Anavex Life Sciences Corp (AVXL)

[Investor2014]

Here is a short article on Placebo and Historical Control Arm comparison to drug effect in Alzheimer's studies: Understanding Placebo Responses in Alzheimer’s Disease (AD) Clinical Trials from the Literature Meta-Data and CAMD Database

Some quotes of note relating to the discussions on the Board:

Baseline cognitive function is an important covariate of disease progression, therefore, it is important to evaluate the baseline severity and predict the disease progression accordingly when comparing trial results. Furthermore, study duration, sample size and study design may affect the placebo response, all of which have the potential to confound understanding of study results.

As has been debated, one must assume that MacFarlane and crew have very carefully evaluated the baseline characteristics of the A2-73 group to select an equivalent control arm comparison from the historical database.

Across studies, the placebo effect is evident to at least week 12. Interestingly, the short Phase II studies (Studies 1000 and 1009, 12 week Phase II studies) had larger placebo effects, perhaps due to expectations from investigators and/or patients. Also, these studies had a relatively small sample size (N=102 and 164, respectively), which might have effects on interpreting trial results. These differences could potentially cause misinterpretation of study results, especially when trying to estimate the disease progression rate across trials of different study durations.

I read this as; placebo effect Alzheimer's washing out beyond 12 weeks of a well designed study. So we can reasonably assume that positive placebo effect is unlikely at 57 weeks and beyond in the A2-73 super responders. Here we need to look for biological explanations particular to this group and positive impact from the drug.

particular interpretive caution should be taken if a treatment effect is observed in one population, but not another, without a plausible (a priori) biological mechanism as to why this may occur

Last, but not least:

The model prediction and placebo comparison against historical placebo data provide a way to double- check the reliability of trial results before making important drug development decisions (e.g. terminating a compound or initiating an expensive lengthy new trial in AD patients)

So, control arm is not a substitute for a placebo controlled study, but a sanity check.

I for one will look forward to the start of and result from the promised P2/3 placebo controlled study of up to 300 patients.

Bring it on Missling!

GTLA