Life is all about choices … Human Subjects Research Ethics.

Life is all about choices …

Human Subjects Research Ethics

Join me as we journey back to an age where•The field of Medicine comes into its own, and

•Optimism, Progress, and Science sit on the Throne of GOD

Welcome to the Ethical Time Machine

All Aboard!

1923 - 1952 Piaget

describes stages of

cognitive development

First T

est T

ube Bab

y Born

197

8

First Human Heart Transplant Year - 1967

First successful Open Heart Surgery - 1952

Penicillin - 1940

sulfa drugs - 1932

First Electrocardiogram 1903

1972 Syphilis Study Exposed

1966 The Beecher Article (NEJM)

1932 The Syphilis Study Begins

Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code

Kefauver-Harris Amendments Food, Drug and Cosmetic Act

Declaration of Helsinki

Belmont Report

Consolidated HHS/FDA Regulations

Common Rule

The Nazi Experiments

US Human Radiation Experiments

The Thalomide Tragedy

Milgram Study

20th Century Research Ethics Milestones

‘Back to the Future’

Nazi Germany at beginning of World War II

• Was the most scientifically and technologically advanced country in the world,

• Had a proposed code of research ethics,

• Supported midwifery, nutrition programs,

• ecology, public health, human genetics, cancer, radiation, and asbestos research

However …

• The Nazis also …• exploited people’s trust in

the medical community • by performing unethical

experiments • on populations they

discriminated against.

Nazi Battlefield Medicine Experiments

• 1942: High altitude or low pressure experiments at Dachau

• 1942-1943: Freezing experiments at Dachau• 1942-1945: Malaria experiments at Dachau• 1943-1944: Phosphorus burn experiments at

Buchenwald • 1944: Seawater experiment at Dachau

At Ravensbruck

• women were shot or slashed on the legs.

• The wounds stuffed with glass, dirt, and bacteria cultures and sewn shut

• then treated with experimental anti-infective agents.




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



The Nuremberg Code

• Key Ideas– Voluntary Informed Consent– Right of the Subject to Withdraw from the

Experiment at any Time– A Human Subject Cannot be Sacrificed for the

Greater Good of Science – Investigator must terminate the experiment at

any time the well-being of his/her subjects is threatened.




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



Human Radiation Experiments• In 1994, President Clinton

appointed the Advisory Committee on Human Radiation Experiments (ACHRE)

• To investigate unethical experiments conducted by our government during WWII and the Cold War Era

http://tis.eh.doe.gov/ohre/roadmap/achre/

http://tis.eh.doe.gov/ohre/roadmap/achre/chap7_5.html



ACHRE’S Investigation Revealed …

• testing on soldiers• feeding radioactive cereal to

teenagers at a school for the mentally retarded,

• irradiating the testicles of prison inmates,

• injecting plutonium into hospital patients,

• intentional releases of radiation into the environment …

4000 human radiation experiments conducted

• In a two prong effort by the US to– Provide for National Security– Provide medical studies to improve human health

• Too often deceptively, secretly, and/or without informed consent

Testimony before ACHRE, 1995

• “My mother, Jan Stadt, had a number, HP-8. She was injected with plutonium March 9, 1946. She was 41 years old, and I was 11 years old at the time. My mother and father were never told or asked for any kind of consent to have this done to them.

• “My mother went in (to the hospital) for scleroderma...and a duodenal ulcer, and somehow she got pushed over into this lab where these monsters were.”

Milton Stadt Son of subject in the Rochester University experiments




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



The Thalidomide Tragedy

Thalidomide was prescribed for morning sickness

• Approved in Europe in late 1950’s but not in US due to diligent efforts by one USDA doctor.

• However as was common practice among pharmaceutical companies …

• some U.S. doctors were supplied samples • and paid to study its safety and efficacy.

It was subsequently discovered that …

• Thalidomide causes severe deformities in babies• and its effects are even passed on to later

generations.




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



1962 Kefauver-Harris Amendments Food, Drug and Cosmetic Act

• Looked at practices of pharmaceutical companies

• Required more testing before widespread use

• Informed consent from patients receiving experimental drugs




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



Socio-Behavioral Studies

• Milgram’s Study of Obedience to Authority– Subjects coerced into feeling they had seriously

injured somebody

• The Stanford Prison Experiment – What happens when you put good people in an evil

place?– http://www.prisonexp.org/

• Radiation experiments on soldiers– Fear

http://www.prisonexp.org/






Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



Declaration of Helsinki 1964

• Research with humans should be based on the results from laboratory and animal experimentation

• Research protocols should be reviewed by an independent committee prior to initiation

• Informed consent from research participants is necessary

• Research should be conducted by medically/scientifically qualified individuals

• Risks should not exceed benefits




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



“Dr. Beecher began his famous article in the NEJM by stating:

• “… medicine is sound, and most progress is soundly attained …”

He then went on to describe …

• 22 examples of research studies• with controversial ethics• conducted by reputable researchers and• published in major journals.

• "Until this article we assumed that unethical research could only occur in a depraved regime like the Nazis.“

Robert J. Levine, MD




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



Syphilis the AIDS of an earlier time

• Untreated, it can lead to – severe heart disease, – brain damage, – paralysis, and – death.

• The problem was, until 1907, no one could treat it.

Then Nobel Prize-winning microbiologist Paul Ehrlich discovered Salvarsan

• an arsenic-based compound.• It was the first chemotherapy.

