Thursday, March 09, 2006

In the news: F.D.A. recommends Tysabri return

An FDA advisory panel has unanimously recommended returning Tysabri to market. From the NYT:
In making its decision, the scientists and doctors advising the Food and Drug Administration said, in effect, that patients and their physicians should have the right to decide whether the considerable benefits the drug offers outweigh risks that can perhaps be reduced but not totally avoided. If the F.D.A. goes along with the recommendation, as it is expected to by the end of the month, the approval would be only the second instance of a drug being returned to the market after having been withdrawn for safety reasons.

Bravo. I'm not sure why there was quite so much handwringing about whether to allow patients and doctors to make this decision. Per the NYT story, the risk of developing PML is about 1 in 1,000. Also per the NYT story, Tysabri is more effective than the CRAB drugs. Assuming this is true, any rational cost/benefit analysis would have to conclude that the MS-related misery prevented in Tysabri patients exceeds the risk of developing PML.

Just about every medical intervention (drugs, surgery) involves some level of risk. As a society, we've decided to allow patients and doctors to sort that out for themselves, up to a certain point, beyond which we figger we need to step in and say, "No, that's not a rational risk." The problem, from the patient's standpoint, is this: in this case, it is relatively easy to quantify the risk. We know how the proportion of Tysabri patients that developed PML, and we know that PML is fatal. That's pretty concrete. The potential benefit to Tysabri patients, however, is much squishier. Maybe we can come up with some numbers, maybe EDSS scores. But the real meaning of those scores, the reality to an MS patient, cannot be represented by a number. Effective treatment for MS might mean the difference between working vs. disability, going out with friends vs. watching TV, making it to the bathroom vs. peeing your pants. If it were possible to know, on an individual level, what Tysabri (or Betaseron or low-dose-naltrexone or hyperbaric oxygen) made possible (and it's not possible), what's that worth?

Which is why I am glad that at this meeting of scientists there were, according to the NYT, some two dozen MS patients who "pleaded at the meeting, some tearfully, for the return of the drug they called their best or only hope." Let us make this decision by hashing it out with a doctor and, daring a little bit of optimism, taking a risk.
Link to NYT story (free reg req'd)
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Beth said...

If you go back and look at the studies, the only ones who developed PML were those who were on multiple immunomodulatory drugs. Everyone has the JC virus in their brain, but normally the immune system keeps it in check. Tysabri taken with anything else immunosuppressive is apparently too much and the JC virus proliferates. You would think they would just change the guidelines. It is also, interestingly enough, the only clinical trial with MS drugs that a combination of immunomodulatory drugs were tested.
It sounds like Tysabri is about two times more effective than the others.
Good point about better disability scales needed. I get the feeling though that most MD's are marginally interested in your quality of life- they just like to prescribe the medicine.

Beth said...

It turns out that one of the three that died of PML in the clinical trial never had any evidence of inflammation in the brain- no lesions on the MRI and a clear spinal tap. She didn't even have any disabilities. Post-mortum/post-study they are thinking that she had migraines not MS! This is one of the many problems with these clinical trials.

This is from a editorial in the March 2006 Lancet. There is also a huge report on the clinical trial in NEJM. I can email the PDF's if you would like- just put up an email address. Seems like your the type who would like to read this stuff.