January 9, 2013

Ethical Considerations in Substance Abuse and Addiction Research

Ethical Considerations in Substance Abuse and Addiction Research

Sandra L. Alfano, Pharm.D.Chair, HIC II and IVResearch Scientist, General Internal Medicine

Sandra L. Alfano, Pharm.D.Chair, HIC II and IVResearch Scientist, General Internal Medicine

January 9, 2013

ObjectivesObjectives

• Understand the ethical foundations of human subjects research

• Explore the conflicts and tension between and among the principles and roles of researchers

• Review special considerations in doing research with human subjects with substance abuse or addiction disorders

• Delineate additional safeguards that may be necessary when involving vulnerable populations in research

• Understand the ethical foundations of human subjects research

• Explore the conflicts and tension between and among the principles and roles of researchers

• Review special considerations in doing research with human subjects with substance abuse or addiction disorders

• Delineate additional safeguards that may be necessary when involving vulnerable populations in research

January 9, 2013

Ethical Foundations of Human Subjects ResearchEthical Foundations of Human Subjects Research

• Nuremberg Code (1949)

– Nazi war crimes

– Code stresses voluntary informed consent

– Idea of ‘do no harm’

• Nuremberg Code (1949)

– Nazi war crimes

– Code stresses voluntary informed consent

– Idea of ‘do no harm’

January 9, 2013

Ethical Foundations of Human Subjects ResearchEthical Foundations of Human Subjects Research

• Declaration of Helsinki (1964, last updated 2008)

• http://www.wma.net/e/policy/b3.htm

– World Medical Association’s best known

policy statement

– Distinction between therapeutic and non-

therapeutic research

– Best care standard raises problems with

placebo controls; 2002 clarification allows

some placebo use

• Declaration of Helsinki (1964, last updated 2008)

• http://www.wma.net/e/policy/b3.htm

– World Medical Association’s best known

policy statement

– Distinction between therapeutic and non-

therapeutic research

– Best care standard raises problems with

placebo controls; 2002 clarification allows

some placebo use

Helsinki, placebosHelsinki, placebos

• The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances:

– The use of placebo, or no treatment, is acceptable in

studies where no current proven intervention exists;

or

– Where for compelling and scientifically sound

methodological reasons the use of placebo is necessary

to determine the efficacy or safety of an intervention

and the patients who receive placebo or no treatment

will not be subject to any risk of serious or irreversible

harm. Extreme care must be taken to avoid abuse of

this option

• The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances:

– The use of placebo, or no treatment, is acceptable in

studies where no current proven intervention exists;

or

– Where for compelling and scientifically sound

methodological reasons the use of placebo is necessary

to determine the efficacy or safety of an intervention

and the patients who receive placebo or no treatment

will not be subject to any risk of serious or irreversible

harm. Extreme care must be taken to avoid abuse of

this optionJanuary 9, 2013

January 9, 2013

Ethical Foundations of Human Subjects ResearchEthical Foundations of Human Subjects Research

• Outrage over Tuskegee Syphilis Trial

• National Research Act enacted in 1974

• Established National Commission for Protection of Human Subjects of Biomedical and Behavioral Research

• Issued Belmont Report (1979)

• Established the IRB system for regulating research

• Outrage over Tuskegee Syphilis Trial

• National Research Act enacted in 1974

• Established National Commission for Protection of Human Subjects of Biomedical and Behavioral Research

• Issued Belmont Report (1979)

• Established the IRB system for regulating research

January 9, 2013

INSTITUTIONAL REVIEW BOARDINSTITUTIONAL REVIEW BOARD

• Responsible for protecting the rights and welfare of human subjects participating in research studies

• Ensure research is conducted in accordance with accepted ethical standards

• Responsible for protecting the rights and welfare of human subjects participating in research studies

• Ensure research is conducted in accordance with accepted ethical standards

January 9, 2013

Role of the IRBsRole of the IRBs

• Each biomedical IRB meets weekly

• Reviews and approves every research protocol involving human subjects, along with consent forms and all materials shared with subjects

• Approval must be in place before the research can begin, and each protocol must be re-approved at least once a year

