Thursday, June 14, 2007

Look at the size of that trial! Avandia fallout? Let's hope not.

Usually, when we determine the sample size of a clinical trial, we calculate based on efficacy first. The International Committee on Harmonisation (ICH) has drug exposure guidelines which define the minimum. And if our efficacy sample sizes aren't quite enough to examine the safety issues outlined in the guidelines, we bump the sample size up.

Via Kevin, MD, I found someone who is sharing my concern that, in the recent swing of focus to drug safety, we are probably passing up drugs that may have ugly side effects, but are necessary in treating ugly diseases. Of course, no one wants to risk liver damage to quell a toothache (or do we? Hey, do you take acetaminophen?).

It goes like this: Steve Nissen's meta-analysis took over 42 trials and 28,000 patients to detect a statisticially significant result in cardiovascular risk for Avandia. If we want to be absolutely sure that a drug is safe and doesn't even have a small risk, this is the patient population size you will have to enroll in a development program.

I pretty much agree with the assessment that big pharma is to blame with dubious marketing practices and the blockbuster mentality. An FDA with the authority and will to enforce post-marketing commitments and safety surveillance will go a long way to identifying safety issues more quickly and identifying patients most at risk of adverse drug effects, much like the way that apolipoprotein E (ApoE) genotyping may identify the patients most at risk of cardiovascular side effects of Avandia.

That is, if we can keep our head on straight and remember the goal of drug research — to help people.