Transcript Michael Goodyear - Looking glass Part II - REB

Part I
Where are We Now?
The Ongoing Problems
• Role Confusion
– Mission Creep
– Administrivia
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The Collapse of Scientific Integrity
Inadequate Resources
Increasing Complexity of Science
Patchwork Quilt
Accountabilty
Inflexible
Gunsalus CK, Bruner EM, Burbules NC, Dash L,
Finkin M, Goldberg JP, Greenough WT, Miller GA,
Pratt MG
Mission creep in the IRB world.
Science. 2006 Jun 9;312(5779):1441.
Mission Creep in the IRB World
• System endangered by excessive paperwork
– Overregulation and underprotection
• Overwhelmed by procedures and
documentation at expense of thoughtful
consideration
• ‘Ethics Police’
• Researchers equate ‘Human Protection’
– with frustrating delays, expensive paperwork
Mission Creep in the IRB World
• *Ethics a Collective Responsibility
• IRBs not a substitute for Ethical Thinking
and Behaviour
• Should cultivate Ethical Culture
• Researchers and IRBs need Support
– local
– central
The Ongoing Problems
• Role Confusion
• The Collapse of Scientific Integrity
– A crisis in trust
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Inadequate Resources
Increasing Complexity of Science
Patchwork Quilt
Accountabilty
Inflexible
Why is There a Crisis in Trust?
Evidence Based Medicine
Archie Cochrane
(1909-1988)
Evidence Based Medicine
Why is There a Crisis in Trust?
• Evidence Based Medicine
– Replaced Opinion, Anecdotes and Experts
– Based on Systematic Reviews of high quality
evidence (RCTs)
– Practice Based Guidelines
• Graded by Strength of Evidence
– So far, so good, BUT
Why is There a Crisis in Trust?
• Evidence Based Medicine
A House of Cards Built on Sand?
Why Is There a Crisis in Trust?
• Public Perceptions (1)
– Law Suits Against Industry
• data suppression
– Publication ethics
June 3, 2004
Spitzer Sues a Drug Maker, Saying It Hid Negative Data
By GARDINER HARRIS
In a novel claim testing the way that the $400 billion worldwide
pharmaceutical industry is regulated, the New York State attorney general,
Eliot Spitzer, sued the British-based drug giant GlaxoSmithKline yesterday,
accusing the company of fraud in concealing negative information about
its popular antidepressant medicine Paxil. (Paroxetine)
The civil lawsuit, filed in State Supreme Court in Manhattan, contends that
GlaxoSmithKline engaged in persistent fraud by failing to tell doctors that
some studies of Paxil showed that the drug did not work in adolescents
and might even lead to suicidal thoughts. Far from warning doctors, the
suit contends, the company encouraged them to prescribe the drug for
youngsters.
Why Is There a Crisis in Trust?
• Public Perceptions (1)
– Law suits against industry
– Publication Ethics
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Publication Bias
Outcome Bias
Altered outcomes
Publication restrictions
Suppressed data
Ghost writing
This past year has been a bumper
year for research and publication
misconduct
COPE Report 2005
Why Is There a Crisis in Trust?
• Public Perceptions (1)
– Law suits against industry
– Publication Ethics
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Publication Bias
Outcome Bias
Altered outcomes
Publication Restrictions
Suppressed data
Ghost writing
Industry Publication Restrictions
Facilitate Selective Reporting
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“If there are disagreements with the investigators’
analyses, new or repeated analyses are required before
publication. The Sponsor remains sole owner of the
data.”
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“Only the Sponsor has the right to publish results.”

“Any information which the Sponsor deems confidential
must be deleted prior to submission.”
AW Chan, Gøtzsche P et al JAMA 2006 295: 1645
Why Is There a Crisis in Trust?
• Public Perceptions (1)
– Law suits against industry
– Publication Ethics
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Publication Bias
Outcome Bias
Altered outcomes
Publication restrictions
Suppressed Data
Ghost writing
Volume 354:1193 March 16, 2006 Number 11
Expression of Concern Reaffirmed
Gregory D. Curfman, M.D., Stephen Morrissey, Ph.D., and Jeffrey M.
Drazen, M.D.
On December 8, 2005, we published an expression of concern
regarding an article by Bombardier et al. on the Vioxx Gastrointestinal
Outcomes Research (VIGOR) study that was published in the Journal
on November 23, 2000. Our expression of concern was prompted by
evidence that the VIGOR article did not accurately represent the safety
data available to the authors when the article was being reviewed for
publication.
…critical data on an array of adverse cardiovascular events that were
not included in the VIGOR article. These data, which should have
raised concern about potential cardiovascular toxicity of rofecoxib…
Why Is There a Crisis in Trust?
• Public Perceptions (1)
– Law suits against industry
– Publication Ethics
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Publication Bias
Outcome Bias
Altered outcomes
Publication restrictions
Suppressed data
Ghost Writing
– David Healey, Carl Elliott
Why Is There a Crisis in Trust?
Ghost Writing
“Dear Dr …., In order to reduce your workload to
a minimum we have had our Ghost Writers
produce a first draft based on your published work
…”
The British Journal of Psychiatry (2003) 183: 22-27
Interface between authorship, industry and science in the domain of
therapeutics
DAVID HEALY, FRCPsych and DINAH CATTELL
North Wales Department of Psychological Medicine, University of Wales College of
Medicine, Bangor, UK
Unacknowledged editorial or writing assistants to academic authors – socalled ghostwriters – are often employed by medical communication agencies
working for pharmaceutical companies. Efforts have been made to quantify
the extent to which ghostwriting is happening, with Flanagin et al (1998)1
reporting that up to 11% of articles published in six peer-reviewed journals in
1996 involved the use of ghostwriters.
