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Merck, Schering-Plough Won't Change Vytorin Trial Following Outcry

Dec 17, 2007 | Parker Waichman Alonso LLP

The makers of Vytorin have backed off plans to change the testing parameters of a clinical trial studying the effectiveness of the cholesterol lowering drug.   Merck & Company, which markets Vytorin in an joint effort with Schering-Plough, had already decided to delay the results of the long-awaited ENHANCE study, and word that  the parameters of the study were to be changed had angered many in the medical community.  While it is good news that Merck and Schering-Plough have reconsidered their decision, the whole episode raises questions about the integrity of studies, such as ENHANCE, that are paid for by drug makers.

Both Merck and Schering-Plough have a lot riding on ENHANCE.  Vytorin is a single pill that combines  the companies’ cholesterol lowering drug, Zetia with simvastatin, the active ingredient in Merck’s Zocor statin.   According to the Wall Street Journal, if ENHANCE produces a favorable result for Vytorin, it would strengthen the case for Vytorin in high-risk heart patients over the generic form of Zocor alone, but a negative finding could encourage insurers to reduce coverage for the more expensive medicine.

The data from the ENHANCE trial was supposed to be released by March 2007, but that didn’t happen.   What’s worse, in November, Merck and Schering-Plough decided to change the ENHANCE study’s endpoint – the medical result it was supposed to measure.  They said the analysis would now focus on an ultrasound measurement at only one point of the carotid artery, as opposed to three points, as originally stated in the study’s plan.   The decisions to delay the release of ENHANCE, together with the announcement that the endpoint would change led many to speculate that the study did not cast Vytorin in a good light.

The companies’ decision to change the ENHANCE endpoint enraged many cardiologists, as well as members of Congress.    It is generally accepted among scientists that for a clinical trial to be valid, the endpoint must be established before it begins and never changed.  But since Merck and Schering-Plough were footing the bill for ENHANCE, there was little anyone outside the companies could do about it.

One person who was in a position to influence Merck and Schering-Plough’s decisions regarding ENHANCE was the companies’ lead investigator on the study, John Kastelein.  Kastelein, a cardiologist at Academic Medical Center, Amsterdam, has said that he regretted not fighting harder to keep the original endpoint of the enhance study.   Why he did not remains a mystery, although the fact that he is paid by Merck and Schering-Plough could be a clue.

At any rate, the Wall Street Journal says that Kastelein is relieved that Merck and Schering-Plough have backtracked on the ENHANCE endpoint.  “It’s never, ever right to change the primary endpoint of a study,” especially after all the data are in, Kastelein told the Wall Street Journal.   “It is statistically not good and it gives the wrong impression to the outside world.”