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Comment by jdawg777 | Hacker News Reader

> will be supplied with an auto-injector, containing either 16mg of selatogrel or a placebo liquid formulation.

Its unfortunate that half the trial patients are getting a placebo, especially when it is life or death, but I suppose that's how drug trials work.

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FWIW, often a trial is halted before being completed if statistical analysis of the preliminary results definitively indicate a positive outcome, or unexpected negative/life-threatening side effects emerge at an unacceptably high incidence.

If the trial is halted prematurely because the drug is deemed effective, immediately all individuals who received placebo are given the real thing. If the trial is completed and it shows the drug is effective, all those who received placebo are given the real thing.

Know also that all participants are paid for participating.

So are they going to wait with their heart attack until trial is over? Maybe read the article first? This makes sense for long term medicine like diabetes drugs etc but this one is for heart attack

Suspect heart attack--you head to the hospital pronto. The trial involves injecting the drug immediately, then going to the hospital. The placebo arm gets exactly the same treatment everyone would get now--rush to the hospital. This drug is purely about trying to keep the heart alive long enough to reach the hospital. A hospital with a cath lab is a far better treatment than this drug--but you can't put that in your pocket.

Yes. That is how clinical trials work. I have run many clinical trials. I read the article twice before I submitted it.

I think the charitable interpretation of who you are replying to is that it would be silly to give this drug for an acute event to people that received control (a life-long standard anti-platelet) weeks after they had an MI event. You're not going to say, oh that guy that had a heart attack and PCI 4 weeks ago who is on DAPT, oh now we're going to give this drug, the horse has already left the barn so to speak and the intervention is no longer indicated. That's how I interpreted the point at least.

The alternative is to see later studies like [1], which finds that several popular heart interventions don't actually improve all-cause mortality in the population of "severe but stable" heart disease patients.

If stents and coronary bypasses don't increase life expectancy (or quality of life!) for that population, then a lot of people from that population took the risks of major surgery for no benefit.

[1] https://med.stanford.edu/news/all-news/2019/11/invasive-hear...

The standard joke here is that the researcher objects to the need for a trial, saying “that would be condemning half my patients to death!” and a medical student asks “which half?”

But you don't know if the new drug is going to be better or worse. Sometimes the placebo arm has a better outcome than the drug arm.

And, unfortunately, sometimes they really mess up the statistics. Consider that huge trial from some years ago that declared hormone replacement for menopause symptoms definitely bad. No, despite the huge size of the study they made a fundamental mistake in recruiting participants--all that study actually proved is what was long known: fat women shouldn't be on hormone replacement.

This is how all drug trial works.

And it regularly ends up being not-so-unfortunate, when the drug turns out to have dangerous side effects that overshadow its benefits.

Not all. The need for a placebo control is weighed against ethics and whether a placebo is even realistic.

Chemotherapy drug trials often just use standard treatments as a control group. They’re likely using placebo here because there’s no other drug in its class yet. Normally emergency life or death trials don’t have placebos unless the treatment is the first of its kind.

Yes. And placebo control is actually quite a weak standard (= better than nothing). Ideally, there should be more head-to-head studies.

Alas, they are also more likely to fail (and give the competition data) so developers avoid them, at least for the initial approval.

And it's something the FDA shouldn't be allowing.

You want to bring a new drug to market, you should be required to demonstrate that it's not strictly inferior to existing options in at least some patients. I'm fine with a head-to-head that comes out a tie (competition is good for the marketplace) and I'm fine with a drug that only works in a subset if that subset can be identified. And I'm fine with a drug that doesn't work as well but is more tolerated. I'm not fine with a drug that loses in all respects in a head-to-head.

That's far too strict. It doesn't do anyone any good to reject less effective drugs unless the safety to efficacy ratio is way off. Most drugs are relatively safe compared to the diseases they treat and identifying the subset that they work for is beyond our capability at the moment (i.e. the entirety of psychiatric medicine).

The FDA drug/therapy pipeline is supposed to give downstream users like doctors, public health officials, and patients more options within a certain risk profile. They're not supposed to be the be-all-end-all of treatment options.

Just because a drug is relatively safe doesn't mean it should be allowed if it's inferior to the existing one in all respects.

They are never inferior to existing ones in all respects for one very obvious reason: allergies.

If you’re allergic to drug A but not drug B, it doesn’t matter how much better A is than B. You need drug B.

All drugs have the potential to cause allergic reactions or other nasty side effects so unless a drug is too dangerous on its own, it should be allowed. It’s absolutely critical to deal with biochemical diversity in humans.

Good point, but many of the me-too drugs are chemically close enough to the original to cross-react. (And in some cases are actually identical--a company finds a compound the body will convert into the original drug.)

Off the top of my head, maybe the shock of being jabbed with a needle would have an effect on people's symptoms that should be controlled for.

It IS controlled for: ALL participants get jabbed with a needle.

Right, that's why you need to load some needles with a placebo.

Participants receiving placebo get the placebo through a needle.

Yes. I'm in favor of this.

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