letter to gk, page-11

Hi Markhas,

Its not usual for subjects to be told when going on to extension trials whether they were in the active or control groups for the main study.

For all sorts of complicated reasons that would take a volume to write.

Skint might like to comment further about the extension trial. But on one reading of it it strikes me that the design is a little bit similar to what the FDA are actually recommending as a way forward for the next generation of AD trials.

Probably haven't thought it through enough but the active group will have had two years on PBT2. The control group will have had one year. If the control group don't catch up to the benefit of active group theres your effect.

Now of-course as we know the active group really haven't established much of a lead on the control group. Which is why the follow-up analyses will be so important.

Everyones focus moves away a little bit from statistical significance to "trends" that things are perhaps headed the right way which gives rise to the hope that in time any small benefit (on one or other measures) will be amplified.

That might be Plan A hope anyway ... and if some halfway plausible biological or methodological reason can be posited to support it that can lead to a bit of sp relief.

Much depends on the how cogent and how well the whole story hangs together. The market does tend to be a little bit once bitten twice shy.

GLTH Southoz