Historical backgrounds of Historical backgrounds of WHY U.S. regulations WHY U.S. regulations cover biomedical and cover biomedical and

social behaviorsocial behavior

Melody Lin, Ph.D.Melody Lin, Ph.D.Deputy Director, Office for Human Research ProtectionsDeputy Director, Office for Human Research Protections

Director, International ActivitiesDirector, International ActivitiesDepartment of Health and Human ServicesDepartment of Health and Human Services

Melody.Lin@hhs.govDec. 12, 2012Dec. 12, 2012

ObjectivesObjectives

Historical cases of unethical researchHistorical cases of unethical research National Research ActNational Research Act National CommissionNational Commission

BiomedicalBiomedical BehavioralBehavioral

NurembergNuremberg

23 German doctors were 23 German doctors were charged with crimes charged with crimes against against humanityhumanity

experiments without subject experiments without subject consentconsent

The Nuremberg Code (1947)The Nuremberg Code (1947)

Rules for "Permissible Medical Experiments"Rules for "Permissible Medical Experiments" voluntary consentvoluntary consent benefits outweigh risksbenefits outweigh risks withdraw from participationwithdraw from participation

Nuremberg CodeNuremberg Code

Informed consent without coercion Informed consent without coercion Prior animal experimentationPrior animal experimentation Justify by anticipated scientific results Justify by anticipated scientific results Qualified scientists Qualified scientists Avoid physical and mental suffering Avoid physical and mental suffering No expectation of death or disabling injury No expectation of death or disabling injury

Did the Nuremberg Code Did the Nuremberg Code Impact the behavior of Impact the behavior of

American scientists who did American scientists who did research on humans?research on humans?

NoNo

But, in AmericaBut, in America

Willowbrook (1950s)Willowbrook (1950s)Mentally Mentally retardedretarded children were deliberately injected children were deliberately injected with hepatitis virus to study its effectswith hepatitis virus to study its effects

Jewish Chronic Disease Hospital (1960s) Jewish Chronic Disease Hospital (1960s) Live cancer cells were injected into 22 senile patients.Live cancer cells were injected into 22 senile patients.

… … with no benefit to patients, with no benefit to patients,

and no consent of kin.and no consent of kin.

The 18th World Medical The 18th World Medical Assembly (1964), in the Assembly (1964), in the Declaration of Helsinki Declaration of Helsinki

Set forth additional recommendations to Set forth additional recommendations to guide medical doctors in biomedical guide medical doctors in biomedical research involving human subjectsresearch involving human subjects

Beecher ArticleBeecher Article

““Ethics and Clinical Research”Ethics and Clinical Research”Henry K. BeecherHenry K. BeecherNew Engl J Med 274 (1966):1354-60New Engl J Med 274 (1966):1354-60

22 published medical studies presenting risk to 22 published medical studies presenting risk to subjects without their knowledge or approvalsubjects without their knowledge or approval

Published in some of the most prestigious Published in some of the most prestigious journals and conducted at some of the most journals and conducted at some of the most prestigious institutionsprestigious institutions

Tuskegee Syphilis StudyTuskegee Syphilis Study

PHS conducted 1932-1972PHS conducted 1932-1972

400 Black American Men400 Black American Men

Natural course of untreated syphilisNatural course of untreated syphilis

Unknowing participantsUnknowing participants

No treatment when drugs were availableNo treatment when drugs were available

National ActionNational Action

1973 - Kennedy Hearings. Tuskegee, etc., and ta 1973 - Kennedy Hearings. Tuskegee, etc., and ta search for ethical issues in social/behavioral research: search for ethical issues in social/behavioral research:

Stanley Milgram’s Obedience StudyStanley Milgram’s Obedience Study Laud Humphreys’ Study of “tearoom trade”Laud Humphreys’ Study of “tearoom trade”

1974 - National Research Act established the 1974 - National Research Act established the National Commission for Protection of Human National Commission for Protection of Human Subjects of Biomedical & Behavioral ResearchSubjects of Biomedical & Behavioral Research

Required IRBs at institutions receiving HEW support Required IRBs at institutions receiving HEW support for human subjects research.for human subjects research.

The Belmont ReportThe Belmont Report

Ethical Principles and Guidelines for the Protection Ethical Principles and Guidelines for the Protection of Human Subjects of Researchof Human Subjects of Research

Respect for personsRespect for personsBeneficenceBeneficence

JusticeJustice

National Commission for the Protection of Human National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Subjects of Biomedical and Behavioral Research,

19791979

The Milgram StudyThe Milgram Study19611961

Psychologist, Yale Univ.Psychologist, Yale Univ.

The Milgram StudyThe Milgram Study Experiment on obedience to authority figures Experiment on obedience to authority figures Study on the conflict between obedience Study on the conflict between obedience

toward authority and ones personal toward authority and ones personal consciousconscious

E – ExperimenterT – Teacher (Subject)L – Learner (Actor)

(E) orders (T) to give what the subject believes are painful electric shocks to (L).

The subjects (T) believed that for each wrong answer, the (L) was receiving actual shocks, but in reality there were no shocks.

