is this?. I might just have to take some Prozac.
Getting the Label
OK, let's talk a little about Vioxx. This is a pharmaceutical legal blog, and Vioxx is the big drug litigation story, so you'd think I'd spend more time on this.
Today, there's a telling AP story about Merck officials "getting the label" they wanted for Vioxx. The "label" is the package insert, which contains all the warnings and side effects about a drug, in addition to indications, pharmakinetics, chemistry information, etc. Getting the label you want for a drug is what clinical trials is all about - negotiating with the FDA, based on whatever trial data you have, to avoid warnings and precaution statements as much as possible. Negotiations sounds like a strange word in this setting, but it's what really happens. The drug company argues that there are too many confounding factors that prevent any assignment of causality. For a drug that is generally taken by sick people, this is an easier process for the company, since there is probably a substantial background rate of all kinds of ailments. For a pain drug, you have to consider the patient population who took the drug during the trials. Did they take it for arthritis pain, and are thus probably elderly? They probably take all kinds of other drugs then, with a whole bunch of side effects of their own. The VIGOR study was for rheumatoid arthritis, and if the patients were anything like my mom, they take a pharmacy every day.
In the big continuum that is drug development, before you even have a compound, you have a Target Profile. The profile tells you that you want a drug that does X, does not have side effect Y or Z (that the existing drugs in the therapeutic area have) and has a sales potential of $$$. Thus, you already have the beginnings of the label you want before you even have a compound.
I heard a lecture once from a drug safety physician in my company concerning a particular psychotropic medicine that had a warning about cataracts on the label, based only on animal studies. He had been told that getting rid of that warning was a high priority for drug safety, since it was responsible alone for losing hundreds of millions in sales annually. This was the first time that I heard a dollar figure attached to a safety issue, and it was clear that our marketing folks wanted us to go to the FDA with every argument possible to get rid of that warning.
So, the Merck folks came to the same conclusion about their drug, but they were more successful in their negotiations. They managed to convince the FDA to keep the heart attack information from VIGOR in the "Precautions" section of the label, instead of the "Warnings." This is significant not because the prescribers would notice the warning by themselves (they wouldn't), but rather the helpful competition would be sure to point it out to them, and feature it prominently in their sales materials. Imagine the script for a Pfizer rep - "Celebrex: the ONLY Cox-2 inhibitor without a heart attack warning."
The damning part of all of this is the attitude of the Merck players, as well as their stupid use of email. EMAILS LIVE FOREVER. Write them like they do. And remember - Merck was the most respected drug company in the country. If you asked a focus group about Merck two years ago, you'd get reactions like science, integrity, and so on. The evidence introduced in these trials should forever pierce that veil. How much of Scolnick's emails about VIGOR and the FDA had anything to do with patient well-being, do you suppose?
Tomorrow - Guidant was off-course!