Managing conflicts of interest in relation to the quality of

medical information

Andrew Herxheimer

19 Sept 2006 2

Conflicts of interest are everywhereA medical expert must do his/her best

for the patient,

for science,

for the hospital or university,

for a minister who asks advice,

for a company which asks advice

for a court of law,

for his/her family!Sometimes there are collisions, and injuries

19 Sept 2006 3

Medical information: Selected facts and opinions

- a salad

• Opinions determine the selection of facts and their respective weight

• Opinions are less stable than the facts

• The setting, human relationships, and diplomatic language influence how they are communicated and understood

19 Sept 2006 4

Effective reception and understanding demand

clarity and transparency

1. The use of concepts and of words appropriate to the listeners/ readers, and well explained

2. Transparency about potential conflicts interest which could influence the messages

19 Sept 2006 5

Who should describe their potential conflicts of interest?

• Researchers, authors of papers • Editors of journals and reviews• Referees and other advisers of editors• Publishers• Teachers in universities and in continuing

medical education • Contributors to debates • Members of committees• Learned societies• Institutions such as hospitals and universities

19 Sept 2006 6

Example 1: myself (a)• I am a retired clinical pharmacologist• I work as a volunteer for the Cochrane

Collaboration• and for DIPEx, a charity which collects narratives

from patients

From time to time I do paid work for a• government, WHO, an NGO, an university,• journal (eg La revue Prescrire, the BMJ)• court, as a medico-legal expert

19 Sept 2006 7

Example : myself (b)

Rarely for a company • but as you know, today for GSK

I don’t accept tasks that concern the public…• but lack transparency

For many years I have offered advice to industry … • but it has never been accepted or appreciated

19 Sept 2006 8

Example 2a

Competing Interests Statements DL Sackett & AD Oxman

HARLOT plc: an amalgamation of the world's two oldest professions

BMJ 2003;327:1442-1445 (Christmas issue)

.

continued…

19 Sept 2006 9

Dave Sackett (DLS)

“DLS's competing interests are so great as

to warrant an entire page on the BMJ's website

http://bmj.com/cgi/content/full/324/7336/539/DC1

They also are on file at several disciplinary bodies on both sides of the Atlantic”

19 Sept 2006 10

The adventurous life of DLS

• David Sackett has been wined, dined, supported, transported, and paid to speak by countless pharmaceutical firms for over 40 years, beginning with two research fellowships and interest-free loans that allowed him to stay to finish medical school

• Dozens of his randomised trials have been supported in part (but never in whole) by pharmaceutical firms, who have never received or analysed primary data and never had power of veto over any reports, presentations, or publications of the results

• He has twice worked as a paid consultant to advise pharmaceutical firms whether their products caused lethal side effects; on both occasions he told them “Yes."

19 Sept 2006 11

The endless life of DLS…

• He has testified as an unpaid expert witness for a patient who sued a manufacturer of oral contraceptives after having a stroke and as a paid expert in preparing a class action suit against a manufacturer of prosthetic heart valves

• He was paid by a pharmaceutical firm to develop "levels of evidence" for determining the causation of adverse drug reactions

• His wife inherited and sold stock in a pharmaceutical company

• While head of a division of medicine he enforced the banning of drug detail personnel from clinical teaching units (despite the threat of withdrawal of drug industry funding for residents' research projects)

19 Sept 2006 12

• He received the Pharmaceutical Manufacturers' Association of Canada Medal of Honour (and cash) for "contributions to medical science in Canada" for the decade 1984-94

• His most recent award (the 2001 Senior Investigator Award of the Canadian Society of Internal Medicine) was sponsored by Merck Frosst Canada

DLS : some highlights!

19 Sept 2006 13

Andy Oxman (ADO)• ADO has received an exorbitant fee (almost as

much as a high priced lawyer earns in an hour) from two pharmaceutical firms on two occasions for showing up

• He has benefited from generous funding from two pharmaceutical firms that have supported his work and has attended conferences that have been partially supported by pharmaceutical firms

• He would be thrilled to receive more money from the drug industry to support his research and that of his colleagues, and to pay off his mortgage, but is

afraid that his involvement with DLS may put an end to any chances of that happening

19 Sept 2006 14

These are models

• They show the sources of potential conflicts of interest, but more than that: they explain what they mean

• If Dr Whoever has a relationship with a company, that may indicate a conflict or not. It depends on the subject and on the closeness of the relationship

• Sackett & Oxman have explained it, but such explanations are still very rare.

