4 ms·

I honestly do not understand what the interpretation means: "In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not assoc

I honestly do not understand what the interpretation means: "In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies."

halfmatthalfcat 7y ago
We need more investigation into clinical significance earlier into disease progression?
djmips 7y ago
I interpreted this to mean that the outcomes were not improved by Remdesivir but perhaps the time to get to that outcome might have been improved (but not confirmed) which is a hospital load / economic benefit.
- mbreese 7y ago
  I believe that this is the correct interpretation. From the findings section: Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]) In other words, the patients that were going to get better, got better regardless of if they got the drug or not. However, those that got the drug got better faster than those who got the placebo (but as gfodor points out, not a statistically significant change, but a trend).
  - gfodor 7y ago
    Yeah, but it isn't statistically significant. So this claim is a statement about the data itself, not about anything beyond that. It does provide a reasonable direction for future research since it's a 'lead', but from a pure interventionary action basis, it seems to contain zero information.
    - mbreese 7y ago
      Yeah, you're right about the significance... but (just using the data they provided in the summary), it does look like a trend, which might be better fleshed out with more numbers. It does seem to at least demonstrate the safety of the drug, but I'm not sure if that was the point of this study. This was the trial with patients with severe disease, so there is still a decent amount to be learned about potential for effects earlier in treatment. But there are other ongoing studies for earlier timepoints. https://www.gilead.com/purpose/advancing-global-health/covid-19/remdesivir-clinical-trials https://www.gilead.com/purpose/advancing-global-health/covid... https://clinicaltrials.gov/ct2/show/NCT04257656 https://clinicaltrials.gov/ct2/show/NCT04257656
  - acqq 7y ago
    I am interpreting, however, "not statistically significant" as: "looking without calculating it appears it is faster, once it's calculated it turns out that appearance could be just a noise, not a real signal."
    - mbreese 7y ago
      From the limited data in the summary, it looks like the mean time to outcome (getting better) was decreased with drug treatment, but the 95% CI is pretty wide and includes "no effect" in the CI. Honestly, there isn't much data here to work with, so it's hard to know exactly what they saw. But, I believe that the last patient would have come off study a little over a week ago (from the summary and clinical trial criteria), so this is all moving very fast.
  - subsubzero 7y ago
    This sounds exactly like what tamiflu does, if you have the flu, get it prescribed early, your duration of having the flu goes from a week+ to 4-5 days. With that scenario being: taking the drug(tamiflu) very early. It is my suspicion that the earlier Remdesivir is taken the better the outcome. These patients are all somewhat late in the disease progression. So not surprised to see these results although the time to improve is a nice bonus.
seemslegit 7y ago
It means the study group was big enough to rule out benefit for those who began treatment in severe stage but not big enough to establish benefits for those who began treatment in a mild stage, which in turn indicates an upper bound to such possible benefit.
deleted 7y ago
[deleted]
andy_ppp 7y ago
I’ve just tried to write down my very clear initial understanding of this but I misunderstood. It seems we can only guess at what the authors mean from that rather unclear paragraph.
lnanek2 7y ago
It means it didn't help people who already had severe symptoms, but might help people if it is given to them earlier. This is actually quite well known when treating the flu with anti-virals. My doctor has said in previous years, if I wake up with full body ache and feel like it's the flu, come in immediately and he'll prescribe anti-virals. He said if I wait, there's no point, though. Makes sense the anti-virals might only be enough to stop viral replication if given early on before it's all over the place.
- glaugh 7y ago
  And while neither effect was found to be stat sig, the “treat earlier” group was close to stat sig (eyeballing it, it probably would have been stat sig at 90% confidence) so that’s good enough reason to try again with a larger sample size. If the effect stayed roughly similar, a larger N would lead to a smaller confidence interval that would not include a non-effect if an odds ratio of 1, and therefore be stat sig evidence of benefit. Edit: Also it looks like they didn’t find an effect overall, but if they slice the data to just those who were treated early, they’re closer to having something stat sig. Hopefully that was a pre-planned cut of the data, but either way the interpretation is still probably “Somewhat promising but needs more data.”
- zebrafish 7y ago
  And the difficulty is that RDV is only available IV, so depending on what "early" means, you would have to come in to the hospital at the first sign of symptoms.
godtoldmetodoit 7y ago
What the NAISD study and Fauci were talking about is that it accelerates time to recover (seemingly among those who were going to recover anyways), which is a big deal as that increases the hospital throughput.
zebrafish 7y ago
No effect when given in late stage severe cases. Unsure effect when given earlier in disease progression but a reduction in “days to improve” in the early administration cohort merits additional research. This happens a lot with covid drug research. Many times treatments given too late have no effect on improving outcomes. That is, if you give it too late, it cannot save you. However, there does appear to be some drugs that improve outcomes when given early in disease progression. Think of it like tamiflu. If you take it 2-3 days post onset, it works. If you take it past that timeframe, it does not work.
deleted 7y ago
[deleted]
hannob 7y ago
It means the primary outcome of the study is the drug failed their test. However they found exploratory results in the data that they think deserve further study.

