27 ms·

Remdesivir in adults with severe Covid-19: random, double-blind, placebo trial

51 points by garraeth 6y ago

refurb 6y ago
Punchline - "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])." That said, this morning Gilead reported that in their own pivotal trial that the drug met it's primary endpoint.[1] What we don't know is how big of an effect it was. [1]https://endpts.com/gilead-pivotal-covid-19-study-of-remdesivir-met-its-primary-endpoint/ https://endpts.com/gilead-pivotal-covid-19-study-of-remdesiv...
- air7 6y ago
  Any line that starts with "Although not statistically significant" should be automatically deleted.
  - sparkie 6y ago
    Not if you want to pump and dump a stock.
  - downerending 6y ago
    In general, yes. In an emergency when there are no other obvious better alternatives at hand, looking at results with relatively poor p-values might still be a pretty reasonable thing to do.
    - seemslegit 6y ago
      Not really.
      - QuesnayJr 6y ago
        But it doesn't mean that drug doesn't work -- it means that the sample was too small to say that it works. If the sample were 100,000, then that would mean that it doesn't work. This was around 225, which isn't tiny, but given that we are well-endowed with people dying of COVID who would rather not, it makes sense to do more testing. Which they call for.
        seemslegit 6y ago
        Didn't say it doesn't make sense to do more testing, but relaxing your reasoning standard in emergencies is a bad idea.
        tarboreus 6y ago
        They said "looking at more results," not "relax our reasoning standards."
        seemslegit 6y ago
        Yes, you should not look at any result in an emergency you wouldn't otherwise - in fact you should probably only increase scrutiny given how much incentive there is to merely get a headline with your drug mentioned as a potential covid19 cure. The OP is basically arguing for a "something must be done and this is something" reasoning.
        downerending 6y ago
        There's always "We've tried nothing, and we're all out of ideas." :-)
        seemslegit 6y ago
        Yes there is. Not having effective options against a new virus is the null hypothesis. So by all means do whatever research has promising leads but don't lower burden of proof for accepting something as clinically effective.
    - jakeogh 6y ago
      also https://news.ycombinator.com/item?id=23013667 https://news.ycombinator.com/item?id=23013667
  - im3w1l 6y ago
    Depends on how much power the study has.
  - klodolph 6y ago
    No, that go against the current standards of scientific ethics. “Not statistically significant” does not mean the effect does not exist. It means that the study provides weak evidence, but weak evidence ≠ no evidence. It tags things for further study. This is one of those cases where people get too hung up on P values. You have to look at the bigger picture; look at the entire scientific process.
    - gfodor 6y ago
      I mean, it does provide no evidence for the specific hypothesis. It may provide evidence of other hypotheses. So you're right, but you're also wrong, without making yourself more clear. Poor precision in the use of language around clinical data has been a major problem in all of this, in the press especially, where for the most part they clearly don't give a damn and just have an agenda to spin in most cases. Because of this, scientists publishing ought to try to use language that ensures their work cannot be misinterpreted. The notes in the results section here about non-statistically significant aspects to the data fail that test, since an average reader would likely walk away with a false mental model of what the data is showing. edit: my comment is wrong, i'm tired and haven't had enough coffee. the criticisms below are valid. i do have a point, but won't jam it in here.
      - klodolph 6y ago
        > I mean, it does provide no evidence for the specific hypothesis. Again, this is incorrect. It provides weak evidence, not no evidence. You talk about precise language here but you are conflating “not statistically significant” with “no evidence”. You can’t just handwave the difference between these two things.
      - jefftk 6y ago
