Application of Application of The Belmont Principles of The Belmont Principles of

Respect for Persons, Beneficence and Justice Respect for Persons, Beneficence and Justice

David M Asmuth, MDDavid M Asmuth, MDDivision of Infectious DiseasesDivision of Infectious DiseasesIRB Committee A ChairIRB Committee A ChairCTSC co-Director of PCIR & RKSCTSC co-Director of PCIR & RKS

Origins of Human Subject Research EthicsOrigins of Human Subject Research EthicsHippocrates (~400 B.C.)Hippocrates (~400 B.C.)

medical practice and medical ethics.medical practice and medical ethics.

physicians should “abstain from whatever is deleterious physicians should “abstain from whatever is deleterious and mischievous.”and mischievous.”

purely observational in nature, his writings did not deal with purely observational in nature, his writings did not deal with research or experimentation with human subjects and therefore research or experimentation with human subjects and therefore did not mention the principle of informed consent.did not mention the principle of informed consent.

William Beaumont (1833)William Beaumont (1833)

Oldest American document dealing with research observing Oldest American document dealing with research observing digestive phenomena through a hole in a gun-shot wound digestive phenomena through a hole in a gun-shot wound survivor’s stomach. survivor’s stomach.

Experimentation is needed; information cannot be otherwise Experimentation is needed; information cannot be otherwise obtained but the investigator must be conscientious and obtained but the investigator must be conscientious and responsible; methodological approach; no random studies.responsible; methodological approach; no random studies.

voluntary consent is necessary.voluntary consent is necessary.

discontinuation of experiment when it causes distress to the discontinuation of experiment when it causes distress to the subject.subject.

Walter Reed and the Yellow Fever Walter Reed and the Yellow Fever Experiments – Camp Lazear, Cuba: 1901Experiments – Camp Lazear, Cuba: 1901

Graduating from Medical School at the age of 18, Graduating from Medical School at the age of 18, he sought more clinical experience at Belview Hospital in he sought more clinical experience at Belview Hospital in NY and soon gained an interest in public health. When NY and soon gained an interest in public health. When Major Walter Reed and Acting Assistant Surgeons James Major Walter Reed and Acting Assistant Surgeons James

Carroll, Aristides Agramonte, and Jesse Lazear gathered on the porch of Carroll, Aristides Agramonte, and Jesse Lazear gathered on the porch of the Columbia Barracks Hospital in June of 1900 on the outskirts of the Columbia Barracks Hospital in June of 1900 on the outskirts of Havana, they designed a series of controlled experiments to learn Havana, they designed a series of controlled experiments to learn whether mosquitoes were the vector for the appalling plague that was whether mosquitoes were the vector for the appalling plague that was yellow fever.  At the time, yellow fever was responsible for thousands of yellow fever.  At the time, yellow fever was responsible for thousands of deaths in the Caribbean and along the coast of the US.deaths in the Caribbean and along the coast of the US.

After 4 unsuccessful attempts to transmit the disease by After 4 unsuccessful attempts to transmit the disease by mosquitoes that had fed on infected individuals, Lazear and Carroll mosquitoes that had fed on infected individuals, Lazear and Carroll became infected when the mosquitoes had been allowed to ‘mature’ for became infected when the mosquitoes had been allowed to ‘mature’ for 12 days prior to the feedings.12 days prior to the feedings.Reed was in Washington at the Reed was in Washington at the time of these ‘successful’ exper-time of these ‘successful’ exper-iments and after the death of iments and after the death of Lazear, withdrew his plans to Lazear, withdrew his plans to be a subject.be a subject.

