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HSTCMP 410 A: Medicine, History, & Society

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Presentation on theme: "HSTCMP 410 A: Medicine, History, & Society"— Presentation transcript:

1 HSTCMP 410 A: Medicine, History, & Society
The End of Therapeutic Optimism May 25, 2016 Laura Harkewicz, Ph.D.

2 Today’s agenda Recap The Thalidomide story Henry Beecher
Film: The Deadly Deception The Tuskegee Syphilis Study Consequences

3 Recap WWII successes like penicillin & blood lead to massive therapeutic optimism Optimism leads to increased funding for scientific & medical research Research into polio leads to massive public clinical trial of vaccine Polio pioneers & success of vaccine

4 Pharmaceutical industry in 1950s
Rapid development 300 new drugs hitting market every year Some useful ones Others more questionable

5 Thalidomide Sedative Chemie Grünenthal, founded
Director of R&D was Heinrick Mückter Henrick Mückter (1914 – 1987)

6 Structure similar to barbiturates
Began testing it in animals for sedative effect No demonstrated effect in animals Non-lethal Thalidomide structure

7 1955 - began distributing free samples of Thalidomide to doctors in Germany
For seizure disorders No effect on epileptic seizures But patients reported had a calming effect Marketed as a non-lethal sedative

8 Marketing as a sedative
“Jiggle cage” over the counter sale Chemie Grünenthal factory

9 Side effects develop Included:
Dizziness, headaches, memory loss, decreased blood pressure Numbing and tingling of the hands and feet (peripheral nephritis) Company denied

10 Birth defects? Cases of extremely rare birth defects in Germany
No one makes connection to drug In Australia - Thalidomide for her acute morning sickness connect the birth defects with the drug

11 Marketing thalidomide in U.S.
Richardson-Merrell and Co. - March for release of Thalidomide in the US Clinical trials did not require FDA approval Distributed “samples” eighteen months before their application 20,000 people received

12 The FDA Had 60 days to respond to an application
No proof of efficacy requirement Drug was automatically approved if agency did not respond in 60 days

13 The FDA and Thalidomide
Application was submitted in September 1960 A huge advertising campaign was planned A newly appointed medical officer received application for review

14 Frances Kelsey & the FDA
Degree in pharmacology from the University of Chicago where she was involved in toxicology studies Science in application not rigorous enough Pressured Kelsey ( )

15 Consequences November, 1961 - drug was being withdrawn in Europe
End of therapeutic optimism of the 1950s Led to reforms in the FDA

16 Estes Kefauver Estes Kefauver (1903 – 63), a crusading Democratic senator from Tenn. Used the publicity about Thalidomide to bring about a series of reforms to FDA practice Along with U.S. Rep. from Arkansas, Oren Harris (1903 – 1997) developed FDA reforms

17 Kefauver-Harris amendments
Passed unanimously in both houses of Congress in 1962 Drugs had to be proven effective as well as safe All side effects had to be reported to the FDA Advertisements had to include a complete report of any risks Clinical trials conducted according to strict protocols

18 Impact on Clinical Medicine
In 1962, an NIH official was asked to report on the “Moral and ethical aspects of clinical investigation” The resulting 1964 “Livingstone Report” admitted …

19 Henry Beecher (1904 – 1976) Early investigator of placebo effect
Harvard Med. School In charge of anesthesiology Massachusetts General Hospital Early investigator of placebo effect

20 A maverick and crusader
Published a 1954 paper, “Study of the deaths associated with anesthesia and surgery” Among the first to insist on controls for clinical trials Bad ethics result in bad science

21 “Ethics of Clinical Research”
In March 1965, at a conference on drug research sponsored by Upjohn, Beecher delivered a paper on ethics in clinical research that named particular cases Use of real cases caught the media’s attention and the NY Times and the Wall St Journal published reports

22 Presented twenty “breaches of ethical conduct” by American clinical researchers
Subjects are not asked for their permission“ Examples included: 23 charity patients who died when treatment for typhoid fever was experimentally withheld from them 50 healthy inmates of a children’s center who were given repeated doses of a drug which caused abnormal liver function 18 children undergoing heart surgery all of whom received unnecessary experimental skin grafts

23 Aftermath to Beecher’s presentation & media attention
Colleagues refute his claims Beecher’s response was to turn the paper into an article JAMA wouldn’t take it so Beecher turned to NEJM