        > it does provide no evidence for the specific hypothesis It does provide some evidence: we are more likely to see this result in a world where the hypothesis is true than a world where it is false.
        gus_massa 6y ago
  - pps43 6y ago
    What if there are 10 independent studies, all showing positive, but not statistically significant effect?
    - im3w1l 6y ago
      That's when you do a metastudy I think.
      - pps43 6y ago
        Either that, or pool the data from all studies and analyze it together, almost certainly finding a statistically significant effect.
  - scythe 6y ago
    Statistical significance is not a bright-line test. The p value reported is the probability that the observed effects occur if there are actually no effects. Notably, p is always greater than zero. In general, when less data is available, larger p values are considered more interesting, while when more data is available, p must be smaller to be interesting. In particle physics, p < 0.001 means almost nothing. In the particular quoted line, p = 0.07ish which is above the human-defined, conventional threshold of 0.05 but in this case there are almost no other useful data and so the phenomenon is interesting.
  - achenatx 6y ago
    The issue with statistical significance is that it might have a strong effect in some people and no effect in most people and statistical significance cant detect that. For example, statistically chocolate doesnt cause acne. Yet I 100% get acne from chocolate. There is enough variance in people that many things that work anecdotally cannot be proven statistically.
lykr0n 6y ago
It's ... something. and that's better then what we had.
- SiempreViernes 6y ago
  Actually, the result is that making pills out of sugar and writing Remdesivir on the box is likely the better treatment.
  - orwin 6y ago
    we don't know yet. it might hasten the recovery speed, and have not been tested with early patients.
- yonaguska 6y ago
  We have hydroxychloroquine with z-paks- which seems to be pretty much the same effect. But much much cheaper. If you treat early with it- it works, late treatment- and it's not effective.
skrowl 6y ago
Lol, it really doesn't take long to go from "Trump team mentions something" to "everyone tries their best to shit on it". There's a reason these are drug TRIALS. They're TRYING things.
- ceejayoz 6y ago
  The point to a drug trial is, in part, "to shit on it" if necessary. "It doesn't seem to work" would be an important finding, and one that has nothing to do with Trump.
bpodgursky 6y ago
Lots of legitimate questions about statistical significance, but it's strong enough that Fauci likes it[1], which tells me it can't all be bunk (given how cautious he's been about *quine): > White House health advisor Dr. Anthony Fauci said Wednesday that data from a coronavirus drug trial testing Gilead Sciences’ antiviral drug remdesivir showed “quite good news” and sets a new standard of care for Covid-19 patients. > Speaking to reporters from the White House, Fauci said he was told data from the trial showed a “clear cut positive effect in diminishing time to recover.” [1] https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-data-from-remdesivir-coronavirus-drug-trial-shows-quite-good-news.html https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-data-f...
- usaar333 6y ago
  That's from a more powered US trial, not the one in China. The argument is that Giliad basically got "unlucky" with this China one (insignificant number of patients/deaths to nullify hypothesis Remdesivir does work)
  - khuey 6y ago
    The Chinese trial got aborted early due to lack of patients as I understand it so that's not that surprising. It also means this isn't any sort of "miracle" drug though.
    - lbeltrame 6y ago
      Nevertheless, it is a drug that has shown some positive efficacy in a real trial (the NIH one, I mean). IMO this is a significant step forward. I hope other viable treatments emerge from the other trials on drugs set to close by June.
- DoofusOfDeath 6y ago
