1. Conflicts of interest: a case study in entanglement

2. 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:

3. 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:

4. 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.

5. 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:

7. 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
Joel Lexchin, Lisa A Bero, Benjamin Djulbegovic, and Otavio Clark Pharmaceutical industry sponsorship and research outcome and quality: systematic review BMJ, May 2003; 326:

8. Does conflict of interest matter
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.
Vandenbroucke JP, Helmerhorst FM, Frits R Rosendaal FR. Competing interests and controversy about third generation oral contraceptives. BMJ 2000; 320: 381.

9. 75% in Annals of Internal Medicine, Lancet, JAMA, and NEJM
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

10. In search of a better relationship between doctors and drug companies

11. 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

12. 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?

13. 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%

14. 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%

15. 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%

16. Trouble 3—the sad story of HRT

17. 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

18. 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:

19. 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

20. The sad tale of HRT
More than 100 million women worldwide have taken HRT
Professor Bruno Müller-Oerlinghausen, 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.

21. 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

22. 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 £ to the society

23. 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."

24. 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

25. 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