4 ms·

Did anyone hear NPR's reporting on this? They said the early study was originally halted BECAUSE of it's positive effects at preventing hospitalization and deat

Did anyone hear NPR's reporting on this? They said the early study was originally halted BECAUSE of it's positive effects at preventing hospitalization and death... very weird, I hope it is a typo or I'm understanding it wrong...

pkulak 5y ago
If something proves to be too effective, too early in a trail, it's no longer ethical to give placebos to the control group.
guerrilla 5y ago
Maybe they meant that further study at that level was not necessary and they were moving on to later stage trials? In order to speed up the release I mean.
peapod91 5y ago
That’s correct. If a positive effect in the treatment arm of the study is found to be strong enough, it is deemed unethical to continue giving patients the placebo as control. Hence, they terminate the study and proceed to the next phase of approval
- orra 5y ago
  That it's unethical to continue giving half the participants a placebo makes sense. I am curious though: do they ever continue with the trial, with the patients on the actual drug? Might that be useful for monitoring rare-ish side effects, even if the drug is highly effective?
  - zerkten 5y ago
    They almost always do this as an approval requirement.
    - orra 5y ago
      Gotcha, thanks.
  - dbbk 5y ago
    I believe they've only halted recruiting for the trial, not the trial itself. The Pfizer CEO this morning also said they're continuing with plans for two other trials starting soon, which is in people with non-co-morbidities, and to household contacts of confirmed cases.
    - orra 5y ago
      Presumably they're kicking the placebo participants out? As others say, it is not ethical to give them ineffective treatment (placebo), given the effectiveness of the drug has been clearly demonstrated.
newsbinator 5y ago
When something obviously works, it's standard practice to halt the study and seek out emergency use authorization. > There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort.
paulryanrogers 5y ago
Maybe to reduce risk to the control group?
HelloMcFly 5y ago
I didn't hear the NPR story, but studies can be halted when it's shown that the treatment is so clearly effective that it becomes unethical to continue administering non-treatments/weak treatments to your comparison groups. This usually indicates that research can and should advance to the next stage immediately. Here's something to read on this (note the three criteria for a TL;DR): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024796/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024796/
mewpmewp2 5y ago
I guess halted because meaning they are confident enough to go to phase 3 with larger amount of trial participants?
TOMDM 5y ago
It's a semi common issue for highly effective novel treatments. In order to continue the study you need to keep some portion as a control group. I can't imagine wanting to keep people in the control group when the experimental treatment is so dramatically effective.
mbreese 5y ago
I haven’t read anything about this study, but this is common for highly effective treatments. Let’s say you have a randomized clinical trial with a control arm (placebo) and test arm (drug). If the vast majority of the test cases do significantly better (like 90% of the test cases), at some point it becomes unethical to continue. Why? Because you already have the evidence that the treatment works, so having the control arm becomes meaningless. You already know that the drug works, so there is no longer a point to collect more data AND you know that the control arm isn’t going to help half the patients. So, you stop the trial early so that you can get started with the approval process so that the drug can get to all patients faster.
- tmoravec 5y ago
  Pardon my naive question, but aren't there more objectives for the clinical trial? Particularly testing for negative side effects? How are those judged if the trial is discontinued?
  - maxerickson 5y ago
    Safety continues to be evaluated during Phase 3 (and after approval), but trials don't proceed to Phase 3 without establishing some reasonable baseline for safety in the earlier phases.
  - sudosysgen 5y ago
    You don't need people to actually have covid to find side effects. So you don't need sick people in your control arm.
    - CydeWeys 5y ago
      To be cleared though, both arms or the trial are people who have COVID. The control arm is not getting the drug. If there are side effects that occur in some combination with having COVID, they will find those.
  - akiselev 5y ago
    Data on the most obvious side effects are collected in the first phase which is a very small group of healthy patients who take the drug under medical supervision in increasing doses until the side effects are so bad they can't keep going. They use this data to establish safety limits for the rest of the clinical trial and continue monitoring the situation until well after the drug is approved.
deleted 5y ago
[deleted]
deleted 5y ago
[deleted]

pkulak 5y ago

If something proves to be too effective, too early in a trail, it's no longer ethical to give placebos to the control group.

