This is bizarre, bordering on stupid. Frist of all, there likely is ~90% failure rate of prototypes; I feel that roughly matches my experience in engineering. Of course the design that makes it through the process, testing, refinement, and into mass production is not going to have a 90% failure rate, but that's a _finished product_, whereas clinical tests are just that -- tests. Finished cars are more analogous to individual pills coming out of the factory. And I'm not even sure the analogy would be very meaningful anyways, because we have different requirements for things of different impact and importance. A 10% manufacturing defect rate is fine in forks, but not for fire extinguishers.

The better we get at doing things, the more ambitious we get. As an example, we can keep babies alive much earlier in gestation, so we try harder if they’re earlier than we would before. We should expect a homeostatic equilibrium between our skill and our ambition.

As with many cases where companies make seemingly bad decisions, I think a lot of the explanation lies in system dynamics. Think about the incentive structure inside large pharma companies - it is generally not a career advancement move for a project manager to kill the drug candidate they oversee. It is career advancing to get it approved for the next stage. What could possibly go wrong in this world?

We are chipping away at that problem but it's not like we have it mostly solved as other engineering areas of knowledge. I would argue that due that phase I successes isn't the benchmark, but phase II success should be the actual measure. I'm sure that if someone charts the accumulative success rate for each phase of clinical trials, you will see that phase I is the most brutal one.

1: https://www.nature.com/articles/nrd.2016.136

The failure rate does not take into account the millions of molecules that are tested by various methods of protein folding or binding properties. The 90% remains stable with time because on one side an end product is more difficult to produce, on the other the technology of molecule discovery has improved in the same amount.

Lower numbers don’t mean we’re doing better, it means we’re trying less.

110M+ animals suffering and dying for nothing each year. And people ask why I choose cruelty-free.

But let’s think about that 91% failure rate for a moment. When I bring this up in presentations, I invite the audience to consider what the auto industry would look like of 91% of new car designs proved unable to roll out of the factory, or if 91% of new airliner models were unable to leave the ground

Is an utterly irrelevant comparison. For physical thing we have engineering, and the practical application of the trades and craft, trial and error.

For modern medicine, we're only just starting to come out of the wild west era. Or perhaps slightly further along than that.

Would make a small correction. It does not have to be people. It can be also be "doctors" or "governments". It is easier to convince or coerce/fool a lesser number of humans (doctors) or a single government regulatory body than to fool/convince every one who use the product, because the people can directly evaluate the product.

And when a single doctor is coerced, then the product is forced on hundreds of their patients. When a government is coerced, then the product is forced on tens of millions of people..

He starts off on the wrong note, there is nothing at all wrong with a high rate of clinical failures. If anything, the reasonable argument standard might be that this rate is too low. It implies researchers are trying things that they expect to have a 10% chance of working out. That means we're missing out on all the cures and techniques that have a 1% chance of working out but but nonetheless do work.

Failed attempts cost society nearly nothing and successes will have compounding benifits for, y'know, lets optimistically say the human race survives for centuries. 1% or 0.1% success rates sound completely reasonable with that sort of lopsided risk profile. There isn't much of a reason not to try anything and everything that has the faintest chance of helping and see what happens.

The FDA has gotten significantly more strict in its review than it was in the 1960s.

A good example is hERG inhibition as an off-target effect. It’s a receptor on heart muscles and will result in QT prolongation and potential arrhythmias.

It wasn’t discovered until the 1990s. Now every molecule is screened and many are dumped. The impact can vary but there are tons of drugs on the market now that are hERG inhibitors (many discovered after the fact).

It’s a good example of the increased rigor that the FDA applies to everything they review that past trials never had to face.