NEWS - NEJM calls for correction to key Vioxx trial data

[Guest guest]

NEJM calls for correction to key Vioxx trial data

Rheumawire

Dec 9, 2005

Gandey

Boston, MA - In a rare move, editors of the New England Journal of Medicine

have published an early-release editorial calling the authors of the Vioxx

Gastrointestinal Outcomes Research (VIGOR) trial-the study that put

rofecoxib on the map-to submit a correction to rectify what they are calling

important " inaccuracies and deletions " of cardiovascular data [1].

In a statement issued to the press, the journal reports that problems first

came to light when plaintiff attorneys in Vioxx-related litigation

subpoenaed one of the editors for information and testimony regarding events

leading up to the publication of the VIGOR trial [2]. " During this process,

we learned that relevant data on cardiovascular outcomes had been deleted

from the VIGOR manuscript prior to its submission to the journal and that

the authors had withheld data on other relevant cardiovascular outcomes. "

Responding to the allegations, lead investigator Dr Bombardier, head

of the division of clinical decision-making and healthcare at the Toronto

General Research Institute, told rheumawire, " I believe that the VIGOR paper

appropriately disclosed the data as per the prespecified plan of analysis. "

She adds, " Events that occurred after the prespecified cut-off date have

been publicly known since the FDA advisory committee in February 2001. "

Bombardier says she and her colleagues will be preparing a formal response

to the editorial.

Executive editor Dr Curfman and colleagues say the Merck-sponsored

VIGOR trial failed to report three adverse events-all in the rofecoxib

group. " The fact that these three myocardial infarctions were not included

made certain calculations and conclusions in the article incorrect, " they

write.

Explaining the journal's role in the omission, Curfman and colleagues note,

" The editors first became aware of the additional myocardial infarctions in

2001 when updated data were made public by the [uS] Food and Drug

Administration. Until the end of November 2005, we believed that these were

late events that were not known to the authors in time to be included in the

article. "

But the editors say this changed when a memo subpoenaed in Vioxx litigation

revealed that at least two of the authors knew about the additional MIs a

couple of weeks before the group submitted the first of two manuscript

revisions-more than four months before publication. The editors aren't

specifying which two authors they are referring to, but a recent Wall Street

Journal article hints that two Merck employees listed among the

coauthors-the vice president of clinical research and a biostatistician-may

be at the center of the controversy.

Curfman and colleagues say the memo contained additional data on

cardiovascular adverse events that they believe should have been included in

the paper. They also accuse the authors of electronically deleting pertinent

data prior to submitting their work. " We determined from a computer diskette

that some of these data were deleted from the VIGOR manuscript two days

before it was initially submitted to the journal on May 18, 2000. "

Although only summary percentages-not actual numbers of MIs-were included in

the VIGOR report, the New England Journal of Medicine editors argue that the

missing events resulted in an understatement of the difference in risk of MI

between the rofecoxib and naproxen groups. They say, " It also resulted in

the misleading conclusion that there was a difference in the risk of

myocardial infarction between the aspirin-indicated and

aspirin-not-indicated groups. "

Responding to the accusations, Merck says, " The VIGOR publication, which was

peer-reviewed, fairly and accurately described the results of the study as

of the prespecified cut-off for analysis. The additional events referred to

in the editorial were events that were reported after the prespecified

cut-off date and therefore were not included in the primary analysis

reported in the New England Journal article. "

The company says these additional events were later disclosed to the FDA and

were subsequently presented publicly and included in numerous press releases

issued by Merck. " We also note that these additional events did not

materially change any of the conclusions in the article. "

Sources

1. Curfman GD, sey S, Drazen JM. Expression of concern:

Bombardier et al. Comparison of upper gastrointestinal toxicity of rofecoxib

and naproxen in patients with rheumatoid arthritis. N Engl J Med 2005;

353:2813-2814.

2. Bombardier C, Laine L, Reicin A, et al. For the VIGOR

study group. Comparison of upper gastrointestinal toxicity of rofecoxib and

naproxen in patients with rheumatoid arthritis. N Engl J Med 2000;

343:1520-1528.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org