guerrilla 5y ago

Maybe they meant that further study at that level was not necessary and they were moving on to later stage trials? In order to speed up the release I mean.

peapod91 5y ago

That’s correct. If a positive effect in the treatment arm of the study is found to be strong enough, it is deemed unethical to continue giving patients the placebo as control. Hence, they terminate the study and proceed to the next phase of approval

orra 5y ago
That it's unethical to continue giving half the participants a placebo makes sense. I am curious though: do they ever continue with the trial, with the patients on the actual drug? Might that be useful for monitoring rare-ish side effects, even if the drug is highly effective?
- zerkten 5y ago
  They almost always do this as an approval requirement.
  - orra 5y ago
    Gotcha, thanks.
- dbbk 5y ago
  I believe they've only halted recruiting for the trial, not the trial itself. The Pfizer CEO this morning also said they're continuing with plans for two other trials starting soon, which is in people with non-co-morbidities, and to household contacts of confirmed cases.
  - orra 5y ago
    Presumably they're kicking the placebo participants out? As others say, it is not ethical to give them ineffective treatment (placebo), given the effectiveness of the drug has been clearly demonstrated.

newsbinator 5y ago

When something obviously works, it's standard practice to halt the study and seek out emergency use authorization. > There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort.

paulryanrogers 5y ago

Maybe to reduce risk to the control group?

HelloMcFly 5y ago

I didn't hear the NPR story, but studies can be halted when it's shown that the treatment is so clearly effective that it becomes unethical to continue administering non-treatments/weak treatments to your comparison groups. This usually indicates that research can and should advance to the next stage immediately. Here's something to read on this (note the three criteria for a TL;DR): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024796/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024796/

mewpmewp2 5y ago

I guess halted because meaning they are confident enough to go to phase 3 with larger amount of trial participants?

TOMDM 5y ago

It's a semi common issue for highly effective novel treatments. In order to continue the study you need to keep some portion as a control group. I can't imagine wanting to keep people in the control group when the experimental treatment is so dramatically effective.

mbreese 5y ago

I haven’t read anything about this study, but this is common for highly effective treatments. Let’s say you have a randomized clinical trial with a control arm (placebo) and test arm (drug). If the vast majority of the test cases do significantly better (like 90% of the test cases), at some point it becomes unethical to continue. Why? Because you already have the evidence that the treatment works, so having the control arm becomes meaningless. You already know that the drug works, so there is no longer a point to collect more data AND you know that the control arm isn’t going to help half the patients. So, you stop the trial early so that you can get started with the approval process so that the drug can get to all patients faster.

tmoravec 5y ago
Pardon my naive question, but aren't there more objectives for the clinical trial? Particularly testing for negative side effects? How are those judged if the trial is discontinued?
- maxerickson 5y ago
  Safety continues to be evaluated during Phase 3 (and after approval), but trials don't proceed to Phase 3 without establishing some reasonable baseline for safety in the earlier phases.
- sudosysgen 5y ago
  You don't need people to actually have covid to find side effects. So you don't need sick people in your control arm.
  - CydeWeys 5y ago
    To be cleared though, both arms or the trial are people who have COVID. The control arm is not getting the drug. If there are side effects that occur in some combination with having COVID, they will find those.
- akiselev 5y ago
  Data on the most obvious side effects are collected in the first phase which is a very small group of healthy patients who take the drug under medical supervision in increasing doses until the side effects are so bad they can't keep going. They use this data to establish safety limits for the rest of the clinical trial and continue monitoring the situation until well after the drug is approved.

deleted 5y ago

[deleted]

deleted 5y ago

[deleted]