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Administering immunotherapy in the morning seems to matter. Why?

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Re: Administering immunotherapy in the morning seems to matter. Why?

#51

Post by ajkjk »

tines wrote: post #14
ajkjk wrote: post #10

Earlier quoted context omitted.

https://en.wikipedia.org/wiki/Randomized_controlled_trial The same thing it means in every context: that (with enough samples) you can control for confounders.

Supposing that patients did better in the morning because, say, the nurses were more alert, no matter how many samples you take you'll find the patients do better in the morning. How does "more samples" help control for confounders rather than just confirm a bias?

"more samples" is not what controls for confounders. Controlling for confounders is what controls for confounders, which you can only do with enough samples that you can randomize out the effect of the confounder.

Whether or not they controlled for nurse-alertness is something you'd have to read the paper (or assume the researchers are intelligent) for.

Re: Administering immunotherapy in the morning seems to matter. Why?

#52

Post by trhway »

levocardia wrote: post #40

Hazard ratio of 0.45 seems implausibly high, especially when it's just the exact same treatment dichotomized to before/after 3pm. My money is on something other than a real circadian effect: either the result of a 'fishing expedition' in the data, or some other variable that incidentally varies by time of day. Maybe breaking randomization, leaving the drugs out for too long at room temp, etc. If you really believe th…

>some other variable that incidentally varies by time of day.

glucose level? low in the morning, and cancer likes glucose (among other effects of low glucose a cancer site would probably have lower local acidity, and the high local acidity is one of the tools used by cancer to protect and spread itself) .

Re: Administering immunotherapy in the morning seems to matter. Why?

#53

Post by tines »

ajkjk wrote: post #51
tines wrote: post #14

Earlier quoted context omitted.

Supposing that patients did better in the morning because, say, the nurses were more alert, no matter how many samples you take you'll find the patients do better in the morning. How does "more samples" help control for confounders rather than just confirm a bias?

"more samples" is not what controls for confounders. Controlling for confounders is what controls for confounders, which you can only do with enough samples that you can randomize out the effect of the confounder. Whether or not they controlled for nurse-alertness is something you'd have to read the paper (or assume the researchers are intelligent) for.

I guess I'm asking, how do you randomize out the confounder in this case.

Re: Administering immunotherapy in the morning seems to matter. Why?

#54

Post by ch4s3 »

sixo wrote: post #50
raylad wrote: post #48

My father was on chemotherapy with fludarabine, a dna base analog. The way it functions is that it is used in DNA replication, but then doesn’t work, and the daughter cells die. Typically, patients who get this drug experience a lot of adverse effects, including a highly suppressed immune system and risk of serious infections. I researched whether there was a circadian rhythm in replication of either the cancer cells…

Amazing. And shameful (for them.)

It’s not shameful, it’s how evidence based medicine works. One case is interesting but not a basis for changing a protocol by itself. Tons of things could have influenced the outcome and you need a proper study to know that.

Re: Administering immunotherapy in the morning seems to matter. Why?

#55

Post by vkou »

sixo wrote: post #50
raylad wrote: post #48

My father was on chemotherapy with fludarabine, a dna base analog. The way it functions is that it is used in DNA replication, but then doesn’t work, and the daughter cells die. Typically, patients who get this drug experience a lot of adverse effects, including a highly suppressed immune system and risk of serious infections. I researched whether there was a circadian rhythm in replication of either the cancer cells…

Amazing. And shameful (for them.)

> And shameful (for them.)

1. A single positive outcome with N=1 should generally not be the basis for making a medical recommendation.

2. It takes a mountain of research work to go from that to a study that you can draw meaningful conclusions from.

3. The hospital is not in the business of doing research, it's in the business of treating patients.

Re: Administering immunotherapy in the morning seems to matter. Why?

#56

Post by ajkjk »

tines wrote: post #53
ajkjk wrote: post #51

Earlier quoted context omitted.

"more samples" is not what controls for confounders. Controlling for confounders is what controls for confounders, which you can only do with enough samples that you can randomize out the effect of the confounder. Whether or not they controlled for nurse-alertness is something you'd have to read the paper (or assume the researchers are intelligent) for.

I guess I'm asking, how do you randomize out the confounder in this case.

I imagine that that particular confounder is not possible to eliminate via randomization. Perhaps you collect a bunch of data on nurse awakeness--day shift vs night-shift, measuring alertness somehow, or measuring them on other activities known to be influenced by alertness--and then ensure your results don't correlate with that.

There is also the mechanistic side: if you have lots of plausible mechanism for what's going on, and you can detect indicators for it that don't seem to correlate with nurse alertness, that's a vote against it mattering. Same if you have of lots of expertise on the ground and they can attest that nurse alertness doesn't seem to have an affect. There are lots of ways, basically, to reach pretty good confidence about that, but they might not be as rigorous as randomized assignments can be.

Re: Administering immunotherapy in the morning seems to matter. Why?

#58

Post by gus_massa »

vhanda wrote: post #3
zevets wrote: post #2

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.

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 m…

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?

Re: Administering immunotherapy in the morning seems to matter. Why?

#59

Post by wyldfire »

ch4s3 wrote: post #54
sixo wrote: post #50

Earlier quoted context omitted.

Amazing. And shameful (for them.)

It’s not shameful, it’s how evidence based medicine works. One case is interesting but not a basis for changing a protocol by itself. Tons of things could have influenced the outcome and you need a proper study to know that.

Though it could certainly inspire such a study.

Re: Administering immunotherapy in the morning seems to matter. Why?

#60

Post by tilne »

vkou wrote: post #55
sixo wrote: post #50

Earlier quoted context omitted.

Amazing. And shameful (for them.)

> And shameful (for them.) 1. A single positive outcome with N=1 should generally not be the basis for making a medical recommendation. 2. It takes a mountain of research work to go from that to a study that you can draw meaningful conclusions from. 3. The hospital is not in the business of doing research, it's in the business of treating patients.

Regarding 3: Shouldn’t the medical system be optimizing for patient outcomes rather than the business their in?

Regarding the first two: I think the anecdote being from 1995 suggests there would have been time to put together said mountain of research.

I’m not agreeing that this is shameful for the original doctor, but I do think it’s shameful if avenues for potential research are not taken because it’s inconvenient for the hospitals.

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