NEJM questions data in Merck's Vioxx study - tossing 3 heart attacks

[Guest guest]

Journal Questions Data in Vioxx Study

3 Heart Attacks Not Mentioned

By Brown

Washington Post Staff Writer

Friday, December 9, 2005; A02

http://www.washingtonpost.com/wp-dyn/content/article/2005/12/08/AR2005120802340.\

html

The editors of the New England Journal of Medicine yesterday accused the

authors of an article on the painkiller Vioxx of underreporting the number

of heart attacks that occurred in a study published five years ago.

Although the article did report a higher rate of heart attacks in Vioxx

users compared with people taking another painkiller, the unreported

cardiac events " call into question the integrity of the data . . . in this

article. " The editors asked the authors to submit a correction.

Vioxx was removed from the market last year by its maker, Merck & Co.,

after evidence emerged that it increased the risk of heart attack in some

users. The question of when Merck discovered Vioxx had that effect is a

major point of dispute between the company and some Vioxx critics.

As of late September, heart attack victims or relatives had filed 6,500

lawsuits against Merck, alleging that the company should have stopped

selling Vioxx earlier, or at least warned patients of the drug's hazards.

Two trials are complete; Merck won one and the plaintiff the other. A jury

in Houston is deliberating in a third case.

Merck is facing potentially huge losses, and last month announced plans to

cut 7,000 jobs and close five plants worldwide.

In a statement released last night, the company said it did not suppress

any data about heart attacks in the study. It said the three heart attacks

the journal editors say should have been mentioned occurred " after the

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

analysis. "

The statement further said the three heart attacks were reported to the

Food and Drug Administration in 2000, and presented publicly to an FDA

advisory panel in February 2001.

The article does not name a cutoff date. However, it does say that the

analysis included only events that occurred during treatment or within 14

days after treatment stopped.

Asked if the journal knew about a cutoff date, Executive Editor D.

Curfman said: " We never knew about it, and it was never in any version of

any version of the manuscript that we had. " He added that even if Merck

had reported only heart attacks that occurred before a certain date, " we

would have expected an update. "

A company document that emerged last month in one of lawsuits showed that

two of the article's 12 authors knew about the three additional heart

attacks in July 2000. That was months after they submitted the first draft

of the article to the journal, but two months before it was accepted in

September. It was published on Nov. 23, 2000.

" Even though it's a small number of heart attacks, it really does have a

substantial impact on the conclusions from the entire data set, " Curfman

said.

The lead author of the article, Bombardier of the University of

Toronto, reiterated the points made in the Merck statement, and added that

" the authors of the paper will be preparing a response " to the editors'

charges.

The study that Bombardier led was trying to determine whether patients

with rheumatoid arthritis who took Vioxx developed fewer ulcers and

stomach hemorrhages than people taking naproxen, a nonprescription

painkiller.

The article said that a higher percentage (0.4 percent) of those taking

Vioxx had heart attacks compared with those taking naproxen (0.1 percent).

However, it did not say how many of those events were in each group.

It turns out the numbers (rather than just percentages) were in an early

version of the paper, but the authors had removed them. This was

discovered in November 2004 when the journal's managing editor,

sey, found a computer disk in the article's file that had not been

examined.

The disk contained an electronic version of the study that Bombardier and

her colleagues had submitted in paper form on May 18, 2000. However, when

the cursor was pointed over the text, changes made by the authors, and the

dates they were made, appeared.

On May 16 -- two days before the paper was submitted -- one of the authors

had removed the information describing the number of heart attacks. There

were 17 in the Vioxx group and four in the naproxen group. The journal

editors subsequently learned there were three more in the Vioxx group,

making the final tally 20 vs. four, an even more striking disparity.

© 2005 The Washington Post Company

The material in this post is distributed without

profit to those who have expressed a prior interest

in receiving the included information for research

and educational purposes.For more information go to:

http://www4.law.cornell.edu/uscode/17/107.html

http://oregon.uoregon.edu/~csundt/documents.htm

If you wish to use copyrighted material from this

email for purposes that go beyond 'fair use', you

must obtain permission from the copyright owner.