Revealed: Schering-Plough backdates Vytorin IMPROVE-IT trial.
Schering-Plough has changed the start date listed in a government database for the key clinical trial testing the now-controversial cholesterol pill Vytorin, which Schering shares with Merck.
The study tests whether Vytorin, which is a combination of Schering-Plough's (nyse: SGP) Zetia and Merck's (nyse: MRK) Zocor, prevents heart attacks, strokes and deaths better than Zocor alone.
The companies have been criticized for taking three years since Zetia was approved to start this key study, called IMPROVE-IT, to demonstrate that Zetia adds further benefit to Zocor, which has already been shown to prevent heart attacks.
Until April 1, the Web site ClinicalTrials.gov said the study started in February 2006. But on that day, the company changed the start-date field, saying, instead, that the trial began in October 2005, six months earlier. The change is publicly accessible by a track-changes function on the ClinicalTrials.gov website.
A Merck/Schering-Plough spokesman said that the February 2006 start date reflected the start of the trial outside the U.S., but the October 2005 date reflects the first patient dosed in the U.S. "We updated it to reflect the accurate start date in the U.S.," he said.
The changes came as the company increased the number of patients in the study from 12,500 to 18,000 and delayed the expected completion date of the study until 2012.
Two days before, a panel at the American College of Cardiology had said that because an artery-imaging study showed no added benefit from Zetia to Zocor, doctors should dramatically scale back their use of Zetia and Vytorin.
The controversies over the artery-imaging study, called ENHANCE, also began with questions about the companies' use of ClinicalTrials.gov. On October 23, Forbes emailed a Merck/Schering-Plough spokesman to ask why the ENHANCE study was not listed on ClinicalTrials.gov. Merck/Schering-Plough listed the study on ClinicalTrials.gov on Oct. 31, according to the site's track-changes function.
On Nov. 19, after the companies offered repeated explanations for a long delay in the study, Forbes was the first to raise questions about ENHANCE. The study’s lead investigator, John Kastelein of Academic Medical Center in the Netherlands, has since said he would have felt ready to present the results as much as nine months before they were released.
In e-mails released first by Sen. Charles Grassley and then by the companies, Kastelein angrily raised the possibility last July that a delay could lead to the appearance of impropriety, even if the companies had good intentions.
In one e-mail, Kastelein wrote, "This starts smelling like extending the publication for no other [than] political reasons, and I cannot live with that." In a second, he added: "You will be seen as a company that tries to hide something, and I will be perceived as being in bed with you!"
According to ClinicalTrials.gov, the details on the ENHANCE and IMPROVE-IT studies were provided by Schering-Plough, which is responsible for the conduct of the trials. Merck is conducting two other large tests of Vytorin as part of the joint venture, under which the companies split the development responsibilities and sales for Vytorin and Zetia.
The people listed as responsible for the study on ClinicalTrials.gov are Enrico Veltri and John Strony, the same two Schering-Plough executives who were responsible for the ENHANCE study. They were also the people involved in the e-mail exchange with Dr. Kastelein.