  Depending on the specifics of "time to recover", this could be pretty good news. My wife became symptomatic with COVID-19 about a month ago. For the first ~8 days, she was in pretty rough shape, although happily she didn't need hospitalization. But the pace of recovery is slower than I've seen with any flu. She still needs to significantly limit her activity or else her pulse gets high and she gets short of breath. (The effect is much greater than you'd expect from someone being bedridden for 8 days.) Each day is a little better, so hopefully she'll make a full recovery. But if I had to spitball a linear extrapolation of when she'll be back to 100%, I'd say another few weeks at the soonest. Obviously we'd rather have a drug that saves lives and/or prevents long-term disability. But if remdesivir could have hastened my wife's recovery by several weeks, our kids and my professional work would have been much better off.
isoprophlex 6y ago
Notwithstanding its effectiveness... I'm not sure if this could quickly be produced on a large scale. For those versed in organic chemistry: looks pretty complicated. Maybe someone with industry experience can guess how difficult this is to productionize on a global scale? https://en.m.wikipedia.org/wiki/File:Synthesis_of_Remdesivir.png https://en.m.wikipedia.org/wiki/File:Synthesis_of_Remdesivir...
- luizfzs 6y ago
  Yeah, from this article, it's pretty complicated and with very low yield https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-it-14665 https://www.acsh.org/news/2020/03/26/problem-remdesivir-maki...
- jbritton 6y ago
  https://www.gilead.com/purpose/advancing-global-health/covid-19/working-to-supply-remdesivir-for-covid-19 https://www.gilead.com/purpose/advancing-global-health/covid...
- akiselev 6y ago
  About a month ago Gilead said they have 1.5 million doses ready to distribute or in the last stages of production but that's only enough for ~360k courses (a course is a enough to treat one person). They said they hoped to have produced a total 1 million courses by the end of the year [1], so yeah it's not enough. [1] https://www.fiercepharma.com/manufacturing/gilead-to-donate-1-5m-doses-covid-19-hopeful-remdesivir-as-manufacturing-skyrockets https://www.fiercepharma.com/manufacturing/gilead-to-donate-...
blakesterz 6y ago
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 6y ago
  We need more investigation into clinical significance earlier into disease progression?
- djmips 6y 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 6y 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 6y 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.
drderidder 6y ago
Nobody seems to be talking much about favipiravir, which seems a bit like not-invented-here syndrome. If it stood to make a lot of money for some US big pharma company I suspect we'd be hearing more about it.
- BurningFrog 6y ago
  Studies are extremely expensive, so there either has to be a payoff for the investment, or Bill Gates has to fund it.
- pbarnes_1 6y ago
  At least this China-based RCT isn't underwritten by GILD? That's something.
- newacct583 6y ago
  It seems to me like people "talking much about" unproven drugs is the problem, and that favipiravir (and its patients) is lucky to have been spared much of that nonsense. People want to talk about this stuff because it feels like a magic bullet. Viral infections don't have magic bullets[1], they just don't. We have to beat this with elbow great: huge amounts of testing and tracing once the outbreak is at a manageable baseline, and high uptake of mitigation strategies like social distancing until it gets there. And yes, that costs a lot of money. [1] Rather: they do, but they're called vaccines and take time.
  - BurningFrog 6y ago
    Tests to prove effectiveness in FDA terms takes years. This virus is 6 months old. So, by definition, we will only have unproven drugs to use for the foreseeable future.
    - fspeech 6y ago
      Not if the effect size is large. That would be proved in no time. The problem is so far all effect sizes are small, so it will take trials with large power (and longer term) to discern any positive benefit.
jfoster 6y ago
It sounds like the patients in the study were a bit far into the illness already. Maybe lots of damage is already done and they are just having to additionally cope with the side-effects of the drug and not getting much of the benefit due to it having been started too late.
- KingOfCoders 6y ago
  Interesting points, did you read the study? Have they adressed those points?
  - jfoster 6y ago
