- Yes U.K. and Australian approved an endpoint change not the FDA. There were no AVATAR trial sites in the U.S. so no need to ask the FDA. - The endpoint change would almost certainly have been only the Anchoring of RSBQ to CGI-I, NOT AUC! - AUC makes no sense in a trial with just two time samples of data as is the case in all 3 Anavex Rett trials with baseline, midpoint and EOT only. Hence, Jin Kun or others have made sure that Missling does not again seeks to 'rescue' a readout using AUC! - That the RSBQ Primary and CGI-I Secondary outcome measures were exactly identical is possible with a very low probability. The two scales and structure is different with RSBQ answered by parent/care-giver and CGI-I by a trained physician. If RSBQ and the Pro CGI-I scores were often or even occasionally identical or very close what would be the point of Anchoring RSBQ to CGI-I? I do not buy this without proof that these two scores happened to be identical!
This guidance document contains no mention of Area Under the Curve (AUC), but provides guidance on Anchoring. In the case of AVATAR this means Anchoring RSBQ to the PRO instrument CGI-I physician subjective scoring of Rett symptoms.
Anavex have offered no references to any guidance for the use of AUC. Imo that was there own invention that rightly caused a lot market consternation as it simply looks like a last minute oh schitt! - the trial outcome was not stat sig. It did not help that Missling refused to release the baseline to EOT results! It did not help either that his explanation for not using AUC in the EXCELLENCE trial was that it has a large n and therefore does not need AUC - complete BS!
I would love to see the SAP for AVATAR, EXCELLENCE and the P2b/3 AD trial. Imo this should be public information and issued certainly with trial readout as it would answer many of the questions some of us here have!