RE:So many questions about the patient protocolMy take, which probably has some errors. I do believe there's some footnotes to the new slide that explain it a bit better and they look cut off. I think the way to look at the first version is that it is sort of like a decision tree explanation of a hypothetical version of the trial, prior to any actual trial data. For instance, they just throw in the fact that if a DLT is observed, you'd lower it down and test more. They don't really show that the protocal says you'd test 6 more or something like that.
I always recall them saying the dosage trial will be between 15 and 25 patients and that never really jibed with the 15 patients they show. So maybe the 15 patient if you are lucky like it shows would only take 28 weeks. But if you have any SAEs you need to dose more and if you have DLTs you dose more and if fewer than 2, keep moving up. All that would add to the 28 weeks. Then you have that final 6 where you dose the planned level for the next trial.
The new version incorporates actual data for the first 9 or so patients. There were no SAEs down in the patient 1-6 levels and no DLTs in 1-6, so it moved up rapidly with each new patient having a higher dose. That one SAE created the need to dose more at that level in order to move on if no further SAEs are seen. I suppose that is where we are and if they pass that, they'll move up one more level.
I think you need to take the first chart as a stylized decision tree sort of approach and the second as one with half factual patients at those levels and the right half still fairly stylized based on what happens. I think somewhere along the line we picked up that they believe the maximum dose they would accept is that one up in the 700's. Perhaps they just felt it's a nuclear bomb so no need to go beyond that if we even get there.
SPCEO1 wrote: Please see the two depictions of the patient protocol below which have raised a number of quesions for me. Admittedly, I may be a little slow when it comes to things like this but maybe some of you can help me out:
1.) Both protocols below indicate the phase 1a will take 28 weeks. Was that just an unrealistic hope or do they count weeks differently since they did not update the second chart to include more weeks which clearly have been chewed up at this point?
2.) Notice we now have a whole new level on the second slide - 745 mg. If this level was found to be safe, would yet another new level be added? How many can they add before they say it is time to stop even if no SAE's ever occur.
3.) While it appears they had no SAE's at the 420 level and that this is likely the fallback level for the MTD if SAE's are seen at the 540 level, if they had seen some at 420, could they just declare the 300 level as the MTD or would they need to go back and test some more patients. They surely could not declare it the MTD just based on one patient, right? Prehaps this is a moot point, however, as I suspect they do have multiple patients at the 420 level.
4.) Do they have to have at least 15 patients in the trial before it ends? If so, what does that mean for how long the trial might yet last? Can they knock out the extra patients very quickly?
5.) Why did the original slide have 3 patients at the 200 and 300 level but then they only apparently tested one patient each at those levels?