Transcript Is the relationship between the industry and prescribers (doctors) in

Conflicts of interest: a
case study in
entanglement
How common are
competing interests?
• A quarter of US researchers have received
pharmaceutical funding
• Half have received “research related gifts”
• An analysis of 789 articles from major
medical journals found that a third of the
lead authors had financial interests in their
research—patents, shares, or payments for
being on advisory boards or working as a
director
• Bekelman JE, Li Y, Gross CP. Scope and impact of
financial conflicts of interest in biomedical
research. A systematic review. JAMA 2003; 289:
454-65.
How common are
competing interests?
• 75 pieces giving views on calcium
channel blockers
• 89 authors
• 69 (80%) responded
• 45 (63%) had financial conflicts of
interest
• Only 2 of 70 articles disclosed
the conflicts of interest
• Stelfox HT, Chua G, O'Rourke K, Detsky AS. Conflict of
interest in the debate over calcium channel antagonists.
N Engl J Med 1998; 338: 101-105
Do authors declare
conflicts of interest?
• 3642 articles in the five leading
general medical journals (Annals
of Internal Medicine, BMJ, Lancet,
JAMA, and the New England
Journal of Medicine)
• Only 52 (1.4%) declared authors'
conflicts of interest
• Hussain A, Smith R. Declaring financial
competing interests: survey of five general
medical journals. BMJ 2001;323:263-4.
Does conflict of interest
matter?
• Is there a relationship between
whether authors are supportive
of the use of calcium channel
antagonists and whether they
have a financial relationship
with the manufacturers of the
drugs?
• Stelfox HT, Chua G, O'Rourke K, Detsky AS. Conflict
of interest in the debate over calcium channel
antagonists. N Engl J Med 1998; 338: 101-105
Sponsored research
• A systematic review found 30 studies that
compared research funded by drug companies
research funded by other sources
• Company sponsored research more likely to be
published
• Studies sponsored by pharmaceutical
companies were more likely to have outcomes
favouring the sponsor than were studies with
other sponsors (odds ratio 4.05; 95%
confidence interval 2.98 to 5.51; 18
comparisons)
• None of the 13 studies that analysed methods
reported that studies funded by industry was of
poorer quality
Does conflict of interest matter?:
third generation contraceptive pills
• At the end of 1998 three major studies without
sponsoring from the industry found a higher risk of
venous thrombosis for third generation
contraceptives; three sponsored studies did not.
• To date, of nine studies without sponsoring, one
study found no difference and the other eight found
relative risks from 1.5 to 4.0 (summary relative risk
2.4); four sponsored studies found relative risks
between 0.8 and 1.5 (summary relative risk 1.1)
• The sponsored study with a relative risk of 1.5 has
been reanalysed several times, yielding lower
relative risks; after this failed to convince, a new
reanalysis was sponsored by another company.
• One sponsored study finding an increased risk has
not been published.
What proportion of trials in the
five major general journals are
funded by industry?
• 75% in Annals of
Internal Medicine,
Lancet, JAMA, and
NEJM
• 30% in BMJ
In search of a
better relationship
between doctors
and drug
companies
Proposals for
disentangling
• Poll on bmj.com; 1479
responding
• Would you like doctors to stop
seeing drug company
representatives, replacing them
with more independent sources
of health information?
• 79% yes
Proposals for
disentangling
• Would you like doctors to stop
receiving all forms of direct and
indirect gifts from drug
companies?
• Yes 84%
• Would you like industry-funded
education of doctors replaced
by education funded by more
independent sources?
• Yes 84%
Proposals for
disentangling
• Would you like doctors' professional
associations and their peer-reviewed
journals to reduce their reliance on
industry funding to specified
maximum levels?
• Yes 85%
• Would you like all financial
relationships between doctors and
drug companies conducted with
transparent contracts that are
disclosed to patients and the public?
• Yes 96%
•
Proposals for
disentangling
Would you like mechanisms that
genuinely create more distance and
independence between
doctor/researchers and their research
sponsors?
• Yes 83%
• Would you like government/public agency
advisory panels, which are responsible
for independent assessment of medical
products or health policies, to reduce
their reliance on doctors with financial
ties to drug companies?
• Yes 87%
Proposals for
disentangling
• Would you like to see these
sorts of changes become
the basis of a charter for a
new relationship between
doctors and drug
companies?
• Yes 90%
Trouble 3—the
sad story of
HRT
The sad tale of HRT
• Hormone replacement therapy for
postmenopausal women was
widely expected to reduce
osteoporotic fractures, deaths
from heart disease and stroke, and
dementia
• A great many observational studies
supported these expectations
The sad tale of HRT
• An early analysis in the BMJ in 1997 of data
from trials suggested that far from from
decreasing deaths from cardiovascular
events HRT might increase them
• Insults heaped on the authors and on the
BMJ for publishing such “rubbish”
• Many of these comments came from
authors with undeclared competing
interests
• Elina Hemminki and Klim McPherson
Impact of postmenopausal hormone
therapy on cardiovascular events and
cancer: pooled data from clinical trials
BMJ, Jul 1997; 315: 149 - 153.
Results of Women’s
Health Initiative
• Began to be published in 2002
• Doubled deaths from breast cancer
• No decrease (and possibly an
increase) in deaths from heart
disease
• Increased thromboembolic disease
and strokes
• Increase in dementia
• No improvement in quality of life
The sad tale of HRT
• More than 100 million women
worldwide have taken HRT
• Professor Bruno MüllerOerlinghausen, the head of the
German Commission on Safety of
Medicines, called HRT a "national
and international tragedy."
• Comparing it to thalidomide, he
said that the "naive and careless
use of a medication that is
perceived as natural and optimal"
had caused many unnecessary
deaths among women.
The sad tale of HRT
• In the 1960s American
physician Robert Wilson wrote
the influential Forever Feminine,
extolling the virtues of HRT as a
virtual fountain of youth for the
"dull and unattractive" ageing
woman
• In 2002 it emerged that Wyeth
paid Wilson for the book
The sad tale of HRT
• In 2002 the New York based
Society for Women's Health
Research, whose "sole mission is
to improve the health of women
through research," held a celebrity
gala celebrating women's "coming
of age"
• The gala was entirely underwritten
by Wyeth
• A few days later Wyeth donated
£250 000 to the society
The sad tale of HRT
• Wyeth’s share price halved when the first
results of the Women’s Health Initiative
was published
• Phyllis Greenberger, CEO of the Society
of Women’s Health Research, and her
staff went on national radio and
television talk shows attacking the
findings of the WHI study and its authors
• "Instead of taking the side of its
constituents the society seemingly took
the side of its donors—and of Wyeth in
particular."
The sad tale of HRT
• Novo Nordisk hired German PR firm
Haas & Health Partner which sent
doctors letters downplaying the
WHI results
• The letters emphasised that the
"absolute risk for women is quite
minimal" and were signed by Dr
Irene Haas (a historian, according
to her company's website)
• Doctors in Britain have been
deluged with similar material
Conclusions
• The drug industry does vital
work
• Doctors and drug companies
have become too entangled
• Some disentanglement would
be good for everybody—
patients, governments, doctors,
and the industry