• Changes to protocols must be approved prior to implementation

• Each biomedical IRB meets weekly

• Reviews and approves every research protocol involving human subjects, along with consent forms and all materials shared with subjects

• Approval must be in place before the research can begin, and each protocol must be re-approved at least once a year

• Changes to protocols must be approved prior to implementation

January 9, 2013

Belmont Report Ethical PrinciplesBelmont Report Ethical Principles

• Respect for Persons

• Beneficence

• Justice

• Contains the ethical principles upon which the U.S. Federal regulations for protection of human subjects are based

• Respect for Persons

• Beneficence

• Justice

• Contains the ethical principles upon which the U.S. Federal regulations for protection of human subjects are based

January 9, 2013

Belmont Report Ethical PrinciplesBelmont Report Ethical Principles

• Provide an analytical framework that will guide resolution of ethical problems

• Acknowledges tensions between principles, need for trade offs

• Provide an analytical framework that will guide resolution of ethical problems

• Acknowledges tensions between principles, need for trade offs

January 9, 2013

First Ethical Principle: Respect for PersonsFirst Ethical Principle: Respect for Persons

• Individuals should be treated as an autonomous agents; avoid paternalism; let subject make decision about what will or will not happen

• However, not every human being is capable of self-determination. Therefore, those with diminished autonomy should be protected

• Voluntary participation

• Individuals should be treated as an autonomous agents; avoid paternalism; let subject make decision about what will or will not happen

• However, not every human being is capable of self-determination. Therefore, those with diminished autonomy should be protected

• Voluntary participation

January 9, 2013

Respect for PersonsRespect for Persons

• Demonstrated through informed consent

• Capacity

• Information, comprehension, voluntariness

• Demonstrated through informed consent

• Capacity

• Information, comprehension, voluntariness

January 9, 2013

Four Elements of ConsentFour Elements of Consent

• Informing

– Convey information

– Not a legal document, avoid legalese

• Assessing comprehension

• Assessing autonomy

• Consenting

– Agreeing to be a subject

• Informing

– Convey information

– Not a legal document, avoid legalese

• Assessing comprehension

• Assessing autonomy

• Consenting

– Agreeing to be a subject

January 9, 2013

Consent issuesConsent issues

• Informed consent is not only a document.

• It is a process: a dialogue between the researcher and the subject. Information exchange needs to take place before, during, and sometimes after the study.

• Information, comprehension, and voluntariness.

• Intended to facilitate understanding.

• Informed consent is not only a document.

• It is a process: a dialogue between the researcher and the subject. Information exchange needs to take place before, during, and sometimes after the study.

• Information, comprehension, and voluntariness.

• Intended to facilitate understanding.

January 9, 2013

Consent Issues: InformationConsent Issues: Information

• Purpose of the research

• Research procedures/expectations explained

• Known (and unknown) risks explained with possible consequences

• Economic considerations (impact on individual)

• Benefits stated reasonably in relation to phase of protocol

• Alternatives noted to inform decision

• Procedures to protect privacy and ensure confidentiality

• Purpose of the research

• Research procedures/expectations explained

• Known (and unknown) risks explained with possible consequences

• Economic considerations (impact on individual)

• Benefits stated reasonably in relation to phase of protocol

• Alternatives noted to inform decision

• Procedures to protect privacy and ensure confidentiality

January 9, 2013

Consent Issues: ComprehensionConsent Issues: Comprehension

• The manner and context in which information is conveyed are as important as the information itself

• Organized presentation of the material

• Providing private, appropriate space, and sufficient time to ask questions and to consider participation

• Investigator getting consent must assure comprehension

• The manner and context in which information is conveyed are as important as the information itself

• Organized presentation of the material

• Providing private, appropriate space, and sufficient time to ask questions and to consider participation

• Investigator getting consent must assure comprehension

January 9, 2013

Consent Issues: VoluntarinessConsent Issues: Voluntariness

• Begin with an invitation to participate

• Free of coercion (overt threat of harm)

• Free of undue influence (offer or promise of excessive or improper reward)

• Participant is free to decline or to withdraw at any time without repercussions

• Begin with an invitation to participate

• Free of coercion (overt threat of harm)

• Free of undue influence (offer or promise of excessive or improper reward)

