The article "Journals are an extension of the marketing arm of pharmaceutical companies" in VetScite's News Update of June 7, 2005 prompted a reader to react. With his permission, we here publish the exchanges between our editorial office and Dr. Thomas H.M.Eun from the Research and Development Department of VIRBAC Santé Animale, Carros France. VIRBAC is the world number ten in its line of business, an industry specializing in products for the treatment and prevention of diseases in pets and farm animals.

Since Veterinary Sciences Tomorrow is a "current awareness" journal, we are grateful for any reaction to articles we have published. We address a global animal health research community and provide it with biomedical news, state-of-the-art reviews and interpretation or opinion on actual issues of importance for animal health. It is especially to encourage interdisciplinary exchange that the VetScite's editors decided to solicit the agreement of Dr.Eun to publish his reaction together with the e-mail exchanges.

The News Update article that evoked the reaction is online and may be read at http://www.vetscite.org/publish/items/002247/index.html . By publishing the following exchange the editors aim to spark a discussion, inviting their readers to take part in a discourse on a topic, which many of us, being writers, publishers or editors of scientific papers, recognize as a point of critical consideration.

14 June 2005, Thomas H.M. Eun (THME), PhD, Virbac, France (personal opinion) to Marian C. Horzinek (MCH), Editor-in-Chief Veterinary Sciences Tomorrow, University Utrecht.

Dear Dr. Horzinek,

In the News Update column of your VetScite (7 June 2005), an essay written by R Smith appeared with the title, "Journals are an extension of the marketing arm of pharmaceutical companies". The article was quite provocative. I felt that such a biased essay obliges a response for the sake of balanced understanding by your readers. With the hope that you would kindly devote an equal space for the response in your column, I send you mine (attached hereunder).If you decide to print it, either use my name only. Or if you prefer to add professional affiliation, please insert a statement that it is my "personal opinion". Please don't hesitate to contact me for any further clarification.

Looking forward to your acknowledgment,

With best regards,

Thomas H.M. EUN, Ph.D.

R&D Department, Virbac

France

(See attached file: Response-to-pharma journal.doc)

Response to a News Update article in Veterinary Sciences Tomorrow
The essay by R Smith, "Medical journals are an extension of the marketing arm of pharmaceutical companies", originally published in PLoS Medicine, 2005, 2(5): e138 and presented as News Update in Veterinary Sciences Tomorrow (7 June 2005), was sensational and thought-provoking. At the same time, it was provocative and outrageous, accusing pharmaceutical companies of being guilty of corruption for manipulating the journals and publishing trial results, especially the "favorable" ones.

As a life scientist-turned-clinical scientist working in a veterinary pharmaceutical company for almost 15 years, a period long enough to see various corners of both academic and industrial R&D activities, I think the essay deserves some comments and especially moderations for the sake of more comprehensive, unbiased understanding by the readers.

Role of medical journals
The purported "cycle of dependency between journals and the pharmaceutical industry" is not just a mundane dependency. It is rather a privileged relationship between the two entities for mutual benefits. Admittedly, however, there is still room for criticism on the way the relationship is managed, and the Smith's description of the regular business of advertising as "the least corrupting form of dependence" may have to be tolerated. I may even raise a more serious concern with respect to the publication of original research as an advertisement, but I would go directly to the "bigger problem" pointed out by Smith - the publication of trial results as "original research" in the journal. The main issue here is whether the journal readers, as a third party, is intentionally misled and, if so, who is responsible for such a misconduct. Does the blame squarely fall on pharmaceutical companies as the essay seems to be pointing at ?

There is no denying that misleading papers or papers with dubious intention, from as many industrial as academic sources, go through the peer-review and get published. We are not surprised anymore to see reports of misconducts involving plagiarism and data faking and retractions of published papers in various journals. Fortunately, these cases are rare and they don't hinder the publication of the majority of "good" papers. Where there are laws, there are outlaws. It doesn't mean that the outlaws are to be excused. Rather, it means that the good ones are still holding the mainstream and they should not be banded blindly together with the bad ones. Assuming that all trial papers coming from the industry or company-sponsored sources are tricked is not only unfair but dangerous and as irresponsible as believing that all other papers are high quality sciences. The wholesale stamping as "bigger problem" or "more corrupting form" for the clinical trials published as original studies in the journals is an insult to the majority of conscientious editors and company-affiliated or -sponsored authors.

