> We just don't have a good system for funding cures you can't sell to millions

(Full disclosure: close family member works at $bigPharma)

I don't think it's about finding treatments you can "sell to millions", it's that in pharma, like in pretty much every other business, it's about ROI.

You definitely don't need millions of patients, but you do need to cover the R&D costs _and_ have enough left over to keep the shareholders happy.

This is such a fucked up incentive structure. Literally having the capacity to save lives but not doing it because otherwise people will pull out their money because Roblox is has a better ROI.

> This is such a fucked up incentive structure [..]

It may well be(!), so let's assume you're right, what better incentive structure should we put in place instead?

Increase general taxation and use that to fund more pharamaceutical R&D?

Break up the pharma companies and let them only be at-cost (!) manufacturers, move all R&D off to universities, and cooperate with other countries in said R&D efforts.

> Break up the pharma companies

For many politicians that would be seen as a "courageous decision" (hat-tip: Sir Humphrey Appleby)

> and let them only be at-cost (!) manufacturers

Won't it be hard to find investors if you do that?

> move all R&D off to universities

I think the "D" in "R&D" might be the problem in this approach. Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.

> Won't it be hard to find investors if you do that?

Better that than paying negative interest for German 20 year bonds, if you ask me.

> Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.

Agreed, universities have historically not been involved into the development part. But that is not a given dogma that can't be changed - the government could fund the establishment of development departments.

Alternatively, international governments could establish cooperative efforts to develop pharmaceutical compounds. Rare diseases and the decline of available reserve antibiotics are a global problem affecting every country on Earth just the same.

Can you illustrate for a lay person the difference between research and development in pharma context?

Research = determining a candidate compound, e.g. a new antibiotic, (e.g. by taking and tweaking an existing compound, by basing off of the actual viral/bacterial genetic code such as with the Biontech/Moderna CoV vaccines or by isolating a compound found in a plant, fungus or other natural agent which has been determined to have the effect you want), and initial checking against cell cultures and/or lab animals for effectivity.

Development = taking a lot of candidate compounds and evaluating them in the classic three-stage procedure - phase 1: determine how the compound is processed in actual human bodies to check if it is actually safe to ingest and what side effects can already be observed (n ~ 20-80), phase 2: determine effective dosage (n ~ 100-500), phase 3: check effectivity in a double-blind trial (n ~ 1k-10k), as well as the fourth phase (after-license monitoring) [1][2].

The more a compound progresses, the more expensive the trials get to conduct, not just because the participants usually get some compensation for their risk, but also because all the data has to be tracked and processed. And a lot of candidate compounds fail somewhere along the path (either because they are ineffective or because the side effects are too severe), which makes the money invested effectively wasted (from a capitalist point of view, not from a scientific!).

[1]: https://en.wikipedia.org/wiki/Clinical_trial

[2]: https://studienteilnehmergesucht.de/ratgeber/die-vier-phasen...

> Development = taking a lot of candidate compounds

At least one $bigPharma defines "research" as being everything up to and including the first proof of concept in a human [Phase I] trial. After that would be "development".

That'll mean no more drug development.

My grandmother had rheumatoid arthritis, and it made her life utterly miserable for her last 10 years. Recently, Enbrel was developed by a biotech for profit company, it is the first effective treatment for rheumatoid arthritis.

No university or government came up with it. A for profit company did.

> Increase general taxation and use that to fund more pharamaceutical R&D?

Take the US military budget and give it to life saving research instead of life taking.

Edit: Also implement a wealth tax instead of income tax. Discourage hoarding of wealth and concentration of power in the hands of top 1%.

Ah yes so China or Russia can invade and establish a totalitarian regime. Excellent idea.

You don't have to give up all of it. The total budget of US is larger than the next 6 countries combined. India, which is actually surrounded by hostile neighbors, one of which is china manages to defend itself with a tenth of the budget. My guy you are giving military money they didn't even ask for in this year's budget. Please stop repeating this line. American budget it not to stop China or Russia, its to assert their own will on the world.

> The total budget of US is larger than the next 6 countries combined.

Not in % of gdp. The only metric that matters. The US economy is massive in size so of course the budget is a big number.

> one of which is china manages to defend itself with a tenth of the budget.

Everything is cheaper in China. You can do a lot more with one million there than in the US.

I don't know why you are talking about china while the point I was making was about India defending itself against china. Also indian % of GDP for military budget is 2.8 while for US its 3.75. US has no neighboring countries actively attacking it, India does.

edit: BTW, is there any actual proof that this whole military budget dissuades Russia and China in any way?

> This is such a fucked up incentive structure.

It has produced far, far better results than communist incentive structures.

> We're not even close to our limits on research capacity.

Maybe not at your stage of research, but it's my understanding that further down the pipeline (eg clinical trials) you're mich closer to the limits, simply due to financial constraints: given that a trial for something you can sell to millions isn't that mich more expensive than one you can sell to dozens,and given that you need to get payed for your job, i don't see how it doesn't make sense to prioritize the lower hanging fruit. Am i missing something?

Thanks for your answer. Yes, this is not a case of lacking science, research, or even treatment capabilities. It is a case of too many hoops to jump.

Maybe twenty years from now some people with a high degree of knowledge, skills, and some resources will be able to get around these hoops illegally (by the laws of certain jurisdictions) and fix these conditions (or kill themselves or somebody else trying, but so does god/nature and doctors, with different[citation needed] probability distributions).

> Both. We're not even close to our limits on research capacity.

Really? From the outside it seems to me like we are beyond our limits on research capacity.

The progress seems to be slowing down everywhere while the price per discovery of a new drug skyrockets with many having rather disappointing efficacy (high NNTs).

None of those limitations seem inherent, nor are we close to the societal limits for what we can do when we actually care about accomplishing something. We may be somewhat close to the limits of what we can do with current R&D structures and incentives, but that's quite different.