Archive for February, 2012

The September 2011 edition of the Quarterly Journal of Medicine contained two review articles which dealt with the use of new oral anticoagulants in patients with atrial fibrillation.

The first was by Prof Richard Hobbs and Isabelle Leach, who works for a reputable sounding organisation called Chameleon Communications. The funding and conflict of interest statements read as follows.

‘F.D.R.H. received no funding for this work. Bayer AG and Johnson & Johnson Pharmaceutical Research & Development, LLC, through funding of the professional medical writing services provided by IL. The sponsors were not involved in writing or editing the material. The authors take full responsibility for all content…F.D.R.H. has received occasional speaker fees or sponsorship from a variety of pharmaceutical companies, some with interests in AF including Boehringer Ingelheim, Pfizer, and Bayer. I.L. is an employee of Chameleon Communications International which received funding from the sponsors for her time on this manuscript.’

Bayer, who funded the editorial assistance, make Rivaroxaban, one of the drugs discussed in the article. Many of the companies from which Prof Hobbs has received money also make new oral anticoagulants. Chameleon Communications has been involved in preparing several other manuscripts in other journals on new anticoagulants over recent months.

The second, by Prof Joerg Kreuzer, was that edition’s ‘Editor’s Choice’ article. Prof Kreuzer’s funding and conflict of interest statement read as follows.

‘This work was supported by Boehringer Ingelheim. The author was fully responsible for all content and editorial decisions. The author received no financial support or other compensation related to the development of the paper. Editorial support was funded by Boehringer Ingelheim…Conflict of interest: None declared… The authors would like to thank Rebecca Gardner of PAREXEL, UK, for editorial assistance in the preparation of this article.’

Boehringer Ingelheim, make Dabigatran etexilate, a drug promoted in the article’s conclusion.

Concerned about these clear conflicts of interests, I wrote a letter to QJM arguing that the involvement of industry in the funding of review articles generates bias, probably above and beyond the mere choice of topics on which they focus. I requested answers to these four questions –

 a)  What is Isabelle Leach’s expertise in this field?

b) Could Chameleon Communications or PAREXEL highlight any published work with which they had assisted that recommends not prescribing a drug manufactured by the sponsor of the work?

c) Would the sponsors, PAREXEL or Chameleon Communications be willing to make public the agreements or contracts between their organizations pertaining to these QJM papers?

and d) Whether the editors had attempted to source an independent review on this topic and, if not, why not?

I concluded –

‘How long are we going to put up with a situation where our practice is informed by biased evidence summarized for us by people who have financial relationships with companies set to profit from alterations to our practice? These flagrant conflicts of interest would not be tolerated in other industries. We need to get our house in order.’

My letter prompted a note from the editor and a response from Prof Hobbs.

Both claimed that conflict of interest was a ‘complex’ area and defended their conduct by claiming all conflicts of interests had been declared and that the articles had been through peer review – claims I had not disputed. None of my questions were answered.

Prof Hobbs noted ‘Dr Yates…does not state what material he considers inaccurate or imbalanced’ and asked ‘Surely Dr Yates does not think that the paper should not have mentioned the emerging evidence base for these novel agents in addition to reviewing the data and associated usage of warfarin and aspirin?’ He asserted ‘The paper underwent independent review by the Journal and the authors responded to feedback. If the paper had not been assessed as a balanced review it would not have been accepted for publication.’

The editor, Prof Michael Bannon, declined to print my response to Prof Hobbs letter stating ‘The editorial decision is that this issue is now closed and no further correspondence will be considered regarding this.’

Happily, the internet offers me the opportunity to conclude a debate I believe to have been prematurely closed. This is the letter I submitted to QJM –


‘I thank the editors and Prof Hobbs for taking the time to respond to my letter on industry supported review articles [1, 2] but note the questions I raised in my letter are yet to be answered.

Both the editors [1] and Prof Hobbs [2] state the peer review process and the declaration of conflicts of interest as factors that protect readers from any bias. I am aware of no body of research that supports this position.

Research on the impact of disclosure of conflict of interest is contradictory [3, 4]. Recent work highlighting systematic differences between industry funded and independent review and comment articles on the rosiglitazone controversy suggest peer review offers no defence against funder bias finding its way into peer reviewed literature [5].

In answer to Prof Hobbs’ question [2], I believe it is important that clinicans are able to access review articles on this topic. However, they should be written by authors who have no financial relationship with the companies who make the products under discussion.

I am no expert on anticoagulation so am unable to critique his paper. Most other readers will be in the same position and thus unable to tell whether his clear conflicts of interest have affected the way in which he has presented the evidence. For this reason, journals should not be publishing reviews by authors with clear conflicts of interest and clinicians should not allow such articles to influence their practice.

Tom A. Yates

1. Notes from editor in response to: Yates TA. Questionable summaries of questionable evidence. QJM 2011; doi:10.1093/qjmed/hcr246.
2. Hobbs R. Challenges of anticoagulant therapy in patients with atrial fibrillation in clinical practice. QJM 2011; doi:10.1093/qjmed/hcr253.
3. Cain DM, Detsky AS. Everyone’s a Little Bit Biased (Even Physicians). JAMA 2008; 299: 2893-95.
4. Lacasse JR, Leo J. Knowledge of ghostwriting and financial conflicts-of-interest reduces the perceived credibility of biomedical research. BMC Res Notes 2011; 4(1): 27.
5. Wang AT, McCoy CP, Murad MH, Montori VM. Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review. BMJ 2010; 340: c1344.’


Amy Wang’s review of articles commenting on the Rosiglitazone controversy, is well worth a read. After reading it, it is difficult to argue peer review offers any defence against bias creeping into the literature.

QJM, sadly, are not alone in printing review articles by authors with clear conflicts of interest. Our profession is up to its eye-balls in conflict of interest and other journals have even lower standards

Happily, there are groups fighting to reassert medicine’s independence from industry. It’s high time we got behind them.


Read Full Post »