Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : IPIC -- Ignore unavailable to you. Want to Upgrade?

To: Grainne who wrote (1239)	5/28/1998 11:47:00 PM
From: NeuroInvestment	Read Replies (1) \| Respond to of 1359

I posted this recently on Yahoo, re: the MRI trial design. To clarify once and for all the MRI trial issue: The MRI trial was started at around the same time as the second US Phase III. It was envisioned as supplemental, offering an empirical (infarct size) variable that would be potentially useful, but not pivotal. The initial plan was to accrue around 160 pts. At the time it started there were very few FDA-approved diffusion weighted MRI machine-equipped centers, the accrual rate was very slow (one a month or less). When the second PhIII ran into problems due to the number of mild cases in the placebo group, this trial become more critical, placed in a role it was not designed for. IPIC could have started another full PhIII(like the one they are now starting), but that is hindsight. Their strategy was to use the MRI study to bolster the 2 PhIIIs that each had a statistical flaw, to reach 'critical mass' of acceptability in the eyes of the FDA. However,even with the now-improved rate of accrual, it would have taken another 9-12 months from now to reach the 160 pt level, since it is much harder to find sites able to conduct MRI studies. The historical data about infarct size indicated that one could reach statistical significance with a sample size around 100, assuming no skews. With the FDA fast-tracking CerAxon, and because completing the trial would have meant a delay in FDA review until early 1999 at best, they unblinded it now. With some patients dying, some dropping out, only 81 were left, and the high placebo response rate meant that the magnitude of infarct size increase (180% in placebo, 38% on CerAxon) had a p=.17; 83% chance of being due to the drug. It is not just a case of sample size, but of variance, how much variability exists in each group. If every placebo pt increased by 180%, and every CerAxon pt by exactly 38%, you would not need a large sample to show that this was significant. The more variability, the larger the sample is required. Because of the placebo group anomaly and the variance, my understanding is that they might have had to go to 200 pts in order to reach .05; in other words, they could have taken the next 9 months, reached n=160, and still not have satisfied the FDA. The two possible errors that one can conceivably attribute to IPIC in hindsight are that they did not start another regular PhIII earlier (rather than hanging on for the MRI study) and that they assumed a best case scenario when unblinding the MRI study as early as they did. They did not leave room for statistical flukes..without that fluky placebo group divergence from what would be expected based on the (limited) data available on MRI changes in stroke, this trial might well have reached or been close to .05, even with n=81. It is the kind of aggressiveness that could have paid off handsomely, but in this case, obviously did not. NeuroInvestment (www.neuroinv.com)