"Thats not how it works ... Small numbers are statistically...

"Thats not how it works ... Small numbers are statistically meaningless!"

In exploratory research (such as this), it's exactly how it works!

Not all experiments are designed to achieve the 5% p-value that is used as a 'standard' for statistical significance. Just the direction towards benefit (or harm) is enough in Phase 1 or 2 trials to give the message or signal.

The expanded cohort of SECURE will still be small, but its what will determine the efficacy gap between 67Cu-Sar-bisPSMA and SOC, and it is the size of this gap that Clarity will show to to FDA and use to calculate the required sample size for a Phase 3 trial.

The important thing with sample sizing is that, you design an experiment with numbers that suit the purpose of the experiment. If small numbers are whats needed at that point, and are the plan, you don't then dismiss results (good or bad) on the grounds that 'surprise, surprise', the numbers are small! It would be unethical to do that.

Imagine if the participants had all gotten worse, or one had died from the use of the product! It would have been a powerful message, in a bad way, and Clarity would have had to stop the experiments! Small numbers do give us strong messages indeed!

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You imply that did not respond? What response was the trial looking for? From my reading, they did respond. The trial was never designed or powered for complete responses, but when that happens, it's a bonus!

Having said that: we must note that the patients in SECURE are already very sick (worse than those in PSMAfore). They have failed multiple lines of therapy (median 5 lines of therapy), including taxanes, 177Lu (Pluvicto), and 225Ac (an alpha), and so a higher mortality rate should be expected. PSMAfore excluded some of those, and it may be that Clarity will do the same in their first Phase 3. The difference is that SECURE is designed to test the limits (Dose Limiting Toxicities), so even those with the poorest prognosis got included, this time. The additional beauty of the exercise is that it showcases the performance of the drug in this group that everyone has sort of given up on: so, if its safe and effective, they have a way in. A bigger trial on just them can still be done. It won't be very big - you are comparing with nothing! From the lesson on sample size: see below!

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Below - an illustration and links to sample size material. As you will see, the bigger the gap (on some primary measure) between 67Cu-Sar-bisPSMA and SOC, the smaller the size of the sample that will be required to show a difference, at whatever the desired level of statistical significance and power.

I do not expect complete respose to be the primary outcome measured though. Its a bonus, and a powerful message or signal.

And by the way: Pluvicto is a good treatment, so I think it shouldn't be looked down upon. 21% versus 2.7% complete recovery is a massive improvement on what we had prior to it. I do not know what the trial design will be like for the Phase 3 here, but just proving equivalence to Pluvicto without the kind of side effects that people get from Pluvicto, will symbolise progress. Early signs are that superiority will be achieved.




SAMPLE SIZE MATTERS
https://doc-aids.com/a-lesson-on-sample-size/
https://clincalc.com/stats/samplesize.aspx