• Participant is free to decline or to withdraw at any time without repercussions

January 9, 2013

Consent issuesConsent issues

• Be sure that the informed consent process is not misleading

• Benefit is not overstated

• Risk/Benefit ratio is carefully considered

• Be sure that the informed consent process is not misleading

• Benefit is not overstated

• Risk/Benefit ratio is carefully considered

January 9, 2013

Process of consentProcess of consent

• Ensure autonomy: begin with an invitation to participate, ensure there is no coercion or undue influence (remove impediments)

• Allow ample time for considered response, take home and sharing

• Consider breaking up the material into multiple sessions

• Pay attention to verbal and non-verbal cues

• Verify understanding, comprehension

• Use of witnesses or consent monitors

• Consider use of quiz

• Ensure autonomy: begin with an invitation to participate, ensure there is no coercion or undue influence (remove impediments)

• Allow ample time for considered response, take home and sharing

• Consider breaking up the material into multiple sessions

• Pay attention to verbal and non-verbal cues

• Verify understanding, comprehension

• Use of witnesses or consent monitors

• Consider use of quiz

January 9, 2013

Process of consentProcess of consent

• Process of consent should be described in the protocol, including time, place, and who will do it

• Involves discussion as an educational interchange (not handing person the form to read)

• Avoid jargon, medical acronyms

• Use the reasonable person standard for amount of information to be shared

• Solicit consent in advance, not day of surgery

• Process of consent should be described in the protocol, including time, place, and who will do it

• Involves discussion as an educational interchange (not handing person the form to read)

• Avoid jargon, medical acronyms

• Use the reasonable person standard for amount of information to be shared

• Solicit consent in advance, not day of surgery

BackgroundBackground

“Confluence of several considerations, including perceived gaps in the federal system for the protection of human subjects; historical and contemporary cases in which the protection of human subjects appears to be inadequate; and the need to ensure that research designed to develop better treatments for mental disorders can proceed with full public confidence in its ethical framework. The continuing vitality of the research enterprise ultimately depends on the public’s trust that appropriate ethical constraints are in place and will be followed.”

 http://govinfo.library.unt.edu/nbac/capacity/TOC.htm

“Confluence of several considerations, including perceived gaps in the federal system for the protection of human subjects; historical and contemporary cases in which the protection of human subjects appears to be inadequate; and the need to ensure that research designed to develop better treatments for mental disorders can proceed with full public confidence in its ethical framework. The continuing vitality of the research enterprise ultimately depends on the public’s trust that appropriate ethical constraints are in place and will be followed.”

 http://govinfo.library.unt.edu/nbac/capacity/TOC.htm

January 9, 2013

BackgroundBackground

• Regulatory citation:

‘When some or all of the subjects are likely to

be vulnerable to coercion or undue influence,

including those with cognitive limitations, the

IRB must be sure that additional safeguards

have been included in the study to protect the

rights and welfare of these subjects {45 CFR

46.111 (b)}

• Regulatory citation:

‘When some or all of the subjects are likely to

be vulnerable to coercion or undue influence,

including those with cognitive limitations, the

IRB must be sure that additional safeguards

have been included in the study to protect the

rights and welfare of these subjects {45 CFR

46.111 (b)}

January 9, 2013

DefinitionsDefinitions

• Adults with decisional impairment:‘Limited decision making capacity covers a broad

spectrum. A healthy person in shock may be temporarily decisionally impaired. Another may have been severely mentally retarded since birth, while yet a third who has schizophrenia may have fluctuating capacity. Researchers should be sensitive to the differing levels of capacity and use assessment methods tailored to the specific situation. Further, researchers should carefully consider the timing of assessment to avoid periods of heightened vulnerability when individuals may not be able to provide valid informed consent.’

http://grants.nih.gov/grants/policy/questionablecapacity.htm

• Adults with decisional impairment:‘Limited decision making capacity covers a broad

spectrum. A healthy person in shock may be temporarily decisionally impaired. Another may have been severely mentally retarded since birth, while yet a third who has schizophrenia may have fluctuating capacity. Researchers should be sensitive to the differing levels of capacity and use assessment methods tailored to the specific situation. Further, researchers should carefully consider the timing of assessment to avoid periods of heightened vulnerability when individuals may not be able to provide valid informed consent.’

