Quote:

---

I seem to hear two competing notions for why DSMC would ask for the 75% review:

1. Things are looking really good. I think you can prove enough at 75% that we would recommend stopping for efficacy.

2. Things are borderline. We want to look again at 75% to give you some new advice (stop, add patients, keep going to the end).

blafarm: Do you have an opinion if it is #1 or #2 above? Or #3?

---

As mentioned, we can't peer into the collective minds of the DSMC. So any thoughts I might have regarding the recommendation they provided at 50% interim is pure speculation on my part.

With that having been said:

- I am assuming the DSMC advised against making any changes to the protocol, sample size, or power -- because the 50% interim results provided a strong signal.

- I am assuming that if there was a problem with either the protocol, sample size, or power -- the DSMC would have advised CytoDyn to make suggested changes earlier -- rather than later.

- I am assuming that in spite of a strong signal, the DSMC was not quite yet comfortable recommending a trial halt for overwhelming benefit.

- I would like to assume that the DSMC called for a 75% interim because they felt the 50% interim P-value and power would likely get stronger with a larger sample size, making it easier for them to possibly suggest halting the trial for overwhelming benefit.

- It is impossible for me to ignore the DSMC's advice to include Mortality at Day 42. There are likely other explanations for this suggestion, but the two that come immediately to my mind are: (1) Whether it's due to the effectiveness of the current SOC or some other variable, the signal of Mortality at Day 28 is not quite as strong as they would like even based on full enrollment, and Day 42 is an insurance policy that is guaranteed to payout, or (2) Mortality at Day 42 offers a much better chance at halting the trial for overwhelming benefit at 75% interim.

- It is also impossible for me to ignore the DSMC's comment: "Sample size reassessment will be considered at that interim analysis."

What exactly does that mean -- and why did they go out of their way to say it?

Would a DSMC include that sentence if they felt pretty confident there was a good chance they'd be advising a trial halt for overwhelming benefit at 75% interim?

Would a DSMC include that sentence if they felt pretty confident that even absent a trial halt for overwhelming benefit at 75% interim, CytoDyn would crush the P-value at full enrollment of 390?

Would a DSMC include that sentence if they already knew CytoDyn would require a minimum of full enrollment of 390, and based on the results at 75% interim, they might need to advise enrolling more than 390?

Or, lastly, did the DSMC include that sentence to tamp-down and temper CytoDyn's expectation of a potential trial halt at 75% interim, thereby going on record with both CytoDyn and the FDA that they did not telegraph an impending trial halt for overwhelming benefit at 75% interim? In other words, it was a little bit of 'theater' which fortifies the notion that the 50% interim results remained fully-blinded and nobody tipped-their-hat or winked.

I have no idea, but the very mention of it gives me pause. Taken at face value, if the DSMC broadcasts the requirement of a sample size reassessment at 75% interim, it almost sounds like CytoDyn should have a low expectation of a trial halt, and possibly be more concerned about being advised to go beyond 390.

This entire post is pure speculation on my part -- and it contains zero facts. But I certainly hope we are approved at 75% interim. I am sick and tired leronlimab being delayed and ignored. How many people have to needlessly die -- before we can start saving them? It's infuriating.