Angry Emails From Ezetimibe Investigator

The US Senate Committee on Finance is hard on the heels of pharmaceutical giants Merck & Co and Schering-Plough Corporation, accusing the companies of deliberately holding back the presentation of data from the ENHANCE trial, which suggests that ezetimibe is an inferior lipid-lowering agent compared to simvastatin. The companies deny any such action, claiming that the 18 month delay was due to problems with the data collection and analysis.

Several emails between the lead investigator, Dr. John Kastelein and Schering-Plough appears to tell another story. These seem to suggest that Kastelein ”was kept out of the loop of important decisions regarding when the data would be presented and what end point would ultimately see the light of day.”

Kastelein’s tirades betray his frustration with the pharmaceutical giant:

“Is it correct that SP [Schering-Plough] has decided not to present at AHA [American Heart Association] but to await the two other, completely unvalidated, end points, which analysis is going to take us straight into 2008??!!??,” writes Kastelein in an email to Schering-Plough executives, including Dr Richard Veltri (Schering-Plough Research Institute, Kenilworth, NJ). “If this is true, SP must have taken this decision without even the semblance of decency to consult me as PI [primary investigator] of the study. I can tell you that if this is the case, our collaboration is over. . . . This starts smelling like extending the publication for no other [than] political reasons, and I cannot live with that.”

The following day, Kastelein wrote again to Schering-Plough:

“I have been traveling half the globe in the past six months to a number of large and important meetings at the strong wish of Merck to chair them or to present ezetimibe data. At every single one of them I was cleared to say that ENHANCE would be presented at AHA.” He adds that a decision to include IMT data on the femoral artery adds nothing to the analysis, a decision contemplated by the company, and that if included, the company will seen as hiding something and “I will be perceived as being in bed with you!”
– from Heartwire

A spokesperson from Schering-Plough says the emails where taken out of context and the issues raised are — by both parties — considered resolved.

The Senate Finance Committee also questioned the ACC and AHA because of statements calling for patients not to panic. I for one agree with the statements since the ENHANCE trial only looked at surrogate endpoints (intima media thickness, LDL levels) and not clinical outcomes (myocarcial infarction and death).

However, the fact that both the AHA and ACC recieve money from both Merck and Schering-Plough further complicates the matter.

“It’s a tough thing to protect ourselves from receiving the money, in terms of advertising and so forth, and then making sure it doesn’t influence us,” said [Dr Jack Lewin, chief executive officer of the ACC]. “But we have set up painstaking efforts over many years to protect our professionalism. That’s an obligation to patients. Is it tough to do? Yes, it’s very tough. It’s requires an enormous amount of vigilance and a high level of scrutiny and professional ethics.”
– from Heartwire

Links to the published studies:

Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358:1431-1443.