    I haven't read the full study, so I don't know whether those have been addressed, but judging from the summary, it may not have been a consideration. I've heard of a few other studies recently where this was completely overlooked; they pick patients who are the most severe and give them the drugs. Antiviral drugs won't reverse damage that's already done.
buboard 6y ago
This is an older study which IIRC terminated early because they couldn’t rectuit enough ppl. There is newer, positive data coming out today from the ongoing study of advanced covid: https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 https://www.niaid.nih.gov/news-events/nih-clinical-trial-sho...
eli_gottlieb 6y ago
Ok, excuse me for just complaining, but this study setup seems... bad. That is, I believe the prior indication was fairly low to null that antiviral drugs would significantly help the treatment of a severe respiratory infection -- in the first place. You don't give someone Tamiflu when they have a sufficiently severe flu pneumonia and fever to be hospitalized, do you? Antivirals are usually indicated for treatment when an infection is still in its early, mild, pre-hospitalization stages. I understand that it's easier to recruit study subjects with severe COVID-19 than mild at this stage, but still, doesn't this study amount to looking for one's keys under the lamp-post because it's brighter there?
lowdest 6y ago
From a nurse in Wuhan who is a family friend: It seemed clear to her and her coworkers that Remdesivir was working when given early, but had little or no effect after the disease had progressed. My take: sounds like great news for a product, since everyone would want this on hand to catch infections early. Unfortunately it is an IV treatment and very difficult to manufacture, and is therefore unlikely to be able to fill that role. I bought a few shares anyway.
- yonaguska 6y ago
  Isn't that effectively the same result with hydroxychloroquine + z-paks?
  - deleted 6y ago
    [deleted]
  - DylanBohlender 6y ago
    Sounds like it (I've also heard of zinc being added in with HCQ and the z-pak as part of that treatment protocol, sometimes called the "Raoult protocol" and referred to hereafter as such for brevity). Both the Raoult protocol and remdesivir appear to help if used earlier in the disease progression; neither seem to do anything if the disease has progressed past a certain point. If early use is the key to efficacy (and if both demonstrate the same degree of efficacy, as it seems currently), the Raoult protocol is the only one that makes sense to scale up. The ingredients for the Raoult protocol are much more easily mass-produced and administered, whereas remdesivir is proprietary, very expensive, and IV-only (as other posters have noted).
- yumraj 6y ago
  Sounds similar to how Tamiflu works for seasonal Flu. Does remdesivir work on coronavirus in a similar fashion?
  - usaar333 6y ago
    Completely different. Tamiflu blocks influenza viruses from being released from its host cell (https://en.wikipedia.org/wiki/Neuraminidase_inhibitor https://en.wikipedia.org/wiki/Neuraminidase_inhibitor) Remdesivir interferes with viral replication itself (https://en.wikipedia.org/wiki/Remdesivir https://en.wikipedia.org/wiki/Remdesivir)
cthalupa 6y ago
Not an expert, not a doctor, etc. My barely informed interpretation and resulting take here is that: 1) This really only shows any efficacy when given shortly after the onset of symptoms 2) Remdesivir is an expensive and IV only drug that is difficult to produce in high quantities 3) The combination of the above makes this not particularly useful for treating the general population - we do not want everyone that shows mild symptoms to be rushing to the doctor for a treatment that has to be provided by a professional, and by the time we know if the symptoms will be severe and life threatening it is too late for remdesivir to be useful 4) That would seem to make it most useful for people that have known risk factors and co-morbidities to be candidates for remdesivir use. I do not know if the results are similarly promising for people that have those criteria, however. If these results hold up it's good news, but I don't know if it's great news - it seems like the factors involved here make it impractical for the large scale treatment of cv19

