VNS is workinig for me how about you?

In contrast, the E05 study had a statistically significant change only in the mean percent change. The median percent change and the number of patients who had greater than a 50 percent response was not statistically significantly different between the high and the low groups. In addition, the E03 study stimulated patients every 90 minutes, as compared to the E05 study, where patients were stimulated every 180 minutes. The sponsor this morning has discussed reasons why the E03 group potentially was so low, and using the inclusion/exclusion criteria of the E05 study, did result in approximately a 15 percent reduction. However, if you examine this data from a type of dose-response in terms of 90 minutes versus 180 minutes, we would still expect a lower value in the E05 group relative to the E03 group. In terms of the open-label E04 study, the mean percent change was not significantly different. It was only a 7 percent change, while the median percent change and the greater than 50 percent responder rate was statistically improved. pg. 128 <a href="http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf" target="_blank">http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf</a> ____________________________________________ DR. COSTELLO: Good afternoon, Dr. Wilkinson and members of the panel. This afternoon, I will be discussing issues regarding the safety and effectiveness of the vagus nerve stimulation device......................One-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase.................This slide shows each of the studies and the percent seizure increase. As you can see, in each of the studies, there were patients who had greater than a 100 percent increase. In the E05 study, the range went up to a 234 percent increase, while in the E04 study, it went even higher, to a 680 percent maximum range. pg. 125 <a href="http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf" target="_blank">http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf</a> ___________________________________________ DR. SNEAD: I think that's a reasonable suggestion. I would like to just say a word of caution about including children at this date. First of all, I am not convinced that we have data to do that. Secondly, what we have heard about today are that the patients will tell you when the stimulus is too high, because they are uncomfortable, because of the voice change. Well, some children are not able to do that, and some children are severely neurologically handicapped; some children are too young, and you really need to be very careful about extrapolating these data into that kind of population. DR. WILKINSON: Any other comment, then, about this question? DR. SPYKER: I'm not sure I understood the suggestion. We already have it back in the has not been shown effective. That's on page 12, and I guess, well, so,the question stands: do we want to leave this in the indication section. I don't propose that we remove it from back in individualization of treatment? DR. WILKINSON: It's already in that paragraph. DR. SPYKER: Yes, sir. Thank you. DR. WILKINSON: Yes. So, leaving it in this paragraph would emphasize the lack of data for the 12-year-old age cutoff, but not listing it as an absolute contraindication would still leave the clinician some leeway, so, perhaps leaving this in does make sense. DR. DUFFELL: Could I make a comment on that? DR. WILKINSON: One quick comment. DR. DUFFELL: I agree with what you're saying, but what we also need to remember is that what the indications state also greatly influences what the payers will pay for. So, the panel needs to consider that as well. We will work with the FDA to constructively work out whatever the label should be, but I wouldn't want you to neglect that in your considerations as well. DR. WILKINSON: And also, the future will come, and with the future may come data. [Laughter.] pg. 201 <a href="http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf" target="_blank">http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf</a> Dr. Wilkinson - Committee Chairman Dr. Snead - Committee voting member Dr. Spyker - FDA Dr. Duffell - Cyberonics _________________________________ The next issue which I would like to address is the long-term data. As can be seen in the extension phase of the XE5 study, here are the results of the randomized, controlled trial and then followup at 4, 6 and 9 months Both the mean percent change and the median percent change during the extension phase showed approximately a 30 percent seizure reduction for these patients. However, this data is confounded by the fact that the patients were changing their medications during this period. Similarly, despite optimal antiepileptic drug therapy, only 20 percent of the patients in the extension phase, using a last visit carried forward analysis, had 50 percent or greater reduction in seizures. One-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase. pg. 130 <a href="http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf" target="_blank">http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf</a>