ISIS Report 01/06/09

Vioxx, A Mercky Story

After paying out almost $5 billion in the US, Merck is defending a class action in Australia where a journal that never was came to light, meanwhile UK victims see no prospect of compensation Prof. Peter Saunders

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Did Merck know that Vioxx causes heart problems?

Five years ago, the pharmaceutical giant Merck announced that it was withdrawing its blockbuster pain killing drug Vioxx (rofecoxib) from the market because a clinical trial had shown that prolonged use increased the risk of heart attacks and strokes.  Many users of the drug who had experienced cardiovascular (CV) problems naturally blamed Vioxx for what had happened to them. Merck, they argued, had known there was a link and had failed to warn them.  

Merck denied this, and still do, but that has been a difficult position to maintain [1]. The problem is that the connection between Vioxx and cardiovascular disease had not come completely without warning. Almost from the time it was launched, in 1999, some doctors and researchers were concerned about the safety of the drug.  As early as 2000, VIGOR, a study designed to study the effects of Vioxx on the digestive tract, found an increased risk of CV events compared with a different pain killer, naproxen [2].  A year later, Mukherjee and co-workers reviewed the literature on Cox-2 inhibitors (including rofecoxib) and concluded that their use might lead to increased CV events [3]. A research team chiefly from Merck then published a meta-analysis in which they found no significant difference in risk between Vioxx and a placebo [4]. The difference between Vioxx and naproxen was ascribed to the beneficial anti-platelet effects of the latter.

However confident Merck may have been that Vioxx was safe, they were aware that not everyone agreed, and they worked to defend and promote their product. The result was that when they eventually found evidence that long term (eighteen months) use of Vioxx significantly increased the chance of a heart attack or a stroke, they were deluged with lawsuits. They began by defending each of them separately, but in the end they reached an out of court settlement of $4.85 billion to be divided among 44 000 claimants. That may sound like a lot of money but you have to see it in perspective; the global sales of Vioxx in 2003 alone were $2.5 billion. And in settling out of court, Merck did not accept liability, which makes it much harder for people in other countries to win law suits than if there had been a class action decision against them in an American court. The settlement applies only for claimants within the US; there are no payments for others.

No compensation for UK victims

About 10 000 people in the UK claim to have been affected by Vioxx. In 2008, a cross party campaign was organised to press for compensation. On 17 June, the Health Minister, Ivan Lewis, gave it his backing (see box). According to Department of Health documents obtained by the Guardian under freedom of information legislation, however, Lewis met with representatives of Merck on 10 July, and soon changed his tune [5]. The UK government line is now that it should not intervene in matters that are “properly for the judicial system”.  The Vioxx users who are seeking compensation have been refused legal aid and they will have to pay Merck’s costs if they take them to court and lose.  Experience in the US has shown it is difficult to judge the chances of success in such cases, and so because Merck can afford to spend millions of pounds on lawyers, they have effectively been granted immunity.  

The Australian trial

Merck is not getting the same free ride in Australia, where over 1000 users have mounted a class action. The trial is expected to last about three months, but it is already giving insights into the way the pharmaceutical industry works.  

One curious story concerns a number of articles favouring Vioxx that appeared in the Australasian Journal of Bone and Joint Medicine.  Even if you work in the field you probably won’t know this journal, because despite its name (there are many bona fide journals with the title “Australasian Journal of ... ”), it was  actually a marketing front for Merck’s products. It was laid out to look like a journal, it had the name of the publisher, Elsevier, on the front cover and an honorary editorial board listed on page 2 (at least one member stated in court that his name was used without his knowledge) and nothing to suggest that it was essentially a piece of advertising for one company, nor how the publication was paid for [6.7].

When the truth of the matter emerged, Elsevier was clearly embarrassed and said that it had failed to meet its own standards, especially that they ought to have disclosed that it was a sponsored journal. The journal had since been discontinued and the people responsible had left the company. Merck, in contrast, are totally unapologetic. The “complimentary publication” had been published by Elsevier, and MSDA (the Australian subsidiary of Merck) had understood it would “draw on the vast resources of Elsevier to deliver novel and timely full-text articles and abstracts to physicians.” They omitted to say who had paid for it or who had chosen the material it contained [8].

The contents of the journal were for the most part what you might expect, which is not surprising as much of it had already been published elsewhere; except for a high proportion of articles showing Merck and its products in a good light. This would have been acceptable in an advertising brochure, but not in what purported to be an independent scientific journal. 

Spin in the pharmaceutical industry

Drug companies use all sorts of ploys to get research favourable to their products into the literature. It is well known that in pharmaceuticals, nutrition and other fields as well, research sponsored by companies is much more likely to be positive than research funded from other sources [9, 10].  Many articles are ghost-written: the work is done in a drug company’s laboratory and then scientists outside the company allow themselves to be listed as authors to give it the appearance of independent research [10, 11]. Harder to pin down are “guest authors”, who are brought in at a late stage in the process and may be listed as lead authors even though they played only a minor role in the research. There are so-called medical education and communication companies (MECCs) whose job it is to write up research in such a way as to [12] “deliver scientifically accurate information strategically developed for specific target audiences.” We now know that the Australasian Journal of Bone and Joint Medicine was not the only “sponsored article publication” put out by Elsevier’s Australian office. There were five others, though Elsevier have so far refused to reveal who the sponsors were [13].

All the same, it is surprising that Merck engaged in this charade. Most of the articles had already appeared somewhere, so other scientists would have seen them and their sales representatives already had plenty of reprints to hand out to physicians. Perhaps they thought doctors would be impressed to see how much space was devoted to Merck’s products by what they took to be an independent scientific journal. It does, however show how far the company and its subsidiaries are willing to use spin, and that matters in this trial because of the nature of the case. Merck still maintain that the evidence does not prove a cause and effect relationship between Vioxx and CV events. Even if they lose on this point, however, the court will have to decide whether they were justified in continuing to promote and sell the drug up until 2004 on the basis of the evidence available at the time. In essence, the court will ask, “What did Merck know, and when did they know it?”  A reputation for being straightforward would be a big asset here.

Is there a duty of care?

One last point, The Australian has been following the trial closely, and in the May 6 issue it reported [14]: “Mr Garling [counsel for MSDA] also pointed out that Merck did not have a duty of care to any members of the class action or any patients using Vioxx, because this duty was taken on by the doctor who prescribed Vioxx to them.” It’s hard to believe that pharmaceutical companies have no duty of care to the people who take the prescription drugs they have developed and manufactured, but if that’s what they think, it could help explain a number of things we’ve reported in SiS recently (see for example [15] Pharmaceuticals ripe for a shake-up, SiS39).

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