Understandably, the benefits of publishing in a medical journal can be enormous for pharmaceutical companies - the prestige behind and publicity for a drug that can be readily translated into financial reward. As such, however, it is not a sin, not any more than for the authors in academia seeking personal glories and competitive edges for their career. Did Mr. Smith never have the idea of accusing that "journals are an extension of the marketing arm of all scientists" ? Whereas the "publishing strategy" is just an accessory for pharmaceutical companies, it is often a matter of life or death for others as appropriately expressed by the slogan, "publish or perish".

Regardless of the misplaced blames, a salient fact is that editors are there to exercise full power and authority in accepting or rejecting a paper on the basis of merits and qualities defined by the Journal. Smith's essay gives the tone as if the editors are under pressure by the pharmaceutical companies submitting the papers, which is absurd.

Is it wrong to publish favorable results ?
Smith writes that "- unfortunately for the credibility of the journals who publish them - these trials rarely produce results that are unfavorable to the companies' products".

I think there is no need to apply powerful statistics to come to the conclusion that the majority of scientific papers published today, regardless of their sources, deal with "positive" and thus "favorable" results. One might wonder if a journal publishing the unfavorable results to the companies' products would get any higher credibility.

Perhaps the issue can be dealt with from two different, partly overlapping sides of a drug : efficacy and safety. For a pharmaceutical company, like independent scientists in academia, a drug trial bearing negative results on efficacy faces a decision - either another trial with modified (or improved) trial designs or abandoning the product in question. In the first case, the study would not be ready to be published and, in the second case, there is simply no need to publish. Only the efficacy trial(s) generating "positive or favorable" results are worthy of pursuing further development, possibly with one or two scientific publications down the road. For those promising drugs only, the safety aspects would become a matter of genuine concern and, as anybody would agree, a greater transparency is required in that matter.

Quality of clinical trials
Clinical trials constitute an essential step for obtaining marketing authorization for a product and, as such, are conducted by pharmaceutical companies under strict regulatory controls in the European Union as in the USA. The regulatory controls will only get stricter in the future. For this reason, and as cited by Smith, the technical quality of the studies funded by the industry is as good - and often better - than that of studies funded by others.

Perhaps it is time to stop looking through the good old tainted glasses the qualities of the papers coming from pharmaceutical industry. As far as the veterinary pharmaceutical industry is concerned, the transformation, under the applicable GCP guidelines, has been relentless and enormous during the past 5 years in the way clinical trials are performed. Unfortunately, some people, perhaps with a certain degree of excuse for those not directly involved in clinical sciences, fail to recognize those changes or, if they do, they see only the tip of an iceberg.

To make an earthly connection, I wish to share two comments, among others, from a reviewer that we had to face during our recent attempt to publish a trial paper in a renowned American medical journal.

·

Regarding animal "inclusion criteria" for a randomized, double-blind, placebo-controlled, multicentric study, "There is sure to be a bias in which owners willingly participate that the authors should at least discuss in the discussion. Also, the authors could summarize the circumstances where owners declined to participate and why. --- I think it is important to summarize all animals that were not included, why, and which group they were in so that reviewers and readers can judge biases."

·

"Animals infected by a virus and coinfected by another virus appear to be analyzed together and not split proportionately into the treatment groups ? For all I can tell, the placebo is full of coinfected animals and thus didn't live as long."

( * The underlined parts were paraphrased to remain neutral to the subject.)

I tend to believe that this kind of distorted and contemptuous comments would not have arisen if the reviewer, no matter how scientifically scrupulous, was aware of the rigor and sophistication with which current clinicals trial have to be performed by the pharmaceutical companies. The paper was published in due course, making us believe that the journal editor filled the gap with the wisdom of King Solomon.

In conclusion, we remain confident that, unlike some editors who oddly prefer to sound the alarm, there are judicious journal editors who solve the real as well as conceived problems while maintaining the journal quality and the mutually beneficial dependency with the pharmaceutical industry.

Thomas H.M. Eun, Ph.D.

