FDA ODAC Meeting Material discussion analysis, page-430

Hi

yes, MSB were a little naughty. They didn’t follow the guidance from the FDA on several items... and that is why the FDA believes it is not a well controlled trial. But that is where MsB and the panel tonight will discuss in the PM session how MSB’s trial design was good and bad. I believe MsB can explain why they chose to deviate from the FDA guidance.

have you looked at the clinical trial results, where at day 28, 69% of those taking Ryoncil responded to the treatment vs a 45% historical control rate.

as it was a single arm trial, the FDA are questioning if the 45% is the right control rate to use... and they will discuss that tonight, and I don’t think you are asking about that anyway.

but assuming they stick with the 45% control rate, the trial met its primary endpoint with a p value of 0.0003. A clinical significant result is a p value of 0.05

in MSB’s instance there is 99.7% confidence that Ryoncil does increase the responder rate when compared to a historical control rate of 45%. A lot depends on the control rate and that is why single arm trials come under extra scrutiny... no difference here. Give the FDA a choice and they will always ask for a randomised controlled trial.. whether that is ethical is another question.

I’m not a statistician, but if the trial design is accepted by the ODAC, specially the historical control rate- then it would be hard to argue against a p value of 0.003.

or how I understand it, it infers that if the trial was run 1000 times.. it would get a different result only 3 times.

but I welcome anyone to correct my understanding above.