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## Better Does Not Mean More Familiar

The first issue I want to discuss is the CGI-I anchoring of RSBQ-AUC, or rather the familiar RSBQ that is here the raw data. If the CGI-I score improves (drops) by one point out of the 3 possible to describe the improvement then the RSBQ scores are accepted for a given patient. So the probaility of bias due to overly enthusiastic (subjective) care giver has been significantly lowered. However I had noticed when analyzing data from RS-001 that physicians were more likely to check off on improvements than care givers. Nevertheless they are here the gate keepers.

Looking at this data and results it is possible that 38.5% patients on placebo are given CGI-I scores one point down (improvement) by physicians and yet producing small scores in RSBQ-AUC., which can be indicated by large Cohen’s d Effect Size between placebo and Anavex2-73 arms. On the other hand I noticed that the overall number of double responders is very close to the one given in RS-001 and related to the quantity of SIGMAR1 protein in blood. **So, what the 30mg/Kg did was to intensify the response not to broaden it. **

## Area Under The Curve or Strength of Signal

From the use of the area under the RSBQ questionnaire scores suggest that more than two points of interest has been recorded. This captures not only the endpoint but the change in time in the RSBQ scores. To give an example, if a patient goes from 0 to X at 2 second point of measument than area under the curve is …1.5X.(Case One) If another patient goes from 0 to X at the 3rd point of measument (the end point) then the area under curve is 1X. (Case Two) If a patient goes from 0 to 0 to the second point of measurment and then to X at the endpoint then area under the curve is 0.5X. (Case Three)

As we just inspect the way of mesuring progress in efficay we see that the area under the curve is greater when the response is immediate and of greater magnitude. From then on we deal with RSBQ-AUC and the data of areas under curveare are used to calculate the mean and the standard deviation to be pluged into the formula for the Cohen’s d Effect Size.

## Converting The Familiar To The Unknown

You can imagine how each area for a particular patient would look like. The highest would be for the blue patient and the lowest for the yellow and the cluster of few barely performing. The data from RS-001 was used to calculate its Cohen’s d Effect Size for the measure of RSBQ-AUC and the result was the value of ES=.517. The calculated value differes from that of simple RSBQ scores, which was ES=1.47.

I have not listened to the presentation as I was busy this morning. My take on the end results is..

- Gaba up, it means that we move towards restoration of the healthy balance between Glutomate and GABA. Great result. I have discussed this before.
- L-AAA decreased. Liver is most important metabolic organ in your body. Decrease of this protein signifies return to healthier liver.
**An engineer would say that 30mg dose has almost 4 times stronger signal than the 5mg dosage. As I already said the magnitude of the signal combined with immediacy of response was almost 4 times larger than during the RS-001. For 6 times larger dose we have almost 4 times larger signal in therapeutic effect.**- From the data I also have impression that the franction of responders in dosed data have not increased. The change is the intensity of response.

**I will rest my case here as the results stretch into a longer list. I guess that the raw data has not been released yet, but it might be published some time in the future. The most important thing is that the change in the data formating has been approved by FDA seeking greater sensitivity to pick up the therapeutic effect of Blarcamesie. I bet that the $ACAD data analyzed the same way would fall in pure insignificance vesus the RSBQ-AUC Effect Size of 1.91 as it had much smaller value compared to ES=1.47 of raw data of RS-001. Also, I am tempted to make a point that Mr. Feuerstein seems to pass judgement without understanding the basics of data analysis. This is indeed deplorable as many people follow him blindly. But being an influencer has its perks.**

My fears that AVATAR would fail to provide greater therapetic effect had been wrong. The dosage is the maximum that can be given to the girls with Rett Syndrome. This is plainly seen in the rise of adverse effects, more numerous than dangerous. LOL.

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