Addressing Bad Research

1. Addressing Bad Research Rels 300 / Nurs 330 24 October 2013

2. 300/330 - appleby The Tuskegee Syphilis Study 1932 to 1972, Macon County, Alabama • 399 African American male sharecroppers recruited for a study on the natural progression of syphilis to death • told that they were being treated for “bad blood” – this was how syphilis was known to them • 201 African American men without syphilis also recruited • all subjects were poor, black, largely illiterate, and had no access to regular medical care

3. 300/330 - appleby • in 1943, penicillin emerged as an effective treatment for syphilis – this was not offered to the Tuskegee subjects • benefits limited to free medicines, burial insurance, free hot meals on examination days, transport to and from hospital

4. 300/330 - appleby Evaluate the Tuskegee Study using the Nuremberg Code (1947) • Voluntary consent • Fruitful results for the good of society • Based on the results of animal experimentation and a knowledge of the natural history of the disease • Avoid all unnecessary physical and mental suffering and injury • No expectation of death or disabling injury • Degree of risk should never exceed the humanitarian importance of the problem to be solved • Protect the experimental subject against even remote possibilities of injury, disability, or death • Conducted only by scientifically qualified persons • Human subject should be at liberty to bring the experiment to an end • Scientist must terminate the experiment at any stage if there is a likelihood of injury, disability, or death

5. 300/330 - appleby President Clinton’s Apology, 1997 (http://clinton4.nara.gov/textonly/New/Remarks/Fri/19970516-898.html ) “The eight men who are survivors of the syphilis study at Tuskegee are a living link to a time not so very long ago that many Americans would prefer not to remember, but we dare not forget. “It was a time when our nation failed to live up to its ideals, when our nation broke the trust with our people that is the very foundation of our democracy…

6. 300/330 - appleby President Clinton with Syphilis Study participant Herman Shaw - May 16, 1997 “So today America does remember the hundreds of men used in research without their knowledge and consent… Men who were poor and African American, without resources and with few alternatives, they believed they had found hope when they were offered free medical care by the United States Public Health Service. They were betrayed. “Medical people are supposed to help when we need care, but even once a cure was discovered, they were denied help, and they were lied to by their government… “The American people are sorry -- for the loss, for the years of hurt. You did nothing wrong, but you were grievously wronged. I apologize and I am sorry that this apology has been so long in coming.” (http://clinton4.nara.gov/textonly/New/Remarks/Fri/19970516-898.html)

7. 300/330 - appleby Tuskegee Legacy 1974 – US National Research Act • National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research The Belmont Report Established 3 basic ethical principles: • respect for persons • beneficence • justice

8. 300/330 - appleby The Belmont Report PRINCIPLE Respect for persons • Individuals should be treated as autonomous agents • Persons with diminished autonomy are entitled to protection. APPLICATION Informed consent • Subjects, to the degree that they are capable, must be given the opportunity to choose what shall or shall not happen to them • The consent process must include three elements: • information, • comprehension, and • voluntariness.

9. 300/330 - appleby The Belmont Report PRINCIPLE Beneficence • Human subjects should not be harmed • Research should maximize possible benefits and minimize possible harms. APPLICATION Assessment of risks and benefits • The nature and scope of risks and benefits must be assessed in a systematic manner.

10. 300/330 - appleby The Belmont Report PRINCIPLE Justice • The benefits and risks of research must be distributed fairly. APPLICATION Selection of subjects • There must be fair procedures and outcomes in the selection of research subjects

11. 300/330 - appleby The Belmont Report Full text can be found at: http://ohsr.od.nih.gov/guidelines/belmont.html Significance of Belmont Report for the developing field of Bioethics? • Respect for persons → Autonomy • Beneficence – and risks / harms – Nonmaleficence • Justice – fairness and equality

12. 300/330 - appleby Willowbrook State Mental Hospital for ChildrenStaten Island, New York – mid 1950s

13. 300/330 - appleby http://www.museumofdisability.org/newyork_timeline_1960s.asp

14. 300/330 - appleby As the institutional population skyrocketed, admissions were suspended unless parents agreed to place their child in the hepatitis ward • new children were deliberately infected with hepatitis to provide optimal control in the study • parents were misled by exaggerations of the potential benefits of the study • doctors claimed that the conditions were so unsanitary that the children would have developed hepatitis anyway

15. 300/330 - appleby Dr. Saul Krugman& Dr. Joan Giles:infectious disease specialists RESEARCH GOALS: • to determine the natural history of viral hepatitis – its mode of infection and the course of the disease • to test the effectiveness of gamma globulin in developing an inoculation against hepatitis Krugman & Giles collected serum specimens before exposure, during the incubation period, and several times post-infection

16. 300/330 - appleby “Therapeutic” Effect Drs. Krugman & Giles claimed that deliberately infecting the children was therapeutic because of their resulting immunity to hepatitis. • the hepatitis strain was mild • had optimum isolation facilities • minimal exposure to other infectious diseases • had consent from parents • could withdraw consent before study was initiated in child • significant scientific progress resulted from study

17. 300/330 - appleby As measured against Nuremberg Code: • Voluntary consent • Fruitful results • Results of animal experimentation • No unnecessary physical and mental suffering and injury • No death or disabling injury • Degree of risk less than humanitarian importance • Protect the experimental subject • Experiment conducted by scientifically qualified persons • Human subject can bring experiment to an end • Terminate experiment if evidence of injury, disability or death

18. 300/330 - appleby As measured againstBelmont Report Principles Respect for persons • Individuals should be treated as autonomous agents • Persons with diminished autonomy are entitled to protection. Beneficence • Human subjects should not be harmed • Research should maximize possible benefits and minimize possible harms. Justice • The benefits and risks of research must be distributed fairly.

19. 300/330 - appleby 1991 Symposium at the NYU School of MedicinehonouringDr. Saul Krugman “Dr. Krugman’s most important scientific achievements were in the unraveling of the mysteries of infectious hepatitis.”