Antonio BeninoAntonio Benino       The undersigned, Antonio Benino being more than twenty-five years of age, native of Cerceda, in the province of Corima, the son of Manuel Benino and Josefa Castro here states by these presents, being in the being in the enjoyment and exercise of his own very free will, that he enjoyment and exercise of his own very free will, that he consents to submit himself to experiments for the purpose of consents to submit himself to experiments for the purpose of determining the methods of transmission of yellow fever,determining the methods of transmission of yellow fever, made upon his person by the Commission appointed for this purpose by the Secretary of War of the United States, and that he gives his consent to undergo the said experiments for the reasons and under the conditions below stated.        The undersigned understands perfectly well that in case of The undersigned understands perfectly well that in case of the development of yellow fever in him, that he endangers his the development of yellow fever in him, that he endangers his life to a certain extent but it being entirely impossible for him to life to a certain extent but it being entirely impossible for him to avoid the infection during his stay in this island, he prefers to avoid the infection during his stay in this island, he prefers to take the chance of contracting it intentionally in the belief that take the chance of contracting it intentionally in the belief that he will receive from the said Commission the greatest care and he will receive from the said Commission the greatest care and the most skillful medical service.the most skillful medical service.       It is understood that at the completion of these experiments, with- in two months from this date, the undersigned will receive the sum the undersigned will receive the sum of $100 in American gold and that in case of his contracting of $100 in American gold and that in case of his contracting yellow fever at any time during his residence in this camp, he yellow fever at any time during his residence in this camp, he will receive in addition to that sum a further sum of $100 in will receive in addition to that sum a further sum of $100 in American goldAmerican gold, , upon his recovery and that in case of his death because of this disease, the Commission will transmit the said sum (two hundred American dollars) to the person whom the undersigned shall designate at his convenience.    The undersigned binds himself not to leave the bounds of this camp during the period of the experiments and will forfeit all right to the benefits named in this contract if he breaks this agreement.    And to bind himself he signs this paper in duplicate, in the Experimental Camp, near Quemados, Cuba, on the 26th day of November nineteen hundred.The contracting party,Antonio Benino On the part of the Commission: Walter Reed - Maj. & Surg., U.S.A.

The 1900 Prussian DirectiveThe 1900 Prussian Directive

Response to public debate on human subject experimentation that Response to public debate on human subject experimentation that included work by Amauer Hansen (1841-1912) who pricked the eye included work by Amauer Hansen (1841-1912) who pricked the eye with a needle contaminated by nodules of a leprous patient in his with a needle contaminated by nodules of a leprous patient in his work towards the bacillus strain that causes leprosy.work towards the bacillus strain that causes leprosy.

The directive prohibited experiments in minors and those not fully The directive prohibited experiments in minors and those not fully competent, required unequivocal consent after explanation of the competent, required unequivocal consent after explanation of the experiment and possible adverse consequences, and only allowed experiment and possible adverse consequences, and only allowed certain people do the research requiring written records.certain people do the research requiring written records.

Did not apply to medical treatment for diagnosis, therapy, or Did not apply to medical treatment for diagnosis, therapy, or immunizationimmunization

Eugenics and Nazi Era ExperimentsEugenics and Nazi Era Experiments

The Eugenics movements in the US and Europe lead to thousands of The Eugenics movements in the US and Europe lead to thousands of sterilizations in the US and later led to the Nazi Prison camps sterilizations in the US and later led to the Nazi Prison camps atrocities.atrocities.

Origins of Human Subject Research EthicsOrigins of Human Subject Research Ethics

Nuremberg Code of Medical EthicsNuremberg Code of Medical Ethics

““first authoritative, most stringent pronouncement on the rights of first authoritative, most stringent pronouncement on the rights of research subjects” (Annas, 1992)research subjects” (Annas, 1992)

adopted by the World Medical Association in 1948adopted by the World Medical Association in 1948

True informed consent; freely given; prior to experimental procedures True informed consent; freely given; prior to experimental procedures and allow discontinuation of participation at any timeand allow discontinuation of participation at any time

Truly necessary, well thought out experiments in which the expected Truly necessary, well thought out experiments in which the expected benefits justify the risks and there is no unnecessary physical or benefits justify the risks and there is no unnecessary physical or mental suffering or injurymental suffering or injury

Requires that the person performing the research tasks be qualifiedRequires that the person performing the research tasks be qualified

No experiment shall be undertaken where death or disabling injury will No experiment shall be undertaken where death or disabling injury will likely occur and with proper preparation and adequate facilities to likely occur and with proper preparation and adequate facilities to protect subjects and prevent further injuryprotect subjects and prevent further injury