R&D Department, Virbac

B.P.27, 06511 Carros Cedex

France

E-mail: teun@virbac.fr

18 June 2005, MCH to THME

Dear Dr. Eun,

Thank you very much for your eloquent reaction to our News Update article in VetScite. As you have noticed, there is much background material relevant to your reply, which you may want to consider. I hasten to add that we should certainly like to run your letter as an opinion article, and incite a discussion on the VetScite pages, but your opposition should perhaps be levelled at the primary publication rather than at our quote, unless you prefer to limit it to a veterinary readership.

As mentioned in PloS: "This article is based on a talk that Richard Smith gave at the Medical Society of London in October 2004 when receiving the HealthWatch Award for 2004. The speech is reported in the January 2005 HealthWatch newsletter [20]. The article overlaps to a small extent with an article published in the BMJ [21]." You might also want to look at the eight points below, which accompanied the original publication:

"Examples of methods for pharmaceutical companies to get the results they want from clinical trials:

·	Conduct a trial of your drug against a treatment known to be inferior.
·	Trial your drugs against too low a dose of a competitor drug.
·	Conduct a trial of your drug against too high a dose of a competitor drug (making your drug seem less toxic).
·	Conduct trials that are too small to show differences from competitor drugs.
·	Use multiple endpoints in the trial and select for publication those that give favourable results.
·	Do multicentre trials and select for publication results from centres that are favourable.
·	Conduct subgroup analyses and select for publication those that are favourable.
·	Present results that are most likely to impress-for example, reduction in relative rather than absolute risk."

Whatever your decision is, I certainly think you have made good points that merit to be published. Looking forward to your reply, I remain

With kind regards

Marian C. Horzinek

Editor

20 June 2005, THME to MCH

Dear Dr. Horzinek,

Thanks a lot for your kind and thoughtful reply. Initially aroused by your News Update, I checked out the original article in PLoS Medicine (May 2005) with the accompanying "eight point - Examples of Methods" and the BMJ (2003) as well. I thought that everything Mr. Smith wanted to say was there and I didn't feel necessary checking the article published in the HealthWatch newsletter (2005).

Frankly, I would not have bothered standing up against the BMJ (2003) article. But in the face of the reviving scandal Mr. Smith was raising "de nouveau" against the pharmaceutical industry, I thought that he was definitely going overboard and perhaps someone has to intervene. I've considered writing directly to the PLoS, but I preferred to write to VetScite for the following reasons. Firstly, as you have correctly guessed, I wanted to limit it to the Veterinary readership. As a scientist in the veterinary field, I thought that what I meant to say would be more coherent and make a better sense by staying in the veterinary area/publication. Secondly, the subject is fresher in your column than in others. (After all, it was your News Update column that sparked my involvement.) It seems to me outdated and pointless to respond to an article published 2 years ago. Unless there is a dilemma for you in carrying an "indirect" response like mine to an article published elsewhere, I will be contented to see it appear as an opinion article in the VetScite.

Looking forward to your reply,

With best regards,

Thomas H.M. Eun

Virbac

teun@virbac.fr

15 August 2005, MCH to THME

Dear Dr.Eun,

We have an editors' meeting this week and our mail discussion will be one of the topics. Would you agree to publishing the 'replique' together with our email exchanges, to make it more lively for our readers. I.e. the text below this message?

Kind regards

Prof. emer.Dr.DDr.h.c.mult. Marian C. Horzinek

Editor-in-Chief Veterinary Sciences Tomorrow

20 August 2005, THME to MCH

Dear Dr. Horzinek,

Sorry for this late response to your mail dated 15/08/05. I found it with pleasure today on my return from my vacations. Regarding the 'replique', it is fine with me that our email exchanges are attached to the text as you suggested.

With kind regards,

Thomas H.M. Eun

Virbac

teun@virbac.fr



In the view of the editors of Veterinary Sciences Tomorrow, the above correspondence is interesting and worth to be brought to our readers' attention. We appreciate hearing your comments and suggestions. These and any other matter should be directed to the Editorial Office at vetscite@vet.uu.nl

Sincerely,

Marian C. Horzinek and Anjop Venker-van Haagen (editors)