My guess is that if HE reimbursement suggests a PFS improvement of 6 mo + some margin for error for not being fully mature yet, then their DMC would recommend an efficacy data read at 248 PFS events, as you say. But if the HE reimbursement suggests a marginal, ie 6 months exact efficacy, or less, then they would recommend just continuing the trial to the end, first re-opening screening, if necessary, to get to the full patient population for the revised trial. As I explain below, I don't think they would need to screen any further patients to reach full enrollment for the revised trial plan, but I am sure others here know better than I about that.
This assumes that either NWBO or their DMC can infer efficacy from the HE allowance for reimbursement.
Alternatively, if the PFS advantage suggested by the HE reimbursement projects much greater than 6 months, then the DMC could recommend some sort of AA with confirmatory be applied for. I don't know those trial details well, ie early approval vs AA, but I think they would only have to carry the confirmatory out to 248 progression events in that case.
Of course the trial is messy with PFS being a difficult read for GBM and with OS being spoiled to an unknown degree by crossover. Further, I don't know if the HE reimbursement level is based on PFS or OS. If OS, then all of the above would be different and more complications ensue. Over my head with this level of detail, just agree that the level of enrollment and screened patients was conspicuous when the hold occurred with the number enrolled being roughly the number needed to demonstrate SS for 6 months PFS advantage (old bar), and I believe the number screened being about the number needed to demonstrate SS for 4 months PFS advantage (new bar), if all those screened were eventually enrolled.
