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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?

#91

Post by levocardia »

trhway wrote: post #52
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) .

AM/PM glucose differences are probably going to be swamped by mundane stuff like who has a snack before treatment vs. who doesn't. Are you not supposed to eat before immunotherapy? If so, maybe (non)compliance with that requirement is what's underneath.

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

#92

Post by anthuswilliams »

owenthejumper wrote: post #62

Sicker patients get emergency treatment in the hospital in the afternoon while healthier ones in the morning in the clinic

The article is reporting on randomized clinical trials, which are not subject to this dynamic.

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

#93

Post by vlovich123 »

_qua wrote: post #65
vlovich123 wrote: post #63

Earlier quoted context omitted.

This is a fairly innocuous change the doctor should be organizing on their own to publish a pilot study. In terms of funding very little would be required since you’re just making a small adjustment to when an existing drug regimen is happening which you already isn’t a controlled factor requiring FDA oversight or anything.

Even simple studies are expensive and difficult. You need IRB approval, data collection and organization, staff to do those things. It seems simple from the outside but making it happen takes time, effort, and money which then means also applying for grants which is a process in and of itself.

If a study like this needs a complicated IRB approval or extra data collection vs what’s already being collected for health records, you’re doing it wrong and the process has become more important than the problem you’re trying to solve.

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

#94

Post by vlovich123 »

vkou wrote: post #70
vlovich123 wrote: post #64

Earlier quoted context omitted.

I agree n=1 generally isn’t enough, but something like this is easily something you ask for volunteers for as an experiment. There’s 0 risk, you’re taking the same drug. The only reason a given time is selected anyway is for administrative ease not because there’s medical requirements.

Its not easy to ask if it messes with staff scheduling.

Clearly they did it for one patient and it was a good result. Doctors and staff generally care about their patients and given there’s plausible scientific reasoning why this worked, they’d help figure out how to make staffing work for 3-5 more patients for a limited time. Additionally, positive results like this start to travel by word of mouth so if this is successful it means more funding for the hospital and more patients seeking care from them. That’s how it should work but bureaucracy of medical care is typically resistant to things like that.

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

#95

Post by tomcam »

_qua wrote: post #89
xvector wrote: post #87

Earlier quoted context omitted.

I am close with a few folks in medical research and the broken nature of the system and sheer amount of red tape has broken their dreams. It is impossible to get anything done. There is a difference between "reasonable guardrails" and suffocating progress until it's nearly impossible barring Herculean efforts by multibillion dollar entities. It cannot be understated how badly the current bureaucracy has destroyed med…

I don’t disagree but the guy below you wants to grow human shells and try head transplants.

Transplant a few heads and suddenly you never get invited to another Christmas party

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

#96

Post by phanimahesh »

finnh wrote: post #21
leereeves wrote: post #9

Earlier quoted context omitted.

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

exactly. that one clause casts doubt on all the other reasoning; randomization controls for patient selection bias but not diurnal clinic performance

It would if the clinic is a controlled setting and they can control when the nursing shift begins.

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

#97

Post by calf »

echelon wrote: post #74
ch4s3 wrote: post #54

Earlier quoted context omitted.

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.

> It’s not shameful, it’s how evidence based medicine works. Yeah, but I'll bet nothing happened as an outcome of this. No study, no communication to anyone else. That information probably just withered on the vine. I did a molecular bio undergrad and had classes with a bunch of pre-med students. They had zero interest in the science, just getting A's. They did care about appearance and money, driving cool cars, and…

"Evidence-based" is a really problematic term when it is used to protect bureaucracies and medical managerialism, rather than actually interact with scientific processes in an ethical way. Their anecdote is actually a good example of why evidence-based logic is not the end-all.

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

#98

Post by renewiltord »

_qua wrote: post #65
vlovich123 wrote: post #63

Earlier quoted context omitted.

This is a fairly innocuous change the doctor should be organizing on their own to publish a pilot study. In terms of funding very little would be required since you’re just making a small adjustment to when an existing drug regimen is happening which you already isn’t a controlled factor requiring FDA oversight or anything.

Even simple studies are expensive and difficult. You need IRB approval, data collection and organization, staff to do those things. It seems simple from the outside but making it happen takes time, effort, and money which then means also applying for grants which is a process in and of itself.

Indeed, as any ethicist worth his salt would argue: we don’t want anyone saving lives without proper approval.

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

#99

Post by raverbashing »

AbrahamParangi wrote: post #68
ch4s3 wrote: post #54

Earlier quoted context omitted.

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.

The razor to use to determine whether something is actually evidenced based under uncertainty is whether you would follow the same policy if it was your own child. There are many things that are simply uncertain and “untrue until proven otherwise” isn’t an exclusively optimal policy.

It's ok, the strongest defenders of EBM are never going to discover anything worthwhile as they get caught in a loop of "no evidence enough to test" and "no evidence for this because nobody tests it"

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

#100

Post by EricPhy »

“Let’s pretend you have very early-stage cancer. The dendritic cells are in their normal cycle of desperately presenting tumor fragments to T cells, the T-cells rightfully getting upset, activating themselves, and going off to hunt the cancer. But cancer simply shuts them down by expressing an immune blocker protein: PD-L1. In response, the T-cell mostly shuts down, wanders back to the lymphatic system, and gets a little bit more ‘exhausted’. It believes that it activated itself for no reason, and thus will require a much higher bar for doing anything else in the future. The more times this occurs, the more exhausted the T-cell becomes, the more unwilling to ever activate again. In the limit, it will simply kill itself. Hence why you need immunotherapy to revitalize these cells!”

That’s a powerful analog for depression and burnout in humans.

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