John, the modus tollens argument you put forward would be precisely my (Popperian/falsificationist) point. More broadly (say, from the POV of Popper’s more fully elaborated critical rationalism), we know our knowledge is always faulty and that the obligation to critically test it never ends. The best way to “keep on keepin’ on” in criticizing our knowledge about medical therapies is to criticise the theories that constitute the deepest part of this knowledge.
If the penumbra theory were true, one would expect to be able to find a signal to this effect in CT infarct volume time-series. One valuable aspect of these time-series data (relative to mRS-type outcomes) is that they are quantitative and possibly more objective in terms of inter-rater reliability.
Are you aware of any existing analysis in the literature, that attempts to check the penumbra hypothesis? I must suppose that natural variation present in observational clot aspiration registries would provide an excellent basis for demonstrating penumbra evolution to infarct—with onset-to-aspiration time providing the instrumental variable. (Disclosure: I was at AAN 2015, where I ‘got religion’ on that account.) Conceptually, that’s the type of thing I had hoped to find possible in NINDS.