1.A. Flanagin et al.
Honorary Authors and Ghost Authors in Peer-Reviewed Medical Journals
JAMA 280 (1998): 222-24
Why Is There a Crisis in Trust?
• Public Perceptions (2)
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Death and Injury of Volunteers
Breaches of integrity
Commercialisation
Unnecessary research
Ellen Roche
Would Ellen be Alive
Today,
if all Hexamethonium
Trials had been
Registered?
Ellen Roche, a Healthy Volunteer
Unnecessary Research
Jesse Gelsinger
“What's the worst
that can happen to
me? …
I die, and it's for
the babies.“1
1 New York Times, 28 Nov 1999
Why Is There a Crisis in Trust?
• Public Perceptions (2)
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Death and Injury of Volunteers
Breaches of integrity
Commercialisation
Unnecessary research
Vol 435|9 June 2005
nature
COMMENTARY
Scientists behaving badly
Brian C. Martinson, Melissa S. Anderson and Raymond de Vries
Serious misbehaviour in research is important for many reasons, not least
because it damages the reputation of, and undermines public support for,
science.
(n=3,247)
Overall, 33% of the respondents said they had engaged in at least one of the top
ten behaviours during the previous three years.
Changing the design, methodology or results of a study in response to
pressure from a funding source 16%
Why Is There a Crisis in Trust?
• Public Perceptions (2)
– Death and Injury of Volunteers
– Breaches of integrity
– Commercialisation
• Conflicts of interest
• Health Care Industry
• Globalisation
– Unnecessary research
Global Corruption Report 2006
Special focus:
CORRUPTION AND
HEALTH
Editorial
Corruption in health care costs lives
Volume 367, 11 February 2006 447
The word corruption—abuse of entrusted power
for private gain—rarely enters health
professionals' vocabulary and is frequently
softened to unethical or unprofessional
behaviour
Testing new drugs
on the world’s poorest patients
Why Is There a Crisis in Trust?
• Public Perceptions (2)
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Death and Injury of Volunteers
Breaches of integrity
Commercialisation
Unnecessary Research
• Ellen Roche
• Aprotinin
Cumulative Meta-analysis of
Aprotinin for Perioperative
Bleeding1
Where was Equipoise?
1 Fergusson, Glass, Hutton, Shapiro: Clinical Trials 2:218, 2005
Why Is There a Crisis in Trust?
• Public Perceptions (3)
– Inappropriate sponsor involvement
– Safety issues
• Paroxetine (Paxil)
• Rofecoxib (Vioxx)
• Class I Antiarrhythmic Drugs
– Disease Mongering
“Widening the boundaries of treatable illness in
order to expand markets for those who sell and
deliver treatments”
Moynihan R, Heath I, Henry D
Selling sickness: The pharmaceutical industry and disease
mongering.
BMJ 2002 324: 886–891
Vol 3(4) April 2006
Why Is There a Crisis in Trust?
• Public Perceptions (4)
– Claims of large numbers of Unnecessary
Deaths from inappropriate publication
– Consumer group websites publish daily
bulletins on wrongdoing in research
Rofecoxib
Cardiovascular Risk Factors
VIGOR Trial (4%)
Increased Risk: 38% CV events
Risk Ratio: 2.5
Event Rate 1.5%
Tennessee Medicaid Study (40%)
Event Rate 11.6
NNH: 556 v 70 (8 fold)
“It is not until drugs go out into the world and they are used in real
patients” EMEA
Why Is There a Crisis in Trust?
• Public Perceptions (4)
– Claims of large numbers of unnecessary deaths
from inappropriate publication
– Consumer Group Websites publish daily
bulletins on wrongdoing in research
Vera Hassner Sharav, M.L.S.
Where Has Science Gone Wrong?
• Has science lost its way?
– Collaboration replaced by Secrecy
– Obsession with Commercialisation
– Lost Sight of Normative Values
Has Science lost its Way?
• The majority of new products since 1990
have not improved health care compared to
less costly and better understood drugs
• Many are analogues (me-too) and
reformulations designed to improve market
share and prolong patents
• Are IRBs legitimising fraud?
Sponsor always Wins!
Heres S, Davis J, Maino K, Jetzinger E, Kissling W,
Leucht S.
Why olanzapine beats risperidone, risperidone
beats quetiapine, and quetiapine beats
olanzapine: an exploratory analysis of head-tohead comparison studies of second-generation
antipsychotics.
Am J Psychiatry. 2006 Feb;163(2):185-94.
If A > B, and B > C, then why is C > A?
Unhealthy Medicine: All Breakthrough,
No Follow-Through
By Steven H. Woolf
Sunday, January 8, 2006
We spend far more money on inventing new
treatments than on research into how to deliver
them
Developing new treatments often does less good
than ensuring the delivery of older drugs to all
those in need
Beyond dissatisfaction, the larger problem with our focus on
medical breakthroughs is that more Americans will die as a
result
We have reached a point when progress in providing good
care – when needed, with compassion and skill and without
errors -- would impress the public as a more meaningful
"medical advance" than the rollout of the latest device or pill.
Department of Family Medicine
Virginia Commonwealth University