aod9604 - efficacy and marketing

GRAS status will allow AOD9604 to be incorporated into food products, such as nutrition bars, nutrition drinks, and nutrition drink mixes.

Thinking about this, it is useful to revisit the human efficacy trials using orally administered AOD9604 that were conducted in 2004, and 2005. Revisiting these trials could be useful in making a judgement about the likelihood of success marketing AOD9606 as a GRAS food additive.

First of all, we have to acknowledge that these trials were widely seen as failing to prove the efficacy of AOD9604, but as we shall see in this discussion, this conclusion may have been premature and was certainly wide of the mark.

Any discussion of these trials, and their findings as to the efficacy of AOD9604, needs to be prefaced with a brief discussion of "statistical significance". Now, it is a fact that has been established by experiment that discussion of statistics can cause complete “brain freeze” in most individuals, so I’ll try to keep it short and sweet.

The phrase “statistically significant” is widely misunderstood, despite its central place in discussion of experimental results. Purely as a convention, when experimental results can be replicated within predefined experimental precision 95% of the time, the results are said to be “statistically significant”.

Many people erroneously think that if this standard is not met, experimental results are “statistically insignificant”. This is utterly false, and the falsity of this notion can be demonstrated easily. Imagine that experimental results can be replicated within predefined experimental precision 94.9% of the time. Would not any reasonable person conclude that these results are for all practical purposes equivalent to experimental results that can be replicated within predefined experimental precision 95% of the time? Statistical insignificance, if it means anything at all, means that experimental results cannot be replicated within predefined experimental precision at any level of confidence.

An experimental result that that could be replicated within predefined experimental precision 90% of the time, while not meeting the notional standard for “statistical significance” is still enormously meaningful.

And such a result is particularly meaningful for holders of Calzada, for this is just the level of reliability (90%) reached in the human trials of AOD9604 reported to the market in December 2004 for a daily oral dose of 1mg – coincidentally the daily dose indicated for GRAS status.

Some secondary measurements, such a rate of weight change reached levels of significance as high as 99% as compared with placebo.

A later human trial in 2005 used AOD9604 in tandem with a rigorous, very closely monitored program of diet and exercise. This particular trial, most likely because the rigorous diet and exercise program masked the effects of AOD9604, did not show AOD9604 to be particularly effective. However, the most noncompliant group, women with poor prior weight loss experience did show meaningful weight loss over placebo.

In short, there is plenty of evidence in the trial record that AOD9604 works efficaciously, even if the trials were unable for one reason or another to show this efficacy reliably enough to claim “statistical significance”.

I think it is worth mentioning here that measurement of weight loss against any particular variable is very problematic due to all the inconsistencies and variation in human metabolism and behavior from individual to individual. Achieving a 90% measure of statistical reproducibility with AOAD9604 is genuinely notable.

So, what does all this mean to us today?

First of all, it means that the company can demonstrate reasonable efficacy to potential partners and licensees. Ditto for safety, but that isn’t the subject of my writing today.

Secondly, it means that judiciously phrased claims of weight loss efficacy can be made for any product that incorporates AOD9604. Any potential partner would find the possibility of making efficacy claims essential. What’s the point of adding a compound to a product if you can’t say what it is for or that it works?

Finally, it means that customers can be judiciously informed about the advantages of AOD9604 and thereby make informed purchase decisions.

It is obvious that the market discounted the possible success of AOD9604 as a pharmaceutical in the years after 2005. Looking at the new reality of much larger market access as a GRAS food additive than was ever possible as a prescription drug, along with proven and meaningful efficacy, the market would be well advised to have another look at the prospects for AOD9604 and CZD.