Upon observing the likely risk of injury, disability or death, the Upon observing the likely risk of injury, disability or death, the research should terminate the experimentresearch should terminate the experiment

Beecher, H.K. Ethics and clinical medicine. Beecher, H.K. Ethics and clinical medicine. 1966 New Engl J Med v274(24):1354-601966 New Engl J Med v274(24):1354-60

22 examples of recent publications in major medical journals where 22 examples of recent publications in major medical journals where questionable ethical research methodologies had been employedquestionable ethical research methodologies had been employed

well known Tuskegee Syphilis Study (1932-1972)well known Tuskegee Syphilis Study (1932-1972) 600 subjects of whom 399 with untreated syphilis and a ‘control 600 subjects of whom 399 with untreated syphilis and a ‘control

group’ without syphilis were only told they had ‘bad blood’group’ without syphilis were only told they had ‘bad blood’

Willowbrook Hepatitis Experiments (1956-1980)Willowbrook Hepatitis Experiments (1956-1980) 700 subjects – Parents provided consent and approval from NY 700 subjects – Parents provided consent and approval from NY

Depts. of Mental Health and Mental Hygiene and NYU School of Depts. of Mental Health and Mental Hygiene and NYU School of MedicineMedicine

Jewish Chronic Disease Study in Brooklyn, NY in 1964Jewish Chronic Disease Study in Brooklyn, NY in 1964 22 subjects injected with cancer cells to learn about rejection 22 subjects injected with cancer cells to learn about rejection

process not told in order to not ‘alarm them unnecessarily.’process not told in order to not ‘alarm them unnecessarily.’

Not in the Beecher exposé but noteworthy are the experiments of Not in the Beecher exposé but noteworthy are the experiments of Stanley Milgram conducted in the 1960’s relating to obedience to Stanley Milgram conducted in the 1960’s relating to obedience to authority.authority.

Congressional MandateCongressional Mandate via The National Research Act (July via The National Research Act (July 1974) included:1974) included:1. The establishment of the Code of Federal Regulations 1. The establishment of the Code of Federal Regulations (CFR) Part 46 Protection of Human Subjects, and(CFR) Part 46 Protection of Human Subjects, and2. The creation of the National Commission for the 2. The creation of the National Commission for the Protection of Human Subjects. Congress’ charges to the Protection of Human Subjects. Congress’ charges to the National Commission included the following:National Commission included the following:“. . .the Commission [is] to identify the basic ethical “. . .the Commission [is] to identify the basic ethical principles that should underlie the conduct of biomedical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to and behavioral research involving human subjects and to develop guidelines which should be followed to assure develop guidelines which should be followed to assure that such research is conducted in accordance with those that such research is conducted in accordance with those principles.”principles.”

US Federal Regulations US Federal Regulations

The Belmont ReportThe Belmont Report

Experts in the field of human research ethics were assembled at Experts in the field of human research ethics were assembled at the Smithsonian Institute Belmont House in Elkridge, MD in the Smithsonian Institute Belmont House in Elkridge, MD in July, 1974.July, 1974.

The Commission was directed to consider: The Commission was directed to consider: (i)(i) the boundaries between biomedical and behavioral research the boundaries between biomedical and behavioral research

and the accepted and routine practice of medicine, and the accepted and routine practice of medicine, (ii)(ii) the role of assessment of risk-benefit criteria in the the role of assessment of risk-benefit criteria in the

determination of the appropriateness of research involving determination of the appropriateness of research involving human subjects, human subjects,

(iii)(iii) appropriate guidelines for the selection of human subjects appropriate guidelines for the selection of human subjects for participation in such research andfor participation in such research and

(iv)(iv) the nature and definition of informed consent in various the nature and definition of informed consent in various research settings.research settings.

The Belmont PrinciplesThe Belmont Principles

1.1. Respect for Persons.Respect for Persons. –– Respect for persons incorporates at Respect for persons incorporates at least two ethical convictions: first, that individuals should be least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection.with diminished autonomy are entitled to protection.

