Very poorly written and expressed post on my part – and quite...

Very poorly written and expressed post on my part – and quite rightly meets with stern rebuttal from the POH family. “Serious” was not the right word.

But Makattack – not as stupid as it sounds – and in fact in part was in response to your earlier questions about why these sorts of developments do not seem to lead to large up-front payments from big pharma.

Lets start simply with the idea that theres no such thing as a free lunch. And so a low cost, low risk, straightforward simple trial to follow the FDA expedited path to commercialisation (505(b)2) is unlikely to be associated with high reward.

In the present case this is because the trial results are unlikely to give rise to new efficacy claims. There are two clues to this. The first is the three arm design. This is an inefficient design compared with a two arm superiority trial. This gives you the best for buck if your aim is to show superior efficacy. The second clue is the single (as opposed to double) blinding which would lead to problems down the track trying to make a new efficacy claim.

And so if its not about efficacy (as this is this not necessary through this approval process) – what is it about. The earlier P1b demonstrated bio-equivalence. Here we (as GC was noting earlier) are looking at side effects side effects (irritation), safety etc. Assuming all is well in these areas (no evidence of causing extra problems) this gives you the tick.

But lets say the trial finds less irritation. Then this gives you a marketing claim. Of-course a critic simply says less irritation compared to what? Well the “market leader”. Is that the new formulation using polymers based on the idea that tretinoin irritation may be reduced if the drug is prevented from migrating into deeper layers of the epidermis. No-one will ever know.

The “never get away with this in a serious trial” sentence is a complete hash up on my part trying to express the idea that null results are useless in the context of trials trying to establish superiority – but they are not useless in this context. This is in fact why the trial is low risk - as long they don't muck up somehow the formulation in a way which causes problems (the absence of "null results").

But it is serious. The trial is costing money and with approval the product could earn money. But much less serious than a $xxm trial of a patch the results from which will add or subtract millions to the market cap of POH in the blink of an eye.

Anyway most often these rights of reply type of posts do little more than dig the hole deeper for the original protagonist and attract further criticism – so I'll shut up from here. But for better or worse thems my arguments – don’t expect anyone to agree here – but hopefully a bit better articulated than before.

Southoz.