51 points by garraeth 6y ago

Punchline - "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])." That said, this morning Gilead reported that in their own pivotal trial that the drug met it's primary endpoint.[1] What we don't know is how big of an effect it was. [1]https://endpts.com/gilead-pivotal-covid-19-study-of-remdesivir-met-its-primary-endpoint/ https://endpts.com/gilead-pivotal-covid-19-study-of-remdesiv...

air7 6y ago
Any line that starts with "Although not statistically significant" should be automatically deleted.
- sparkie 6y ago
  Not if you want to pump and dump a stock.
- downerending 6y ago
  In general, yes. In an emergency when there are no other obvious better alternatives at hand, looking at results with relatively poor p-values might still be a pretty reasonable thing to do.
  - seemslegit 6y ago
    Not really.
    - QuesnayJr 6y ago
      But it doesn't mean that drug doesn't work -- it means that the sample was too small to say that it works. If the sample were 100,000, then that would mean that it doesn't work. This was around 225, which isn't tiny, but given that we are well-endowed with people dying of COVID who would rather not, it makes sense to do more testing. Which they call for.
      - seemslegit 6y ago
        Didn't say it doesn't make sense to do more testing, but relaxing your reasoning standard in emergencies is a bad idea.
        tarboreus 6y ago
        They said "looking at more results," not "relax our reasoning standards."
        seemslegit 6y ago
        Yes, you should not look at any result in an emergency you wouldn't otherwise - in fact you should probably only increase scrutiny given how much incentive there is to merely get a headline with your drug mentioned as a potential covid19 cure. The OP is basically arguing for a "something must be done and this is something" reasoning.
        downerending 6y ago
        There's always "We've tried nothing, and we're all out of ideas." :-)
        seemslegit 6y ago
        Yes there is. Not having effective options against a new virus is the null hypothesis. So by all means do whatever research has promising leads but don't lower burden of proof for accepting something as clinically effective.
  - jakeogh 6y ago
    also https://news.ycombinator.com/item?id=23013667 https://news.ycombinator.com/item?id=23013667
- im3w1l 6y ago
  Depends on how much power the study has.
- klodolph 6y ago
  No, that go against the current standards of scientific ethics. “Not statistically significant” does not mean the effect does not exist. It means that the study provides weak evidence, but weak evidence ≠ no evidence. It tags things for further study. This is one of those cases where people get too hung up on P values. You have to look at the bigger picture; look at the entire scientific process.
  - gfodor 6y ago
    I mean, it does provide no evidence for the specific hypothesis. It may provide evidence of other hypotheses. So you're right, but you're also wrong, without making yourself more clear. Poor precision in the use of language around clinical data has been a major problem in all of this, in the press especially, where for the most part they clearly don't give a damn and just have an agenda to spin in most cases. Because of this, scientists publishing ought to try to use language that ensures their work cannot be misinterpreted. The notes in the results section here about non-statistically significant aspects to the data fail that test, since an average reader would likely walk away with a false mental model of what the data is showing. edit: my comment is wrong, i'm tired and haven't had enough coffee. the criticisms below are valid. i do have a point, but won't jam it in here.
    - klodolph 6y ago
      > I mean, it does provide no evidence for the specific hypothesis. Again, this is incorrect. It provides weak evidence, not no evidence. You talk about precise language here but you are conflating “not statistically significant” with “no evidence”. You can’t just handwave the difference between these two things.
    - jefftk 6y ago
      > it does provide no evidence for the specific hypothesis It does provide some evidence: we are more likely to see this result in a world where the hypothesis is true than a world where it is false.
      - gus_massa 6y ago
- pps43 6y ago
  What if there are 10 independent studies, all showing positive, but not statistically significant effect?
  - im3w1l 6y ago
    That's when you do a metastudy I think.
    - pps43 6y ago
      Either that, or pool the data from all studies and analyze it together, almost certainly finding a statistically significant effect.
- scythe 6y ago
  Statistical significance is not a bright-line test. The p value reported is the probability that the observed effects occur if there are actually no effects. Notably, p is always greater than zero. In general, when less data is available, larger p values are considered more interesting, while when more data is available, p must be smaller to be interesting. In particle physics, p < 0.001 means almost nothing. In the particular quoted line, p = 0.07ish which is above the human-defined, conventional threshold of 0.05 but in this case there are almost no other useful data and so the phenomenon is interesting.
- achenatx 6y ago
  The issue with statistical significance is that it might have a strong effect in some people and no effect in most people and statistical significance cant detect that. For example, statistically chocolate doesnt cause acne. Yet I 100% get acne from chocolate. There is enough variance in people that many things that work anecdotally cannot be proven statistically.

lykr0n 6y ago

It's ... something. and that's better then what we had.

SiempreViernes 6y ago
Actually, the result is that making pills out of sugar and writing Remdesivir on the box is likely the better treatment.
- orwin 6y ago
  we don't know yet. it might hasten the recovery speed, and have not been tested with early patients.
yonaguska 6y ago
We have hydroxychloroquine with z-paks- which seems to be pretty much the same effect. But much much cheaper. If you treat early with it- it works, late treatment- and it's not effective.

skrowl 6y ago

Lol, it really doesn't take long to go from "Trump team mentions something" to "everyone tries their best to shit on it". There's a reason these are drug TRIALS. They're TRYING things.

ceejayoz 6y ago
The point to a drug trial is, in part, "to shit on it" if necessary. "It doesn't seem to work" would be an important finding, and one that has nothing to do with Trump.

bpodgursky 6y ago

Lots of legitimate questions about statistical significance, but it's strong enough that Fauci likes it[1], which tells me it can't all be bunk (given how cautious he's been about *quine): > White House health advisor Dr. Anthony Fauci said Wednesday that data from a coronavirus drug trial testing Gilead Sciences’ antiviral drug remdesivir showed “quite good news” and sets a new standard of care for Covid-19 patients. > Speaking to reporters from the White House, Fauci said he was told data from the trial showed a “clear cut positive effect in diminishing time to recover.” [1] https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-data-from-remdesivir-coronavirus-drug-trial-shows-quite-good-news.html https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-data-f...

