Opinion: The Twitter Twits Torture The Truth
Summary of FUD Claims from the PowerPoint Entitled "Cassava Sciences: A Shambolic Charade: The investigator (Cassava Sciences) got to hand-select AD patients, excluding any patient from the trial for whatever reason. The trial cites 42 separate exclusion criteria including.....ambiguous criterion. Note: There is a decrease in number of exclusion criteria down to 15 for phase 3.
Exclusion/inclusion criteria is standard procedure and is well known to those who conduct clinical trials.
Inclusion/exclusion criteria are important for many reasons. Examples include:
Excluding those without Alzheimer’s
Excluding those that have such severe Alzheimer’s that they are already comatose, therefore unlikely to show improvement.
Excluding patients who have too many co-existing issues. For example, patients with severe heart problems or active cancer could be negatively impacted by new medication. Additionally, if a drug is cleared by the kidneys, it would be bad to give it to renal failure patients. Excluding the above patients is wise in order to avoid future potential harm.
Exclude people who are unlikely to complete the trial for any reason.
Include patients that fit the criteria of those you are looking to treat. Ultimately, this will lead to more reproducible results
That having been said, there must always be some sort of logical and predefined reason to exclude any particular patient population. I looked at Cassava’s exclusion list of 42 from phase 2 and it is actually all very standard.
And now to deliver a real one-two punch, I shall address an even more outlandish FUD claim directly below.
Summary of FUD Claims (Page 27 of the PowerPoint Entitled "Cassava Sciences: A Shambolic Charade: The second point in the short seller’s claims is that Cassava added or “dropped in” 4 “twice as severe” patients to go from 1.6 points improvement to 3 points improvement.
This assertion plays upon the fact that most people do not understand how the trials are run. The trials are run at medical clinics where this type of corruption would be impossible without the help of many people. It would have to be a coordinated effort across a number of independent facilities. These clinics also run trials for SAVA’s competitors such as Eli Lilly and Company (LLY), amongst many others. SAVA is not able to just move patients around as they wish. To suggest they have organized a string of collaborators, within facilities also used by their competitors, is not even a reasonable hypothesis, it is completely absurd and is absolutely sensational. Should we also doubt the clinical trials that major competitors like LLY have done at these same facilities? This is a farcical FUD claim that also unintentionally attacks the integrity of every single clinical study completed at these facilities by LLY and others.
The accusation that SAVA simply threw 4 new more advanced AD patients in there to skew the data, and stated without hard proof of such event, may even constitute libel against SAVA and all of the professionals involved in this clinical trial. The other thing of note is, even if SAVA did this (which they absolutely did not, nor could they have), the already more sick patients than the original would deteriorate even faster. Simply stated, Alzheimer's is a disease where patients with higher baseline ADASCog11 scores decline at an even faster rate than Alzheimer's patients with lower baseline scores. To suggest that SAVA somehow slipped in sicker AD patients into the cohort at the 6 month mark (without requiring them to complete 6 months of actually taking Simufilam) would only work against SAVA's data! To be clear, the patients were recruited into the study at different dates and grouped together into a cohort. When all of the patients in the cohort (at different times because they have been recruited at different dates) finished taking Simufilam at the 6, 9, or 12 month marks then the data can be analyzed and reported by SAVA so we can all see the progress of the study. The improvements at the 6, 9, and 12 month marks are literally indicators that the average patient treated with Simufilam is not experiencing a slowing of cognitive decline, but in many cases is actually seeing a reversal of cognitive decline. Their AD is getting better over time, not worse! To add patients with worse average ADASCog11 scores to the trial than the original cohort (which SAVA did not do, but it is claimed that they did) and to still show an improvement at the 9 month and 12 month marks would actually suggest the drug is highly effective at treating not just mild Alzheimer's but possibly even moderate/advanced Alzheimer's.
The third point is statistics. If 5 patients were switched out as are a result of the 10% dropout rate, the mean ADASCog11 of the replacements would have to be 26.5 to fit the narrative of the Twitter Twits; the probability of which is 0.0021 or 1 out of 476. If 4 patients were replaced as part of the 10% dropout, the mean ADADCog11 of the replacements would have to be 29.25 which has a probability of 1 in 2174. Accounting for rounding of the means (up to 15.549 from 15.5 and down to 16.55 from 16.6) the corresponding mean values for 5 and 4 replacements would have to be 25.66 and 28.06, the probabilities of which are 0.00473 or 1 in 211 and 0.0015 or 1 in 667. This is highly unlikely. Ta-ta to the the Twisted and Tortured "Truths" of the Twitter Twits.