Transcript The Third World as Guinea Pig? Unethical clinical trials

“Is the Developing World the
Answer?”
Unethical clinical trials in the Third World
Sammy Almashat, MD, MPH
Sidney Wolfe, MD
Public Citizen’s Health Research Group
Outline
• History and structure of human
experimentation
• The commercialization of human
experimentation: conflicts of interest abound
• A story of self-regulation and the honor code
• Globalization of clinical trials: “Is the
developing world the answer?”
• Case studies of double-standards for the Third
World and efforts to stop unethical trials
Clinical Trials
• Thousands of trials of pharmaceuticals and
medical devices conducted on tens of
thousands of people every year
• Human testing necessary to ensure safe and
effective products prior to marketing
• The question is: who’s doing the testing on
whom, and who’s watching them?
The Birth of a Drug
Test tube (in vitro) testing
Animal testing
Human testing
Phase 1
• Few healthy patients, testing safety
Phase 2
• First study with sick patients, testing safety and efficacy
Phase 3
• Largest trials with sick patients, testing safety and efficacy
Time is Money
• Drug development is risky, expensive, and
time-consuming
• Average drug reaches market 7-10 years after
first tests at a cost of anywhere from $55
million to $800 million per drug
• Incentive is high to cut costs (and corners) and
speed up the process
The Economics of Drug Development
• Human Experimentation Corporations (HECs)
– Started in the 1970s as small companies specializing in
biopharmaceutical (bench) testing
– Grew dramatically in the past few decades and moved
into clinical (human) research, growing to a $20 billion
industry by 2008, with annual growth rates of 15-17%
• The IRB industry
– Paralleled growth of HECs
– Increasingly for-profit
– “IRB-shopping”
Birth of Research Ethics
• Atrocities of human experimentation in the
20th century prompted the development of
universal ethical principles to govern all such
research in the future
Universal Principles in Human Subjects
Research
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What do we mean by “unethical”?
Nuremburg Code
Declaration of Helsinki
Belmont Report and Common Rule (U.S.)
FDA (abandoned Helsinki in 2008)
Universal Principles in Human Subjects
Research
•
•
•
•
Informed consent
Truly voluntary (not coerced) participation
Beneficence
Equity and justice
Clinical trial oversight
X
U.S./Host Govt.
X
IRBs
X
Drug Company/HECs
2009 – GAO goes undercover
• Fake IRB
• Fake medical device company with fake device
• Real medical device and IRB companies – and
the Feds – all took the bait
“Globalization” of the Clinical Trial
Industry
Clinical Trials in the Developing World
Globalization of Clinical Trials
• 80% of drugs are now approved based on data
from foreign clinical trials
• Over half of clinical trial subjects and sites are
located outside the United States
• One-third of trial investigators are now from
foreign sites
Why are companies moving abroad?
• Cost
• Speed
– The “patient advantage”
• Escaping regulatory “burdens”
Special considerations with vulnerable
populations
Exploitation is almost inherent in these trials
- Lack of informed consent
- Direct and indirect coercion
- Lack of Equity
- Lack of Recourse
- Companies are not liable for intentional let alone
unintentional harm caused by experimental
drugs (certainly not liable for NOT giving
effective treatment to a placebo group).
Case Studies:
Double standards for the Third World
Case Study: Unethical HIV trials
• 1997: Nine U.S. government-funded studies of
pregnant women in Africa, Asia, and the
Caribbean
• Half the women in these trials received AZT, a
therapy proven to help prevent HIV
transmission to the fetus
• The other half received ineffectual placebos
Provision of Antiretroviral Drugs in Perinatal
Trials
Number of studies
18
16
14
12
All studies
10
Studies with active
controls
8
6
4
2
0
Studies in
U.S.
Studies in
developing
countries
Case Study: The Surfaxin trial
• Title of internal FDA meeting: “Use of
placebo-controls in life threatening
diseases: is the developing world the
answer?”
• Location: Mexico, Peru, Bolivia, Ecuador
• Design: Surfaxin vs. placebo (vs. approved
surfactant)
Case Study: The Surfaxin trial
• Discovery Laboratories (Johnson & Johnson),
Doylestown, PA
• Synthetic surfactant (Surfaxin)
• 4 surfactants on the market (1st in 1990)
• Associated with 34% relative reduction in
neonatal mortality (Cochrane meta-analysis)
“Without doubt the most thoroughly studied
new therapy in neonatal care” (NEJM review)
Case Study: The Surfaxin trial
• “Further placebo controlled trials of synthetic
surfactant are no longer warranted.”
(Cochrane)
• FDA: “Conduct of a placebo controlled
surfactant trial for premature infants with RDS
is considered unethical in the USA.”
• European trial: Surfaxin vs. approved
surfactant
42 Randomized Trials of Natural and
Synthetic Surfactant in the Treatment of
Neonatal Respiratory Distress Syndrome
9
Number of trials
8
7
6
5
No Placebo
Placebo
4
3
2
1
0
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Year of Publication
Case Study: The Surfaxin trial
• February 2001: Public Citizen writes to HHS
Secretary Tommy Thompson
• March 2001: Bolivian health ministry says the
study is “totally prohibited” for legal, ethical
and social reasons
• April 2001: Discovery announces study
changed to compare to known effective
surfactant
Advertisement by Human Experimentation Corporation
(HEC) Quintiles to the Pharmaceutical Industry: January,
1998
What needs to be done
• More oversight
• Addressing conflicts of interest
• Tying in with more high-profile Third World
health justice causes (e.g. access to
medicines)
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