[zevets]

This is bad science. Patients schedule when they go to immunotherapy appointments. People who go in the morning are still working/doing things, where once you get _really_ sick, you end up scheduling mid-day, because its such a hassle to do anything at all.

[vhanda]

From the article -

> this paper was not a retrospective study of electronic health records, it was a randomized clinical trial, which is the gold standard. This means that we’ll be forced to immediately throw away our list of other obvious complaints against this paper. Yes, healthier patients may come in the morning more often, but randomization fixes that. Yes, patients with better support systems may come in the morning more often, but randomization fixes that. Yes, maybe morning nurses are fresher and more alert, but, again, randomization fixes that.

[leereeves]

> Yes, maybe morning nurses are fresher and more alert, but, again, randomization fixes that

How does randomization fix that?

[vibrio]

"Forced to throw away" biases is strong. If run well, RCTs surely help manage potential biases, but it does not eliminate them. The slides saw available on X-itter didn't show a Consort diagram (accounting of patient count between screening and endpoint) or the balance of patent characteristics between the arms. This seems to be a single site study, which is significant caveat IMO. The lack of substantial mechanistic explanation, and alleged study redesign mid-stream are also caveats. All that said the reported effect is very large, and I'd like to see a more detailed reporting and analysis. If the effect that size is real, it should be able to be found in some relatively quickly retrospective studies (yes, many caveats there, but that could probably provide very large numbers rapidly in support of the RCT).

[tines]

What does randomization mean in this context, and why does it fix those problems?

[gus_massa]

How many dose this treatment has? How many between them?

How many patients dropped out? (Or requested a schedule change) Do they count like live or dead?

[abhishaike]

Writer of the article here: randomization fixes most of this, but the other commenters are correct in that doesnt fully account for the clinic performance (e.g. nurse performance, which does dip during the night according to the literature). I previously thought it wasn't a major issue for clinical trials, since a separate team independent from the main ward are giving the drugs, but there isn't super strong evidence to support that. I will update the article to admit this!

This said, I am inclined to believe that this isn't a major concern for chronotherapy studies, since I haven't yet seen it being raised in any paper yet as a concern and the results seem far too strong to blame entirely on 'night nurses make more mistakes'. Fully possible that that is the case! I just am on the other side of it

[majormajor]

I always have seen mid-day appointments as also a luxury for those doing well (at least professionally/financially). If you have to go first thing in the morning, it's often because your boss wants you in relatively early and won't let you take time mid-day. If you're in a position where you can go in at 2PM and not have to sacrifice sleep to do so, that feels healthier.

Given the highly-evident strong circular nature of the body, a hypothesis that it has something to do with that seems highly likely, certainly worth following up on.

[pbhjpbhj]

Surely your boss legally has to let you attend a health appointment? Though they might not have to pay you. That seems like a very basic workers right, the sort of thing you'd have a general strike over if it didn't exist??

[JumpCrisscross]

> mid-day appointments as also a luxury for those doing well

Irrelevant to this study given randomization.

[detourdog]

I can schedule appointments whenever I want. I'm an early riser and prefer my appointments first thing in the morning.

[munchler]

The appointment schedule was randomized, so your objection is incorrect.