(L) set up a tape recorder integrated with the electro-shock generator, which played pre-recorded sounds for each shock level.

The Milgram StudyThe Milgram Study Only the "teacher" is an actual subject, Only the "teacher" is an actual subject,

i.e. unaware about the actual setupi.e. unaware about the actual setup The subject and the learner were told by The subject and the learner were told by

the experimenter that they would be the experimenter that they would be participating in an experiment helping participating in an experiment helping his study of memory and learning in his study of memory and learning in different situationsdifferent situations

The Milgram Study: ResultsThe Milgram Study: Results In the first set of experiments, 65 percent In the first set of experiments, 65 percent

of the subjects administered the of the subjects administered the experiment's final massive 450-volt shockexperiment's final massive 450-volt shock many were very uncomfortable doing so; many were very uncomfortable doing so; some said they would refund the money they some said they would refund the money they

were paid for participating in the experimentwere paid for participating in the experiment

Ethical IssuesEthical Issues

Respect for Persons:Respect for Persons: Stanley Milgram deceived Stanley Milgram deceived his study's subjects (failure to disclose important his study's subjects (failure to disclose important aspects of study to allow a voluntary decision to aspects of study to allow a voluntary decision to participate)participate)

Beneficence:Beneficence: Subjects (T) were placed under Subjects (T) were placed under more pressure than many believe was more pressure than many believe was necessary to test the study hypothesisnecessary to test the study hypothesis

Respect for Persons:Respect for Persons: Subjects were coerced into Subjects were coerced into remaining in study against their willremaining in study against their will

Humphreys: Tearoom TradeHumphreys: Tearoom TradePh.D. dissertation (sexual) DeviancePh.D. dissertation (sexual) Deviance

Sociologist, Wash. U.Sociologist, Wash. U.

Laud Humphreys studied homosexual Laud Humphreys studied homosexual encounters in “tearooms” – public encounters in “tearooms” – public restroomsrestrooms

Homosexuals who engage in sex in Homosexuals who engage in sex in tearooms like to have a third person tearooms like to have a third person present, someone they call a “Watch present, someone they call a “Watch queen”queen”

Humphreys (cont’d)Humphreys (cont’d)

As a “Watch Queen” Humphreys made As a “Watch Queen” Humphreys made observations in order to do researchobservations in order to do research

He wrote down the license plate numbers He wrote down the license plate numbers of the men and traced their home of the men and traced their home addressesaddresses

A year later, he visited them at home, and A year later, he visited them at home, and conducted a follow-up surveyconducted a follow-up survey

Humphreys (cont’d)Humphreys (cont’d)

38% of men having tearoom sex were 38% of men having tearoom sex were marriedmarried

Most identified themselves as Most identified themselves as heterosexualheterosexual

It turns out, most of these men were It turns out, most of these men were frustrated their wivesfrustrated their wives

Ethical issuesEthical issues

The researcher acted as a lookout, alerting The researcher acted as a lookout, alerting participants engaged in an illegal activityparticipants engaged in an illegal activity

Unknown to the subjects, the researcher noted Unknown to the subjects, the researcher noted the license numbers of their carsthe license numbers of their cars

License numbers were traced to reveal the License numbers were traced to reveal the name and address of each car ownername and address of each car owner

Traced subjects were interviewed as part of a Traced subjects were interviewed as part of a larger public health survey (true purpose of their larger public health survey (true purpose of their participation not revealed)participation not revealed)

Ethical ProblemsEthical Problems

Aiding in crimeAiding in crime Since the Missouri law forbade homosexual Since the Missouri law forbade homosexual

activity Humphreys was assisting in a crime activity Humphreys was assisting in a crime by acting as a lookout (i.e., the “watch by acting as a lookout (i.e., the “watch queen”)queen”)

Ethical Problems (cont’d)Ethical Problems (cont’d)

Informed consentInformed consent Did not seek informed consentDid not seek informed consent

Likely they would have refused participationLikely they would have refused participation

Endangering subjectsEndangering subjects Took some care here: the names in safety Took some care here: the names in safety

deposit box in another state, refusing to tell deposit box in another state, refusing to tell police what he was doingpolice what he was doing What if name had been released?What if name had been released? Would the publication lead to a “crack down”?Would the publication lead to a “crack down”?

Laud Humpheys’ PostscriptLaud Humpheys’ Postscript

Because of his study, the sociology Because of his study, the sociology department lost federal funding, many department lost federal funding, many senior faculty leftsenior faculty left Sociology program later eliminatedSociology program later eliminated

Laud Humphreys (1930-1988) received his Laud Humphreys (1930-1988) received his Ph.D. Career SUNY (Albany, NY)Ph.D. Career SUNY (Albany, NY)

SummarySummary

National Research Act. 1974National Research Act. 1974 Federal response to harm arising from Federal response to harm arising from

biomedical and behavioral experimentationsbiomedical and behavioral experimentations National commission for the protection of human National commission for the protection of human

subjects of biomedical and behavioral researchsubjects of biomedical and behavioral research National commission outlined ethical principals National commission outlined ethical principals

upon which the ethics of research study are upon which the ethics of research study are evaluated in the U.S.evaluated in the U.S.