halfmatthalfcat 7y ago

We need more investigation into clinical significance earlier into disease progression?

djmips 7y ago

I interpreted this to mean that the outcomes were not improved by Remdesivir but perhaps the time to get to that outcome might have been improved (but not confirmed) which is a hospital load / economic benefit.

mbreese 7y ago
I believe that this is the correct interpretation. From the findings section: Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]) In other words, the patients that were going to get better, got better regardless of if they got the drug or not. However, those that got the drug got better faster than those who got the placebo (but as gfodor points out, not a statistically significant change, but a trend).
- gfodor 7y ago
  Yeah, but it isn't statistically significant. So this claim is a statement about the data itself, not about anything beyond that. It does provide a reasonable direction for future research since it's a 'lead', but from a pure interventionary action basis, it seems to contain zero information.
  - mbreese 7y ago
    Yeah, you're right about the significance... but (just using the data they provided in the summary), it does look like a trend, which might be better fleshed out with more numbers. It does seem to at least demonstrate the safety of the drug, but I'm not sure if that was the point of this study. This was the trial with patients with severe disease, so there is still a decent amount to be learned about potential for effects earlier in treatment. But there are other ongoing studies for earlier timepoints. https://www.gilead.com/purpose/advancing-global-health/covid-19/remdesivir-clinical-trials https://www.gilead.com/purpose/advancing-global-health/covid... https://clinicaltrials.gov/ct2/show/NCT04257656 https://clinicaltrials.gov/ct2/show/NCT04257656
- acqq 7y ago
  I am interpreting, however, "not statistically significant" as: "looking without calculating it appears it is faster, once it's calculated it turns out that appearance could be just a noise, not a real signal."
  - mbreese 7y ago
    From the limited data in the summary, it looks like the mean time to outcome (getting better) was decreased with drug treatment, but the 95% CI is pretty wide and includes "no effect" in the CI. Honestly, there isn't much data here to work with, so it's hard to know exactly what they saw. But, I believe that the last patient would have come off study a little over a week ago (from the summary and clinical trial criteria), so this is all moving very fast.
- subsubzero 7y ago
  This sounds exactly like what tamiflu does, if you have the flu, get it prescribed early, your duration of having the flu goes from a week+ to 4-5 days. With that scenario being: taking the drug(tamiflu) very early. It is my suspicion that the earlier Remdesivir is taken the better the outcome. These patients are all somewhat late in the disease progression. So not surprised to see these results although the time to improve is a nice bonus.

seemslegit 7y ago

It means the study group was big enough to rule out benefit for those who began treatment in severe stage but not big enough to establish benefits for those who began treatment in a mild stage, which in turn indicates an upper bound to such possible benefit.

deleted 7y ago

[deleted]

andy_ppp 7y ago

I’ve just tried to write down my very clear initial understanding of this but I misunderstood. It seems we can only guess at what the authors mean from that rather unclear paragraph.

lnanek2 7y ago

It means it didn't help people who already had severe symptoms, but might help people if it is given to them earlier. This is actually quite well known when treating the flu with anti-virals. My doctor has said in previous years, if I wake up with full body ache and feel like it's the flu, come in immediately and he'll prescribe anti-virals. He said if I wait, there's no point, though. Makes sense the anti-virals might only be enough to stop viral replication if given early on before it's all over the place.

glaugh 7y ago
And while neither effect was found to be stat sig, the “treat earlier” group was close to stat sig (eyeballing it, it probably would have been stat sig at 90% confidence) so that’s good enough reason to try again with a larger sample size. If the effect stayed roughly similar, a larger N would lead to a smaller confidence interval that would not include a non-effect if an odds ratio of 1, and therefore be stat sig evidence of benefit. Edit: Also it looks like they didn’t find an effect overall, but if they slice the data to just those who were treated early, they’re closer to having something stat sig. Hopefully that was a pre-planned cut of the data, but either way the interpretation is still probably “Somewhat promising but needs more data.”
zebrafish 7y ago
And the difficulty is that RDV is only available IV, so depending on what "early" means, you would have to come in to the hospital at the first sign of symptoms.

godtoldmetodoit 7y ago

What the NAISD study and Fauci were talking about is that it accelerates time to recover (seemingly among those who were going to recover anyways), which is a big deal as that increases the hospital throughput.

zebrafish 7y ago

No effect when given in late stage severe cases. Unsure effect when given earlier in disease progression but a reduction in “days to improve” in the early administration cohort merits additional research. This happens a lot with covid drug research. Many times treatments given too late have no effect on improving outcomes. That is, if you give it too late, it cannot save you. However, there does appear to be some drugs that improve outcomes when given early in disease progression. Think of it like tamiflu. If you take it 2-3 days post onset, it works. If you take it past that timeframe, it does not work.

deleted 7y ago

[deleted]

hannob 7y ago

It means the primary outcome of the study is the drug failed their test. However they found exploratory results in the data that they think deserve further study.