usaar333 6y ago
That's from a more powered US trial, not the one in China. The argument is that Giliad basically got "unlucky" with this China one (insignificant number of patients/deaths to nullify hypothesis Remdesivir does work)
- khuey 6y ago
  The Chinese trial got aborted early due to lack of patients as I understand it so that's not that surprising. It also means this isn't any sort of "miracle" drug though.
  - lbeltrame 6y ago
    Nevertheless, it is a drug that has shown some positive efficacy in a real trial (the NIH one, I mean). IMO this is a significant step forward. I hope other viable treatments emerge from the other trials on drugs set to close by June.
DoofusOfDeath 6y ago
Depending on the specifics of "time to recover", this could be pretty good news. My wife became symptomatic with COVID-19 about a month ago. For the first ~8 days, she was in pretty rough shape, although happily she didn't need hospitalization. But the pace of recovery is slower than I've seen with any flu. She still needs to significantly limit her activity or else her pulse gets high and she gets short of breath. (The effect is much greater than you'd expect from someone being bedridden for 8 days.) Each day is a little better, so hopefully she'll make a full recovery. But if I had to spitball a linear extrapolation of when she'll be back to 100%, I'd say another few weeks at the soonest. Obviously we'd rather have a drug that saves lives and/or prevents long-term disability. But if remdesivir could have hastened my wife's recovery by several weeks, our kids and my professional work would have been much better off.

isoprophlex 6y ago

Notwithstanding its effectiveness... I'm not sure if this could quickly be produced on a large scale. For those versed in organic chemistry: looks pretty complicated. Maybe someone with industry experience can guess how difficult this is to productionize on a global scale? https://en.m.wikipedia.org/wiki/File:Synthesis_of_Remdesivir.png https://en.m.wikipedia.org/wiki/File:Synthesis_of_Remdesivir...

luizfzs 6y ago
Yeah, from this article, it's pretty complicated and with very low yield https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-it-14665 https://www.acsh.org/news/2020/03/26/problem-remdesivir-maki...
jbritton 6y ago
https://www.gilead.com/purpose/advancing-global-health/covid-19/working-to-supply-remdesivir-for-covid-19 https://www.gilead.com/purpose/advancing-global-health/covid...
akiselev 6y ago
About a month ago Gilead said they have 1.5 million doses ready to distribute or in the last stages of production but that's only enough for ~360k courses (a course is a enough to treat one person). They said they hoped to have produced a total 1 million courses by the end of the year [1], so yeah it's not enough. [1] https://www.fiercepharma.com/manufacturing/gilead-to-donate-1-5m-doses-covid-19-hopeful-remdesivir-as-manufacturing-skyrockets https://www.fiercepharma.com/manufacturing/gilead-to-donate-...

blakesterz 6y ago

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 6y ago
We need more investigation into clinical significance earlier into disease progression?
djmips 6y 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 6y 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 6y 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.

drderidder 6y ago

Nobody seems to be talking much about favipiravir, which seems a bit like not-invented-here syndrome. If it stood to make a lot of money for some US big pharma company I suspect we'd be hearing more about it.

BurningFrog 6y ago
Studies are extremely expensive, so there either has to be a payoff for the investment, or Bill Gates has to fund it.
pbarnes_1 6y ago
At least this China-based RCT isn't underwritten by GILD? That's something.
newacct583 6y ago
It seems to me like people "talking much about" unproven drugs is the problem, and that favipiravir (and its patients) is lucky to have been spared much of that nonsense. People want to talk about this stuff because it feels like a magic bullet. Viral infections don't have magic bullets[1], they just don't. We have to beat this with elbow great: huge amounts of testing and tracing once the outbreak is at a manageable baseline, and high uptake of mitigation strategies like social distancing until it gets there. And yes, that costs a lot of money. [1] Rather: they do, but they're called vaccines and take time.
- BurningFrog 6y ago
  Tests to prove effectiveness in FDA terms takes years. This virus is 6 months old. So, by definition, we will only have unproven drugs to use for the foreseeable future.
  - fspeech 6y ago
    Not if the effect size is large. That would be proved in no time. The problem is so far all effect sizes are small, so it will take trials with large power (and longer term) to discern any positive benefit.

jfoster 6y ago

It sounds like the patients in the study were a bit far into the illness already. Maybe lots of damage is already done and they are just having to additionally cope with the side-effects of the drug and not getting much of the benefit due to it having been started too late.

