H’mm, Remdesivir may be promising . . .

_{kairosfocus

April 18, 2020

Medicine, Sci-Tech watch}

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I am seeing a report:

Gilead Science’s experimental antiviral medicine remdesivir is reportedly showing promise for the treatment of people plagued with the novel coronavirus, with nearly all patients in a closely monitored clinical trial at a Chicago hospital discharged in just days, an early assessment of data released this week revealed . . . .
STAT, a medical news outlet, first reported that an early peek at the data from the clinical trial in Chicago suggested that coronavirus patients were responding to the Gilead Science drug.
“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital, declared, according to STAT.
On Thursday, STAT revealed that the drug is prompting “rapid recoveries in fever and respiratory symptoms, with nearly all patients [at the Chicago hospital] discharged in less than a week,”

Of course, this is a leak. And of course due cautions apply. All of these developments fall under the strong reminder: pharmacology is the study of poisons in small doses. END

Comments

@JVL Under naturalism, what is the role of remdesivir? Yes, it is a drug. Synthesized by Intelligent humans. -'natural' selection? -'artificial' selection? Oh, but wait, if viruses are not alive, then the ToE can not explain the process, because it is concerned with living entities. What a conundrum.Truthfreedom_{April 19, 2020
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KF
BO’H: Actually, in many cases, Placebos “work,” such that two pills have more effect than one, also that if a patient is not told it is a placebo it has more effect and if it comes with a name-brand big pharma house label, it works better than the same sugar with no label. And more. Belief kills and belief cures. KF
Once again you are demonstrating your ignorance of how and why clinical trials are used. It is well known that the placebo effect is real. Many people, for whatever reason (hope, lowered stress...) show an improvement when they are given a placebo. These improvements, however are generally not long term. Clinical trials with placebos are used to demonstrate whether the drug has a real beneficial effect. There is nothing unethical about this process as the patients enrolled in a trial must give informed consent.Ed George_{April 19, 2020
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JVL, see the gold standard thinking? KFkairosfocus_{April 19, 2020
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Other bedside advice given to COVID19 patients
The good news is that HCQ could save your life from COVID19. The bad news is you will be proving President Trump right if you take it. The choice is yours. We can always give you a placebo. It has also been shown to work in some cases.
Liberal response: Proving Trump right is a fate worse than death. I couldn’t live with myself and face my peers. I’ll take the placebo. New breaking press stories.
HCQ seen as secret re-elect Trump strategy as liberal voters refuse treatment that would save their lives. Lowering anti-Trump votes at polls now seen as primary reason for Trump endorsement of HCQ.
And
Breaking Story: People posing as liberals give advice undermining medical advice provided by Trump administration. These stories coming from fake liberals believed by many in the anti-Trump camp. Example of “Fake News working.” Some suspect Russian influence.
jerry_{April 19, 2020
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There are also many more who are alive and got the placebo. Therefore the placebo works!
Interesting comment. Right up there with joke headline
CNN says HCQ not as safe as dying
Or
Critical Finding of Study: Statisticians Determine Placebo Don’t Kill Everyone. Conclusion: Placebos Work. To be used in all medical treatments from now on instead of drugs.
Or
Until world is sure miracle cure works, drug to be withheld from treating deadly disease. Conclusive results expected in 18 months. Placebos will remain treatment of choice
jerry_{April 19, 2020
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From The Economist: https://www.economist.com/science-and-technology/2020/04/17/is-remdesivir-the-drug-that-can-kill-the-coronavirusJVL_{April 19, 2020
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BO'H, to see where this trial may be coming from, kindly see 6 above; which is also relevant to Raoult et al. KFkairosfocus_{April 19, 2020
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BO'H: Actually, in many cases, Placebos "work," such that two pills have more effect than one, also that if a patient is not told it is a placebo it has more effect and if it comes with a name-brand big pharma house label, it works better than the same sugar with no label. And more. Belief kills and belief cures. KFkairosfocus_{April 19, 2020
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F/N: I do some headlining in a fresh OP: https://uncommondescent.com/ethics/on-scientific-methods-and-alternatives-to-the-placebo-control-is-the-gold-standard-view-in-the-face-of-pandemics/ KFkairosfocus_{April 19, 2020
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There is a control group of several thousand dead people from the virus. They got the placebo.
There are also many more who are alive and got the placebo. Therefore the placebo works!Bob O'H_{April 19, 2020
