I'm surprised.

I am very surprised.

And, you know, on the surface.

it looks, it looks great.

Right.

Um, but just from a, from a Bayesian perspective, from a prior perspective, I mean, I, I'm not buying it because yes, they get more radiation exposure, but surely they're different in a lot of other ways.

And, um, you know, and, and I, I mean, I looked at the table, other cancers, non, non radiation related cancers, um, Other cancers are 1.21 are statistically higher in flight attendants, but not pilots.

what did you know

effective medicines we have.

Not so strong endpoints.

Now we have not so strong.

Now I'm going to just put up another warning.

Trigger warning for our listeners.

You can't unsee what I'm going to show you.

And this is Emperor Preserved.

And that's sort of an interesting discussion to have and you may get to the point where that this is part of it

because kind of the one remaining market for us, Altamavir, disappears.

Can I show you my marketing versus...

All right, so I just wanted to...

Adam told me he was going to do this.

I just had...

A couple slides on this, because when I start critical appraisal talks, I often start with the first question is that you should be thinking about when you open a journal article is, is this science? Are we asking a question to investigate nature and to learn something? Or is it designed to market a drug? And I think that there is overlap, but I think it's also good to have that as sort of a prior when you go into it.

So here's an example of a study that I think is really asking an important scientific question.

No

You're comparing the poor, unfortunate people in the control arm who had no other options or ability to get any other drug than a drug that's not going to work, that has been beaten by alternatives, and 50% of people with options, they leave, against everybody.

um and some of these really bad uh trials that really flawed trials and the procedures are flawed a lot of times in in cardiology it's done with regulatory authorities are are involved and they're they're okay with it are these

um it's open to interpretation uh but that's the basis of this problem but the second part is the investigators have no obligation to participate in these studies um in a prior analysis we showed we showed these unethical control arms and then they were going to say something like well we didn't know you know we didn't know it was a bad control arm we showed that the authorship overlap 77 percent of the time it's the same authors on the same damn papers they know it's beaten you did you prove you beat it last

week you know it but i mean i i I ask the question because sometimes one of the criticisms of our criticisms is that they're like, well, if we get up in arms about, say, the non-inferiority margin, then the proponents will just come back and say, it was done in conjunction with the FDA.

The FDA was okay with that.

All right, everybody, we're back with another lecture.

And I'm going to talk about how people improve for many reasons.

And we're going to talk about control groups and placebo effects.

And this is off the beaten path a little bit, but I think pretty important in terms of practice of medicine and trials.

So here's a slide showing why patients improve, reasons patients improve.

So a patient could get better because of the true effect of the treatment, like... drug really works.

Who's this clever researcher?

Really clever.

Right.

Yeah, I said it's unbelievable because of course it's believable to you and Adam and myself and most sensible listeners, medicine listeners, because we understand the nature of atherosclerosis and we understand courage trial and ischemia trial and all these things, but The listeners need to know that this preoperative clearance industrial complex is like a cash machine.

I mean, patients get sent, and our nuclear medicine cameras run, and many of these are just preoperative clearance tests.

And they're done on a routine basis.

The sky is blue and people are getting preoperative stress tests for their surgery.

And, you know, I haven't done a preoperative test in maybe ever or maybe one in 10 years.

But, yeah, I mean, it's really crazy how much testing and things are done in the name of decreasing surgical risk, and yet you have this trial, and really, yeah, it's just so incongruent with the way medicine is practiced.

What was your take on this study?

Yeah, I wrote about it

because of all those reasons.

I'll start with the fact that unlike so many studies published in the New England Journal of Medicine, I think the authors were trying to answer an important clinical question that was curious.

I unfortunately see MSSA and MRSA because we have devices that, you wouldn't believe this, but sometimes get infected and cause bacteremia.

And so I see MSSA and I always thought naphthalene, which was, you know, an anti-staphylococcal antibiotic was fine or better or whatever.

But here is, you call it a simple trial, but it was in 91 sites in eight countries.

So I suspect that the authors probably didn't think it was that simple.

And when they look at the analysis of the protocol adherent population, we sort of lose the benefit.

But there's a big denominator, or is there? Uh, are, are any things that turn out [laughs] to actually work?

Well, yes.

I, I, I see where you're going with this question.

There are a lot of reversals, more than there should be, mainly because of, of our hubris and our ability to be bamboozled by observational non-random studies.

There's a lot of those.

There's too many in my opinion, and there's a way around that, I think, which gets to the medical conservatism.

But there are many, many more things that work in medicine, and it's never been a better time to be a doctor or a patient.

Is this a lonely club that you're in with, with Adam, Vinay, and Andrew, or is it a growing recognition of our limits as interveners? Tell me, talk about it.