Wednesday, October 26, 2011

FDA Slams Viibryd: Better Sexual Profile Claim “Not Supported by the Data”

The September 2011 issue of the Journal of Clinical Psychiatry created history in two ways.

First, the journal published this article written by FDA staff critically reviewing the efficacy and safety data of Viibryd, a new antidepressant that the same FDA staff had just approved.

Second, it was not just any journal that published the article, but the Journal of Clinical Psychiatry. Why is this so historic? Anybody who has followed this blog over the years has noticed a certain…shall we say, skepticism...toward many of the articles published in JCP, especially those published in its industry-funded supplements. But in this case I'm happy to give the journal kudos for having the courage to publish an article critical of an antidepressant made by a company that pays for drug ads.

Not that any of this information is truly new. Back in April of 2011, my own Carlat Psychiatry Report actually scooped JCP on this issue, when Jim Phelps and I reported in this article that Viibryd-funded authors had tweaked sexual side effect data to make the drug appear “cleaner” than its SSRI competitors.  (Some of this tweaking, interestingly enough, occurred in the pages of the Journal of Clinical Psychiatry).

In fact, as we reported and as this new paper elaborates, the studies proved nothing at all about Viibryd’s side effects, because they artfully omitted a crucial element—the inclusion of a comparator SSRI known to cause sexual dysfunction.

The other claim put to bed by the FDA is the idea that Viibryd is quicker to work than other antidepressants. This was based on one of Forest’s trials which showed that Viibryd separated from placebo by week one. The FDA’s article pointed out two problems. First, this data was from Trial 04, which was only one of two large trials submitted as part of the new drug application. In the other trial, Trial 07, Viibryd did not separate from placebo until week 4. Second, neither trial compared Viibryd with an already approved SSRI, meaning that no statements can be made about the new drug working faster than any other drug.

It’s nice to see the FDA stepping up to the plate and proactively publishing articles that dispel company-spread rumors about drug effectiveness. And it’s also great that a usually industry-friendly journal like JCP would publish this.

Tuesday, October 11, 2011

New Study: Biomarkers are Cool, but Nearly Useless for Predicting Alzheimer's

Everybody would like to find a brain scan or a blood or spinal fluid test to predict Alzheimer's disease. Such objective tests seem inherently more reliable than the clinical interview.

Recently we've seen various studies identifying biomarkers for predicting who will develop Alzheimer's. The problem is that most of the studies are merely suggestive, though they are so complex that they create a veneer of definitiveness. The usual technique is a sort of statistical fishing expedition. First, you identify a group of people who are at risk of developing Alzheimer's. Second, you collect boatloads of data, such as from brain scans, blood draws, or spinal fluid specimens. Third, wait a couple of years to see which patients develop Alzheimer's. Finally, have a computer sort through dozens--sometimes hundreds--of possible biomarkers until you find one, or a combination  of several, that correlate with developing Alzheimer's.

There are many variations on this theme, of course, but this is basically how biomarker research is done. The problem is that the more biomarkers you test, the higher the risk that you'll find a correlation that isn't a valid biomarker--but is just a random finding that has little to do with Alzheimer's.  In order to test the utility of biomarkers, you have to choose a few likely candidates, and see if they actually predict Alzheimer's...and you have to compare the predictive power of the expensive biomarkers with the cheap old fashioned method--the clinical interview.  Amazingly, almost no such studies have been done--and not a single study has compared multiple types of biomarkers with the clinical interview. That is, until now. 

An article published in the latest issue of the Archives of General Psychiatry compared specific neuroimaging findings and spinal fluid markers with a clinical interview. Over a two period, the researchers found that only three variables were able to significantly predict which patients would develop Alzheimer's: two clinical measures of memory, and one neuromaging finding--the thickness of a part of the temporal lobe. By far the most important predictor of cognitive decline was a combination of a brief survey of activities of daily living and 5 minute paper and pencil test. These two combined explained 50% of the variance in outcomes, which is a very large number in these kinds of studies.

The bottom line is that if you want a test to predict whether a patient is going to progress from mild cognitive impairment to Alzheimer's, stay away from the needle.  A careful clinical interview, repeated over time, is overwhelmingly more effective than these expensive tests.