100% response, zero side effects?
This sounds like world changing news. Can anyone with domain expertise explain the catch, if any?
This sounds like world changing news. Can anyone with domain expertise explain the catch, if any?
Other treatments may eventually prove to have too many serious negative side effects. That's a good reason to abandon them.
IIRC it was more about production methods than developing new treatments.
This isn’t really an obstacle, at least not as much as it’s made out to be.
There are numerous examples of drugs being brought to market at high prices despite having been generic compounds. Even old drugs can be brought back at $1000/month or more at different doses or delivery mechanisms.
One example: Doxepin is an old antidepressant that is extremely cheap. It was recently re-certified for sleep at lower doses and reintroduced at low doses at a much higher price, despite being “off patent”.
This happens all the time. The drug companies aren’t actually abandoning usable treatments due to patent issues as much as journalists have claimed. If they couldn’t, for some reason, find a way to charge for it they could still use it as a basis for finding an improved relayed compound with more targeted effects, better pharmacokinetics, etc.
They’re not just dropping promising treatments anywhere if there’s a market for them.
I am a lifelong sufferer of insomnia (though mostly sleep onset) and tried all sorts of increasingly risky things. CBT cured me in ~2 months.
Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need because a disease is so lethal/debilitating, regulatory agencies can give latitude in approvals.
Likelihood patient compliance - if it is the most effective drug in the world, but requires intravenous infusion six times a day - nobody is going to adhere to that. GLP drugs are effective, but there is a needle-phobia that is preventing patients getting on board with the idea. Which is why there is an arms race for the first company to develop an oral version.
Toxicity - all chemicals are poisonous. Yet some have a lower therapeutic window than others. If you drug does what it should, but if you take 2x as much and it gives you a heart arrhythmia that is going to be a tough approval for anything but the most deadly conditions.
If your treatment works, that’s an improvement of what you had before. Once you know that, you can treat all patients. For some, that will be too late, but without your tests, it would be too late for them, too.
If your treatment doesn’t do anything at all, it keeps things the same, but the patients in the test group likely will have had some inconveniences (having to visit a doctor, getting an injection, etc), so you shouldn’t do the test.
If your treatment makes things worse, you of course shouldn’t do the test.
Problem is that you typically only can only know in hindsight which of these applies.
So, you think carefully on whether a treatment could fall in category 3, and, if so, first do it on a group of patients who consent to be Guinea pigs and, often, are already terminally ill, as any negative outcomes will cause less harm to such patients.
Then, as soon as during the test your stats tell the drug does or doesn’t work, you stop the test and either treat all patients or stop treating the test subjects.
So the comparison is between old and new, to ensure the new treatment is better than the current standard one.
Simplest "bad" reasons are the wealth of the patients. Malaria, river blindness, guinea worm, etc are terrible diseases that mostly impact poor people out of sight from Western eyes. Spending $X billion developing a drug for a population that can barely afford to feed themselves is not going to make a financial return on investment.
Best bad reason: it would cannibalize an inferior drug currently in your portfolio that's still under patent protection.
I think this behavior is at the far "evil" end of the spectrum of behaviors that drug developers systematically engage in (which I believe is far more banal + less evil than what they're accused of), but it does happen and it's a really nasty
Where it gets especially nasty is when companies buy drugs in development or pre-development from other companies in order to squash (or at least delay) a potentially competitive asset before it reaches the market.
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Another great bad reason, but mostly applies to devices/procedures: the device/procedure is fantastic but for various structural reasons outside of the control of the device/procedure developer, there is insufficient incentive for healthcare providers to actually deploy said device/procedure.
A trivial example would be a pacemaker that requires fewer leads than the competitors and has fewer complications. Great for patients, but potentially totally uninteresting to the electrophysiologists who install it and would get paid less due to the less complex procedure.
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Best good reasons all fall under: making a therapy is unfathomably difficult and most efforts are destined to fail OR (separately) proving a therapy works is unfathomably expensive and most efforts can't produce a positive ROI after that process.
* Most drug candidates just don't work
* Even among the drug candidates that do, figuring how to safely deliver them to their target is very hard (looks similar to "just doesn't work")
Bad reasons:
* It's too expensive to prove that a drug works
* It's too difficult to differentiate the patients for whom a drug works and the patients for whom it does not
* It is very hard to predict recruitment and to actually recruit patients for clinical trials
* There aren't enough people with the disorder who are also rich enough to afford treatment to justify development
I'm not sure that is necessary a bad reason. You need to factor in a lot of concerns to determine what "too expensive" means.
But if you are going to spend billions of dollars to develop a drug that only treats about 2 people a year it is likely too expensive even if it is 100% effective. That money would be better spent on treatments that have wider applicability.
Of course this is not simple to measure. Costs aren't known upfront and the research may end up proving invaluable to more widely applicable treatments.
So it is a judgment call and not necessarily a bad reason.
In other cases it's a bad reason for failure: it's also incredibly expensive to prove your drug works even if it does work for a lot of people.
That's bad! It'd be better if it were cheaper.
Actually counterintuitively, due to a weird drug approval and payor reimbursement policy arbitrage, pharma companies are highly incentivized to produce drugs for tiny populations.
One of my hobby horses is railing against this specific dynamic.
That patient was hit and killed by a car two days after finishing their treatment.
Along with the CEO's stubborn refusal to give up any more equity in the company, they went under, and the world will never know if that treatment worked.
I agree with GP that it is very notable.
I mean if it works on humans, which is not a stretch, colorectal cancer is done. It's huge.
I wouldn't describe it working in humans as "a stretch" per se. I'm not identifying a specific reason it shouldn't work in humans. I'm just saying that's true of thousands and thousands of really great looking treatments (per year!) that, nonetheless, end up not working in humans, or not being convincing enough to even warrant putting them in humans once.
The only thing such a state of affairs clearly indicates is broken is using mice as proto-human test subjects.
Which of course, when you state it like that, is obviously suboptimal. But no one knows what to do about it.
If that particular bacteria doesn't work in humans it may still trigger a search for a bacteria that does.
Still being optimistic about this :)
It's useful as a very early test. They used a shotgun approach, they tested 9 bacterias and 1 of them was suspenseful. At least it was suspenseful for 2 weeks, until the study ended. It's very difficult to extrapolate that to the 5 year survival rate in humans.
I wonder if anyone has tried to engineer a mouse that lives forever by applying all these life enhancing mouse therapies at once.
The bar for an acceptable side effect profile in an FDA-approved drug would also be a lot higher than "five genetically near-identical mice did not show evidence of pathology in a single study."
I'm not saying this work is bad (skimming, it seems fine for what it is, though haven't read in detail), but it's quite preliminary if we're talking about developing a medical treatment that could eventually be deployed in humans. There's a reason it ended up in a mid-tier microbiome journal.