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Clinical failure rates over the decades: yikes

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Re: Clinical failure rates over the decades: yikes

#61

Post by asdff »

halperter wrote: post #23
roenxi wrote: post #18

> I’m fond of saying that the most important single statistic about the drug industry is the clinical failure rate, which is (by any reasonable standard) appallingly high. 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 hav…

Rather notably, companies are profit-driven, not good-for-society driven. If 99% of your attempts which cost millions to do fail, the company either has to raise the prices of the drug insanely high or not work as a company. In addition, most drugs aren't humanity saving or crucial for humans to live. You could solve all forms of cancer tomorrow, which would be a great thing, but you aren't "saving humanity". You add…

This goes to show why private r and d is not going to get us that star trek future. Private capital is too risk adverse and short term in outlook for a lot of potential innovation. Interesting to think about how stifled our innovation potential is these days, given that things are expected to be immediately and massively profitable if they are to be invested into.

Re: Clinical failure rates over the decades: yikes

#62

Post by bonsai_spool »

s1artibartfast wrote: post #50
bonsai_spool wrote: post #45

Earlier quoted context omitted.

This comment makes no sense. Why would anyone make a drug if the current prevalent treatment was as good as a functional cure? What do lorbrena and keytruda have to do with the rate of failures being constant?

Keytruda revenue is 30+ billion per year. If your new drug performs 1% better than Keytruda, that revenue becomes yours. If your drug perfroms 1% worse, you become a failure in the statistics.

That isn’t how a rational person would pursue this - it costs $1B to make a drug start to finish, and there’s no reason to believe your new mechanism will work.

If you’re talking about copycat mechanisms, that is fine but we’re still left discussing successes when OP is about failures

Re: Clinical failure rates over the decades: yikes

#63

Post by bonsai_spool »

evandijk70 wrote: post #55
bonsai_spool wrote: post #45

Earlier quoted context omitted.

This comment makes no sense. Why would anyone make a drug if the current prevalent treatment was as good as a functional cure? What do lorbrena and keytruda have to do with the rate of failures being constant?

Lots of reasons. The new drug could be cheaper to manufacture, fewer side effects, a full cure in stead of a functional cure.

Cost of manufacture is not a meaningful driver of pricing outside the biological

How will your clinical trial of the ostensible full cure work if standard of care is curing people?

Re: Clinical failure rates over the decades: yikes

#64

Post by asdff »

tchalla wrote: post #20

I’ve been hearing for 10 years now on how “AI” will change this clinical rate. It’s now like the “This is the year of Linux” prediction meme. And like Derek has mentioned multiple times you can’t statiscialise biology. I don’t think many people get it so we have tech bros like us throw AI at data.

People saying this stuff aren't in the game. ML has been used in clinical research for basically as long as various ML methods have been around. Basically a century now in other words. AI leaders are trying to get money from people who don't understand the methodology such as investors or trump administration officials. Imagine trying to convince people who actually work day in day out with classic ml and deep learning to use your llm goobly goop bot.

Re: Clinical failure rates over the decades: yikes

#65

Post by fabian2k »

pinkmuffinere wrote: post #56

> 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 - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them…

A large part of that failure rate is in phase 3. Your comparison with prototypes would be more like drug development before even phase 1. Phase 3 is enormously expensive, much more than the earlier parts. And what's even worse, you don't get to learn all that much from failures in drug development in many cases. You can't just fix the problem and try again, you essentially have to try a completely new molecule.

Re: Clinical failure rates over the decades: yikes

#66

Post by asdff »

calf wrote: post #40
analog31 wrote: post #16

Earlier quoted context omitted.

It's not for lack of trying. People are definitely trying to find better ways of finding stronger candidates earlier. People are trying to gain a more precise understanding of disease mechanisms. There are breakthroughs that I could have never imagined such as mRNA vaccines.

I would have to reread the piece carefully but I don't think "lack of trying by Biopharma" is consistent with the author's main argument. Because he is still being somewhat critical of the way it is currently done (why he cites the other industries). I simply disagree with his final sentence since it requires a different set of essay arguments, and also is subjective in the way say a political centrist might say "the…

Most other industries barely innovate. Most industries are just buying off the shelf components and putting them together into larger widgets. Cars, computers, airplanes, that's the business. The components might get more efficient or performant but they generally do the thing they always did. If you squint it is basically the same car/plane/laptop as x years ago. They worked out the optimal car/plane/laptop shape a while ago and now everything sold is exactly that shape and will be for probably the rest of both of our lives and then some, in those industries.

Life science on the other hand is actually on a bleeding edge. Something actually revolutionary might emerge tomorrow after a grad student has an acid trip tonight.

Re: Clinical failure rates over the decades: yikes

#67

Post by qsera »

>So when we do get something to work and something that people are willing to pay money for, we try to squeeze every dollar out of it because we never know when the next one will come along.

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..

Re: Clinical failure rates over the decades: yikes

#68

Post by rcxdude »

pinkmuffinere wrote: post #56

> 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 - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them…

The prototypes are generally cheap though: you're not standing up a full production line for them before you find out that they're duds.

Re: Clinical failure rates over the decades: yikes

#69

Post by pinkmuffinere »

fabian2k wrote: post #65
pinkmuffinere wrote: post #56

> 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 - and if you only found that out after spending all the R&D money to build them at full size and trying to fly them…

A large part of that failure rate is in phase 3. Your comparison with prototypes would be more like drug development before even phase 1. Phase 3 is enormously expensive, much more than the earlier parts. And what's even worse, you don't get to learn all that much from failures in drug development in many cases. You can't just fix the problem and try again, you essentially have to try a completely new molecule.

That's fair, phase 3 testing isn't an early prototype, it's a prototype with many years of effort behind it. But I still think it is _more_ like a prototype than it is like a product coming off an assembly line. Perhaps phase 3 is like the latest prototype from boom (the company trying to bring back super-sonic jets). Those prototypes represent 100s of engineering-years put together, and are not much like the prototypes you'd encounter in consumer product development. I still think 90% failure rate is believable for that. How many significant design iterations has Boom gone through so far? I don't really know, but I could believe it's been 10 significant iterations.

Re: Clinical failure rates over the decades: yikes

#70

Post by mbnielsen »

Many comments so far seem to try to handwave away the 90 % failure as somehow "optimal" in the system, which seems absurd to me. It is clearly not advantageous for individual companies to keep a drug candidate alive long enough for it to fail in stage III or IV. One obvious question is why they don't and it is very, very tempting to speculate that it's because the problems are getting harder, we are targeting novel mechanisms etc. Again, I think this misses a simpler explanation:

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?

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