Monday, November 26, 2007

Is it (Clinical) Research, or is it (Pharmaceutical) Marketing? - the ENHANCE Trial of Ezetimibe

The story of the delay in reporting results of the ENHANCE trial of ezetimibe (Zetia, by Schering-Plough, and one component of Vytorin, by Merck) was reported by Matthew Herper in Forbes, Alex Berenson in the New York Times, and theHeart.org and MedScape. Then several prominent skeptical bloggers, including Howard Brody on the Hooked: Ethics Medicine, and Pharma blog, Dr Aubrey Blumsohn on the Scientific Misconduct Blog, and Dr Scott Aberegg on the Medical Evidence Blog analyzed the situation. Therefore, I need not post a lot of detail.

Basically, although ezetimibe has been shown to reduce LDL ("bad") cholesterol, it has never been shown that using the drug to do so produces any clinical benefit, e.g., prevents heart attacks or strokes, prolongs life, etc. The ENHANCE trial was designed to determine whether the drug at least reduced arterial obstruction, thought to be a good predictor of bad clinical events. After reporting of the trial's results was delayed, it became evident that:
  • The trial's Principal Investigator had no access to the trial's original data, and no control over how the data was analyzed.
  • The data was owned and analyzed by the drug companies that nominally "sponsored" the trial.
  • The same drug companies decided to change the trial's endpoint after the trial was implemented and the data was collected.
  • The companies justified the decision as coming from an expert panel they convened (and presumably paid for.) However, they did not reveal who was on the panel.

As Doctors Brody, Blumsohn, and Aberegg pointed out, this trial is just the latest poster child for how pharmaceutical manufacturers (and other health care corporations) can manipulate the design, implementation, analysis, and reporting of clinical research they sponsor so as to make their products look as good as possible. Is it (clinical) research, or is it (pharmaceutical) marketing?

My main addition to the expert commentary already made about this trial is that not only does the control of clinical research by organizations with vested interests in having the research turn out a certain way challenge the research's validity. It also is an affront to the research subjects who thought they were participating in a study meant to advance science and possibly health care.

2 comments:

Anonymous said...

The Nov. 21 WSJ Health Blog highlights a call from Medicus Int. Dr. Jean E. Sealy received to ghost write an article regarding the drug nebitolol that is seeking FDA approval by the end of the month.

Dr. Sealy was given one week to complete the study, but the company would do all of the heavy lifting, including handling distribution. When Dr. Sealy asked to see the raw data the phone line went dead.

One really does not have to look far to see an attempt to spin data with a high profile name attached. Once again we see a company trying to manipulate the reporting of clinical research for gain. Fortunately, Dr. Sealy asked the right questions.

Steve Lucas

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