Thursday, March 02, 2006

New Vioxx Revelations

More disturbing news about what Merck may or may not have revealed in its Vioxx studies, according to the New England Journal of Medicine's release last week.

NEJM wrote: "The information we have indicates that the Vigor article...did not contain relevant safety data available to the [Merck] authors more than four months before publication."

On its site, NEJM has a table from a July 2000 internal Merck memo analyzing the risk to the heart for patients taking Vioxx during the trial. The table is found in a Merck memorandum and notes the three heart attacks that were not included in the medical journal.

Merck developed a plan to analyze cardiovascular events only late in the trial. But instead of selecting the same cutoff date for cardiovascular problems, as it did for stomach side effects, Merck picked a cardiovascular cutoff date one month earlier, in effect excluding heart attacks that occurred in the final weeks of the trial. This part of the trial "inevitably skewed the results," per the NEJM.

A Secret End Date?: Merck didn't tell ELEVEN other academic researchers working on the paper. The 11 academic co-authors of the paper have told NEJM that each was "unaware" of this cutoff date--Feb. 10, 2000. The company says that it did this to give it time to analyze the heart-attack data, and that the cutoff was appropriate. Go here for the PDF.

Clotting Adverse Events: Among data available to Merck before the article was published but apparently not included in the NEJM release was information that a half dozen people who took Vioxx developed clots in the arms and legs during the trial -- compared with only one on naproxen.

A key question for doctors was whether Vioxx benefits to the stomach outweighed any risk of increased heart attacks. VIGOR suggests that there was indeed a benefit. Looking at the July 5, 2000 memorandum however, those who took Vioxx had 27 more "thromboembolic events" such as heart attacks and strokes than those on naproxen.

Merck, to the surprise of no one, denies it all.

You can go to Forbes as well as the NEJM to read more. The NEJM is released 3/16/06.