Remdesivir II
This is, in fact, another post on Coronavirus, but it will take me a while to get to the point. To put the conclusion here, I think that it is important to get the FDA out of the way (by executive order if necessary).
The Food and Drug Act, as currently interpreted, requires the assumption that people should (generally) not be treated with pharmaceuticals which haven’t been proven to be safe and effective. The rule is first do no harm, second do no harm. This only makes sense if results with current standard of care are acceptable. In this case, they aren’t. I think there should be mass production and use of Remdesivir starting on the 5th of March, based on one case where it seems to have cured a patient overnight.
To be honest, I think it should have been approved based on evidence that it is safe (from failed efforts to treat Ebola) and evidence that it inhibits the RNA dependent RNA polymerase of the MERS Coronavirus
Obviously one case is not proof. Still more obviously a pre-clinical study of a related organism isn’t strong evidence about the novel coronavirus.
So ?
It isn’t as if the current approach is working so well, that we should stick with it until there is proof that a new approach works better.
I think the trace of information is enough that, given almost no knowledge and a very diffuse posterior, one can conclude that the expected welfare of a patient treated with Remdesivir is higher than of one not treated with Remdesivir.
At this point, the standard ethical rule that decisions should be made in the patients’ intererests would mandate use of Remdesivir
(I personally do not accept that rule)
Instead, the approach will be “slow and sure wins the race” and “better safe than sorry” and almost all patients will have to wait while a clinical trial is conducted to find if it is proven beyond reasonable doubt that they are better off with Remdesivir.
Prescribing a new pharmaceutical is, legally, like locking someone up, except the procedure is actually followed by the FDA. That is we are really protected from unproven pharmaceuticals, while many people currently presumed innocent are in jails.
This makes sense under two conditions. First that the status quo is acceptable, so that one shouldn’t run risks attempting to improve it. Second that the status quo is a stationary steady state (or approximately a steady state) so it is an available option.
The second condition is not met in this case. We can’t choose that things remain as they are. The current dynamic is one of exponential increase of Coronavirus infection.
Rather the small c conservative option is business as usual, that is we keep doing what we have been doing. I think resorting to English rather than plain Latin is a sign that new evidence has forced rethinking
(I delete a tangent on the old simple classification “Homo sapiens” and the relatively new highly technical term “modern human” introduced because the old terms “Homo sapiens” , “Homo neandrathalis”, “Homo sapiens sapiens” and “Homo sapiens neandrathalis” all asserted falsifiable hypotheses by definition and off to the ontological proof of the existence of God)
Consider an anology — Global warming. A clearly invalid argument is that we don’t know enough to decide what to do, so now we should collect more data so we can decide. This argument is made by (interested) opponents of green policy. The implicit assumption is that waiting to act until we have more information is not an irreversible decision. But of course it is. That is why the very alarming estimates of the consequences of following this crazy advice are called the “business as usual” scenario. It isn’t sticking with the status quo, because the world is changing as we debate getting warmer.
Similarly, we can’t stick with the Covid 19 status quo. We can stick to business as usual such that new treatments are allowed only when they are proven beyond reasonable doubt to be effective. Or we can consider costs and benefits in a halfway sane manner and try things as soon as we know they are safe.
Remdesivir is known to be safe, because it was used (unsuccessfully) to treat Ebola. There is good reason to hope it is effective. There is no good reason to deny sick people treatment with Remdesivir. Now.
I am glad to say that I am not the only person worried about the FDA get
ting in the way
Yes yes yes get on it.
— Robert Waldmann (@robertwaldmann) March 18, 2020
update. Thanks @pgl for this link https://www.fool.com/investing/2020/03/14/early-results-dampen-outlook-for-experimental-covi.aspx
To me the text does not correspond to the title. I note
Given the lack of available virus-attacking treatments for COVID-19, some gastrointestinal discomfort isn’t such a big deal, but elevated liver enzymes could nail remdesivir’s coffin shut.
Too early to judge
While all three experienced gastrointestinal issues, one was complaining of diarrhea before receiving remdesivir. Nothing tanks an experimental new drug faster than elevated liver enzymes, but concentrations among some patients that weren’t treated with remdesivir peaked higher than those that were.
Here I think the logic is that *given* the FDA rule of first do no harm second do no harm and third do no harm, this might delay or prevent approval of Remdesivir. It doesn’t seem close to me to suggesting that it *should* prevent use of remdesivir. Elevated liver enzymes are not typically a sign of problems with a high risk of death. Covid 19 in the elderly is a problem with a high risk of death. In any case, there isn’t much evidence that Remdesivir use is correlated with elevated liver enzymes.
