Vioxx study questioned by medical journal

The New England Journal of Medicine (NEJM) has published an editorial questioning the integrity of the VIGOR (Vioxx Gastrointestinal Outcomes Research) study, published in the NEJM on 23 November 2000, saying that it contains 'inaccuracies in data'.

Vioxx, dubbed an 'arthritis and acute pain medication' by Merck, was voluntarily withdrawn by Merck on 30 September 2004 following clinical trial data which revealed an increased relative risk of heart attack and stroke ('cardiovascular events') after 18 months of treatment in comparison to patients taking placebo.

'Three myocardial infarctions (MIs) [heart attacks in layman's terms], all in the rofecooxib (Vioxx) group, were not included in the data submitted,' states the NEJM. 'The editors first became aware of the additional MIs in 2001 when updated data were made available by the [US] Food and Drug Administration [FDA].

'Until the end of November 2005, we believed that these were late events that were not known to the authors [Claire Bombardier, MD, a Toronto rheumatologist, et al.] in time to be included in the article published in the NEJM on 23 November 2000. It now appears, from a memorandum dated 5 July 2000 that was obtained by subpoena in the Vioxx litigation, that at least two of the authors knew about the three additional MIs at least two weeks before the authors submitted the first of two revisions and four and a half months before publication of the article, ample time to include the data in the article.'

Furthermore, the NEJM claims to have 'determined from a computer diskette that some of these data were deleted from the VIGOR manuscript two days before it was initially submitted to NEJM'.

The original VIGOR study reported 17 MIs in the Vioxx arm and four in the naproxen arm, for a relative risk of 4.25. The actual events are 20 MIs in the Vioxx arm versus four in the naproxen arm for a relative risk of 5.0.

The NEJM has asked Dr. Bombardier and colleagues to submit a correction. As things stand, Merck has issued a response, stating that it 'promptly and appropriately disclosed the results of the VIGOR study, which was peer-reviewed, as of the pre-specified cutoff for analysis.

'The additional events referred to in the editorial were events that were reported after the pre-specified cut-off date, [and] were disclosed to the FDA in 2000, presented publicly at the FDA's Advisory Committee in February 2001, included in numerous press releases subsequently issued by Merck, disclosed to physicians given a copy of the article by Merck and detailed in the updated prescribing information for VIOXX.

The company goes on to claim that the 'additional events did not materially change any of the conclusions in the article'. While other analysts have made similar claims, as the initial study showed Vioxx to carry a higher risk of heart attack than a common painkiller, the article may have Merck worried considering the 6,000 lawsuits it is facing up to in the US from former Vioxx users who claim to have been harmed by the drug.

Jeff Cooper of Simmons Cooper, who is representing around 700 Vioxx plaintiffs, said: 'They [Merck] are never are going to be able to walk into a courtroom again and say we told you everything about this drug. It leaves them much more susceptible to judges granting motions to seek punitive damages against them. It obviously raises the potential recovery in these cases and it raises the value of each case.'

However, defence attorney John Brenner, a partner at McCarter & English, who has defended major drug companies but does not represent Merck, had a much more tempered reaction: 'My initial impression is, in terms of the litigation, here may be a little less there than immediately meets the eye. What I'm waiting to see is what the authors [of the study] are going to say in response. That is critical.' Like Merck, he believes that the information, while not included in the journal article, was already available to attorneys on both sides of the litigation.

Merck was found liable in the first case to go to trial and was ordered pay damages of $253m to the widow of a 59-year-old Vioxx user. While it is appealing that decision, it recently won a case in which Frederick Humeston, from Boise, Idaho, alleged that he suffered a heart attack at the age of 56 as a result of intermittent use of Vioxx over a two-month period. Merck was ruled to have provided adequate warning to doctors about health risks associated with Vioxx; to not have committed consumer fraud in marketing the drug; and to not have misrepresented, suppressed or concealed information about increased risks of heart attack and stroke from the pain and arthritis medicine.

The company's shares fell nearly 2% to $29.11 on the New York Stock Exchange following the NEJM announcement.