2.2. Beneficence.Beneficence. – Persons are treated in an ethical manner – Persons are treated in an ethical manner not only by respecting their decisions and protecting them not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-from harm, but also by making efforts to secure their well-being. In this document, beneficence is understood in a being. In this document, beneficence is understood in a stronger sense, as an obligation. Two general rules have stronger sense, as an obligation. Two general rules have been formulated as complementary expressions of been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms.maximize possible benefits and minimize possible harms.

3.3. Justice.Justice. –– Who ought to receive the benefits of research and Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in the sense bear its burdens? This is a question of justice, in the sense of "fairness in distribution" or "what is deserved. of "fairness in distribution" or "what is deserved. ""

The Belmont Principles: The Belmont Principles: Respect for PersonsRespect for Persons

1. Double coverage: (a) respect for the free autonomous choices 1. Double coverage: (a) respect for the free autonomous choices of competent persons and (b) special protection for those of competent persons and (b) special protection for those who lack or have a “diminished” level of autonomy.who lack or have a “diminished” level of autonomy.

2. Applications: This principle directly pertains to informed 2. Applications: This principle directly pertains to informed consent (IC) and explains why IC must encompass 3 consent (IC) and explains why IC must encompass 3 components: information, comprehension, and components: information, comprehension, and voluntariness.voluntariness.

Respect for persons requires that subjects, to the Respect for persons requires that subjects, to the degree that they are capable, be given the degree that they are capable, be given the opportunity to choose what shall or shall not opportunity to choose what shall or shall not happen to them. While the importance of happen to them. While the importance of informed consent is unquestioned, controversy informed consent is unquestioned, controversy prevails over the nature and possibility of an prevails over the nature and possibility of an informed consent. Nonetheless, there is informed consent. Nonetheless, there is widespread agreement that the consent process widespread agreement that the consent process can be analyzed as containing three elements: can be analyzed as containing three elements:

1)1) information, information,

2)2) comprehension andcomprehension and

3)3) voluntariness.voluntariness.

Respect for Persons & Informed ConsentRespect for Persons & Informed Consent

Information.Information. Most codes of research establish specific Most codes of research establish specific items for disclosure intended to assure that subjects are items for disclosure intended to assure that subjects are given sufficient information. given sufficient information.

These items generally include:These items generally include: a) the research procedure, a) the research procedure, b) their purposes, b) their purposes, c) risks and anticipated benefits, c) risks and anticipated benefits, d) alternative procedures (where therapy is involved), d) alternative procedures (where therapy is involved), e) a statement offering the subject the opportunity to ask e) a statement offering the subject the opportunity to ask

questions and to withdraw at any time from the questions and to withdraw at any time from the research. research.

Additional items have been proposed, including how Additional items have been proposed, including how subjects are selected, the person responsible for the subjects are selected, the person responsible for the research, etc. However, a simple listing of items does research, etc. However, a simple listing of items does not answer the question of what the standard should be not answer the question of what the standard should be for judging how much and what sort of information for judging how much and what sort of information should be provided. should be provided.

Informed Consent: InformationInformed Consent: Information

Information as that provided for Information as that provided for procedures in the hospitalprocedures in the hospital is not is not sufficient. This is inadequate since research takes place precisely when a sufficient. This is inadequate since research takes place precisely when a common understanding does not exist. common understanding does not exist. Another standard, currently popular in malpractice law, requires the Another standard, currently popular in malpractice law, requires the practitioner to reveal the information that practitioner to reveal the information that reasonable persons would reasonable persons would wishwish to know in order to make a decision regarding their care. This, too, to know in order to make a decision regarding their care. This, too, seems insufficient since the research subject, being in essence a seems insufficient since the research subject, being in essence a volunteer, may wish to know considerably more about risks gratuitously volunteer, may wish to know considerably more about risks gratuitously undertaken than do patients who deliver themselves into the hand of a undertaken than do patients who deliver themselves into the hand of a clinician for needed care. clinician for needed care.

It may be that a standard of It may be that a standard of "the reasonable volunteer" "the reasonable volunteer" should be should be proposed: the extent and nature of information should be such that proposed: the extent and nature of information should be such that persons, knowing that the procedure is neither necessary for their care persons, knowing that the procedure is neither necessary for their care nor perhaps fully understood, can decide whether they wish to nor perhaps fully understood, can decide whether they wish to participate in the furthering of knowledge. participate in the furthering of knowledge. Even when some direct Even when some direct benefit to them is anticipated, the subjects should understand clearly benefit to them is anticipated, the subjects should understand clearly the range of risk and the voluntary nature of participation. the range of risk and the voluntary nature of participation.

