UPDATE -- 07.28.09 @ 8 AM EDT: FDA's PDAC Materials are now posted -- it is a daunting 19.1 Mb download; 1,067 pages. Paging Salmon. . . .
We have a new working thread on it, for your collective observations.
It is the policy of FDA that the Advisory Committees release background materials for committee meetings two business days prior to meeting date. The Saphris (asenapine) meeting is July 30 2009. So, I expect that sometime during the day -- perhaps whilst I am off the grid, attending to other matters -- FDA will post the asenapine materials right here.
Until that happens, do go take a look at the latest installment of Salmon's "Continuing Asenapine Chronicles" -- right here, in the comments. Do go read all of his, but here is a teaser, to encourage you to follow that link:
. . . .Found a little bit of info on this study at [Medical News Today]:". . . .In the study, SAPHRIS was significantly more effective than olanzapine in the reduction of negative symptoms as measured by change from baseline to Day 365 in the NSA-16 total score, the primary endpoint of the study. By using a mixed model for repeated measures (MMRM), least square mean changes in the NSA-16 total score were -15.8 for SAPHRIS vs. -11.0 for olanzapine (P=0.015). Full results of the trial, including efficacy, safety and tolerability data, will be submitted for presentation at a medical meeting at a later date. . . ."
Another report for up to 6 months shows no difference in effect but a higher incidence of EPS with asenapine but less weight gain (possibly a "side effects" wash):". . . .There was no difference in effect between olanzapine and asenapine on negative symptoms at 6 months. This study continued things for another 6 months and found a statistically significant difference at 12 months. There was also a lot more weight gain reported with olanzapine. . . ."
[The] study uses MMRM (mixed modeling of repeated measures) as a statistical technique. My experience with this is that you need to know what is making people drop out of the study and account for each different reason. In practice even when attempted you can't get reliable data for this and so you have to impute the reasons and that's not a very good assumption because what is true for one drug is not necessarily true for another.
When I see MMRM I immediately know the statistical analysis is likely based on a bunch of fudge factors that are likely wrong.
Plus without a placebo and knowing the scale it's hard to interpret whether this is of any real benefit.
Lastly, even if it is real it may imply that there's poorer efficacy on the positive symptoms and may be why 3 of 4 pivotal trials in support of the acute treatment of an acute psychotic episode in schizophrenia were negative.
FDA needs to be more transparent in the future and release all reports and data. . . .
[And, From A Later Update from Salmon:]
. . . .So if we see a summary written by FDA management without individual reviews or without individuals reviews in clinical pharmacology, and pharmacology/toxicology or these reviews are redacted (they shouldn't be at all) then I would say something fishy is going on.
And I know fishy.
Indeed. If the background materials happen to show up while I am away, feel free to comment on them in this thread. [I suppose it is a possibility that -- though rather unlikely -- the FDA Advisory Committee meeting on Schering-Plough's Saphris (asenapine) has been postponed, and thus the materials are not posted.]