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Clinical failure rates over the decades: yikes

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Re: Clinical failure rates over the decades: yikes

#91

Post by estearum »

calf wrote: post #37
mlyle wrote: post #8

Earlier quoted context omitted.

If you can think of a way that you can have a much higher chance than 9% of success in getting a useful treatment to market, you can make a boatload of money. Go ahead, reform it.

Not knowing of a way is inequivalent to inexistence of any way. This is basic and apparently some bloggers are bad writers and or political conservatives of the type "there is no alternative".

The alternative is "have a complete mechanistic understanding of biology." People are definitely working on it, but we are nowhere close to as complete an understanding as we need. The evidence for precisely this claim is in the failure rate of clinical trials, into which we encode our best-known understanding of biology and we still end up being wrong 90% of the time. And that's not including all the pre-clinical candidates, which drive our wrongness rate (i.e. knowledge gap) to 99.99999%+

Re: Clinical failure rates over the decades: yikes

#93

Post by estearum »

arjie wrote: post #31

Can’t agree with the premise. It seems that through changing regulatory regimes and technology a 1 in 10 chance is the economic optimum for this. Interesting stability, certainly, but I’d expect that as technology improves success rate, funding increases until the marginal project is unprofitable. The better we get at doing things, the more ambitious we get. As an example, we can keep babies alive much earlier in ges…

But technology isn't improving the success rate. And the marginal project is already expected to be unprofitable. Pharma is a hits driven business and the hits are getting simultaneously more expensive to produce, harder to find, and enter into a much more competitive market environment.

Re: Clinical failure rates over the decades: yikes

#94

Post by hibikir »

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…

It's not that much better in plant breeding: You'll find hundreds upon hundreds of supposedly better varieties tried, and 5 years later, you are lucky to get 1 good one that one would consider commercializing. And that's after years of testing changes in smaller settings. We just don't have models that are predictive enough without planting, and waiting for plants to grow takes time.

Re: Clinical failure rates over the decades: yikes

#95

Post by s1artibartfast »

bonsai_spool wrote: post #62
s1artibartfast wrote: post #50

Earlier quoted context omitted.

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

Why isnt it rational?

You spend the 1 billion for a ticket to win 30 billion/yr for the next several years.

Is it rational to spend 1$ to make $100 10% of the time? A 99% failure rate would be break even.

Re: Clinical failure rates over the decades: yikes

#96

Post by rwmj »

hibikir wrote: post #94
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…

It's not that much better in plant breeding: You'll find hundreds upon hundreds of supposedly better varieties tried, and 5 years later, you are lucky to get 1 good one that one would consider commercializing. And that's after years of testing changes in smaller settings. We just don't have models that are predictive enough without planting, and waiting for plants to grow takes time.

Way more than hundreds! Page about finding new varieties of roses: https://eu.davidaustinroses.com/pages/breeding-programme

Re: Clinical failure rates over the decades: yikes

#97

Post by tchalla »

asdff wrote: post #64
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 learni…

Yeah ML is used in clinical research but the narrative right now is that "AI" will take a target, find a molecule and we will magically have a safe drug in 3 years instead of 12 years. At best, it misunderstands biology and chemistry. At worst, it's one of those tech bro reductive statements.

Even today, I am on a newsletter that has said AI drug will pass clinical trial in 2022 ... 23 .. 24 .. 25. Even the candidates that they talk about are mostly just repurposing. Don't get me wrong, ML has a solid place in clinical research but not like this.

Re: Clinical failure rates over the decades: yikes

#98

Post by refurb »

bonsai_spool wrote: post #78
inglor_cz wrote: post #76

Earlier quoted context omitted.

"Why would anyone make a drug if the current prevalent treatment was as good as a functional cure?" I am not sure whether you ask for economic why, or an overall why. The overall why seems easier to explain: a. The new drug may be cheaper. b. The new drug may be safer. (e.g. no risk of anaphylaxis etc.) c. The new drug may not need cold storage (huge problem outside the First World). d. The new drug may have other pr…

This is very facile thinking - are there any examples of a-e in the real world (namely, a brand new drug program was spun up to exploit a-e) ? I think not, which is why I asked the question.

Look at the GLP-1s. Lilly spent tens hundreds of millions developing an oral version that was otherwise the same as the injectable’s.

And the notorious inhaled insulin that Pfizer launch (and horribly failed).

There are many ways to differentiate drugs, not just efficacy.

Re: Clinical failure rates over the decades: yikes

#99

Post by bonsai_spool »

inglor_cz wrote: post #80
bonsai_spool wrote: post #78

Earlier quoted context omitted.

This is very facile thinking - are there any examples of a-e in the real world (namely, a brand new drug program was spun up to exploit a-e) ? I think not, which is why I asked the question.

IIRC there are serious attempts at "vaccination plasters", which would solve the cold storage problems of classical vaccines. Some really bad infections survive in reservoirs far from the closest hospital with reliable electricity. And frankly your comment about "facile thinking" is totally unwelcome. Have you seen someone vomiting their guts out after chemo? That is torture. Oncology is one field where every less pu…

I have seen these people, but we are speaking about drug companies making new drugs. I am not aware of an example of a new chemotherapeutic developed to reduce the side effects of a previous agent - that seems even less reasonable from an ROI perspective since we have good agents to control chemo-associated nausea. (edit) If a new agent happens to cause fewer side effects, that is welcome. But how would you justify the risk of the new agent not working at all?

The search for different formulations of an active agent seems a little unrelated (sibling comment to yours) but I concede that I didn't exclude that in my earlier argument.

--

My point is that several posters here are giving arguments from first principles ('yes of course we would want to keep trying to make more medications because more options is better than fewer options') but not engaging with the enormous cost such a rationale would entail.

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