Information: what is the standard that Information: what is the standard that should be used?should be used?

A special problem of consent arises where informing subjects of some A special problem of consent arises where informing subjects of some pertinent aspect of the research is likely to impair the validity of the pertinent aspect of the research is likely to impair the validity of the research. In many cases, it is sufficient to indicate to subjects that they research. In many cases, it is sufficient to indicate to subjects that they are being invited to participate in research of which some features will are being invited to participate in research of which some features will not be revealed until the research is concluded. In all cases of research not be revealed until the research is concluded. In all cases of research involving incomplete disclosure, such research is justified only if it is involving incomplete disclosure, such research is justified only if it is clear that: clear that: (1)(1) Incomplete disclosure is truly necessary to accomplish the goals of Incomplete disclosure is truly necessary to accomplish the goals of the research, the research, (2)(2) there are no undisclosed risks to subjects that are more than there are no undisclosed risks to subjects that are more than minimal, and minimal, and (3)(3) there is an adequate plan for debriefing subjects, when appropriate, there is an adequate plan for debriefing subjects, when appropriate, and for dissemination of research results to them. and for dissemination of research results to them. (4)(4) Information about risks should never be withheld for the purpose of Information about risks should never be withheld for the purpose of eliciting the cooperation of subjects, and truthful answers should always eliciting the cooperation of subjects, and truthful answers should always be given to direct questions about the research. be given to direct questions about the research. (5)(5) Care should be taken to distinguish cases in which disclosure would Care should be taken to distinguish cases in which disclosure would destroy or invalidate the research from cases in which disclosure would destroy or invalidate the research from cases in which disclosure would simply inconvenience the Investigator.simply inconvenience the Investigator.

The Need for Informed Consent and DeceptionThe Need for Informed Consent and Deception

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

For example, presenting information in a For example, presenting information in a disorganizeddisorganized and rapid fashion, and rapid fashion, allowing too little time for considerationallowing too little time for consideration or curtailing opportunities for or curtailing opportunities for questioning, all may adversely affect a subject's ability to make an questioning, all may adversely affect a subject's ability to make an informed choice. Because the subject's ability to understand is a function informed choice. Because the subject's ability to understand is a function of intelligence, rationality, maturity and language, it is necessary to of intelligence, rationality, maturity and language, it is necessary to adaptadapt the presentation of the information to the subject's capacities. the presentation of the information to the subject's capacities.

Investigators are responsible for ascertaining that the subject has Investigators are responsible for ascertaining that the subject has comprehended the information. While there is always an obligation to comprehended the information. While there is always an obligation to ascertain that the information about risk to subjects is complete and ascertain that the information about risk to subjects is complete and adequately comprehended, when the risks are more serious, that adequately comprehended, when the risks are more serious, that obligation increases. On occasion, it may be suitable to give some oral or obligation increases. On occasion, it may be suitable to give some oral or written tests of comprehension. Special provision may need to be made written tests of comprehension. Special provision may need to be made when comprehension is severely limited -- for example, by conditions of when comprehension is severely limited -- for example, by conditions of immaturity or mental disability. Capacity assessment should be applied immaturity or mental disability. Capacity assessment should be applied here.here.

http://www.ucdmc.ucdavis.edu/clinicaltrials/tools.htmlhttp://www.ucdmc.ucdavis.edu/clinicaltrials/tools.html

Informed Consent: ComprehensionInformed Consent: Comprehension

Whenever possible, investigators will attempt to obtain Whenever possible, investigators will attempt to obtain informed consent directly from the subject. informed consent directly from the subject.

The application reviewed by the IRB must detail a protocol-The application reviewed by the IRB must detail a protocol-specific plan for the assessment of the decision-making specific plan for the assessment of the decision-making capacity of the subject that will be conducted by the capacity of the subject that will be conducted by the investigator for any subject who may qualify for surrogate investigator for any subject who may qualify for surrogate consent. consent.

