Remdesivir 6
Bad news from China. There was not a statistically significant benefit for patients with severe Covid 19 in the large Chinese controlled trial of Remdesivir for patients with severe Covid 19. The death rate was actually a tiny bit higher in the treated group.
As a long time Remdesivirenthusast, I feel I have to note this result here. Now I will go off and cry.
OK also be stubborn. One argument is that the treatment was given too late when autoimmunity not viral replication was the main problem. A counterargument is that the trial of treatemnt for patients with moderate Covid was suspended and one suspects not with promising data.
Another argument is that the better end of the 95% confidence interval of the estimate of the relative hazard of improvement (mostly needed less extreme oxygen therapy) is 1.75 which is high. Part of the dismay is due to the error of considering failure to reject evidence in facor of the null. Priors should be updated with the likelihood and roughly in the direction of the point estimate. Here, as usual, there is a problem with treating current regulations as the scientific method. This is not as bad as looking only at the most pleasing part of a 95% interval, as I just did. I couldn’t resist.
On the other hand note the (slightly statistically insignificantly) worse death rate for the treated group.
But all in all a horrible disappointment (there were warning signs including the premature end of the trial)
Gilead, of course, contests the Statnews interpretation. They note that due to trouble recruiting patients the power of the test was low (my point above). They note there was (statistically insignificant) evidence that it helped. Needless to sau, they are even more biased than I am.
https://edition.cnn.com/2020/04/23/health/remdesivir-trial-gilead-premature/index.html
update: Again someone who might be biasd pro remdesivir, but definitely interesting.
Frederick Hayden, an infectious disease expert at the University of Virginia School of Medicine who helped the Chinese doctors conduct the study, disputed the characterisation that the study had failed.
“That is not correct,” Hayden said in an interview, when asked whether the results showed remdesivir had flopped. “My interpretation of them is not consistent with that headline.”
[skip]
Hayden said there was a mistake in the original manuscript and that it had since been revised. He said that the study was under review at a journal, which he would not identify. and that the authors were still waiting for page proofs. He declined further comment or elaborate until the study was published.
I want to believe that the mistake was saying that Remdesivir didn’t show ntiviral activity based in RT PCR
FWIW, the U of C had a promising experience with the drug but without a control group.
Jack:
I do not know why it failed. Supposedly it mimics COVID and COVID replicates it. I am not sure if it is also a gateway drug like hydroxychloroquine which then uses Zinc as the inhibitor which gains entry to the cells because of the hydroxychloroquine.
Right now remdesivir is a bunch of anecdotes and a lot of hope versus the results of some not all that great (small N, unclear endpoints, recruitment issues, bad controls, other stuff) clinical trials. In other words, it has been like developing a new drug for any disease. I follow the process over at In The Pipeline which is written by a drug development chemist and has commenters who have been through all this before which accounts for a lot of the black humor. The fact is that most clinical trials fail and not because the medical field has ridiculous standards. Promising drugs in development rarely live up to their promise. If software development had been like that, I would have shot myself. I have no idea of how these people keep working. I suppose it is the occasional success that keeps the industry going.
(e.g. AIDS appeared on medical radar in 1980, but the first drug, AZT, didn’t come out until 1987. Granted, it is easier to avoid sex and blood transfusions than breathing. Still, 40 years later, AIDS is now a chronic disease, like diabetes, in developed countries and has been for a good while.)
What Gilead wrote:
We regret that the WHO prematurely posted information regarding the study, which has since been removed. The investigators in this study did not provide permission for publication of results. Furthermore, we believe the post included inappropriate characterizations of the study. Importantly, because this study was terminated early due to low enrollment, it was underpowered to enable statistically meaningful conclusions. As such, the study results are inconclusive, though trends in the data suggest a potential benefit for remdesivir, particularly among patients treated early in disease. We understand the available data have been submitted for peer-reviewed publication, which will provide more detailed information from this study in the near future.
There are multiple ongoing Phase 3 studies that are designed to provide the additional data needed to determine the potential for remdesivir as a treatment for COVID-19. These studies will help inform whom to treat, when to treat and how long to treat with remdesivir. The studies are either fully enrolled for the primary analysis or on track to fully enroll in the near future.
pgl:
Funny how Gilead is plagued with leaks. The U of Chicago study which appears to be successful was leaked to “STAT.” An actual copy of a conference video turned up at the authors of the STAT article. This was ~ 1 week before the apparent release of info at WHO concerning China. The same two reporters at “STAT” also reported on the China/WHO issues of an early release. Chicago had success and China did not. I would be worried about why? more than the releases. I would also be concerned with Gilead’s inability to control its internal information. The information comes from “In the Pipeline” blog.
Interesting little paper; “Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture” from “2010.” The issue here is how does zinc get into a cell unless it is associated with a gateway drug such as Hydroxychloroquine or the harsher variety Chloroquine. On Angry Bear on one of Robert’s posts, one person from France (now in the US) has pointed to success in southern France using hydro and another AZT(?). Another person has provided links to how a combo of hydro and zinc would work.
COVID 19 will kill the elderly more likely than the younger set. People and a Swedish micro expert also of the WHO is promoting the herd immunity approach. In other words we advise you not to socialize, wear a mask, you can associate with groups up to 50, and practice social distancing. Protect the elderly as they are the weaker set. What he does not tell you is the impact of getting COVID 19 besides death. Those who get it and if it progresses will suffer lung capacity issues which will limit your ability to be a normal person. In Sweden, it is your choice . . .
Others far more knowledgeable in medicine or microbiology may differ with my healthcare supply/pharma manufacturing -layman’s commentary or opinion.
It appears neither of these two drugs will help those extensively and further along in their affliction. The two drugs must be administered early-on. Anecdotally, the hydro-zinc potion worked on my neighbor’s father with no casting of the bones. Meanwhile medical research moves along at a glacial pace and arguing along the way, deciding who will receive the real stuff and who will receive a saline solution, and there is no motivation being applied by the Whitehouse “loon” other than dumb ass remarks. If we had a real president or “I ruled the world,” this project could be as serious as the race to get a man in outer space. Kennedy seem to understand the necessity to sponsor such a program, the loon does not.
Meanwhile #2, we are arguing the politics of it.
Run,
How do you know the ” hydro-zinc potion worked”?