[schizoidboy]

My favorite quote from Ioannidis:

“Science is a noble endeavor, but it’s also a low-yield endeavor,” he says. “I’m not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcomes and quality of life. We should be very comfortable with that fact.”

https://www.theatlantic.com/magazine/archive/2010/11/lies-da...

[User23]

A competent medicinal chemist can spend a lifetime in drug discovery and never get a candidate molecule out of clinical trials. I learned this from the excellent Derek Lowe, whose blog at http://blogs.sciencemag.org/pipeline/ is on my daily list.

Quote from an interview[1]: "I’ve been doing this for 27 years, and I have never once put a drug into a pharmacy. I tell people: “If you want to know why your prescriptions cost so much, it’s me.” I’ve done nothing but spend money the entire time."

[1]https://www.statnews.com/2016/03/05/derek-lowe-chemist-blogg...

[hannob]

> “If you want to know why your prescriptions cost so much, it’s me.” I’ve done nothing but spend money the entire time."

Sounds nice, the best evidence we have disagrees: https://news.ohsu.edu/2017/09/11/how-much-does-it-cost-to-br...

[aaavl2821]

That's a widely criticized study because it ignores the cost of failure. It only looks at the r&d investments of companies that received FDA approval for a drug. It's like doing a study of the odds of winning the lottery, and only analyzing people who won the lottery

Considering the fact that 90% of phase 1 drugs never get approved and that study seems quite biased. That study conveniently assumes that all those medicinal chemists, who've worked decades and never seen a drug approved, simply don't exist

[User23]

Interestingly this contributes to why drug companies spend so much money on advertising: it has a predictable measurable return, whereas R&D is virtually a lottery.

[dekhn]

what's really crazy is how much money it takes to not make much progress, either. Modern labs are washing cash down the drain.

[api]

Is there a shortcut? I'm sure some improvements can be made but I am skeptical of the idea that science is just doing it wrong.

[jdietrich]

>Is there a shortcut?

Controversially, I think we need to do less research. The publish-or-perish culture has created a perverse incentive to crank out junk papers. Most working scientists will privately admit that most research isn't actually advancing our understanding of nature, it's just a desperate effort to dredge up something sufficiently novel to publish. Conversely, there's a substantial amount of research that is potentially useful to clinicians, but is languishing unread in some third-tier journal. Most research is never published at all because it supports the null hypothesis, but we can't do good meta-analyses based on a cherry-picked set of studies. We're glutted with data, but we have a remarkable paucity of actionable information getting to the people who need it.

The problem isn't that scientists are doing a bad job, but that the funding mechanisms of science incentivise the wrong kind of work. We should be focusing a far larger proportion of our funding - perhaps even a majority - on replication, meta-analysis and dissemination. Primary research is only one small part of the information architecture of science, but it dominates our spending.

In the case of nutrition, we're spending huge amounts of money on figuring out whether coffee increases or decreases your life expectancy by a fraction of a percent, but almost nothing on behavioural research to figure out how to stop people from gorging themselves to death on food they know to be terrible for them. There's a morbidly obese elephant in the room, but we're preoccupied by the micronutrient-rich mice scuttling around the periphery.

[api]

This is the only good reply I've seen so far.

I think a lot of information economies suffer from oversupply. I've heard it said that there are too many books, too much music, too many different open source projects trying to solve the same problems, and so on. It causes information overload on the demand side and perhaps paradoxically increases the odds of something genuinely important being neglected.

[pixl97]

>but almost nothing on behavioural research to figure out how to stop people from gorging themselves to death on food they know to be terrible for them.

I'd also say the converse is true. Corporations spend lot on how to get you to eat their low cost high profit food that is not good for you. Think if we treated junk food like cigarettes in many countries where they had to be in a generic white box and no advertising.

[pas]

Junk or not, if someone's daily caloric intake is in the sky, they can overeat themselves on the most non-junkiest of foods. Let's say a lot of vegtable seeds, superhealthy all organic bread, some premium right out of the cow diary stuff, and some fruits, just to get more sugar.

[dekhn]

I don't think there's a shortcut. There would have to be a massive change in approach. In my field of expertise, molecular biology, it;'s common to just run experiments over and over until you get a positive result- throwing away thousands of dollars in gels and other things along the way. This isn't even intellectually honest (it's fishing for significance) but it's what nearly everybody does to get publishable results.

As a response, I work at a company that is automating biology, with a goal of making much more reliable clean data for machine learning, but even then, it's very expensive. A decent robot arm costs well over $50K (I could build an equivalent for $1-2K, but at a cost of $100K of my time) and all the other equipment is often in the $100K+ range. Just to automate what you could hire a human to do for $75-100K a year!

So yeah, some scientists are doing it wrong, but even the folks doing it right are still wasteful. I think it's endemic to the enterprise, but we could still do better.

[selimthegrim]

How can we find out more about your company?

[dekhn]

insitro.com and https://medium.com/@daphne_38275/insitro-rethinking-drug-dis...

[hannob]

There's not really a shortcut to the fact that science is difficult.

But more quality science and less garbage science would help. Doing 10 studies with a small likelyhood of any of them having a true result is less helpful than 1 high quality study that almost certainly is true.

[kansface]

> Is there a shortcut?

A much, much deeper understanding of how humans work.

[ryanwaggoner]

Facepalm! How could we have forgotten to pick that up before heading down this road of frustratingly hit-or-miss basic research?!

[selimthegrim]

Maybe the real research was the friends...

[gbear605]

And how do we acquire that?

[Steel_Phoenix]

When you're looking for something, you always find it in the last place you look.