HomeLatest ThreadsGreatest ThreadsForums & GroupsMy SubscriptionsMy Posts
DU Home » Latest Threads » Forums & Groups » Topics » Science » Science (Group) » Clinical Improvement in C...

Thu Apr 30, 2020, 10:07 AM

Clinical Improvement in Covid Remdesivir Double Blind Study Is Not Statistically Significant.

This morning I'm seeing noise that Remdesvir is working in treating Covid patients.

Yesterday, the results of the first randomized clinical trial were published.

The results study were published yesterday in Lancet: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.

(The publication is open sourced; anyone can read it.)

Here is the summary of the findings, for convenience:

Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 123 [95% CI 087175]). 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 152 [095243]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.


A small benefit was observed, however it cannot be ruled out that this benefit derived from chance.

I wouldn't call the results "clear evidence" that this drug is a worthy treatment, unless I'm missing something.

18 replies, 718 views

Reply to this thread

Back to top Alert abuse

Always highlight: 10 newest replies | Replies posted after I mark a forum
Replies to this discussion thread
Arrow 18 replies Author Time Post
Reply Clinical Improvement in Covid Remdesivir Double Blind Study Is Not Statistically Significant. (Original post)
NNadir Apr 30 OP
secondwind Apr 30 #1
NJCher Apr 30 #3
NNadir Apr 30 #11
NJCher Apr 30 #13
NNadir Apr 30 #16
NNadir Apr 30 #5
unblock Apr 30 #2
gibraltar72 Apr 30 #4
Igel Apr 30 #14
Botany Apr 30 #6
NNadir Apr 30 #9
hlthe2b Apr 30 #7
NRaleighLiberal Apr 30 #8
NNadir Apr 30 #18
Bernardo de La Paz Apr 30 #10
drray23 Apr 30 #12
Sancho Apr 30 #15
NNadir Apr 30 #17

Response to NNadir (Original post)

Thu Apr 30, 2020, 10:09 AM

1. I understand that Gilead has ties with Kushner.. That is all we need to know

Reply to this post

Back to top Alert abuse Link here Permalink


Response to secondwind (Reply #1)

Thu Apr 30, 2020, 10:11 AM

3. yeah, but then it means

Fauci has been compromised because it was Fauci that gave this claim some credibility.

Wow, am I ever disappointed.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NJCher (Reply #3)

Thu Apr 30, 2020, 10:23 AM

11. It most assuredly does NOT mean that. The study to which I referred did not rule out...

...a clinical benefit. A small benefit was observed but what the authors said is that they could not rule out that the results were by chance. This is because the study size was too small.

Dr. Fauci may have other results beyond this study.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Reply #11)

Thu Apr 30, 2020, 11:10 AM

13. so were you aware of what Fauci said when you wrote this post?

Just curious as to why you would not point out "Dr. Fauci may have other results beyond this study" in your original post.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NJCher (Reply #13)

Thu Apr 30, 2020, 12:25 PM

16. I did not review exactly what he said, but heard it by osmosis. The news item leading to the...

...Lancet article I linked had the following headline: "COVID-19 Trial of Remdesivir Suggests It Is Not Associated With Significant Clinical Benefits, More Research Needed." It was a news item, albeit from a technical news feed.

In general, news reporting can mangle science badly, even technical news items; this is why I always refer to the original papers where possible in my writings here.

The original paper, from Lancet, did not say that the drug was proved worthless, but rather that the observed benefits might be due to chance.

I wrote my original post very quickly but I did include "unless I am missing something."

I don't think that anything implied that Dr. Fauci lacks integrity or that he's "in Gilead's pocket." If my post implied as much - I don't think it did - I have been misinterpreted, and to the extent that is my fault, I apologize.

This said, over many years of discussing science on this blog - and I'm very careful to access wherever possible original research - I have seen spectacular misinterpretations of what that research seems to imply to me.

The news item did say "More research needed."

Dr. Fauci certainly has larger access to what's going on than I do. It may be that a larger clinical trial does show significant clinical benefit. However that benefit is not the same as a cure. It may, for example, pull some people who otherwise would have died without it, back from over the edge.

If I get Covid - and I could - if offered the chance to be a subject in a double blinded clinical trial of this drug, I would take it.

Drugs are not approved solely on being a cure, but are approved as being an improvement on the "standard of care."

My career has been (gasp!) in support of the pharmaceutical industry. I've seen it all, but since I have been involved in the development of drugs that saved lives - particularly in HIV but in other areas as well - I sometimes forget that pharmaceutical companies and pharmaceutical scientists are generally held in wide contempt by the general public, and that people automatically assume the worst.

Having worked in the industry for decades, I am quite sure that not every Gilead employee agrees with Donald Rumsfeld or Kushner or any other of our many political demons. Some of them, believe it or not, are very proud of saving peoples lives I'm sure.