24 Despite such critiques, Beecher’s article was published in the NEJM in 1966

25 Consequences of Beecher’s article
NIH recognized the need for reform but argued “it is not possible to convey all information to the subject” However, this was the birth of the Institutional Review Board – the peer review committee appointed by a research institution to monitor human subject research

26 IRBs & informed consent
IRB should be fellow scientists Widespread resistance to the principle of informed consent One Harvard scientist said…

27 Waffling on informed consent
NIH - “You will be asked to sign a statement indicating that you understand the project and agree to participate in it. If you find your assigned project to be intolerable, you may withdraw from it.” FDA rules were also a bit hazy on the concept of informed consent

28 Loopholes Therapeutic research? Non-therapeutic research?
Informed consent for all non-therapeutic studies Why distinction important? The major loophole concerned “exceptional cases”

29 “Exceptional cases” Consent not feasible or not in the patient’s best interests “Not feasible” meant the patient was unable to understand the information “Not in the patient’s best interest” meant that seeking consent would “seriously affect the patient’s disease status” Left up to the researcher

30 War on disease continues

31 War on Cancer In 1971, President Nixon declared “War on Cancer”
Dozens of different concepts tried None produced magic bullet “Medical Vietnam”

32 Break

33 Film The Deadly Deception

34 The Tuskegee Syphilis Study

35 Macon County, Alabama Home to Tuskegee Institute – founded by former slave Booker T. Washington, most famous black college in nation Populated by poor farmers, 90% black County had few doctors Public facilities rigidly segregated by race Typical farm cabin Sharecropper

36 Beginnings of Study 1932 – announcement of day of free health assessments & screening tests Clinic flooded with people Hundreds had blood drawn

37 “Bad Blood” Those who tested positive for syphilis were called back
Told they were to be treated for “bad blood”

38 Non-treatment treatment
Vitamins & mercury salves Had to do spinal taps to verify the diagnosis Announcement “REMEMBER, THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT. BE SURE TO MEET THE NURSE.”

39 When people showed up they ran the spinal taps and selected 399 men to study
With 200 uninfected men being selected as controls Gave the infected subjects aspirin

40 The Players U.S. Public Health Service Dr. Eugene Dibble
[head of local hospital – encourage cooperation with study] Dr. Taliaferro [Tolliver] Clark [started study] Dr. Raymond Vonderlehr [on-site director of study] Nurse Eunice Rivers [chief on-site asst.]

41 Tuskegee Study of Untreated Syphilis
In 1934, PHS docs met with local black physicians PHS circulated a list of men in the study to the draft board penicillin first became available as a treatment By 1955, the subjects were dying at twice the rate of the control group 40 wives were infected and 19 children were born with syphilitic birth defects

42 The story comes out...? 1965, Students for a Democratic Society held a rally urging that it be stopped Ignored A doctor in Detroit wrote PHS The letter was never answered

43 The Study was never secret

44 The Whistleblower Peter Buxtun
In 1966, he filed an official complaint with his superiors asking that the Study be stopped Buxton left the PHS Peter Buxton

45 The story comes out...finally
By 1969, 100 of the participants had died of syphilis On July , Jean Heller of the Associated Press broke the story

46 Consequences to Tuskegee Study

47 Consequences Public outrage was followed by the promise of government action In August, 1972 an investigation was launched Panel concluded that reforms to federally- funded human research policies were needed and that

48 Human research regulations
1974 – National Research Act – creates Common Rule – – updated in 1991 1976 – NIH creates Office for Protection from Research Risks – later renamed Office fro Human Research Protection 1979 – National Commission for the Protection of Human Subjects of Biomedical & Behavioral Research – issues “Belmont Report”

49 Summary: Belmont Principles
Application Respect for persons Autonomy Obtain consent Protect vulnerable populations Beneficence Benefits outweigh risks Minimize risks Justice Subject selection

50 Ethical dilemmas in human subject research
Good of individual versus good of society Weighing risks versus benefits Joint distribution of benefits & harms Research versus practice (e.g. therapy)

51 Medical Nemesis book entitled Limits to Medicine: Medical Nemesis and the Expropriation of Health Written by Ivan Illich Austrian philosopher, Roman Catholic priest, & social critic Illich argued… Ivan Illich (1926 – 2002)

52 The end of therapeutic optimism
By the end of the 1970s, the therapeutic optimism that had characterized the immediate post-war period was at an end. Medical research was viewed with suspicion, medical paternalism was under attack, and the pharmaceutical industry’s reputation was at an all-time low.

53 Ironies....

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