Thursday, April 12, 2007

Merck - Arcoxia: those who forget history......

This post seems worth a re-airing:

Double blind or vision impaired?

by Mike Lascelles of Pharma Watch (from May 2005)

A double blind trial is supposed to be the gold standard of evidence. But what good is it when a trial is run by company drones who suppress any worrying data? The Annals of Internal Medicine is this week publishing a cautionary note on its website, saying that some data from a Vioxx trial it publised may have been manipulated by Merck. The company reported only six major cardiac events and suppressed others by classifying them as of "unknown origin".

This is what the NYT said back in April:

The Advantage trial was completed in 2000, but its results were not published until 2003, when they appeared in the Annals of Internal Medicine, a well-regarded journal.

Dr. Jeffrey R. Lisse, a rheumatologist at the University of Arizona who is listed as the study's first author, said in an interview that at least two other journals had rejected the study because its results were not novel.In the published study, Dr. Lisse reported that five patients taking Vioxx had suffered heart attacks during the trial, compared with one taking naproxen, a difference that did not reach statistical significance.

But the paper never mentioned the three additional cardiac deaths of patients taking Vioxx, including the 73-year-old woman.

Dr. Lisse said that while he was listed as the paper's first author, Merck actually wrote the report, an unusual practice.

''Merck designed the trial, paid for the trial, ran the trial,'' Dr. Lisse said. ''Merck came to me after the study was completed and said, 'We want your help to work on the paper.' The initial paper was written at Merck, and then it was sent to me for editing.''

Dr. Lisse said he had never heard of the case of the woman who died, until told of it by a reporter. ''Basically, I went with the cardiovascular data that was presented to me,'' he said.

The 73-year-old woman who became the subject of the debate inside Merck died on Oct. 21, 1999, a few minutes after calling her son to tell him she felt short of breath.

By the time her son reached her house, she was dead. Records show that she had been taking 25 milligrams of Vioxx a day as part of the clinical trial.

Both the Advantage and Vigor trials were ''double-blinded,'' a common practice in drug research. Neither patients nor their doctors were aware whether patients were receiving Vioxx or naproxen. Results from the trials were also supposed to be blinded when they were examined, so that Merck researchers could not bias the results.

In 1998, Merck had created a committee of academic researchers to review the case reports for many patients who had suffered suspected heart problems in clinical trials of Vioxx or Arcoxia, a Merck arthritis drug that has still not been approved.

But the woman's case never reached the outside committee because the cause of death listed on the death certificate from an independent autopsy -- hypertensive heart disease -- did not fall into a category that would automatically prompt Merck to refer the case.

As a result, Merck reviewed the case internally.

After examining the case, Dr. Eliav Barr, a Merck scientist, initially judged that the woman had probably died of a heart attack.''Common things being common, the clinical scenario is likely to be MI,'' Dr. Barr wrote in an e-mail message in November 2000 to Dr. Alise Reicin, the clinical research executive.

MI is an abbreviation for myocardial infarction, or heart attack.

''Certainly, it is not definitive. I just used my clinical judgment.''

Dr. Reicin quickly responded, ''I think this should be called an unknown cause of death.'' A few hours later, she wrote, ''I would prefer unknown cause of death so we don't raise concerns.'

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