Surrogate consent can be obtained from:Surrogate consent can be obtained from:

Informed Consent: Surrogate ConsentInformed Consent: Surrogate Consent

1.1. The person's agent designated by an advance health care directiveThe person's agent designated by an advance health care directive2.2. The conservator or guardian of the person having the authority to The conservator or guardian of the person having the authority to

make health care decisions for the personmake health care decisions for the person3.3. The spouse of the personThe spouse of the person4.4. An individual as defined in Section 297 of the Family Code (Domestic An individual as defined in Section 297 of the Family Code (Domestic

partners) partners) 5.5. An adult son or daughter of the personAn adult son or daughter of the person6.6. A custodial parent of the personA custodial parent of the person7.7. Any adult brother or sister of the personAny adult brother or sister of the person8.8. Any adult grandchild of the personAny adult grandchild of the person9.9. An available adult relative with the closest degree of kinship to the An available adult relative with the closest degree of kinship to the

personperson

An agreement to participate in research constitutes a valid consent An agreement to participate in research constitutes a valid consent only if voluntarily given. only if voluntarily given.

This This element of informed consent requires conditions free of coercion and element of informed consent requires conditions free of coercion and undue influence. undue influence.

CoercionCoercion occurs when an occurs when an overt threat of harm overt threat of harm is intentionally presented is intentionally presented by one person to another in order to obtain compliance. by one person to another in order to obtain compliance.

Undue influenceUndue influence, by contrast, occurs through an offer of an excessive, , by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order unwarranted, inappropriate or improper reward or other overture in order to induce the potential volunteer to put themselves at a risk that they to induce the potential volunteer to put themselves at a risk that they would otherwise not do. would otherwise not do.

Unjustifiable pressuresUnjustifiable pressures usually occur when persons in positions of usually occur when persons in positions of authority or commanding influence -- especially where possible sanctions authority or commanding influence -- especially where possible sanctions are involved -- urge a course of action for a subject. are involved -- urge a course of action for a subject.

A continuum of such influencing factors exists, however, and it is impossible A continuum of such influencing factors exists, however, and it is impossible to state precisely where justifiable persuasion ends and undue influence to state precisely where justifiable persuasion ends and undue influence begins. But undue influence would include actions such as manipulating a begins. But undue influence would include actions such as manipulating a person's choice through the controlling influence of a close relative and person's choice through the controlling influence of a close relative and threatening to withdraw health services to which an individual would threatening to withdraw health services to which an individual would otherwise be entitle.otherwise be entitle.

Informed Consent: VoluntarinessInformed Consent: Voluntariness

Persons are treated in an ethical manner not only by Persons are treated in an ethical manner not only by respecting their decisions and protecting them from respecting their decisions and protecting them from harm, but also by making efforts to secure their well-harm, but also by making efforts to secure their well-being. Such treatment falls under the principle of being. Such treatment falls under the principle of beneficence. The term "beneficence" is often beneficence. The term "beneficence" is often understood to cover acts of kindness or charity. In this understood to cover acts of kindness or charity. In this document, beneficence is understood in a stronger document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been sense, as an obligation. Two general rules have been formulated as complementary expressions of formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible (2) maximize possible benefits and minimize possible harms. harms.

The Belmont Principles: The Belmont Principles: BeneficenceBeneficence

1. Double coverage: the moral obligations to:1. Double coverage: the moral obligations to: (a) maximize benefits for research (a) maximize benefits for research subjects and subjects and (b) protect them from harm (b) protect them from harm

2. Applications: systematic, explicit, and2. Applications: systematic, explicit, andthorough assessment of the probable or thorough assessment of the probable or possible harms and benefits. possible harms and benefits.

The Belmont Principles: The Belmont Principles: BeneficenceBeneficence

BeneficenceBeneficenceWhat kinds of harms are there?What kinds of harms are there?

EconomicalEconomical

PrivacyPrivacyversusversus

ConfidentialityConfidentiality

PsychologicalPsychological

SocialSocial

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PhysicalPhysical

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efit

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Beneficence - How is Harm Beneficence - How is Harm Minimized and Benefit Maximized?Minimized and Benefit Maximized?

