The recent article in your journal [ Enligt nya dokument: Merck mörkade uppgifter om överdödlighet i Vioxx-studier] (Endast på webben. LTs anm) referenced several articles about Merck and Vioxx that appeared in the Journal of the American Medical Association. Those articles, two of which were co-authored by litigation experts hired by the plaintiffs in U.S. lawsuits, include comments that are false, misleading, and lack context. Merck was not given the opportunity to respond to the allegations in these articles prior to their publication. We therefore take this opportunity to provide you with the following information concerning the two main topics of the articles: the Alzheimer´s studies and the authorship of scientific manuscripts about Vioxx studies.

The Alzheimer´s studies
There were three Alzheimer´s disease-related trials with Vioxx: Protocols 078, 091 and 126. All of the trials were designed to examine a hypothesized benefit with anti-inflammatory medicines, specifically that they could help in the treatment or prevention of Alzheimer´s disease.

The Alzheimer´s trials were important for another reason, however – they provided a large body of placebo-controlled data from which the cardiovascular safety of Vioxx could be examined. Indeed, the on-treatment incidence of cardiovascular events among people taking Vioxx compared to people taking placebo in these trials was virtually identical (RR=1.01). There was therefore no suggestion from these data of an increased cardiovascular risk among people taking Vioxx.

There was, however, an increased incidence of all-cause mortality among people taking Vioxx compared to people taking placebo in the Alzheimer´s trials. Merck carefully analyzed and appropriately disclosed these data.

First, it is important to understand the types of deaths that occurred in the Alzheimer´s trials. While there was a disparity in deaths between the Vioxx and placebo arms of the trials, a significant portion of that disparity was due to causes unrelated to the use of Vioxx, including automobile accidents, poisonings, electrocutions, infections, and trauma.

Second, the data from the Alzheimer´s trials should not be interpreted without reference to the rest of the extensive body of clinical trial data in Vioxx. In fact, Merck carefully analyzed those data – including many thousands of people – and none of the other studies on Vioxx showed an increased risk of all-cause mortality associated with Vioxx. In fact, in the Phase IIb/III osteoarthritis trials, there was a statistically
significantly lower rate of all-cause deaths on Vioxx compared to the NSAID comparators. Even in APPROVe – the results of which in 2004 led to Merck´s voluntary withdrawal of Vioxx – there was no increased incidence of all-cause mortality on Vioxx compared to placebo. This was strong evidence to Merck that the Alzheimer´s data were an anomaly; if there were a true increased incidence of all-cause mortality on Vioxx, Merck would have expected to see it elsewhere in Vioxx clinical trials, and it did not.

Finally, Merck did not keep these data to itself. In July 2001, Merck disclosed the on-drug all-cause mortality data to the U.S. Food and Drug Administration, and informed the FDA that off-drug data were also being collected, and would be submitted with the clinical study reports. This is exactly what Merck did. The disparity in all-cause mortality was clear in the July 2001 submission, and indeed the FDA asked Merck additional questions about these data, which Merck answered.

Thus, contrary to the suggestion in the JAMA articles, strong scientific evidence supported the conclusion that the all-cause mortality data from the Alzheimer´s studies did not represent a safety issue with the drug, and Merck appropriately disclosed those data to the FDA.

The »ghostwriting« accusations
The JAMA articles suggest that in many scientific articles about Vioxx studies, Merck recruited outside academic authors who had little or no involvement with the actual study or the drafting of the article. This is simply inaccurate. Perhaps the best evidence to refute this comes from the outside academics themselves – a source that the authors of the JAMA articles clearly did not check prior to making their accusations.

For example, one of the outside authors of one of the Alzheimer´s papers, Dr. Stephen Ferris, a member of the endpoint adjudication committee for the study, described the accusation of the article being ghostwritten as ”simply false.” Similarly, the lead author of the VIGOR paper, Dr. Claire Bombardier, stated in the Canadian Press: ”Let me dispel any doubt. Our paper was not `ghost written.´ Dr. Laine, Dr. Reicin and I worked diligently, along with our co-authors who were members of the VIGOR steering committee. We were, and remain, proud of the important contribution our article made to medical science.”

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In conclusion, we believe in the importance of appropriate scientific debate in the peer-reviewed medical literature. The recent articles by JAMA did not meet that standard.