ENHANCE Study: More Much Ado About Suboptimal Data

Schering-Plough, Merck, and the delayed ENHANCE study results continue to receive negative attention thanks to the recent salvo of Congressional letters to the drugmakers and others. The WSJ Health Blog reported yesterday that Representatives John Dingell and Bart Stupak (leaders of the House Committee on Energy and Commerce) sent a letter to SP's CEO, Fred Hassan, and to the CEO of Merck (comarketer of Vytorin [ezetimibe/simvastatin]), Richard T. Clark, asking follow-up questions generated by SP's ENHANCE study timeline. Specifically, the congressmen want to know the names of the SP biostatisticians who were involved in the "routine quality review" of the ultrasound data as early as 2005.

The congressmen also fired off a letter to Andrew C. von Eschenbach, MD, FDA Commissioner, asking for the agency’s protocol information on the ENHANCE trial. And last, not to leave cyberspace out of the mix, the Representatives sent a letter to the webmaster of the freewheeling Cafepharma, asking for the identities of anonymous (and presumed insider) posters who indicated that they knew about the negative ENHANCE results as early as March 2007.

Now this last, arguably laughable Congressional step amounts to wanting to know who scribbled what graffiti on the wall of a public restroom.* However, the representatives, perhaps sensing the absurdity of their request, do give the website operators an out by stating, "If such information is not available, please provide your companies' policies relating to maintaining and/or storing such information relating to messages posted on Cafepharma.com"—to which Cafepharma is likely to reply with their privacy policy ensuring anonymous message-board posting.

No matter. The ENHANCE timeline provided by SP clearly indicates that their biostatisticians knew of data-quality problems during the latter of half of 2005. It'd be surprising if that information hadn't percolated up the SP executive ladder by 2006. Now whether insider knowledge of the ENHANCE data influenced SP or Merck execs to unload stock is yet to be determined. But the answer hinges on whether execs were sufficiently clairvoyant to know that suboptimal data from a relatively small study in a population with an uncommon form of genetically determined atherosclerosis would attract such fanatical attention.

And if I’ve written it once, I’ll write it again: Given the poor quality of the ultrasound data in the ENHANCE study, we still don't know if the combination of ezetimibe and simvastatin is associated with greater atherosclerotic-plaque stability, or even reduction, than simvastatin alone in patients with heterozygous familial hypercholesterolemia.

*I’m sure there's a joke to be made here about the attraction between Congressmen and public restrooms, but I can't quite work out a draft.