More problems with Ezetimibe (Zetia, Vytorin): Let there be light

Yet more problems with Zetia (ezetimibe) clinical trials are now being reported in the New York Times (see background to the Enhance trial of ezetimibe Ezetimibe (Zetia, Vytorin): the smell of bad science). This has to do with hidden data in other studies of the drug.

Part of the problem here is the redefinition of what we mean by scientific fraud, and a redefinition of science itself. If I (as an individual scientist) were to study 20 rats, and then plot a graph showing only the results from those rats "I liked", or those rats I "considered important enough" then I would be guilty of scientific fraud.

Somehow when the stakes are higher we confuse power with honesty, and the deception is tolerated. It's an oddly familiar pattern of deception.

From 2000 to 2003, Merck and Schering-Plough conducted eight long-term safety studies of Zetia in combination with statins. Only three of those studies were published. Now some questions are being asked about what those studies showed, and why prescribers and patients were not given a full view of the evidence.

A Schering executive, Dr. Robert J. Spiegel, said "the companies had not considered the studies scientifically important enough to publish their findings. Some may eventually be published".

Well fuck you Dr. Spiegel, it's not your decision. When patients might die it's always "scientifically important". You might personally think that other scientists and even patients don't need to know what the evidence is, but it really isn't your call. If you want to sell your product under the banner of science you have to behave like a scientist. Science which cannot be scrutinized is not science at all. If you disable doctors and patients from making rational (and scientific) decisions about the use of your product, then you cannot claim to be a science based-enterprise. There are many other serious problems with suppressing clinical data. Patients in these trials exposed themselves to unknown risks in the interests of all of us. Suppression or distortion of that data is an affront to their dignity as human beings.

Science is, as Carl Sagan put it, a candle in the dark. It shines a light on the world around us and allows us to see beyond our superstitions and fears, beyond our ignorance and delusions, and beyond the magical thinking of our ancestors, who rightfully fought for their survival by fearing and trying to master occult and supernatural powers.

Let there be light.

From other blogs:

1. Brody, Howard (2007-12-21). New Cholesterol Controversies: Regaining Perspective. Hooked: Ethics, Medicine, and Pharma.
2. Aberegg, Scott (2007-12-22). Patients and Physicians should BOYCOTT Zetia and Vytorin: Forcing MRK and SGP to come clean with the data. Medical Evidence Blog.
3. Aberegg, Scott (2007-12-20). Are Merck and Schering-Plough "enhancing" the ENHANCE data?. Medical Evidence Blog.

From the NY Times, By ALEX BERENSON, Published: December 21, 2007:

The discovery of the unpublished research comes as Merck and Schering are already under criticism for not yet releasing data from an important Zetia study, called Enhance, that they completed early last year.

"The unpublished Zetia studies, devised as safety tests, would not prove the drug’s effectiveness. But they would give the public more information about Zetia’s potential risks. All the unpublished studies covered periods at least one year in length and were intended to show whether long-term use of Zetia might pose dangers that short-term use did not.

Most of the studies about Zetia in which Merck and Schering have published the results covered periods of only 12 weeks — not enough time for liver problems to develop in most patients.

The unpublished studies, conducted from 2000 to 2003 according to the F.D.A. documents, were not listed on the industry Web sites where companies are supposed to register the results of all drug trials that were ongoing after October 2002. The New York Times discovered references to the studies in briefing papers on the F.D.A. Web site.

“We keep telling people we want to practice evidence-based medicine, and what we keep finding out is that much of the evidence is obscured,” said Dr. Harlan Krumholz, a cardiologist at Yale, when told about the previously undisclosed studies. “There is important evidence, but it’s not in public view. It’s hidden from investigators.”"

“You don’t want to have data missing,” said Dr. Bruce Psaty, a professor of medicine and epidemiology at the University of Washington. “When there have been adverse effects, when the benefits don’t look impressive, those are the trials that historically don’t make it to press.”

A Schering executive, when asked by a reporter about the unpublished studies, confirmed their existence. But the executive, Dr. Robert J. Spiegel, said the companies had not considered the studies scientifically important enough to publish their findings. Some may eventually be published, he said.

“We’re pretty comfortable that people don’t have trouble tolerating Zetia,” said Dr. Spiegel.

Dr. Eric J. Topol, a cardiologist and director of the Scripps Translational Science Institute in La Jolla, Calif., said that he had asked Merck and Schering more than four years ago to conduct a large, long-term trial to prove that Zetia could reduce heart attacks and strokes. But the companies had little interest, he said.

“They looked at me like I was an alien,” Dr. Topol said.

Dr. Mark Stolk, a gastroenterologist in the Netherlands, last year reported two cases of patients who had developed hepatitis, a liver disease, after taking Zetia alongside Lipitor. One of the patients has since died.

But Dr. Beatrice A. Golomb, an associate professor at the University of California, San Diego, said doctors have lost sight of the purpose of prescribing drugs like Zetia.

The goal of prescribing cholesterol-lowering drugs is not reducing cholesterol, Dr. Golomb said. It is reducing the number of deaths and heart attacks in patients, he said. And without data to prove that Zetia actually reduces heart attacks, doctors cannot be sure they are helping patients when they prescribe the drug, she said.

See post followup: On swearing versus thuggery: a statistical analysis
Earlier|Later|Main Page