This is how it is likely to play out. Any comments are welcome.
In earlier data, TNF+Standard-of-care has shown essentially the same survival rate as Standard-of-care for patients that were either treated recently (patients enrolled < 11 months ago) or treated long ago (patients enrolled > 24 months ago). TNF+SOC shows higher survival chances than SOC only in the middle (patients enrolled 11 months – 24 months ago), so we can try to estimate (with several assumptions) on how much better TNF+SOC might be than SOC in that time period, given the fact that 92 event mark was reached in end-Aug.
Using known survival curve for SOC, and looking backwards from end of August 2008 (when 92 deaths were reached), • Roughly 58 patients had been enrolled < 8 months ago. Assuming 2% trial dropout and 10% death rate for both TNF+SOC and SOC (as shown in earlier trial data), this would have likely led to 5.7 deaths • Roughly 17 patients had been enrolled 8-11 months ago. Assuming 3% trial dropout and 30%-40% death rate for both TNF+SOC and SOC (as shown in earlier trial data), this would lead to 4.9 likely deaths • Roughly 43 patients had been enrolled >24 months ago. Assuming 10% trial dropout and 90% death rate for both TNF+SOC and SOC would lead to 36.8 likely deaths So total dead amongst patients treated recently or long ago = 47.4
Roughly 71 patients were enrolled in middle between 11-24 months ago. Assuming 5% trial dropout, 22 of participating patients would be on SOC and 45 on TNF+SOC. If we assume SOC patients had 75%-80% death rate (very realistic given earlier data), we would need to have likely achieved 55-65% death rate amongst TNF+SOC patients so that all deaths add up to 92.
Based on plugging several iterations of these several assumptions, my best guess is that upcoming data in next few days will show that TNF+SOC achieves 40-45% survival (versus 20-25% survival on SOC alone) in patients that were enrolled between 11-24 months ago, and no statistical advantage either in patients early into treatment (enrolled <11 months ago) or late into treatment (enrolled > 24 months ago). Even though interim data had earlier shown a 8+ month improvement in median survival, the upcoming data will show < 4 month improvement in median survival so GenVec would likely try to use 18 month or 24 month survival rate as a key efficacy end point.
Where do you get your data from for patients in both arms treated for more than 24 months? You stated that the survival rate will be the same for both. It is my belief that the TNFerade arm will have superior survival results for patients in the PACT study for more than 24 months.