Risk is a function of both the probability and the magnitude Risk is a function of both the probability and the magnitude of the harm whereas benefit can be thought of in terms of of the harm whereas benefit can be thought of in terms of the opportunity to produce benefit.the opportunity to produce benefit.

Who ought to receive the benefits of research and Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in bear its burdens? This is a question of justice, in the sense of "fairness in distribution" or "what is the sense of "fairness in distribution" or "what is deserved." deserved."

1. Belmont relies on the principle of justice 1. Belmont relies on the principle of justice (equality of treatment) to focus on injustice in two (equality of treatment) to focus on injustice in two senses: senses:

(a) the injustice of keeping persons from (a) the injustice of keeping persons from receiving what they deserve and receiving what they deserve and

(b) imposing undue burdens on emotionally, (b) imposing undue burdens on emotionally, socially, and economically disadvantaged socially, and economically disadvantaged persons. persons.

2. Application: the selection/recruitment of 2. Application: the selection/recruitment of research subjectsresearch subjects

The Belmont Principles: JusticeThe Belmont Principles: Justice

The Ethical Principles of The Ethical Principles of The Belmont ReportThe Belmont Report: :

vs. the Federal Regulations in 45CFR Part 46vs. the Federal Regulations in 45CFR Part 46

1. Risks to subjects are minimized1. Risks to subjects are minimized

2. Risks to subjects are reasonable in relation to 2. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably importance of the knowledge that may reasonably be expected to result. be expected to result.

3. Selection of subjects is equitable. 3. Selection of subjects is equitable.

4. Informed consent will be sought from each 4. Informed consent will be sought from each prospective subject or the subject's legally prospective subject or the subject's legally authorized representative, in accordance with, authorized representative, in accordance with, and to the extent required by §46.116.and to the extent required by §46.116.

5. Informed consent will be appropriately documented, 5. Informed consent will be appropriately documented, in accordance with, and to the extent required by in accordance with, and to the extent required by §46.117.§46.117.

6. When appropriate, the research plan makes 6. When appropriate, the research plan makes adequate provision for monitoring the data adequate provision for monitoring the data collected to ensure the safety of subjects.collected to ensure the safety of subjects.

7. When appropriate, there are adequate provisions to 7. When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain protect the privacy of subjects and to maintain the confidentiality of data.the confidentiality of data.

8. When some or all of the subjects are likely to be 8. When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disabled persons, or economically or educationally disadvantaged persons, additional safeguards disadvantaged persons, additional safeguards have been included.have been included.

1.1. Respect Respect for Persons for Persons

2. Beneficence 2. Beneficence

3. Justice3. Justice

Discussion PointsDiscussion Points

1)1) When does research not require IRB When does research not require IRB review? review?

2)2) Issues related to privacy and Issues related to privacy and confidentiality.confidentiality.

3)3) Research into Standard of Care Research into Standard of Care methodologies. methodologies.

Is it Research?Is it Research?

Research is defined by federal regulations as a systematic Research is defined by federal regulations as a systematic investigation that contributes to generalizable knowledge investigation that contributes to generalizable knowledge (Common Rule 45CRF46:102d). If the goal of the (Common Rule 45CRF46:102d). If the goal of the intervention is entirely therapeutic, then it may not be intervention is entirely therapeutic, then it may not be research. Medicine includes many “experimental therapies” research. Medicine includes many “experimental therapies” that are not treated as research. Students often conduct that are not treated as research. Students often conduct educational projects designed to teach research methods educational projects designed to teach research methods and techniques that may not be considered to be research.and techniques that may not be considered to be research.

Is it human subjects research? Research may involve human Is it human subjects research? Research may involve human tissues but not human subjects. “A human subject is a tissues but not human subjects. “A human subject is a living individual about whom an investigator… obtains data living individual about whom an investigator… obtains data through interaction or intervention with the individual or through interaction or intervention with the individual or identifiable private information.” Research on stored human identifiable private information.” Research on stored human tissue is not covered by current federal regulations and tissue is not covered by current federal regulations and presents IRBs with some important ethical and policy presents IRBs with some important ethical and policy dilemmas. dilemmas.

http://www.research.ucdavis.edu/http://www.research.ucdavis.edu/home.cfm?id=OVC,1,1081,1433home.cfm?id=OVC,1,1081,1433

When are Scholarly When are Scholarly Efforts not Research?Efforts not Research?

