- Since there is no individual data on each patient performance and their membership in the efficacy biomarker group as per page 12 & 13, we extrapolate individual performance in linear fashion ( doubtful yet the only tool available ) to 148 weeks. For some data is given up to 109 weeks: patients 1014, 2006, 2010 & 1013. Other we simple assume that they continue the pattern of progress of disease up to 57 weeks through to 148 week: 1007, 2008. 2001, 2002, 1002 & 2001. Patients 2001, 1002 & 2002 decline so rapidly that by 148 week they could be among the dropouts. By 148 weeks patient 2001 is considered “ALMOST DEAD” (MMSE 5 (?)).
- The decline of -2.0 MMSE points over 148 weeks for the cohort from CTAD 2018 presentation is a mean of three groups of patients. Those who continuously improve: 1014, 2006 & 2010 ( “CURED” ). Those who “SLOWLY DECLINE”: 1013, 1007 & 2008. Patients 1007 and 2008 are hypothetical since their condition is not known after 57 weeks. The same applies to patient 2001, the only one in “ALMOST DEAD” group.
- The shifting membership in the group “SLOWLY DECLINING” makes the total of patients from 6 to 7. For 6 patients current in the biomarker selection is 66% of the High Concentration Cohort population, for 7 patients it is 77% of population.
Following is the illustration of that those assumptions:
To verify this complete this (27*3 + 16.6*3 + 5)/7 = 19.4 very close to ~19 MMSE (if drop is about 2.0 points per 148 weeks).
- It seems that by the power of addition, multiplication and division out of 9 patients 7 might be in the trial by 148 weeks. Are they all fulfilling the requirements of those four criteria on page 12 & 13 CTAD Presentation? Are there any more dropouts? 7 out of 9 is 77% of the total population that would be miraculously in line with the 80% of general population carrying the genes variants most responsive to ANAVEX 2-73.
- With time the composition of trial population changes from one description to another. This plot illustrates this:
- The same for general population of Alzheimer sufferers:
- Benefits for the group No Decline/”CURED” is self-evident. Group Decline -2.0/Year/”SLOWLY DECLINING” declines slower than octogenarians on placebo (-1.6/Year vs. -2.6/Year placebo) (see my earlier posts). This group accrues benefits as well. The only variable which can be controlled in clinical practice is the early detection of onset of the disease, and here ANAVEX 2-73 seems to offer greater benefits given at higher MMSE scores. This points to 66% of Alzheimer patients benefiting in meaningful way from ANAVEX 2-73.
- Caveat here is that I am not familiar with sophisticated statistical tools. As data becomes available I try with simple assumptions and tools illustrate the data’s implications in more accessible way. No doubt that I oversimplify things but I hope at least my not too far from what the data says at the moment.
All patients number are from CTAD 2017 November presentation.