If you do start munching on advil; note there are rumors, by medical researchers, case reports, and more, that if you dig beneath the shiny surface to find, do show a lot of compelling data for GI damage, heart risk and other serious side-effects. And depending on how fair one wants to be with 'evidence' -- almost all wording describing NSAIDs as "protective", uses easy-to-miss but distinct qualifiers such as "potential" and other such vague 'maybe'-equivalents that alone have been used to suppress and dismiss many other...potential medicines. Sometimes, conclusive just means inspired. And sometimes ambiguity means certainty, depending on levels of inspiration involved.

Of course, one might pause for a moment to consider just how potential the alluded benefits really are with ibuprofen, and ask why doctors aren't recommending it for mental health, or as a general health product. But that might point to the peculiar fact that there is substantially more evidence suggesting risk over health benefits, and the benefits really depend on what one wants to see. There is a reason it's not marketed as a health product, but with the way it's framed, it should be, nu? I mean, potential benefits sells a lot of snake oil and lowfat yogurt. Why not advil and acetaminophen?

And by similar logic used to dismiss acetaminophen here as a health risk, eg because there's no link with autism/ADHD it's safe; why not apply the same logic to opiates? We could just say opiates do not directly cause, eg , parkinsons, or AIDS, therefore it's safe for babies. Myself, I never correlated acetaminophen with autism/ADHD, but I know it has more side-effects than listen on the bottle.

Yeah I work in clinical trials so I'm very comfortable with all the caveats the need to be applied to correlative studies like these.

Which also answers your other question of why doctors don't recommend it: we don't actually know that it does this.

As for the rest of the ramble, you (or I) definitely don't know hardly anything that hasn't been established in clinical trials. Certainly can't just vibes-based assess a label and its completeness. It's really, really hard to know things.

The precise wording as far as safety is: "we have no substantive or high-quality evidence that the drug is unsafe."

Because we couldn't possibly modify

"we have no substantive or high-quality evidence that the drug is unsafe." - (damn all the research showing it is)

--to

"we have no substantive or high-quality evidence that the drug is safe." - (damn all the research suggesting it isn't)

Well, that's as good a green light for an ad campaign as one could ask for. "we don't actually know that it does this." ain't never stopped a motivated pharmaceutical rep before. You have my official endorsement for feeding advil and acetaminophen to all. And protection from dementia is just what America needs. !Win / !Win

Maybe restless leg and depression too! And don't tell me fetuses don't get depressed there in that dark womb. We know damn well they get restless.

Drugs are approved for the specific uses based on extremely high-quality evidence. That evidence balances the benefits against the detectable downsides/costs/side-effects. Those downsides are also on the label.

That's almost entirely generated by the highest quality evidence generation system we could possibly have, which is RCTs. And no, pharma reps actually aren't allowed to encourage (or even talk about) off-label uses of drugs.

I get the sense that you don't know much about this space.

>highest quality evidence generation system we could possibly have, which is RCTs.

The "best we have" does not mean it is good enough for the task at hand. Just saying.

Basically what I am saying is that qualifying something by saying "best we have", does not justify its using on its own..

1. I didn't say "the best we have." I said the best we could possibly have. There is no form of evidence generation, real or hypothetical, greater than the randomized controlled trial.

2. That doesn't necessarily make it always "sufficiently good evidence", but the beauty of statistics is we actually can know – quite precisely – whether a given evidence generation method gives us sufficient certainty. When an RCT is used as evidence for approval, it is not "well you did an RCT so I suppose it's fine." Approvals actually are not dependent whatsoever on the evidence generation method. The only thing that matters is whether you prove – to sufficient statistical certainty – the claims you are making. It's very hard to do this without RCTs (again being the greatest evidence generation form that could exist), which is why they tend to be the default. But you can run an RCT that fails to produce certainty, and your drug application will be denied. You can also get approval based on a non-RCT (but again it's hard to do because statistics).

We've had this discussion before and the crux of the issue is that you do not understand statistics while the people who design, run, and evaluate clinical trials do. I highly recommend taking a statistics course or four.

>There is no form of evidence generation, real or hypothetical, greater than the randomized controlled trial.

Wrong. You are lying by omission.

Randomization and controlling are essential. But the version of RCT that we currently employ have problems with control and evaluation. If you have a flaw in control or evaluation, then the whole thing becomes flawed.

So the idea of RCT is good, but we are limited by our ability to control and evaluate.So there can be a better version of RCTs that we currently employ, but with precise control and evaluation.

> but the beauty of statistics is we actually can know

The beauty of statistics is also that it is quite easy to hide falsehoods behind statistics.

There Are Three Kinds of Lies: Lies, Damned Lies, and Statistics

(I am not even going into the fraud problem, which is what we have discussed before, which turned out to be quite useless)