Another drug to think about:
https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china
Administering an intervention to potentially millions of people based on a case study is a “really bad idea.” I get the impetus here, but there are so many examples of jumping to conclusions based on promising data that have not worked out well. The’ve either led to unintended harm, or diverted attention and effort away from interventions that actually work.
1. We don’t know what is safe for people infected with COVID-19. Assuming safety based on studies in another population is… risky.
2. I’ve not read deeply into the evidence, but it seems VERY preliminary. Maybe it will work, but maybe it won’t. The degree of its efficacy, which you’ll need an actual study to get at, is critical to know as it would tie into how stringent to make the epidemiological interventions.
If you really want to throw individual ethics out the window in favor of the greater good. You should probably support the immediate randomization of treatment in a subset of new COVID-19 cases identified next week, regardless of their consent. Making the data available daily, you could answer the efficacy question pretty quickly.
All that said, I would support the FDA basically rubber-stamping any approval from a developed nation.
Ian:
Malaria meds have also displayed some impact. We are talking Lombardy. The entire population of Lombardy is 10 million. We are talking tens of thousands in which to test a drug. They may die anyway. Why not try??? You will not force their death. They will die most likely. Let the patient decide.
My last tour, Rituxan worked with my disorder after 3-weeks of steroids with a different disorder. I argued with the doctors. I was the walking dead and you would never know I was ill.
There is no reason to take an ineffectual medicine. In a disorder where most patients have minimal symptoms, it is easy to become attracted by something that actually doesn’t work. This has happened quite frequently. Sorry, the scientific process is frustrating, but there is no substitute.
Mark:
Welcome to Angry Bear. New comments and commenters always go to moderation to weed out spam, spammers, and advertising.
Mark:
If I remember correctly, the 21st Century Cures Act allows actual usage of a new drug in trials. Am I correct?
Run75441:
If by test you mean randomized trial, then I agree with you. Try.
Ian:
You have an interesting site. I did manufacturing throughput decades ago at Ingersoll Engineers. I am guessing you are very much into manufacturing and throughput.
Back to the issue. The Chinese have reported there were several pharmaceuticals which appeared to work also and in particular drugs for malaria, Chloroquine and HydoxyChloroquine. One small clinical test in France had positive results recently as reported March 17, 2020. EN24 HydoxyChloroquine
Remdesivir appears to have worked in a limited number of cases also. An issue which we are missing is bacterial infection following viral infection. The Chinese followed up with antibiotics for Strep. The French study uses Azithromycin for treatment of the resulting pneumonia. NYT says it failed and they are sensationalistic in their reporting. The French clinical test had a success rate of 75%. They are calling for a larger load test. Italy presents an opportunity.
Gilead’s stock is up to $81 a share, The market is watching this possible treatment.
Gilead’s stock price continues to climb. Check out the conversation board and these folks have a lot of hope in this treatment apparently.
https://finance.yahoo.com/quote/GILD/community?p=GILD
https://talkingpointsmemo.com/live-blog/white-house-coronavirus-task-force-briefing
Trump told reporters that there’s a “very powerful drug” in the works that has shown “very very encouraging early results. And we’re going to be able to make that drug available almost immediately,” he said. “And that’s where the FDA has been so great. They’ve gone through the approval process. It’s been approved.”
WTF? Nothing has past phase III trials. But our lying cheerleading President just said something has.
It is my understanding that they are testing this and other drugs on current Covid-19 patients. There were three that had promising results and were being tried on more patients. As expected, better results on earlier cases before severe symptoms. Not so much improvement after severe symptoms. If there are significant results, even early in testing, it will be pushed out, this has happened for other drugs where results were dramatic. Even pushing people out of the hospital a week earlier would help.
Remdesivir has a number of downsides. It is an infusion, so it requires a hospital bed. It works moderately well for low viral loads, but not with high viral loads. It has a number of side effects, so it is not great for prophylactic use.
Hospital beds are likely to become a scarce commodity, so the ideal patient would be one already so sick as to need a hospital bed. Unfortunately, that means that they already have a high viral load, so remdesivir is only going to be of limited use.
It is being tried clinically at a number of doses and in conjunction with other drugs. It is tempting to just say just approve it for use, but that doesn’t solve the manufacturing and dosing problem. Even if it were trivial to manufacture by the firkin, there would still be the problem of who to give it to and how much.
Odds are it would simply be given to the worried wealthy and influential and do little good with regards to the spread or cure of the disease.
For some good discussion of COVID-19 from the pharmaceutical side, check out the pharma nerds at In The Pipeline at https://blogs.sciencemag.org/pipeline/