By The Numbers - part the seventy fourth

For some years, all of them while I've been keeping track, the pharma bulls have bitched and moaned about the onerous steeplechase that has to be navigated to get these wonderful (new, occasionally) drugs approved. About 3 decades ago, FDA more or less caved to this bitching, and created a less onerous track called, as one might expect, accelerated approval. The gig was that if a drug had stat sig (mostly), clinically meaningful (mostly) benefit before doing a PIII trial(s), and (mostly) targeted an unmet need in the population, then the drug could be sold. The gotcha was that this was a conditional approval, requiring a full-blooded PIII trial post-approval.

The cynical among us (raises hand, very high) found this regime ripe for gaming. And so it has been. Today's Derek Lowe post reviews a rigorous study of these accelerated approvals in oncology. It ain't a pretty sight. In fact, recently FDA now requires that the all-important full-blooded PIII be underway before the accelerated approval can be granted; fobbing off the PIII has not been as rare as hen's teeth.

But the trends in these oncology trials are worth noting: the failure rates of the traditional Phase III oncology trials have been gradually falling over this period (with an overall Phase III failure rate of about 41%, but currently at 34%), whereas the confirmatory post-marketing Phase III oncology trial failure rates have been increasing in recent years, from around 14% during the 1992-2015 period to 33% in 2016-2023.

Conmen will con.

And, it's worth knowing that truly good new drugs don't have to complete a PIII. If the sponsor really, really believes that New Drug X is better than high button shoes, then the sponsor has the option to schedule (not make up as the trial goes along; mostly) interim analysis. It's a bit more convoluted than simply doing the same arithmetic that gets done with the full data set after all patients have been run through the trial; the stat requirements are a tad more stringent. If New Drug X meets the stat requirements, and FDA agrees with the trial data, then New Drug X will get standard approval before trialing all patients. But, as I say, if the sponsor really, really believes in New Drug X, then such is the more ethical avenue.

One might wonder how much worse the situation is in the CNS world. Alzheimer's strikes a familiar note. If you watch carefully on the teeVee, the mood altering compounds display some less than stellar efficacy in the fleeting, tiny print at the end of the advert.

Here's another report in that same space.