Comment by A_D_E_P_T | Hacker News Reader

Comment by A_D_E_P_T | Hacker News Reader

Parent Full thread

> This is not a call to attack on the FDA

At this point, I honestly think that we'd be much better off without an FDA at all.

It costs >$2B to develop a drug. Most of this is on account of efficacy testing -- phases 2 and 3 of the drug development process -- which are nearly impossible to run. And when drugs exhibit poor or nil efficacy, the FDA sometimes approves them anyway, making the entire process unprincipled. See, e.g., flibanserin, aduhelm, and others.

The result is total regulatory capture. If you're a small firm -- a biotech startup -- you quite literally can't introduce a new drug to the market. Your only hope is to push it through preclinical trials and then partner with -- or get bought out by -- a large "prime" like Pfizer which specializes in regulatory compliance and has the deep pockets required.

Back in the 1940s and 1950s, there were lots of small firms that competed in drug development. Syntex, for instance. That was a period the industry still calls "The Golden Age of Drug Development," and it would be utterly impossible to recreate today.

All of this is without even going into the bureaucratic hurdles which delay new treatments from reaching patients, the chilling effect that the red tape has on pharmaceutical R&D, the way they gatekeep generics, and I could go on all day. It's not just a bad system, it might be among the worst systems possible, as it concentrates all power and all wealth in the hands of a few -- and the patients are the ones who suffer for it.

it's very bureaucratic, but I'm curious what phases of the process you think we can skip? was the golden age entirely due to lack of procedural burden, or just low hanging fruit?

I agree that it's all a miserable mess, for sure, the solutions are just unclear to me; the relationship between the public and those developing drugs is increasingly hostile due to the need for blockbuster hits and really questionable effect sizes that get pushed due to sunk costs

Efficacy testing -- those phases 2 and 3 -- are entirely unnecessary. They didn't exist prior to 1962's Thalidomide backlash, ironically despite the fact that Thalidomide failed safety testing in the US and was not approved for use.

So it's simple: After phase 1 safety testing, allow drugs to be marketed, but mandate postmarketing surveillance for a period of 5 years to try and tease out real-world safety, efficacy, and drug interactions. This would ultimately result in a better and safer system, as quite a lot of drugs have problems that aren't revealed in phases 2/3 anyway. (e.g. rosiglitazone.)

This simple fix would not only speed up drug development, it would also make drug development a lot cheaper. Compared to the current paradigm, it would heavily incentivize R&D, and bright young minds might see the development of therapeutics as something potentially rewarding. Whereas, today, nobody in their right mind wants to get into pharmaceutical development when they could be making much more money, with much less red tape, in tech.

how would someone under such a system decide to take a drug or not? what information would they have?

Insurance companies would decide.

Raise your hand if you think that would be better.

The largest single payer in the US is the Federal government. Medicare, Medicaid, Tricare, the VA... The problem won't be fixed for the vast majority of expenditures because the government will need to perform the same function the FDA is now for it's drug costs.

Maybe. But cheaper drug development should also make for cheaper drugs, which will weaken the stranglehold the insurance companies have on drug supply and distribution.

That's what USA has now. It sucks.

Physicians' associations, such as the American Heart Association, can issue treatment guidelines based on available clinical evidence, real-world data, and expert consensus. They already do this anyway, and in most cases their guidelines are the default prescription.

Also: Postmarketing surveillance data, peer-reviewed journals, mechanistic analysis, etc. There are lots of ways to decide which drugs might be of benefit. Leaving the decision to the FDA has, to this point, done far more harm than good.

An easy reform would be to allow reciprocity with other countries' drug approval organizations.

https://marginalrevolution.com/marginalrevolution/2013/11/th...

I'm drug discovery and the FDA absolutely _does_ keep all the crazies in check.

Many people died during that golden age, and don't forget that the same golden age produced many of the problems we're drowning in / trying to fix today (PFAS, etc.)

> Many people died during that golden age

I've written about this before. Basically, the FDA's position is that it's better for 10,000 patients to die of neglect than have 1 patient die of quackery.

Drug development is in shambles because the FDA requires >99.99% confidence that pharmaceutical companies are not selling quack cures. Do we need that level of confidence? Especially for cancer, is that degree of confidence warranted? Is the process efficient?

There's legitimate fear of quack medicine -- and then there's whatever the FDA is gripped by, which seems to me a lot like insanity.

> PFAS

Not exactly something that goes through the usual drug approval process. What other problems come to mind?

There's a lot of quackery around these days, especially with regard to tech and finance.

There's quite of bit of quackery just with nutritional supplements, too. And people and companies try to bypass the FDA all the time with fake cures, the COVID-19 epidemic was just the latest version of that.

The FDA is over-zealous with their testing requirements. However, without them we will see an explosion of fake cures for everything. The legitimate pharma companies will lose money, or otherwise start cutting a lot of corners in the pursuit of profit.

We need something like the FDA to keep things in check.

I tried to upvote both of you to keep this civil.. I think there are important points to consider on both sides -- and I find this repartee between you and A_D_E_P_T most informed!

it might take some time to reconcile your points though, some moderate data might help, what do I know, being peripheral to drug-development..

I don’t think they’ve kept all the crazies in check. Most pain and anxiety “medicines” are harmful. People are dying today due to drugs the FDA has deemed safe.

It's not just about the nutjobs in the past. There are plenty of modern nutjobs, and one of the shit-on-shit sandwiches that is fuck cancer is getting (at best) the clueless to (at worst) psychopathic opportunists peddling quack cures, all this at a time when the patient and/or caregivers may be willing to grasp at any straw, no matter how slender, offering hope of a cure, or even a few more good days.

I'd run interference on this some years ago, before the emergence of the public Internet / WWW, and ... it was already bad enough. Whilst online fora are often praised as being of tremendous benefit to patients and caregivers of chronic or terminal conditions, increasingly they're overrun by that same set of dramatis personae, and it absolutely, absolutely boils my blood.

There are criticisms to be made of the FDA and Pharma, but for the most part those engaged are largely subject to poor incentives rather than outright fraud and opportunism.

One of the tremendous values of jseliger's account is his exploration of alternatives, and candid commentary (especially recently) of how even what does work for a while can stop working.

Cancer is a complex set of phenomena which share a common symptom: unconstrained "crab" growth (the tendrils which spread outward from tumors). In German, "cancer" is literally "krebs", that is "crabs" (which of course has its own confusing connotations in direct translation to English). What's coming to be appreciated is that each individual cancer case is ultimately its own evolving community which adapts to, and often overwhelms, the treatments and countermeasures deployed against it. That said, there are cancers which are remarkably amenable to treatment, and are wholly curable. Others not so much. Details in this case matter immensely.

> In German, "cancer" is literally "krebs", that is "crabs"

Crayfish, I think. The German for crab is Krabbe. (AFAIK.)

I hear you..

Reply on news.ycombinator.com