Washington, DC - The US House of Representatives Energy and Commerce Committee chair, John Dingell (D-MI), and the chair of its Subcommittee on Oversight and Investigations, Bart Stupak (D-MI), have written a letter to Merck and Schering-Plough expressing their concern about the "withholding of clinical trial data that may significantly affect the medical management of hypercholesterolemia."

The letter is referring to the ENHANCE trial, which is evaluating ezetimibe plus simvastatin vs simvastatin alone on the progression of atherosclerosis in the carotid artery, which has been in the news recently for being behind schedule.

The letter states: "The ENHANCE trial was completed in April 2006, and yet no data from the trial have been published or presented in their entirety. In fact, it appears that the study itself was not registered with ClinicalTrials.gov until October 31, 2007, a full 18 months after completion of the study. In addition, the end point indicated in the ClinicalTrials.gov website appears to differ from the end point described in the initial study design." It adds: "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."

Dingall and Stupak request that the director of the trial, Dr Enrico Veltri (Schering-Plough, Kenilworth, NJ), and principal investigator, Dr John Kastelein (Academic Medical Center, Amsterdam, the Netherlands), as well as company representatives, meet with the House Committee to discuss these issues. They also want details of the identities of the members of the expert panel that recommended changing the study end point and any records of that meeting.

However, Schering-Plough says that it has now decided not to change the primary end point of the study after all.

In a "Frequently Asked Questions and Answers" on its website, the company states: "We will present the original prespecified primary end point for the ENHANCE trial." It adds: "We view the expert panel's advice to focus the primary end point on the common carotid artery as helpful, as the common carotid artery is viewed by many clinicians and experts of the [intima media thickness] IMT procedure as the most reliable, reproducible, and clinically meaningful segment of the carotid artery and least subject to artifact and variability. In consideration of this independent expert advice and the evolving medical science, Merck/Schering-Plough and the lead investigator have had further discussions about the trial, including input from other respected clinical trialists and scientists. . . . As a result, we are planning to examine closely the data from the common carotid artery and to present that data from the prespecified end points, in accordance with the study protocol and study analysis plan."

A Schering-Plough spokesperson told heartwire that the company is reviewing the letter from the committee and will respond "in a timely manner." He said the company had discussed changing the primary end point of the study to focus on one measurement in the common carotid artery on the advice of an outside expert panel, as this measurement is now believed to be the one that is most sensitive to changes in atherosclerosis progression, but that after further discussions with experts, it was decided to keep the original primary end point—which includes three measurements in different sites of the carotid artery—so as not to deviate from the original clinical trial protocol. That decision was made, the spokesperson said, before the House Committee letter was received.

He added that the trial began in 2002 and the legal requirement to post details of studies on ClinicalTrials.gov did not come into force until 2004; Schering-Plough voluntarily decided to add it into the website this year. On the issue of the delay in releasing the results, the spokesperson repeated the explanation previously given by Kastelein: that the trial had indeed been completed since April 2006 but that the results were still blinded, as discussions had been taking place over how to handle some confounding data. "Some of the blinded image readings were implausible, and we wanted to make decisions on what to do about that. It now appears that this is normal, and the results are currently being analyzed," the Schering-Plough spokesperson said.

The results of the ENHANCE study are planned to be presented at the American College of Cardiology meeting in 2008.