1 Informed consent Bernard Lo, M.D. August 13, 2009

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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?

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?

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

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

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?

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?

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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