NOTE: AND, once again, thanks to PM for the heads-up on all of this (Gooz’s
her latest, on the benefits and costs of Avastin, the very-pricey Genentech cancer drug, is very-well-laid-out — do go read it) and do go read this, on preventible inpatient death rates, by PM. . . .
UPDATED — 07.06.08 @ 7:00 PM EDT: The Insider, at Pharmagossip is on the case — and has featured my derivative graphics, at right. Brilliant!
Now, the graphic at left (a part of this longer editorital) was originally derived from the data presented in this NEJM paper. What I want the readers to notice is that — at every subgrouping — ezetimibe did not outperform the statin-regimen in any statistically-significant fashion.
Perhaps even more importantly, in the sub-groupings in which ezetimibe performed worse — it did much worse. Note how “right weighted” those dots are (click the image to enlarge it). Only three of 25 sub-groups were fully-over the “zero-line”, and into the “left side — ezetimibe better” result — and all of those three were just barely better.
Now, let’s hear from Dr. Taylor, himself (do go read all of his, though):
. . . .[Earlier] in this issue of the Cleveland Clinic Journal of Medicine, Dr. Michael Davidson, a respected lipid expert but one invested in ezetimibe’s development, assures us that all is in order and that the results of ENHANCE can be explained away by several arguments, most notably that most of the trial’s participants had previously received lipid-lowering treatment, which obscured the effects of ezetimibe.
Moreover, he argues that ezetimibe’s mechanism of action is well understood and that the drug is safe and well tolerated and thus should remain a first-line treatment for hyperlipidemia.
These arguments may eventually prove to be correct, but as of now they are merely wishful post hoc hypotheses awaiting more data apart from ENHANCE. Negative clinical trials do occur as a matter of chance, but we should be cautious in any attempts to explain away a trial that was designed, executed, and reported as conceived simply because the results do not match our expectations.
Confronted with ENHANCE, the astute clinician should ask three questions: Do we really understand ezetimibe’s mechanism of action? Do other lines of evidence indicate the drug is beneficial? And how reliable is the arterial thickness as a surrogate end point?. . . .
That is exactly right — the bottom line?
There can be no <font color =”#FF0000
“>lipstick red enough for this pig — the pig called ENHANCE.
UPDATED: I think Dr. Davidson’s opposing conclusion — in the vein of “the lady doth protest too greatly” — tells me all I need to know about his biases:
. . . .Enormous challenges are on the horizon for the pharmaceutical industry, with a shrinking pipeline of potential new drugs, increasing regulatory hurdles, greater liability risk, political pressure for price controls, enhanced scrutiny of sales practices, and a growing media bias. As a cardiologist and clinical researcher [appeal to emotion omitted]. . . . I am concerned that, unless change occurs, a vibrant pharmaceutical industry with the financial and intellectual capital to find and develop new, more effective treatments will cease to exist. . . .
With all due respect, Dr. Davidson, that is a conclusion not remotely supported by the actual data. This silly mantra of the “death of US Pharma” [as Samuel Clemens, in 1897, sort of intoned — “is greatly exaggerated. . . .” and] — simply must stop. It is beneath the abilities of the people offering it. It suggests there is little else, of worth, to write in defense of the failed study. Perhaps that is the case.
Perhaps that is the object lesson, here.
[In the interest of being complete, here is the introduction of this Journal’s editor — Dr. Brian F. Mandell — to the above point-counterpoint debate, found in this month’s Cleveland Clinic Journal of Medicine. All of the pieces are PDF files — emphasis here supplied.]