http://grants.nih.gov/grants/policy/questionablecapacity.htm

January 9, 2013

Assessment of CapacityAssessment of Capacity

• Society has not decided what degree of impairment counts as a lack of capacity

• Case by case basis

• Protocol-specified method

• Quizzes, consent monitor, formal assessment via Mc-CAT, etc

• Society has not decided what degree of impairment counts as a lack of capacity

• Case by case basis

• Protocol-specified method

• Quizzes, consent monitor, formal assessment via Mc-CAT, etc

January 9, 2013

Transitional capacityTransitional capacity

• Fluctuating: consider delaying consent process, or re-consenting

• Progressive: consider using advance directives while capacity is retained

• Fluctuating: consider delaying consent process, or re-consenting

• Progressive: consider using advance directives while capacity is retained

January 9, 2013

January 9, 2013

Second Ethical Principle: BeneficenceSecond Ethical Principle: Beneficence

• Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being (an obligation)

• Two general rules

– Do not knowingly cause harm

– Maximize possible benefits/minimize possible harms

• Are the risks presented justified?

• Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being (an obligation)

• Two general rules

– Do not knowingly cause harm

– Maximize possible benefits/minimize possible harms

• Are the risks presented justified?

January 9, 2013

BeneficenceBeneficence

• Not exactly the Hippocratic Oath

• Even avoiding harm requires learning what is harmful

• Researchers and their IRBs must decide with imperfect knowledge when it is justifiable to seek certain benefits despite the risks involved, versus when the potential benefits are so small that the risks outweigh the benefits

• Not exactly the Hippocratic Oath

• Even avoiding harm requires learning what is harmful

• Researchers and their IRBs must decide with imperfect knowledge when it is justifiable to seek certain benefits despite the risks involved, versus when the potential benefits are so small that the risks outweigh the benefits

January 9, 2013

BeneficenceBeneficence

• Initial analysis as part of approval of the proposed protocol: sound scientific design, and favorable risk:benefit assessment

• Ongoing monitoring of risks and benefits throughout the study (via data and safety monitoring plan)

• Initial analysis as part of approval of the proposed protocol: sound scientific design, and favorable risk:benefit assessment

• Ongoing monitoring of risks and benefits throughout the study (via data and safety monitoring plan)

January 9, 2013

Research RisksResearch Risks

• Research by its very nature involves risk

• Subjects may be exposed to risk and may be harmed

• Obligation to minimize probability of harm, maximize potential benefits and never knowingly cause (permanent) injury

• IRBs must ensure risks are reasonable in relation to benefits expected; an acceptable risk:benefit relationship must exist for a protocol to be approved

• Research by its very nature involves risk

• Subjects may be exposed to risk and may be harmed

• Obligation to minimize probability of harm, maximize potential benefits and never knowingly cause (permanent) injury

• IRBs must ensure risks are reasonable in relation to benefits expected; an acceptable risk:benefit relationship must exist for a protocol to be approved

January 9, 2013

Research RisksResearch Risks

• Investigators must identify risks and objectively estimate magnitude and likelihood

• Both the risks and the benefits should be presented to prospective subjects in the consent form

• Vulnerable subjects deserve special protections; may be reasonable to place limits on the level of risk to which these subjects may be exposed

• Investigators must identify risks and objectively estimate magnitude and likelihood

• Both the risks and the benefits should be presented to prospective subjects in the consent form

• Vulnerable subjects deserve special protections; may be reasonable to place limits on the level of risk to which these subjects may be exposed

January 9, 2013

Research DesignResearch Design

• Need reasonable precautions when designing a study

• Good design, data and safety monitoring, and selection of least susceptible subjects

• Identify opportunities for risk exposure

• Need reasonable precautions when designing a study

• Good design, data and safety monitoring, and selection of least susceptible subjects

• Identify opportunities for risk exposure

January 9, 2013

Risks in Consent formRisks in Consent form

• What to disclose?

• At least what a “reasonable volunteer” would find important to decision making

• Reasonable Man Theory: the reasonable person is a hypothetical, rational, reasonably intelligent individual who is intended to represent a sort of ‘average’ citizen

• How would a reasonable person act under the circumstances?

