 million profiles STRs at 13 locations Full genome sequence identifies these STRs Re-identification low probability, high
impact
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Re-identification in whole genomic sequencing
Reference samples with SNPs at
recreation genomics companies
Companies not subject to HIPAA If bankrupt, confidentiality agreements
voided
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What are the ethical dilemmas?
When materials collected, whole
genome sequencing not envisaged Donors not consider this possibility
If donors had been told, would they
object?
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Options
Re-consent participants? Selection bias in sample Make research much more difficult
Strict security and confidentiality
safeguards How share sequence with other
researchers?
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Take home message
Consent is important but challenging
Important exceptions to consent
justified But some exceptions problematic
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Genome-wide association studies
Specimens and clinical data in
biobanks General consent for “research” at time of
surgery Consent for “cancer” or “genetics” research
Researchers get anonymized materials
without consent
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