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>> If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem.

The usual story for why we allow patenting of drugs and high prices is that development is very costly - particularly the cost of doing trials. If they're going to allow this on the market without trials that show efficacy, the least they can do would be to allow generics at low prices while we're doing the efficacy testing on the general public ;-) </sarcasm>

> If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem.

Hmm, what if we added a new phase where it's approved but can only be sold at a low, regulated price? Then if/when it is proven effective, they can transition to charging more.

Without getting into whether it's actually a good idea, in theory the high prices are meant to be a reward that makes it worthwhile to invest in drug development. Delaying the reward would still allow that incentive but keep it tied to actually creating drugs that work while still allowing patients earlier access.

The risk with that is that it creates a ‘perverse’ incentive for the FDA to not fully approve drugs because the approved drugs might shoot up in price 1000x the moment they exit the ‘purgatory approval’, and granting the official approval might kill some people who can afford the purgatory price, but not the fully approved official one.

So lock in the price for the ones that started taking it before it was fully approved.

That then would create the ‘perverse’ incentive for poorer people who are dying of major diseases to sign up for any and all trials possible to lock in prices, regardless of relevance, and make things much, much worse for themselves due to misuse. Richer people would not do that since they can pay the full price without locking the old price in, so this risks converting the sick and poor people already battered by life into lab rats.

If you instead don’t enforce the requirement to actually take the drugs to lock in the price, then everyone signs up for everything and your drug companies will stop making any new drugs.

> In their case, it's likely that the disease has multiple causative factors and the drug in question only treats one specific cause.

The problem is that every drug that has targeted amyloid has failed to do jack shit in any cohort--not early, not late, not alien--none of them.

Any rational science system would conclude "The amyloid hypothesis for Alzheimer's is WRONG."

But, no, the bio people just plow on further because amyloid gets published, and funded, and, now, approved.

One day we'll look at this time as the alchemy period of neuro.

Just the fact that we have not been able to find a medicine to reduce plaques does not imply that

"The amyloid hypothesis for Alzheimer's is WRONG."

Amyloid plaques are correlated with Alzheimer. AFAIK it is still an open question if they play a role in the causation of the symptoms.

Amyloid plaques seem to be correlated with lots of things--they seem to be a general response to damage to the brain.

Almost all of the evidence seems to point that amyloid plaques are not causative with Alzheimer's.

The fact that every single drug (including this one!) targeting amyloid plaques (some of which are actually effective at reducing amyloid plaques) has failed to do anything for Alzheimer's suggests that amyloid plaques are the WRONG target.

Mean drug effect is possibly a bad metric to measure. If the distribution is bimodal, or has very high variance, the FDA could take that into account when approving a drug.

I believe SSRIs often vary in effectiveness, for example; some people are just very good responders. Fortunately, their mean effectiveness is high enough.

(Not a doctor, etc)

I think we can improve access to experimental and unapproved drugs while still protecting consumers from malicious marketing of these drugs or sabotaging the current drug approval process.

How much more access can you possibly want on top of the previous FDA expanded access guidelines as well as the newer Right to Try Act?????

Hopefully, eventually we'll be able to figure out why a drug works for one person but not for the next so that we can get pinpointed approvals for just that subpopulation.

A simpler solution is to get rid of the approval process and let people operate their own bodies how they personally choose.

So the solution to the problem of doctors and medicine makers not being able to figure out what's gonna be safe and effective for whom is to just tell the patient to try to figure that out on their own?

Choosing != Figuring out

We know the top-down approach is ineffective. Is the other one worse?

The terms "patent medicine" and "snake oil" didn't just appear from the aether.

Yes. We don't have to wonder; we have a supplements industry to show us what happens.

The supplement industry has some problems. But it also has a few things going for it. It's far cheaper, and the only people that have been harmed from it made a choice to take that risk.

I don't know anyone personally who's life has been screwed up by supplements. But I do know two people personally whose lives were wrecked for years because of FDA regulations.

Not to mention the absurdity that was restricting the j&j and AZ vaccines.

Yes. Definitely. One has to admit that the supplements industry acquitted itself well during the coronavirus crisis.