• What to disclose?

• At least what a “reasonable volunteer” would find important to decision making

• Reasonable Man Theory: the reasonable person is a hypothetical, rational, reasonably intelligent individual who is intended to represent a sort of ‘average’ citizen

• How would a reasonable person act under the circumstances?

January 9, 2013

Minimizing RisksMinimizing Risks

• Highly competent research team

• Well designed study

• Procedures that have the least likelihood of harm

• Adequate monitoring

• Adverse events quickly identified, managed and reported

• Privacy and confidentiality protected

• Highly competent research team

• Well designed study

• Procedures that have the least likelihood of harm

• Adequate monitoring

• Adverse events quickly identified, managed and reported

• Privacy and confidentiality protected

January 9, 2013

Risk:Benefit AssessmentRisk:Benefit Assessment

• Probability and magnitude of possible harms

Versus

• Anticipated benefits

• Imperfect knowledge

• Probability and magnitude of possible harms

Versus

• Anticipated benefits

• Imperfect knowledge

January 9, 2013

Therapeutic MisconceptionTherapeutic Misconception

• prone to misunderstand the risks and potential benefits associated with participation and to have unreasonable expectations about potential individual benefits

• May lead to discounting of risks and overestimating personal benefits

• Especially problematic when treating physician is researcher as well

• prone to misunderstand the risks and potential benefits associated with participation and to have unreasonable expectations about potential individual benefits

• May lead to discounting of risks and overestimating personal benefits

• Especially problematic when treating physician is researcher as well

Risk:Benefit Assessment ApproachRisk:Benefit Assessment Approach

• In the absence of a regulatory framework, many people will adopt a model that incorporates aspects of an existing regulatory framework, such as Subpart D, Children

• In the absence of a regulatory framework, many people will adopt a model that incorporates aspects of an existing regulatory framework, such as Subpart D, Children

January 9, 2013

January 9, 2013

Third Ethical Principle: JusticeThird Ethical Principle: Justice

• The Belmont Report tells us, “An injustice occurs when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly…”

• Ethical Obligation: fair sharing of burdens and benefits

• Requirement: Equitable selection of research subjects; fairness in inclusion and exclusion criteria

• The Belmont Report tells us, “An injustice occurs when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly…”

• Ethical Obligation: fair sharing of burdens and benefits

• Requirement: Equitable selection of research subjects; fairness in inclusion and exclusion criteria

January 9, 2013

JusticeJustice

• Fair distribution of the burdens and the benefits of research

• Must be borne by some but not all members of a society

• ‘Representative’: should not select for convenience/ease

• Good research design

• Fair distribution of the burdens and the benefits of research

• Must be borne by some but not all members of a society

• ‘Representative’: should not select for convenience/ease

• Good research design

January 9, 2013

JusticeJustice

• Does the research involve individuals who are unlikely to benefit from the results of the research?

• Who is likely to benefit? What connection do they have to the research subjects?

• Does the research involve individuals who are unlikely to benefit from the results of the research?

• Who is likely to benefit? What connection do they have to the research subjects?

January 9, 2013

Inclusion/Exclusion CriteriaInclusion/Exclusion Criteria

• Attributes necessary to accomplish purpose of the research

• Well defined criteria increase the likelihood of producing reliable and reproducible results, decrease likelihood of harm, and guard against exploitation of vulnerable populations

• Attributes necessary to accomplish purpose of the research

• Well defined criteria increase the likelihood of producing reliable and reproducible results, decrease likelihood of harm, and guard against exploitation of vulnerable populations

January 9, 2013

Conflicts between PrinciplesConflicts between Principles

• One does not ‘trump’ the others

• Weighing and prioritizing conflicting ethical norms is a difficult task

• Discussion, debate, struggle

• One does not ‘trump’ the others

• Weighing and prioritizing conflicting ethical norms is a difficult task

• Discussion, debate, struggle

January 9, 2013

IRB Approval considerationsIRB Approval considerations

– Risk:Benefit ratio reasonable?

– Selection of subjects equitable?

– Appropriate informed consent?

– Data collected adequately monitored?

