DMC delay thoughts:
I know this has been beaten to death lately, but I’d like a reality check on my take on the DMC delay. For the record this is only my opinion and I have no information that is not already public.
The critical factor to me seems to be how the Phase III trial defined an “event” as tumor recurrence or death and how that relates to the primary and secondary end points. An event will either occur in the control group or the experimental group. At that time a data point is created for the DMC to analyze once enough events have occurred to trigger interim analysis.
The data based just on an event is pretty simple, how long from the beginning of the treatment until the event. The main metric for the trial is simply progression free survival of the experimental group vs. the control group. The secondary arms of the trial are really irrelevant to that metric since they are no longer blinded. They can only be used as a secondary supporting data set.
The DMC’s main job is to make a recommendation based on 2 things:
1. Are there any evident safety issues with DCVax?
2. Is DCVax on track to meet it’s primary endpoint?
There are of course other things for the DMC to consider, but I don’t think they would have a material impact on whether or not to give a particular recommendation.
I am forced to dismiss 1 because of the complete lack of any safety issues in the prior trials. So that leaves just 2.
There are 3 options for the DMC to recommend:
1. Continue
2. Halt for futility
3. Halt for efficacy
I have to dismiss 3 because of how rarely that happens. It is an outside possibility but I’d rather buy a lottery ticket than make any decisions expecting that outcome.
1 and 2 should both be pretty easy for the DMC to analyze. Simply look at each “event”, determine whether the event came from the control or experimental group and do a statistical comparison. Remember the main job of the DMC is to make a recommendation based on whether or not DCVax is likely to meet its primary endpoints. So why would it be taking so long?
Here is my hypothesis:
They received far fewer events from the experimental group than would be expected based on the primary end point goal of 6 months progression free survival. This would logically create a delay as is would force DMC to double-check not only the data, but also analyze to trial design itself to ensure that there was not some systematic error.
I am not saying they will stop for efficacy, Just that NWBO set the bar for the trial to low compared to their experimental results to date. If DCVax is performing nearly as well in the current trial as it has in the past trials I believe the delay is to be expected as the analysis would have to be much more exhaustive than normal.
Any halt for futility should be a pretty easy call for the DMC based on the endpoint criteria IMO. Am I off base here or is this a rational supposition?
AI