CQICQI

case reportscase reports

archived specimensarchived specimens

Research versus PracticeResearch versus Practice

a physician may alter the standard order of a physician may alter the standard order of medications or a surgical technique to meet the medications or a surgical technique to meet the needs of his/her patients.needs of his/her patients.

what happens when the research is into minimal what happens when the research is into minimal risk interventions or common steps in procedures risk interventions or common steps in procedures that are not strictly defined or adhered to?that are not strictly defined or adhered to?

should different criteria exist for IRB review and should different criteria exist for IRB review and the informed consent process?the informed consent process?

do you think research ‘for the public good’ should do you think research ‘for the public good’ should be assessed with different or unique criteria?be assessed with different or unique criteria?

A few years ago, anthropologist A few years ago, anthropologist Scott Atran, who has done Scott Atran, who has done pioneering work on what drives pioneering work on what drives people to become terrorists, asked people to become terrorists, asked the panel at the University of the panel at the University of Michigan, where he is a professor, to Michigan, where he is a professor, to OK a study funded by the National OK a study funded by the National Science Foundation (NSF) in which Science Foundation (NSF) in which he would interview terrorists, he would interview terrorists, including jailed members of the including jailed members of the group behind the 2005 Bali group behind the 2005 Bali bombing. The panel balked. bombing. The panel balked. Prisoners are in no position to give Prisoners are in no position to give informed consent, it said. There was informed consent, it said. There was grave concern that the prisoners grave concern that the prisoners might reveal plans that could get might reveal plans that could get them in more trouble. The panel, them in more trouble. The panel, which included a musicologist and a which included a musicologist and a journalist, forbade Atran from asking journalist, forbade Atran from asking the jihadis personal questions (even the jihadis personal questions (even though a goal of the study was though a goal of the study was learning what motivates someone to learning what motivates someone to become a terrorist); doing so would become a terrorist); doing so would violate their right to privacy.violate their right to privacy.

Privacy is about people and their freedom from Privacy is about people and their freedom from unauthorized oversight or observation – ‘access to unauthorized oversight or observation – ‘access to themselves.’ Privacy is in the eye of the subject; not the themselves.’ Privacy is in the eye of the subject; not the Investigator or the IRB – i.e., Investigator or the IRB – i.e., the subjects’the subjects’ expectation. expectation.

Confidentiality is about data and the agreements with the Confidentiality is about data and the agreements with the participant about how data are to be handled. Main participant about how data are to be handled. Main methods have to do with restricted access to data with methods have to do with restricted access to data with passwords and perhaps Certificates of Confidentiality.passwords and perhaps Certificates of Confidentiality.

Privacy versus ConfidentialityPrivacy versus Confidentiality

Additional Questions for Discussion:Additional Questions for Discussion:

1)1) Is the media paying too much, just enough or too little attention Is the media paying too much, just enough or too little attention to questionable research with human subjects?to questionable research with human subjects?

2)2) Do you think freedom of inquiry should surpass other values? Do you think freedom of inquiry should surpass other values? Why?Why?

3)3) What risks would you and members of your family take for What risks would you and members of your family take for public good? Why?public good? Why?

4)4) In your opinion, should there be a difference between informed In your opinion, should there be a difference between informed consent for volunteering as a human subject and informed consent for volunteering as a human subject and informed consent for medical treatment? What would those differences consent for medical treatment? What would those differences be, if any? Why?be, if any? Why?

5)5) Do you think IRBs are doing a good job of protecting human Do you think IRBs are doing a good job of protecting human subjects? Can they? How would you improve the system, if you subjects? Can they? How would you improve the system, if you believe improvement is needed?believe improvement is needed?

6)6) How would you design a system to ensure enrollment of How would you design a system to ensure enrollment of mentally ill individuals into research studies while protecting mentally ill individuals into research studies while protecting them from harm? Why?them from harm? Why?