Ann: COVID ARDS Trial Topline 60-Day Results, page-296

I'll give it a crack. Multiplicity is basically a way for regulators to force trials to be more than 100% correct when making multiple claims ( end points )

For example, if you had 5 primary end points instead of just 1, if the P value targetted was 0.05, then for the 1 primary end point hypothetically , you could be effective for 95% of patients, and 5% not effective and trial is a success. If you took exactly the same single end point, and added 4 others, and they all showed 0.05 P value individually, the trial will fail because generally they add the p values when using multiple claims... 0.05 x 5 = the adjusted p value is now 0.25 ( its dumb when the product actually works in a critical end point ). So the more end points that are used, once adjusted for multiplicity the harder it is to achieve. Its designed clearly to stop pharmacies from targetting multiple potential end points and having 2 pass by fluke and 3 fail but still pass the trial.

It doesn't mean the product doesnt work, it meant the wrong end points were selected to class the trial as a success.

Msb has now got enough data i think to pick a single end point, and treatment group and knock this out of the ballgame completely.

Its done this way to stop therapies from selecting 200 end points, and then picking the ones that work for approval(to avoid increased odds of outlying sucess)

The remarkable thing about mesoblast is that they are failing when using market standard surrogates, and instead passing using mortality which is extremely rare and counter intuitive.

You can bet for gvhd, ards, and heart failure any future trials will go for the gold standard of mortality.