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Monday, December 24, 2007

Data About Ezetimibe Adverse Effects Suppressed?

Here we go again. Last week, an article by Alex Berenson in the New York Times reported that Merck and Schering-Plough conducted trials of ezetimibe (Zetia, by Schering-Plough, and a component of Vytorin, by Merck) "that raise questions about its risks to the liver," but never publicly reported their results.

Partial results of the studies, alluded to in documents on the Food and Drug Administration’s Web site, raise questions about whether Zetia can cause liver damage when used long term with other cholesterol drugs called statins.

A Schering executive, when asked by a reporter about the unpublished studies, confirmed their existence.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.

The unpublished Zetia studies, devised as safety tests, would not prove the drug’s effectiveness.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 All the unpublished studies covered periods at least one year in length and were intended to show whether long-term use of Zetia might pose dangers that short-term use did not.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The unpublished studies, conducted from 2000 to 2003 according to the F.D.A. documents, were not listed on the industry Web sites where companies are supposed to register the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.

Together those studies cover several thousand patients who took Zetia along with statins for one to two years. The statins include Lipitor and Crestor, as well as Zocor, which is usually prescribed generically as simvastatin and is the statin used in the Vytorin pill. Doctors often add Zetia to a low dosage of a statin, because Zetia reduces cholesterol in a different way than the statins do and leads to deeper overall cholesterol reductions.

'We’re pretty comfortable that people don’t have trouble tolerating Zetia,' said Dr. Spiegel, the chief medical officer of the Schering-Plough Research Institute, Kenilworth, N.J.

I agree more with this response by Dr Harlan Krumholz, from Yale.

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.

There is important evidence, but it’s not in public view. It’s hidden from investigators.

As I have noted now it seems ad infinitum, to make the best decisions about patient care, physicians and patients need access to the best relevant evidence from clinical studies. Concealing evidence about, say, the toxicities of a particular drug may lead to bad decisions, specifically, prescribing the drug when its possible harms outweigh its risks.

In addition, suppressing the results of clinical research betrays the trust of human research subjects who were participating because they thought the research might advance science and/or patient care. Obviously, suppressed research can do neither.

This is one more anecdote suggesting that either clinical research sponsored by the companies who make the products the research is meant to evaluate needs much stronger regulation, or such research should be taken entirely out of the hands of the companies who stand to benefit if its results turn out a certain way.

See also comments in the Clinical Psychology and Psychiatry Blog, the Hooked: Ethics, Medicine and Pharma blog (with clinical and clinical epidemiologic background), the Medical Evidence Blog (suggesting a boycott of ezetimibe), and the Scientific Misconduct Blog (warning, contains adult language.)

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