Maker of Vioxx Is Accused of Deception

In the in-house document, the Merck researchers included people who died while taking either Vioxx or a placebo as well as people who died after stopping, as quite a few did because they had side effects, changed their minds or moved away. This method of accounting automatically captures any delayed effects of a drug (sometimes measured in months), although it unavoidably includes deaths that are very unlikely to be linked to the drug, such as a car accident occurring a year after a person stops taking a medicine.

In its FDA filing, however, Merck reported only deaths that occurred while "on treatment" and up to two weeks later (for one arm of the study) or three months later (for the other). This gave a mortality risk that was less dramatic than the 3 to 1 ratio calculated with the method the company used in-house.

Merck reported all the mortality data to the FDA two years later, and the information appeared in journal articles in 2004 and 2005. Psaty thinks it should have been done earlier.

"This was a large 'safety signal,' " said Psaty, who has received no payments from plaintiffs' attorneys. "If this had been made public in a timely fashion, many fewer patients would have used Vioxx, and fewer might have been harmed by it."

James Fitzpatrick, a lawyer at the New York firm handling Merck's Vioxx defense, said that in the 2001 report, the company was not hiding anything and that it told the FDA it was still collecting data.

"The disparity in mortality was quite clear if you looked at the on-drug data. Adding some off-drug mortality would not have changed the analysis in any way," he said.

In many clinical trials that carry a risk of death, researchers create a "data monitoring committee" of outside experts who are empowered to look at a study's interim results and stop the study if evidence of harm is found.

The FDA did not require such a committee for the Merck studies, but Psaty said the company should have had one. "That protection wasn't there. You'll have to ask Merck why it wasn't," he said.

Kent Jarrell, a spokesman for the company, said Merck opted for in-house monitoring because Vioxx was already on the market and being taken, apparently safely, by many elderly people.

"With Vioxx, the safety profile had already been studied in thousands of patients," he said.

The evidence that Merck had research papers ghostwritten is circumstantial and indirect.

It includes an e-mail from Scientific Therapeutics Information of Springfield, N.J., which Merck paid to write eight articles reviewing the usefulness of Vioxx in various types of patients. The message notes the "intended author" and "intended journal" for each paper, as well as the delivery date.