At the heart of the Vytorin scandal three years was a decision to change the primary endpoint in a key clinical trial, a move that called into question not only the integrity of the so-called Enhance study but the veracity of the drugmakers, Merck and Schering-Plough. The trial, of course, ended in failure (see this), raising questions about whether patients received sufficient benefit for a heavily promoted and expensive pill.
Merck, however, may have learned a lesson. The drugmaker, which has since bought Schering-Plough, recently resisted a recommendation by the steering committee for another Vytorin trial called Sharp to redefine the composite endpoint, according to Sanford Bernstein analyst Tim Anderson, who notes that such a move "would actually make it easier for Sharp to show positive results." The Sharp trial, by the way, is examining Vytorin's use in people with chronic kidney disease among some 9,000 patients.
Given the controversy over the Enhance trial, it is suprising the Sharp steering committee would suggest a change. Now, though, it appears, according to Anderson, that both sets of results – the original composite endpoint and a new composite endpoint – will be presented at the upcoming American Society of Nephrology meeting next month in Denver. He adds that positive results would be a big surprise.
A Merck spokesman wrote us to confirm that, in a paper published last month in the American Heart Journal (see abstract), "there was a recommendation made by the steering committee to change the primary endpoint earlier this year. Merck declined to approve a protocol change to revise the primary endpoint so late in the study."
He added that the independent steering committee "decided to modify the statistical analysis plan of the study to adapt to knowledge that has been accumulated from evolving science collected since the study began. The primary endpoint of the study (major vascular events) remains the same. Merck agrees with the direction Oxford (University) has chosen to take in the statistical analysis plan."
Oxford researchers, by the way, have previously clashed with Congress over findings from another Vytorin trial called Seas and evidence suggesting a link to cancer (look here).