The Vytorin Study Controversy - Now Congress is Getting Into the Act

In recent weeks, the controversy has grown regarding the continuing delay in releasing the results of the ENHANCE trial - a study comparing the use of the widely-advertised cholesterol drug Vytorin (ezetimbe plus simvastatin, Merck and Schering-Plough) to simvastatin alone. (Vytorin is the drug advertised in those commercials that make your Aunt Hilda look like a strawberry sundae.)

The ENHANCE trial was designed to show that Vytorin is more effective than simvastatin alone in arresting the progression of atherosclerosis (hardening of the arteries). The controversy stems from the fact that the trial was completed in April, 2006 - but no results have yet been reported. Furthermore, it has been alleged that the industry sponsors have spent the last 20 months manipulating data - and even changing the end points of the trial. The suspicion is that the trial has not come out the way the sponsors wanted it to, and they're looking for ways to salvage something positive before releasing the results.

The suspicion has grown sufficiently that the US House of Representatives Energy and Commerce Committee felt compelled to write a letter to the companies and the clinical investigators alleging the same things. Noting that the endpoints that were described when the ENHANCE trial was finally registered (not until Oct. 31, 2007) on ClinicalTrials.gov differed from the endpoints that were described in the original study design, the letter says, "We are concerned with the delay in releasing the results of the study, the timing of ENHANCE trial registration, and the apparent manipulation of trial data." The letter further called for principles from the companies and the clinical trial to appear before the committee to explain themselves.

Schering-Plough now says it is sticking to the original endpoints, and will present data from the trial at the 2008 American College of Cardiology Scientific Sessions.

At this point, that's not good enough. The very best interpretation that can be assigned to the behavior of the sponsors of this trial is that they are incompetent. The delay itself is suspicious. But the fact that the endpoints of the trial were apparently changed after the study was concluded, followed by the fact that apparently now they have been changed back, is strong evidence that the data is being vigorously manipulated. And if the data's being manipulated, one could naturally conclude that the data, analyzed as originally intended, is unfavorable to Vytorin. Which, just as naturally, raises the final question: Are the results "merely negative" (that is, Vytorin appears no more beneficial than simvatatin alone), or are they "really negative" (that is, Vytorin is substantially worse than simvastatin alone)?

It is entirely possible, of course, that the sponsors are just truly incompetent, are indeed not trying to manipulate away some unfavorable results, and it is by sheer stupidity that they have maneuvered themselves into the public spectacle of congressional hearings before a hostile chairman (Rep. Dingell). Fine. But if it turns out that Vytorin is no better (or is worse) than a generic statin drug, and that the delay in reporting the data turns out to be aimed at creating an extra two years to heavily market an expensive drug that the sponsors know will die (once the data is finally reported) as suddenly as poor Aunt Hilda surely will, then even DrRich, who has no love for witch-hunting congressional subcommittees, will TiVo the proceedings to enjoy over and over again.