research ethics: history and scandals
DESCRIPTION
Research Ethics: History and Scandals. Hemantha Senanayake, Chairman, Ethics Review Committee, Faculty of Medicine, University of Colombo. Research Ethics: “Born in Scandal”. Some historical anecdotes. Edward Jenner, (1749 – 1823). Edward Jenner. Discovered vaccination in 1796 - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/1.jpg)
Research Ethics: History and Scandals
Hemantha Senanayake,Chairman,
Ethics Review Committee, Faculty of Medicine,
University of Colombo
![Page 2: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/2.jpg)
Research Ethics: “Born in Scandal”
![Page 3: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/3.jpg)
Some historical anecdotes
![Page 4: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/4.jpg)
Edward Jenner, (1749 – 1823)
![Page 5: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/5.jpg)
Edward Jenner• Discovered vaccination in 1796
• Saved countless lives
• During an epidemic he noticed that his patients who worked with cattle were immune to smallpox
• Inoculated 8-year old James Phipps with serum from cowpox sore
• Later inoculated the boy with serum from smallpox vesicle
![Page 6: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/6.jpg)
Edward Jenner
• Could have been liable to murder charges if James died
• Research community felt more evidence was needed
• He recruited other children
• Even did a similar experiment on his 11 month old son
![Page 7: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/7.jpg)
Jesse William Lazear, (1866 - 1900)
![Page 8: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/8.jpg)
Jesse William Lazear
• Demonstrated important characteristics of the transmission yellow fever
• “I think I am on the track of the real germ” – JWL wrote to his wife from Cuba
• Died 17 days later from Yellow Fever• Investigations showed he inoculated himself for
the experiments• Other members of the team also had themselves
inoculated as a precondition to joining
![Page 9: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/9.jpg)
Yellow Fever• 1897 Sanarelli claimed he isolated the organism• To prove his claim he inoculated five men
![Page 10: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/10.jpg)
William Osler
• 1898 - Osler condemns Sanarelli:
“To deliberately inject a poison
of known high degree of virulence
into a human being,
unless you obtain that man’s
sanction,
is not ridiculous,
it is criminal”
![Page 11: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/11.jpg)
Yellow Fever• Three years later Walter Reed was
commissioned to study the epidemic in Cuba• Laid down the condition about members serving
as subjects; only adults to be recruited• Drew up a contract – the first written consent
form• $ 100 for participants and $100 for those
infected
![Page 12: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/12.jpg)
Nazi Experiments 1939-1945
Over 7000 people in 70 experiments
200 physicians
![Page 13: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/13.jpg)
Nazi experiments
• Intrauterine injection of silver nitrate during routine examination
• High altitude
![Page 14: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/14.jpg)
![Page 15: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/15.jpg)
Nazi experiments
• Poisons
• Sulphonamides
• Biological warfare experiments
![Page 16: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/16.jpg)
The Nuremberg Code 1947
![Page 17: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/17.jpg)
The Nuremberg Code
• The third part of the judgement
• 10 principles of ethical research
“the voluntary consent of the human subject is absolutely essential”
![Page 18: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/18.jpg)
Was it enough to stop unethical experimentation?
![Page 19: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/19.jpg)
Ethics and Clinical Research
Henry K. Beecher
New Engl J Med. 274 (1966)
![Page 20: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/20.jpg)
Henry K Beecher
• Discussed 22 papers with questionable ethical backgrounds
• All conducted in reputable organizations by reputable researchers
• A landmark publication
• “thoughtlessness and carelessness”
• “NOT a wilful disregard for patient’s rights account for most of the cases”
![Page 21: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/21.jpg)
Henry K Beecher
• Not to blame, but to draw attention
• The belief at the time was that adherence to Nuremberg was unnecessary for research in democracies
• Indispensable components = informed consent + virtuous researcher
![Page 22: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/22.jpg)
The Willowbrook Study
• Willowbrook school for children with mental and motor retardation
• Hepatitis virus was injected to children between 1963-1966 to learn the natural progress of infectious hepatitis
• The school was closed to new admissions during the trial• Only parents who consented to have their children
entered into the trial were allowed to register for admission
• It was known that children admitted to these facilities almost invariably developed Hepatitis
![Page 23: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/23.jpg)
The Jewish Chronic Disease Hospital Study
• Live cancer cells were injected into patients in advanced states of cancer
• Results suggested that the defence mechanisms of those developing cancer may be impaired
• Live cancer cells injected into young healthy volunteers were promptly rejected
• Consent was said to have been obtained• Probably obtained fraudulently
![Page 24: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/24.jpg)
May 16, 1997
Tuskegee trial
President Clinton apologised from USA citizens because of Tuskegee trial
![Page 25: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/25.jpg)
Tuskegee trial
• Started in 1932; ended 1972
• Study group of 400 men with syphilis; 200 healthy controls
• Offered free treatment
• Observation only, subjects not told
• Death rate x 2 in study group
• Penicillin available from 1952
![Page 26: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/26.jpg)
Other Guidelines
• Declaration of Helsinki – 1964
• Belmont report – 1979
• CIOMS and WHO international guidelines – 1991 & 1993
![Page 27: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/27.jpg)
“Death at the Hands of Science”
Ellen Roche, 24, died June 2001
Johns Hopkins University
![Page 28: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/28.jpg)
Ellen Roche• A study on inhaled hexamethonium in the
treatment of asthma
• A 24 year old healthy volunteer
• Worked at Johns Hopkins
• Died despite vigorous treatment for pulmonary and renal failure
• JH accepted “institutional responsibility” for the death
![Page 29: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/29.jpg)
Ellen Roche
External Review Report • “Oversight and regulatory mechanisms at JH are
a hindrance to research”• Subtle coercion may have been used in
recruitment• IRBs (ERCs) were totally inadequate to deal with
the number of projects• PI was criticized for not sterilizing the drug• FDA approval not sought• The state temporarily stopped 2400 experiments
being conducted at JH
![Page 30: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/30.jpg)
Research is Big Money!!
Research is subcontracted to companies
![Page 31: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/31.jpg)
TGN 1214 Phase I Study
Contracted to PAREXEL by the developers
![Page 32: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/32.jpg)
• TGN 1412 designed to treat rheumatoid arthritis, leukaemia and multiple sclerosis
• A monoclonal antibody
• Six healthy volunteers developed multiple organ failure within hours of being administered the drug
• Required vigorous intensive care, and survived
• All six given the drug at the same time
![Page 33: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/33.jpg)
Adherence to Ethical Principles by Researchers: Experiences of a Sri Lankan
Biomedical Research Ethics Committee
Hemantha Senanayake
Rohini Fernandopulle
Sumudu Bujawansa
Hemal Ariyaratne
![Page 34: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/34.jpg)
Experience in Sri Lanka
2002 2003
Specified written consent would be sought
32% 46%
Verbal consent only 51% 32%
Applied after commencement 8% 16%
Recruitment by doctor providing care
14% 39%
Inadequate justification for study 53% 62%
![Page 35: Research Ethics: History and Scandals](https://reader035.vdocuments.net/reader035/viewer/2022081419/56812ae5550346895d8ecb46/html5/thumbnails/35.jpg)
Cautions for Sri Lanka
• Easy to get into ‘scandals’
• Rigid review
• Adequate justification
• Beware doctors recruiting patients
• Application for clearance after commencement/completion
• Training of ERC members
• Lay members