The 1920’s was a progressive era in medicine

• Armed with confidence and the Scientific Method,

• Public Health Service officials were determined

• to control syphilis in their time.• They set up free treatment clinics

throughout the south, • including Macon county, Alabama,• home to the Tuskegee Institute.

• While writing the final report, • Dr. Taliaferro Clark, head of the PHS

Venereal Disease Division • conceived an idea to salvage the

study …• Macon county “offered an

unparalleled opportunity • for the study of the effect of untreated

syphilis”• in the Negro male.

But in 1932, the funding for treatment ran out.

The Study of Untreated Syphilis in the Negro male (1932 – 1972)

• was only supposed to last a year …• but then Dr. Raymond Vondelehr • advocated continuing the study • to get autopsies.• Autopsies would confirm clinical

observation • and therefore greatly contribute • to the scientific reliability • of the study’s findings.

“Bringing them to Autopsy”

•By the time Jean Heller broke the story •in the Washington Star in 1972•The experiment had gone on for 40 years.•During all this time, it was no secret •to the wider medical community.•Results of the study had been published •in well known medical journals.•Yet no one ever questioned the study.

399 Participants

•None were ever told they had syphilis.•None were ever offered a cure •even when penicillin became available in 1943.•Researchers had even interfered •to keep subjects from getting penicillin•so the study could continue.

• 28 men died of syphilis• 100 men died from related complications• at least 40 wives were infected• 19 children had contracted the disease at birth • a whole people’s trust was shattered

“Nothing Learned will Prevent, Find, or Cure a Single Case”

“Bad Blood”

• Macon county residents were very poor.• They lived and died without medical care• because they could not afford it.• They didn’t distinguish between syphilis• and a host of other maladies • which they called “bad blood.”• They trusted the government doctors and• they traveled great lengths • to get a little free medical care.• They were told they were being treated for

“bad blood.”

“I, like most everybody else, • “was horrified at the things

that were practiced upon these Jewish people, such as doing experiments while the patients were not only alive but doing such things as would cause their deaths.

• “All these sorts of things were horrendous to me and I, like most everyone else, deplored them.”

Dr. John R. Heller, Researcher, Tuskegee Syphilis Study

Final Report of Tuskegee Syphillis Study

• "Society can no longer afford • to leave the balancing of

individual rights • against scientific progress • to the scientific community."




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



In 1974 at Belmont, the National Commission for the Protection of Human Subjects began deliberations …

Kenneth John Ryan, M.D., Joseph V. Brady, Ph.D., Robert E. Cooke, M.D., Dorothy I. Height, President, NCNW, Albert R. Jonsen, Ph.D., Patricia King, J.D., Karen Lebacqz, Ph.D., David W. Louisell, J.D., Donald W. Seldin, M.D., Eliot Stellar, Ph.D., Robert H. Turtle, LL.B., Attorney.

Which led in 1978 to the opening words of the Belmont Report

• “Scientific Research has produced substantial social benefits.

• “It has also posed some troubling ethical questions.”

The 3 Basic Ethical Principlesof the Belmont Report

Respect for Persons

Benefice

Justice

Respect for Persons

Definition:• Individuals should be treated as

autonomous agents• Persons with diminished autonomy are

entitled to protection

Application:• Voluntary Informed Consent

Belmont Report

Benefice

Definition:• Do not harm• Maximize possible benefits• Minimize possible harms

Application: • Assessment of risks and benefits

Belmont Report

Justice

Definition:• Who ought to receive the benefits of

research?• Who ought to bear its burdens?

Application:• Equitable Selection of Subjects

Belmont Report




Trigger Events

1947

1962

1964

1979

1981

1991

Nuremberg Code



Belmont Report


Common Rule




Milgram Study



1923 - 1952 Piaget

describes stages of

cognitive development

First T

est T

ube Bab

y Born

197

8

First Human Heart Transplant Year - 1967

First successful Open Heart Surgery - 1952

Penicillin - 1940

sulfa drugs - 1932

First Electrocardiogram 1903

‘Home free’ in the 21st Century?• Research is still Risky

– Gene Therapy Trials• Death of 18 year old Jesse Gelsinger in 1999

• Conflict of interest

– Cloning – Nanotechnology– Internet Research– Artificial Intelligence– Chemical and Biological terrorism– Space travel …

Institutions where Studies have been temporarily suspended July

1998 – July 2001

• Rush Presbyterian – St. Luke’s Medical Center

• Friends Research Institute

• Veteran Affairs Greater LA

• Virginia Commonwealth University

• John Hopkins

Questions to Consider• Why should we be concerned about Human Subject Research?• • Do you think another Tuskegee could happen in the future?• • Do you think a Tuskegee could ever happen to you?• • Can you envision yourself ever being faced with an ethical dilemma in

Human Subjects research? What are some guidelines or resources you could turn to?

• • And finally,• • The Tuskegee Study started in the United States in 1932 and continued for

40 years, well past the Nuremberg trials. It was also no well kept secret. Research articles were published in major medical journals during this time. Why do you think nobody saw a connection between Nuremberg and the Tuskegee Syphilis Study?

The 1997 Presidential Apology to Tuskegee Participants

choices have consequences

Now it’s your turn - how will YOU choose?

Life is all about choices …

Life is all about choices … Human Subjects Research Ethics.

Documents

future slide

dachau slide

unethical experiments

syphilis study

freezing experiments

malaria experiments

govohreroadmapachre

environment slide