A medical journal published a study on Monday of deaths related to the anti-inflammatory drug Vioxx after withholding the report because the researcher said he had been threatened by superiors at the US Food and Drug Administration.
The Lancet, which originally planned to publish the paper on November 17, released the study online.
Dr David Graham, who works in the FDA’s office of drug safety, has said he was firmly discouraged from publishing his data questioning the safety of Vioxx, which was withdrawn from the market in September.
“I was sent an e-mail by one of my supervisors threatening me with severe consequences” if the paper was published, Graham said in a telephone interview. Believing he was threatened with dismissal, he said he asked the Lancet to withdraw the paper from publication in November.
The FDA agreed earlier this month that the study could be published. Graham’s conclusion that the drug was responsible for between 88,000 and 140,000 excess deaths had previously been disclosed.
Kathleen Quinn, a spokesman for the FDA in Washington, said the agency had no comment on the Lancet’s publication of Graham’s report.
Dr Steven Galson, acting director of the FDA’s Centre for Drug Evaluation and Research, had contacted the Lancet before the originally proposed publication date, raising questions about the paper.
“Some of the questions involve basic data integrity. (Graham) has declined to address these issues, and we think it’s important that your readers know this,” Galson said in an e-mail to Lancet editor Richard Horton.
The manufacturer, Merck & Co, is now defending at least 700 lawsuits in the United States related to the drug. The company withdrew it from sale in September after a study concluded that it doubled a patient’s risk of heart attacks and strokes.
The study by Graham and colleagues published by the Lancet compared the incidence of coronary heart disease in patients taking Vioxx and similar drugs known as cox-2 inhibitors.
Graham’s team analysed data from 1.4 million people in California who had used those and similar drugs from 1999 to September 2004.
They concluded that those taking Vioxx had a 34 per cent higher chance of coronary heart disease when compared with other drugs.
“An estimated 88,000-140,000 excess cases of serious coronary heart disease probably occurred in the USA. over the market life of rofecoxib,” Graham said, using the generic name of Vioxx.
“The US national estimate of the case-fatality rate (fatal acute myocardial infarction plus sudden cardiac death) was 44 per cent, which suggests that many of the excess cases attributable to rofecoxib use were fatal.”
In a commentary published by the Lancet, Simon Maxwell and David Webb of the University of Edinburgh in Britain said that researchers should now look at other similar drugs.
Pfizer also announced that a study of its pain drug Celebrex showed it had similar problems at high doses.
“It now falls to the manufacturers, under the careful review of the regulatory authorities, to provide all the evidence that this class of drugs is safe, if necessary including studies that directly address cardiovascular morbidity as a primary outcome,” Webb wrote.