The development of effective medications is a very, very, very challenging field, with many ethical and financial quandaries inherent it. During the AIDS crisis, there were many people who were claiming that we were being too cautious and wanted answers and treatments NOW! NOW! NOW!

On the other hand, all medications have risks, and we need to measure them to be sure we're not killing patients with the treatments.

I hope this clarifies my position if I have been misleading.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to secondwind (Reply #1)

Thu Apr 30, 2020, 10:14 AM

5. There is a very valid scientific reason for evaluating this drug in Covid.

Antivirals of this type have successfully done what was essentially impossible before the 1990's: Treat active viral diseases.

Gilead - irrespective of who owns them - successfully developed a drug (which they did not discover, although the discoverers became rich) that cures previously untreatable Hepatitis. Whether or not Donald Rumsfeld profited as a result does not mean that the drug didn't save lives.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 10:11 AM

2. That was my first guess when I heard 15 days shortened to 11 days

That sounds like a small improvement that would take a large sample size to make statistically significant.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 10:11 AM

4. Also a nice look over there moment for Trump when he's getting pummeled.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to gibraltar72 (Reply #4)

Thu Apr 30, 2020, 11:17 AM

14. A few things.

It gives people hope. If it's hyped and hopes are dashed because they're overinflated, that's bad. But hope is often what gives a lot of people the motivation to go on--not just the will to power and control. Or the toxic-masculinity "gotta win at all costs" crap.

It's still the best way to bet for a way of reducing the death toll and severity, even after a vaccine comes out. No vaccine is 100% effective, vaccines do not reach everywhere. חי.

If this drug doesn't work, it means that we really don't understand this virus and have no idea what might work. May as well run clinic trials on the efficacy of a mega-bacon diet or sage burning or rubbing the forehead with olive oil. While being number-fenced and data-bound, I still want the trial to work.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 10:17 AM

6. On Remdesivir ... in 1,090 test cases it dropped the mortality rate from 11.6% to 8.0%

Results from the preliminary trial show remdesivir improved recovery time for coronavirus patients from 15 to 11 days. That's similar to the effect that the influenza drug Tamiflu has on flu. Tamiflu also doesn't cure patients quickly, but can reduce how long they are sick.
"Although a 31% improvement doesn't seem like a knockout 100%, it is very important proof of concept," Fauci said of remdesivir.

"What it has proven is that a drug can block this virus."

Remdesivir also may reduce the likelihood that patients will die.

"Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group," the NIAID said.

https://www.cnn.com/2020/04/29/health/gilead-sciences-remdesivir-covid-19-treatment/index.html

Reply to this post

Back to top Alert abuse Link here Permalink


Response to Botany (Reply #6)

Thu Apr 30, 2020, 10:21 AM

9. We'll see. The study to which I referred did not say the drug didn't have any effect...

...what it said is that the observed clinical effect is not statistically significant.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 10:17 AM

7. Time will tell. With more numbers treated, it may well reach statistical signficance

It surely is sufficiently clinically significant to continue the studies.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 10:21 AM

8. after working in big pharma for 25 years, I looked at the data

this AM and was reminded why they hire statisticians. Numbers can be massaged for all sorts of desired outcomes.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NRaleighLiberal (Reply #8)

Thu Apr 30, 2020, 12:44 PM

18. And that is the reason, the FDA always assembles a committee of scientists to review the data.

Many drugs are approved on split recommendations. Ultimately however, there are many unknowns and many tradeoffs.

I participated in the development of a drug in the 1990's that treated recalcitrant high blood pressure that was highly observed in people of African American descent. (Omapatrilat) It was expected to be a blockbuster and went all the way through phase III clinical trials. It was abandoned because of a subset of subjects developed angioedema that risked closing their airways.

I always wondered if more people died from strokes from not having blood pressure control than would have died from angioedema. (There were no deaths, but there were statistically significant close calls if I recall correctly.)

The drug might be approvable today if a biomarker for the angioedema side effect could have been identified, i.e. in a "personalized medicine" setting.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 10:23 AM

10. Note: STOPPED early because of adverse events 12% versus 5% in placebo. . . nt

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 11:09 AM

12. That's the impression I had as well reading this.

I am surprised at how upbeat Fauci was about it. He did say that there was not enough statistics and it would need further analysis. I think he was encouraged not by the sheer percentage of reduction in death or shortening of the outcome but rather by the fact thus may have identified a mechanism that can be exploited to make further progress.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to NNadir (Original post)

Thu Apr 30, 2020, 12:02 PM

15. Also, it appears that "adverse effects" were more than double in the Remdesivir group...

...pretty weak evidence for a minimal effect.

Reply to this post

Back to top Alert abuse Link here Permalink


Response to Sancho (Reply #15)

Thu Apr 30, 2020, 12:29 PM

17. Every drug has side effects. This one, since it acts on nucleic acid synthesis...

...should be expected to have adverse events associated with it.

In any medication, the true measure is whether the benefit outweighs the risk.

Reply to this post

Back to top Alert abuse Link here Permalink

Reply to this thread