I mentioned yesterday that my opinion of Merck and their handling of the Vioxx cases isn't very high these days. The reason for this is the press release that the company sent out a few days ago on follow-up data to the APPROVe study, which is the one that caused the company to withdraw Vioxx in the first place.
That study was looking at possible use of Vioxx for the prevention of precancerous colon polyps. That may sound slightly insane if you're not following the field, but there's some biochemical rationale that suggests a role for inhibition of COX-2 against colon cancer. (This would be another huge market, naturally, which is why Merck - and Pfizer - have both looked into it). As the world knows, the study also showed clear evidence of an increased cardiovascular risk after 18 months of Vioxx use., and that's what started us all on the bumpy road to where we are today.
The APPROVe study was designed to have a one-year follow-up period to evaluate how long any colon-related benefits persisted. Unfortunately, it wasn't really designed (or powered, as the clinicians say) to address cardiovascular safety, so everyone just has to take what they can from the data we have. Merck, naturally, takes the current data to mean that Vioxx is doing just fine. They point out that in the post-drug follow-up year, the cardiovascular risk for the group that was taking Vioxx doesn't seem to be statistically different from the group that had been taking placebo.
Which is fine, as far as it goes. A more objective look at the data, though, show that they didn't miss statistical significance by all that much. The numbers seem to be all against Vioxx, which is enough to make you wonder if the lights would have truly flashed red in a more statistically appropriate study. As it is, Merck is in the position of saying that a study which wasn't expected to show a statistical difference between Vioxx and placebo heart safety didn't show a difference - and that that's good news.
Even if the numbers had gone the company's way, statistical arguments are a notoriously hard sell for the defense in front of a jury. Having a bunch of muddy but trending-ugly data is one of the worst things that could have happened to Merck, actually. No one knows, from these numbers, just when the effect of Vioxx on cardiovascular risk might wear off. It's a playground for the lawyers - can't you just hear it? "Isn't it true that more patients had heart attacks on Vioxx? Even during the year after they'd stopped taking the drug? No, no, I didn't ask you for a lesson in statistics - just tell me if more people had heart attacks or not!"
No, no courtroom help there. I hope, for Merck's sake, that no one at the company believes there is, and that no one's charging them by the hour to try to convince them otherwise. At this point, they're going to need something better, and I'm not sure where they're going to get it. It's past the time when we can usefully argue about whether Vioxx should have been withdrawn, about what its risk-benefit ratio is, and whether Merck should be facing thousands of lawsuits or not. They are, and more than this latest batch of data will be needed to fight them.
(See also Jim Hu's comments).
Update: According to today's WSJ, things have gotten even muddier. Here's the subscriber link, and this is a Reuters summary.