A quick recap: the study was designed to measure plaque in neck arteries, but results weren't released for nearly two years. The drugmakers blame the delay on difficulty reading ultrasound images. But they briefly changed the primary endpoint without consulting their lead investigator; there was no data safety monitoring board, and they appointed an 'independent' panel to review the data, but three members had financial ties to the companies. The results found no statistical significance, prompting some docs to question whether Vytorin should be prescribed, although Vytorin did lower LDL cholesterol more than the much cheaper Zocor (which, along with Zetia, forms Vytorin).
"While the Enhance trial was time consuming and took longer than originally anticipated to complete, our companies acted with integrity and good faith in connection with the trial," says Tom Koestler, Schering-Plough's chief scientist. "We took numerous actions to assure the quality of the reading of the ultrasound images." And Peter Kim, Merck's chief scientist, adds: "We stand behind Vytorin and Zetia and stand behind our science that has brought these cholesterol-lowering medications to millions of people around the world."
And so they offer a chronology (look here), indicating the trial began in October 2002 and the last patient visit occurred in April 2006. Following the last patient visit, the study required "meticulous examination" of roughly 30,000 ultrasound images of the carotid arteries and 10,000 ultrasound images of the femoral arteries. Examining the images was a "challenging process" and the data analysis took "significantly longer than expected." Numerous steps were taken in 2006 and 2007 to address quality issues and finalize the data analysis, the drugmakers continue.
Then, they attempt to address the allegations of insider stock trading by Carrie Smith Cox, Schering-Plough's president, and some of her colleagues, which has drawn Congressional scrutiny, along with their handling of the trial; Vytorin advertising; financial support of the American Heart Association and the American College of Cardiology (both of which issued statements supporting Vytorin use) and Medicaid payments.
"Until December 31, 2007, the study remained blinded; that is, neither the patients nor the researchers nor the companies knew the group of patients that received each therapy. On that date, statisticians for Schering-Plough Research Institute first became unblinded. Additional personnel at the companies were made aware of the findings during the first two weeks of January, 2008." In other words, they argue the execs wouldn't have known the results at the time they sold their stock.
We've written this before, and we will write this again: changing a primary endpoint - and doing so without consulting the lead investigator - is inappropriate. And failing to provide more meaningful updates to a widely anticipated trial much sooner in the process only caused skepticism and suspicison. And naming a so-called independent panel without releasing names compounds the matter, especially when some panel members aren't independent. If Merck and Schering-Plough execs are upset over "mischaracterization," they have only themselves to blame.