Friday, November 30, 2007

Eltrombopag: Alas data that speak for themselves

In this week's NEJM, two articles describe the results of two phase 2 studies of Eltrombopag, a non-peptide, oral agonist of the thrombopoetin receptor, one in patients with HCV and thrombocytopenia:
and another in patients with ITP:

I have grown so weary of investigators who must speak for their data - massaging them, doing post-hoc analyses, proffering excuses for them, changing their endpoints and designs to conform to the data, offering partial analyses, ignoring alternative interpretations, stacking the deck in favor of their agent - that I breathe a sigh of relief and contentment when I see data like these which are robust enough to speak for themselves - both in level of statistical significance and effect size which is clearly clinically meaningful.

Of course, we should be clear what these studies can tell us and what they can't. This is a phase 2 trial and it certainly demonstrated efficacy and a dose response which should satisfy even the harshest critics (e.g., me). However, the time of treatment was relatively short so we don't know if the response can be sustained over time; and the study was wildly underpowered to detect side effects at all but the highest frequencies. What untoward effects of stimulating megakaryocytes through this pathway might there be? What about thrombotic complications?
(This is an interesting question also - supposing there are increased thrombotic complications with this agent - how will we know whether this is a direct adverse effect of the agent or whether it results from reversal of protection against thrombosis conferred by ITP itself, if that even exists?)

So, we await the results of larger phase 3 trials of Eltrombopag, hoping that they are well designed and attuned to careful measure of adverse effects, content for now that a novel and apparently robust agent has been discovered to add to the currently inadequate treatments for cirrhotic thrombocytopenia and that associated with ITP.

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