I'm adamant the FDA requested an RCT, but I was trying to...

I'm adamant the FDA requested an RCT, but I was trying to understand why "those in the know" were making statements that were inconsistent with an RCT. It therefore seems that MSB are trying to create a workaround to the RCT requirement.

So my take is MSB will go into the Type A meeting with pilot data and advise the FDA they plan to conduct a targeted, controlled study in the highest-risk adults with the greatest mortality to obtain the data the FDA requires, and the only outstanding issueis what control would satisfy the FDA.From MSB's perspective, the ideal trial design will probably be a single-arm trial using a historical control. However we've all been here before and I doubt the FDA will be keen on this design.

Given that MSB seem to be trying to find a workaround to the RCT, their next best option is a crossover trial. That is to divide the cohorts into two groups; group 1 receives Rux first then Rem-L, and group 2 receives Rem-L first then Rux. Efficacy can therefore be determined by the number of patients that progress to the second treatment option from each group based on whether or not they respond to the first treatment. Rux, from memory, does not work well in the highest-risk groups, so Rem-L will have the advantage if it works as SI suggests. For this trial design, the trial will still need to be randomised but not blinded and can be conducted quickly and terminated early for futility or efficacy.

So back to your comment "It's why we have to be careful with what SI reports back". We not only have to hear backthat the FDA have agreed to the trial design, but that the FDA also stated a positive outcome will satisfy all outstanding requirements of the CRL. Not we believe, but that the FDA agreed it will.

Good luck to all holders. A dark period for sure, but here's hoping things turn for the better.