– Adequate provisions to protect privacy and maintain confidentiality of data/information?

– Risks are minimized?

– Additional safeguards for those who need it (children, prisoners, etc.)?

– Risk:Benefit ratio reasonable?

– Selection of subjects equitable?

– Appropriate informed consent?

– Data collected adequately monitored?

– Adequate provisions to protect privacy and maintain confidentiality of data/information?

– Risks are minimized?

– Additional safeguards for those who need it (children, prisoners, etc.)?

January 9, 2013

How are the principles applied?How are the principles applied?

• Careful review of the protocol

– Inclusion/Exclusion Criteria

– DSMP and Stopping Rules

– Risks/Benefits

– Consent Process

– In Case of Injury Section

• Careful review of the protocol

– Inclusion/Exclusion Criteria

– DSMP and Stopping Rules

– Risks/Benefits

– Consent Process

– In Case of Injury Section

January 9, 2013

How are the principles applied?How are the principles applied?

• Careful review of the consent form

– Purpose

– Research Procedures

– Risks

– Anticipated Benefits

– Alternative Treatments

– Voluntariness

– Confidentiality

• Careful review of the consent form

– Purpose

– Research Procedures

– Risks

– Anticipated Benefits

– Alternative Treatments

– Voluntariness

– Confidentiality

January 9, 2013

RecruitmentRecruitment

• Advertisements

• Internet

• Registries

• Targeted letters

• Phone calls

• All considered beginning of consent process

• IRB must review and approve methodology and content

• Advertisements

• Internet

• Registries

• Targeted letters

• Phone calls

• All considered beginning of consent process

• IRB must review and approve methodology and content

January 9, 2013

Economic Considerations and ICOIEconomic Considerations and ICOI

• Inform participants about costs of participation, and payments to made (if any)

• Costs of research should be clearly differentiated from costs of standard care

• Tell them what will happen in case of injury (who will pay)

• Inform participants about costs of participation, and payments to made (if any)

• Costs of research should be clearly differentiated from costs of standard care

• Tell them what will happen in case of injury (who will pay)

January 9, 2013

Additional protectionsAdditional protections

• For those who need them

• Vulnerability of a given population or person sometimes changes

• For those who need them

• Vulnerability of a given population or person sometimes changes

January 9, 2013

Vulnerability Vulnerability

• A condition, either permanent or temporary

• Substantial inability to protect one’s own interests

• Interferes with autonomy or decision-making capacity

• Personal circumstances may make them subject to intimidation or exploitation

• A condition, either permanent or temporary

• Substantial inability to protect one’s own interests

• Interferes with autonomy or decision-making capacity

• Personal circumstances may make them subject to intimidation or exploitation

January 9, 2013

Special considerations in human subjects research: Vulnerable subjectsSpecial considerations in human subjects research: Vulnerable subjects

• “…vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons…”

• “…additional safeguards have been included in the study to protect the rights and welfare of these subjects.”

Subparts B, C, D

• “…vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons…”

• “…additional safeguards have been included in the study to protect the rights and welfare of these subjects.”

Subparts B, C, D

January 9, 2013

Examples of Potentially Vulnerable PopulationsExamples of Potentially Vulnerable Populations

• Clinic population

• Prisoners

• Critically ill

• Students who need money

• Homeless who need money

• Third world countries who need care

• Clinic population

• Prisoners

• Critically ill

• Students who need money

• Homeless who need money

• Third world countries who need care

January 9, 2013

Additional SafeguardsAdditional Safeguards

• IRB may place limits on level of risk to which subjects may be exposed

• IRB may require consent monitor, subject advocate, use of quizzes to assess comprehension, require a DSMB, introduce a delay in consenting process

• Substituted judgment?

• Paternalism?: ‘Father (doctor, researcher, IRB) knows best’

• IRB may place limits on level of risk to which subjects may be exposed

• IRB may require consent monitor, subject advocate, use of quizzes to assess comprehension, require a DSMB, introduce a delay in consenting process

• Substituted judgment?

