Emil Gilels — Apr. 17, 08 at 09:14 PM

This statement:

"the very same Alzheimer's trials data found that Vioxx was less likely than placebo to result in cardiovascular events"

is actually false.

It is true if you look at
what Merck published, but that's because Merck
never published the as-randomized analysis
that their data analysis protocol called
for. That analysis shows a vioxx cardiovascular
problem very similar to that in the APPROVe study
that led to the withdrawal of vioxx in 2004.

Ted Frank — Apr. 18, 08 at 08:39 AM

Emil, I'm working off of FDA analyses of the Merck studies, including one done in 2005, http://www.fda.gov/OHRMS/DOCKETS/ac/05/briefing/2005-4090B1_02_MERCK-Vioxx.pdf, when they would have had every incentive to criticize Merck to divert unfair criticism of the FDA approval of Vioxx. If your claim was true, we'd see Psaty/Kronmal trumpet it as further evidence of Merck perfidy in these two studies, but they made no such claim. So if you're aware of something that Psaty, Kronmal, the FDA, and I all missed, please drop me an e-mail, and I'll correct my analysis.

David Egilman — Apr. 21, 08 at 05:55 AM

There was an increase in cardiac events on Vioxx in the AD trial 078.

The published article misrepresented the cardiovascular outcomes of the trial. Although the study protocol stated that the primary endpoint would be an ITT analysis, the published paper did not report any such analysis. Merck presented the on-drug and off-drug data separately and disaggregated fatal and nonfatal myocardial infarctions and cardiac arrests. When combined, the results indicated that Vioxx treated-volunteers had suffered a statistically significant increased rate of MI/SD (sudden death)* of 2.16 (CI 1.12, 4.35). In addition, there was a statistically significant increase in adjudicated CV/T deaths RR = 4.72 (CI 1.59 – 14.00). These volunteers used prophylactic anti-thrombotic medications, including Plavix and aspirin. (Thal LJ 2005). Aspirin’s anti-thrombotic capabilities may have concealed the negative cardiovascular effect of Vioxx, thus acting as a significant confounder.

Merck did not give the FDA the ITT analysis and there is no evidence the FDA never calculated the above from the data or the paper. The FDA missed a few other things like the death excess (sat on this for six months), the fact that Merck removed the planned DSMB after the study was approved by the FDA & the IRBs and of course the death excess.

Had the FDA reported all their misses they would have looked worse than they did. It is hardly a surprise that the FDA did not report these events after the drug killed and injured so many. Of course that is part of the point. The FDA is, as Merck research lab presidents Drs. Peter Kim and Edward Scolnick stated, "overworked" and look like "grade D high school students."

From the "infamous" David Egilman MD, MPH. Knowledge can make you a dangerous infamous person.

* Sudden death was considered a myocardial death. This is how most studies characterize SD.

David Egilman — Apr. 21, 08 at 08:23 AM

Could the real Emil Gilels please email me if you are not a lawyer. (degilman@egilman.com)

No one from Merck has ever come forward.