The Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) marketing trial in support of Vytorin produced a negative result for the potential claim. Unfortunately, after the media handled this otherwise medically not so important news, patients and physicians were very confused about cholesterol lowering and the value of statins.
The trial results were not peer-reviewed (given a stamp of approval by experts to understand their significance), so in the media, they became the focus of physian opinion at the extremes on the value of cholesterol-lowering medications and every other issue, like the perhaps overuse of these medications which is probably true for patients having low risk, and numerous medically underinformed commentators and newspeople looking for a story that day. The important result is that these results don’t in any way negate the carefully done clinical trials in support of the approved indication for cholesterol-lowering. (Michael O’Riordan, Heartwire, Feb. 28, 2008)
Dr Philip Greenland (Feinberg School of Medicine, Chicago, IL), coauthor of a new commentary, along with Dr Donald Lloyd-Jones (Feinberg School of Medicine, Chicago, IL), in the February 27, 2008 issue of the Journal of the American Medical Association, review key features of the controversial study. “Greenland and Lloyd-Jones call the fallout from ENHANCE “an unfortunate medical research experience” and suggest lessons to be learned by drug companies, researchers, clinicians, health agencies, and the media to avoid repeating the same mistakes with other trials.” (O’Riordan)
“For one thing, ENHANCE was not a clinical-end-point trial, as was reported in the media, nor were the results “negative,” said Greenland. They were not statistically significant, a big difference lost among some in the media. Moreover, the end point was not “fatty plaque,” as reported by others, but intima-media thickness. More concerning, however, was the fact that ENHANCE “mushroomed” to the point where almost 50 years of “serious and logical research has been damaged and defamed for no good purpose,” write Greenland and Lloyd-Jones.”
They suggest that companies shouldn’t be doing clinical trials for making marketing claims as even a positive effect in a poorly statistically-powered trial would have been meaningless. Instead, in the current environment, it places the future sales of the drug at grave risk. It also raises a question about the risk of direct-to-consumer advertising where a public poorly trained about the meanings and signficance of medical trials can result in an outcome never foreseen.
The full Heartwire article can be accessed at http://www.theheart.org/viewArticle.do?primaryKey=845925&nl_id=tho04mar08 for free.
Audrey