19 Sept 2006 15

The rules of the Cochrane Collaboration 2006

A. Financial interests Please list, if in the last 5 years you have:1. Received research funding: any grant, contract or gift,

commissioned research, or fellowship from a related organisation to conduct research?

2. Had paid consultancies: any paid work, consulting fees (in cash or kind) for an organisation?

3. Received honoraria: one-time payments (in cash or kind) from a related organisation?

4. Served as a director, officer, partner, trustee, employee or held a position of management with a related organisation?

5. Possessed share-holdings, stock, stock options, equity with a related organisation (excludes arrangements where the individual has no control over the selection of the shares)?

6. Received personal gifts from a related organisation?

7. Had an outstanding loan with a related organisation? 8. Received royalty payments from a related organisation?  

19 Sept 2006 16

Cochrane Collaboration 2

• B. Non-financial interests• Do you have any other competing interests

that could pose a conflict of interest that would reasonably appear to be related to the primary interest? If yes, explain.

19 Sept 2006 17

The experience of JAMA

Catherine DeAngelis

The influence of money on medical science

JAMA 2006; 296:996-8 (23/30 August)

WORTH READING

19 Sept 2006 18

JAMA 2

Since 1985 JAMA has required authors to make a specific declaration of potentially conflicting financial interests relating to their article

In 1990 JAMA started to publish these declarations

Since 1999 authors have had to explain any role of the sponsor in the study or in the preparation of the resulting article

19 Sept 2006 19

JAMA 3In 2005 an editorial re-emphasised these rules, but

many authors remained who had not understood them.

Then in July 2006 JAMA became even stricter: in cases where an author failed to declare conflicting interests, this breach of the rules was published in the journal with a letter from the author apologising to the readers, sometimes accompanied by an editorial commentary. Non-declaration is now a more visible scandal.

19 Sept 2006 20

JAMA - conclusion

But there can be no guarantee that all conflicts of interest have been disclosed.

One tool is more powerful than any editorial group: full investigations by the deans of the author’ institutions.

In 2006 this was effective on two occasions, in the College of Medecine of the Mayo Clinic and at the University of Nebraska, where the deans have introduced a broad programme of education on conflicts of interest.

19 Sept 2006 21

A serious gap in current education

Extract from an editorial in La revue Prescrire, Oct 2006

“In France it is planned that in 2008 that the exam taken by all medical students at the end of their second cycle of studies will for the first time test ‘critical reading of a medical article’.

But this test of critical reading deals only with original studies, not reviews, syntheses of knowledge, consensus statements or guidelines for practice. Although these documentary resources are the most relevant for clinical practitioners, the official teaching aims exclude any apprenticeship in the critical reading of such texts. Moreover, the test focuses on the methodological aspects of the original studies (appropriateness of experimental design, the statistics used, etc.).” [continued>

19 Sept 2006 22

Editorial LRP (2)

“University teachers who want to train good doctors must guard against reducing the role of critical reading in this way. Current teaching of the critical reading of medical literature, especially in the context of a narrowly focused national examination, provides a varnish of critical spirit and of greater insight into research. But it risks deceiving trainee clinicians by giving them the wrong and harmful impression, that it is a simple intellectual exercise which applies to primary scientific studies, and is only distantly related to the everyday work of clinicians.”

19 Sept 2006 23

What’s to be done?

• We need a clear policy that will ensure transparency and the management of conflicts of interest.

• It is a delicate problem

• The lack of such a policy damages the quality of medical information– Many examples are well known

rofecoxib, paroxetine, cerivastatin, phenylbutazone, benzodiazepines, human insulin, prolonged hormone replacement for the menopause …

19 Sept 2006 24

A range of solutions• Doctors pay for their own continuing education – not

industry• Provision of trustworthy independent information, for

example Prescrire, DTB, IsF • Clinical investigators become personally responsible

for their studies and the analysis of the results – not the sponsors

• Journal editors alone beconme responsible for the contents of their journals – not the publishers

• To the devil with ghost writers• No more direct and indirect promotion by

Key Opinion Leaders• ‘No thank you’ to medical reps; Nofreelunch.org

19 Sept 2006 25

Towards coherence and consistency

• The policy should be transparent and easy for professionals and the public to understand

• Capricious variations should be avoided: organisations should adopt similar policies

• Language that is too formal is distrusted and bores people; direct language inspires confidence

19 Sept 2006 26

Thank youI thank the Haute Autorité de la Santé

for inviting me to take part in its seminar for Deans of French Medical Schools and

Directors of Continuing Medical Education; the Faculty of Medicine in Lille, which

hosted the seminar; and GSK, who made the practical arrangements on behalf of the HAS