This seems like cherry-picking. Quackery doesn't care about regulation (for example, hydroxychloroquine is prescription-only in the US), and shady hucksters abound in all industries (including ours; look at all the meaningless "threat intelligence" hype).

You could also just as easily look at the situation where poultry practices banned in Europe are the norm everywhere in the single-hand-countable poultry producers in the US, or the "regulation" they apply to tobacco products (which kill 7x more than opiates in the USA). It's a farce.

The FDA isn't doing what they ostensibly exist to do, and they are doing a whole bunch of stuff they're not. It's the worst of both worlds.

The supplements market is literally the largest unregulated market for pharmaceuticals. I'm not sure how it could be cherry-picked.

The supplements market is quite tiny ($36bn) compared to the "unregulated market for pharmaceuticals" that most people mean by that phrase ($150bn+).

For me and many, many others, that market serves us far better than the regulated one.

You're cherry-picking supplements quackery and hucksterism out of the 6x larger "unregulated drugs" market on Earth, which exists despite insanely harsh penalties prohibiting it. It would likely be much larger if not illegal.

I'm not sure I understand your argument. The supplements market is an even bigger fraction of the pharmaceuticals market than I thought, so I'm even more convinced of my point now. But, again: the literal point of the supplements market is to function the way you suggest the pharmaceuticals market should. I think that we should rather regulate the remaining $36B in supplements out of existence.

Thalidomide.

Tobacco, "regulated" by the FDA, currently kills 7x as many as opiates in the USA.

Whatever the FDA is supposed to be doing, they're not doing it.

If you don't understand the legislative history of tobacco regulation in the US, you should probably not comment.

The solution to doctors and medicine makers not being able to figure out if it's safe and effective is to let patients make choices as to what they can put in their own bodies.

We can have both an approval process and an end to the prescription system. We almost do already with prescriptions for off-label uses being common, although that turns every doctor into a drug dealer.

The approval process would then be a regulation on advertising, rather than a regulation on what is banned and what is not.

I think the FDA was in a difficult spot. There have been no new Alzheimers drugs in decades and patients are desperate for treatments. There is reason to believe that beta amyloid blockers need to be given in the earliest stages of Alzheimers (when diagnosis is difficult) to have any impact on cognitive decline. The trials did not focus on early stage patients, so there may be positive impacts if it can be given early enough.

Great! So let's figure out a way to make this study happen so that the drug can be given effectively (if it does indeed work) rather than have a blanket approval of a drug that lacks any proof of efficacy at all.

That a drug hasn't been approved for a treatment in years is no reason to approve one that doesn't work.

> So let's figure out a way to make this study happen so that the drug can be given effectively (if it does indeed work) rather than have a blanket approval of a drug that lacks any proof of efficacy at all.

It isn't a blanket approval, but it does sound way too generous in terms. From the linked article:

> The agency seems to have approved it based on its demonstrated ability to clear beta-amyloid, and is asking Biogen to run a confirmatory trial to show efficacy.

> They will be absolutely overjoyed to do that, of course, because the whole time that’s going, they will be selling the first drug that (in theory) targets the etiology of Alzheimer’s. The backed-up demand is going to be gigantic, and Biogen is going to make enormous amounts of money. They have nine years, as it turns out, to get this trial done, and I feel safe in predicting that it’s going to take alllll niiiiine loooong sloooow years to get this done.

I guess the thinking is that it could take years to know whether it's working or not through an RCT. I believe they are currently allowed 9 years by FDA to show efficacy. If the side effects aren't significant why not let people in need try it?

The side effects are significant. It comes with some risk of brain bleeds and a high risk of cerebral oedema in patients who have APOe4. This is an important genetic profile for those who understand Alzheimer’s, as homozygotes for APOe4 are 12x more likely to develop Alzheimer’s.

This is a cop out decision by the FDA. Efficacy can be determined by a RCT - instead a decision was made which supports biogen’s share price

The trial did focus on early stage patients - mild cognitive impairment (MCI) and early stage AD to be precise.

Medicare would pay no where close to 56k/year. There are mandated rebates and price controls in medicare.