• Paternalism?: ‘Father (doctor, researcher, IRB) knows best’

January 9, 2013

Special considerations in human subjects research: Vulnerable subjectsSpecial considerations in human subjects research: Vulnerable subjects

Proposed Risk:Benefit assessment approach

• Categories of approval tied to risk and benefit of the protocol

• no more than minimal risk

• greater than minimal risk, but potential for direct benefit to the subject

• Greater than minimal risk without potential for direct benefit: set parameters for level of risk and necessary societal benefit

• Not otherwise approvable : set parameters for alternate review mechanism

Proposed Risk:Benefit assessment approach

• Categories of approval tied to risk and benefit of the protocol

• no more than minimal risk

• greater than minimal risk, but potential for direct benefit to the subject

• Greater than minimal risk without potential for direct benefit: set parameters for level of risk and necessary societal benefit

• Not otherwise approvable : set parameters for alternate review mechanism

January 9, 2013

Special considerations in human subjects research: Vulnerable subjectsSpecial considerations in human subjects research: Vulnerable subjects

Decisionally impaired

• Example: patient with Alzheimer’s

• Assess capacity to consent

• Certain populations may be predisposed to impairment (e.g. brain mets, new devastating diagnosis, etc)

• Precautions in place to add protections, such as surrogate consent, consent monitor, independent evaluator

• Precautions required are tied to risk level of protocol

Decisionally impaired

• Example: patient with Alzheimer’s

• Assess capacity to consent

• Certain populations may be predisposed to impairment (e.g. brain mets, new devastating diagnosis, etc)

• Precautions in place to add protections, such as surrogate consent, consent monitor, independent evaluator

• Precautions required are tied to risk level of protocol

January 9, 2013

Other potentially vulnerable subjectsOther potentially vulnerable subjects

Non-English speaking

• Principle of Justice: do not overly burden one group, nor exclude a group from potential benefit

• Translation issues

• Issue of ongoing communication (consent process)

Non-English speaking

• Principle of Justice: do not overly burden one group, nor exclude a group from potential benefit

• Translation issues

• Issue of ongoing communication (consent process)

Researcher InvestmentResearcher Investment

• Justification for inclusion of vulnerable subjects must be rigorous and defensible

• Cannot target vulnerable population if you can achieve the research objective through enrollment of others (Relevant principle of distributive justice)

• Justification for inclusion of vulnerable subjects must be rigorous and defensible

• Cannot target vulnerable population if you can achieve the research objective through enrollment of others (Relevant principle of distributive justice)

January 9, 2013

Researcher InvestmentResearcher Investment

• Points to Consider: additional safeguards

– Consent monitors

– Subject advocates

– Family education/consultation

– Consent process waiting period

– Use of a DSMB

• Points to Consider: additional safeguards

– Consent monitors

– Subject advocates

– Family education/consultation

– Consent process waiting period

– Use of a DSMB

January 9, 2013

Trust in researchersTrust in researchers

“No matter how many regulations are put in place or guidelines are written, and no matter how intense the scrutiny by IRBs or other authorities, there can be no substitute for the ongoing commitment by researchers and the institutions in which they work to ethically appropriate behavior throughout the research process.”

 http://govinfo.library.unt.edu/nbac/capacity/TOC.htm

“No matter how many regulations are put in place or guidelines are written, and no matter how intense the scrutiny by IRBs or other authorities, there can be no substitute for the ongoing commitment by researchers and the institutions in which they work to ethically appropriate behavior throughout the research process.”

 http://govinfo.library.unt.edu/nbac/capacity/TOC.htm

January 9, 2013

January 9, 2013

ConclusionsConclusions

• Belmont principles are the ethical underpinnings of our work

• Application of the principles to the protocol development and review process

• Tension/struggles

• Belmont principles are the ethical underpinnings of our work

• Application of the principles to the protocol development and review process

• Tension/struggles

January 9, 2013

ConclusionsConclusions

• Justice requires balancing the burdens and benefits of research among a representative sampling of society

• Vulnerability can be situational, necessitating implementation of additional safeguards to minimize potential for undue influence

• Limits on risks associated with certain vulnerable populations set by federal regulations

• Justice requires balancing the burdens and benefits of research among a representative sampling of society

• Vulnerability can be situational, necessitating implementation of additional safeguards to minimize potential for undue influence

• Limits on risks associated with certain vulnerable populations set by federal regulations