KingOfCoders 6y ago
Interesting points, did you read the study? Have they adressed those points?
- jfoster 6y ago
  I haven't read the full study, so I don't know whether those have been addressed, but judging from the summary, it may not have been a consideration. I've heard of a few other studies recently where this was completely overlooked; they pick patients who are the most severe and give them the drugs. Antiviral drugs won't reverse damage that's already done.

buboard 6y ago

This is an older study which IIRC terminated early because they couldn’t rectuit enough ppl. There is newer, positive data coming out today from the ongoing study of advanced covid: https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 https://www.niaid.nih.gov/news-events/nih-clinical-trial-sho...

eli_gottlieb 6y ago

Ok, excuse me for just complaining, but this study setup seems... bad. That is, I believe the prior indication was fairly low to null that antiviral drugs would significantly help the treatment of a severe respiratory infection -- in the first place. You don't give someone Tamiflu when they have a sufficiently severe flu pneumonia and fever to be hospitalized, do you? Antivirals are usually indicated for treatment when an infection is still in its early, mild, pre-hospitalization stages. I understand that it's easier to recruit study subjects with severe COVID-19 than mild at this stage, but still, doesn't this study amount to looking for one's keys under the lamp-post because it's brighter there?

lowdest 6y ago

From a nurse in Wuhan who is a family friend: It seemed clear to her and her coworkers that Remdesivir was working when given early, but had little or no effect after the disease had progressed. My take: sounds like great news for a product, since everyone would want this on hand to catch infections early. Unfortunately it is an IV treatment and very difficult to manufacture, and is therefore unlikely to be able to fill that role. I bought a few shares anyway.

yonaguska 6y ago
Isn't that effectively the same result with hydroxychloroquine + z-paks?
- deleted 6y ago
  [deleted]
- DylanBohlender 6y ago
  Sounds like it (I've also heard of zinc being added in with HCQ and the z-pak as part of that treatment protocol, sometimes called the "Raoult protocol" and referred to hereafter as such for brevity). Both the Raoult protocol and remdesivir appear to help if used earlier in the disease progression; neither seem to do anything if the disease has progressed past a certain point. If early use is the key to efficacy (and if both demonstrate the same degree of efficacy, as it seems currently), the Raoult protocol is the only one that makes sense to scale up. The ingredients for the Raoult protocol are much more easily mass-produced and administered, whereas remdesivir is proprietary, very expensive, and IV-only (as other posters have noted).
yumraj 6y ago
Sounds similar to how Tamiflu works for seasonal Flu. Does remdesivir work on coronavirus in a similar fashion?
- usaar333 6y ago
  Completely different. Tamiflu blocks influenza viruses from being released from its host cell (https://en.wikipedia.org/wiki/Neuraminidase_inhibitor https://en.wikipedia.org/wiki/Neuraminidase_inhibitor) Remdesivir interferes with viral replication itself (https://en.wikipedia.org/wiki/Remdesivir https://en.wikipedia.org/wiki/Remdesivir)

cthalupa 6y ago

Not an expert, not a doctor, etc. My barely informed interpretation and resulting take here is that: 1) This really only shows any efficacy when given shortly after the onset of symptoms 2) Remdesivir is an expensive and IV only drug that is difficult to produce in high quantities 3) The combination of the above makes this not particularly useful for treating the general population - we do not want everyone that shows mild symptoms to be rushing to the doctor for a treatment that has to be provided by a professional, and by the time we know if the symptoms will be severe and life threatening it is too late for remdesivir to be useful 4) That would seem to make it most useful for people that have known risk factors and co-morbidities to be candidates for remdesivir use. I do not know if the results are similarly promising for people that have those criteria, however. If these results hold up it's good news, but I don't know if it's great news - it seems like the factors involved here make it impractical for the large scale treatment of cv19