Healthy Skepticism Library item: 788

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Hensley S.
Pfizer Disputes New Allegation Of Failure to Publish Test Data
THE WALL STREET JOURNAL 2005 Feb 2

Full text:

Pfizer Inc. disputed allegations that it failed to disseminate results from a four-year-old study that found patients taking Celebrex to treat mild Alzheimer’s disease ran a risk of heart attacks and other cardiovascular side effects.

The consumer-advocacy group Public Citizen on Monday said the study showed Celebrex increased by nearly four times the risk of cardiovascular problems, such as heart attack, compared with a sugar pill. The analysis was based on data Pfizer posted in an online clinical trial registry.

During the study and afterwards, the independent safety board that monitored the test of Celebrex for Alzheimer’s treatment didn’t find safety problems significant enough to stop the study, according to one of the board members. Nonetheless, the independent doctors on the panel urged the drug maker to get the results into print so they could be factored into the medical assessment of the painkiller, which is a Cox-2 inhibitor drug.

At the time, Pharmacia Corp. made Celebrex and co-marketed the drug with Pfizer, which acquired Pharmacia in 2003. The companies ignored the advice, a safety-board member said. “This is more a failure-to-publish issue than a Cox-2 issue,” said Lon S. Schneider, the safety-board member who is a professor of psychiatry, neurology, and gerontology at University of Southern California Keck School of Medicine in Los Angeles.

The Public Citizen analysis was flawed, he said, because it lumped together side effects that could have different causes. In some cases, he said, the same patient might have been counted more than once as well. And it happened by chance that the patients in the Celebrex group were sicker overall than those in the placebo group, he said.

In a Dec. 24, 2004, letter to Pfizer, Dr. Schneider, writing on behalf of the members of the safety-monitoring board, said: “As the only independent body with this information and having had past responsibility for the safety of the subjects in this trial, we have an obligation to ensure the visibility of this trial….Finally, we note that this trial was never published, just orally presented in 2002” at an medical meeting in Stockholm. “It should have been fully published in 2000, and perhaps if it had been some attention might have been drawn to potential safety issues. (Yet one more example of why the results of all clinical trials of marketed drugs must be published).”

A Pfizer spokeswoman said the drug maker, based in New York, acted responsibly and shared the results with regulators around the world. The spokeswoman also said that an abstract of the results was presented at a scientific congress in 2000. She noted that it isn’t unusual for a small, Phase II study that doesn’t meet its efficacy goal not to be published. In this case, Celebrex showed no beneficial effect on Alzheimer’s disease.

The company maintains the study, completed in 1999, was too small to make definitive conclusions about the risks of Celebrex. Further, the safety board overseeing the study allowed it to run until completion, an indication that any problems weren’t serious.

For all the trial’s limitations, Dr. Schneider said: “The overall information from this study should be combined with information from other studies to see how strong a signal there is.”

In the study at issue, two of 285 patients taking 200-milligram Celebrex twice daily for a year had heart attacks, compared with none of the 140 patients taking a sugar pill. Six Celebrex patients had strokes, compared with three in the placebo group.

But a Pfizer statement yesterday noted that there was a “large difference in the underlying cardiovascular risk profile” of the Celebrex and placebo patients. For instance, Pfizer said, more patients assigned to Celebrex had hypertension, diabetes, took aspirin or had undergone a previous heart by-pass surgery than those patients taking placebo.

The Food and Drug Administration has scheduled an advisory committee meeting for this month that will examine the safety of Celebrex and other drugs in its class. Public Citizen has asked the agency to ban such drugs and the group also sent the FDA a letter about the little-noticed Celebrex study. An FDA spokeswoman said the agency will review the letter.

In December, a safety board analyzing data from a study of Celebrex to prevent colon cancer found an increased risk of cardiovascular side effects compared with patients taking a sugar pill. The review of those data was prompted by Merck & Co.‘s decision to pull its rival drug Vioxx from the market in late September. In a 2,600-patient study testing Vioxx to prevent colon cancer, the risk of heart attack and stroke was twice as high for patients taking Vioxx longer than 18 months than for those patients taking placebo.

In a separate development, Pfizer halted the clinical trial for its stomach-cancer drug early because it was proven effective. Members of a data-monitoring board, made up of independent researchers, had recommended that the company stop the trial because it had met its targets. The drug, SU11248, is used to treat tumors in patients where the standard treatment, Novartis AG’s Gleevec, is ineffective. The move greatly speeds up the approval process for the Pfizer drug.