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kf @ 4 - I don't know. This was only part of the trial, so possibly it was designed as a Phase II trial, to find out what dose to use. Or it might be that there for logistical reasons, the hospital is the unit of study, so other hospitals might be the control. Either way, this information on its own is not as helpful as a full trial would be.Bob O'H_{April 19, 2020
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Jerry, you are quite correct, and your remarks point to decision theory and sustainability strategies. There is a de facto standard set of treatments tied to blocks of patients, with associated tracking results and outcomes. That is standard process, to the point that a fever chart on a clipboard attached to a bed is a stock cartoon gag. This forms the baseline and de facto benchmark or yardstick. Once one introduces an alternative, it is possible to similarly track performance then key to known demographics, once one has enough cases to reasonably span the demographics of sex, age, preconditions etc. Though, obviously the novel treatment should have a priori credibility that points to a reasonable prospect of success that makes it worth taking the human life and health risk of trying it, as well as implied financial and resource commitment costs. For instance, in vitro studies show chemical plausibility and as there are often relevant physiological similarities, animal analogues may be relevant. (BINGO: The lab(s) in Wuhan were apparently using bats as animal analogues, likely in studying corona virus treatments in the aftermath of SARS, MERS etc. We know HCQ etc were on the table since SARS. So, they may well have had background, classified knowledge on its potential that added reason to the explanation, it works on inflammation responses out of control. Remember, that is indeed a known complication leading to potentially deadly cytokine storm, which especially affects the elderly. Where, too, associated secondary bacterial infections can be a contributory factor. So, if a bat corona virus, under drugs pressure, mutates and bridges to humans then leaks into the population, we could project a pandemic possibility. That raises questions of behind the scenes batteries of tissue cultures and testing cultures of drugs and cocktails. Penicillin was discovered because a mould contaminated bacterial cultures and hindered growth in a ring. Currently, multidrug resistant bacterial strains are so common that it is a standard test to swab and culture vs an array of drug possibilities. This is leading to a tendency to prescribe double antibiotic cocktails that seem to be synergistic. Certainly, that is my experience. Indeed, there are strains that are now disinfectant resistant. No wonder soap and water, alcohols, vinegar as well as bleach are back as seriously considered sanitisers and disinfectants. At this point, I infer, the Chinese knew from their level 4 lab, that HCQ was a plausible candidate for not only anti-inflammatory but anti-viral action in vitro AND in animal analogue. Of course, explaining containment failure would be a truth/state secret/ losing face challenge.) Now, let us say we have some reason for credibility, for an alternative. This then brings up a strategic decision making, sustainability frame based on SWOT, scenario projections across world models, use of proxies or known direct metrics, and the sustainability options: Business as Usual vs Credible Alternative[s]. The issue is to consider strategic alternatives informed by empirical evidence and scenario based broad spectrum models. Such models here obviously have to consider epidemiological, economic, sociocultural, political, legal and media factors, trends and issues as well as Game theory extensions to simultaneously playing against nature and human players. Where, statistical aspects come from Monte Carlo scattershot runs, to see a plausible -- notice, not probability distribution -- pattern of possibilities, risks, opportunities, uncertainties. On situation analysis, we get an environment threat and opportunity profile, ETOP. We extend this to strengths and weaknesses profiling. A robustly sustainable strategy fits a SWOT matrix:
* build on strengths, * counter threats [here, natural and human in a highly polarised environment], * exploit opportunities [here, potential new treatments involving further research], * compensate for and where possible/ advantageous, correct weaknesses [here, need for effective broad spectrum antivirals and need to correct faulty, cumbersome drug development protocols in a world of pandemics]
To do so, one must project across integrated world models, the spectrum of plausible outcomes on BAU trends. Which leads to the cluster of expected futures. Expected, as BAU is the result of the balance of power across factions that dominate in a situation. (This is also where the Seven Mountains picture is a handy way to discuss and explain.) We then run plausible alternatives similarly, at first as games or scenario exercises, then pick best options and do additional research. From this, we have credible alternatives and may have plausibly feasible and more desirable futures. That can be identified through comparison, i.e. gap analysis. When that is identified, we may then proceed to creating change strategies to migrate to more desirable, robust, sustainable alternatives. That is, we have a framework for a change strategy, which normally implies conflict with not just nature but entrenched power factions wedded to BAU. It should be obvious, that at least elements of this framework are in play and help us "read" the situation, explaining a lot of what is playing out. Now, this brings us back to the factor that conventional placebo control studies building on in vitro and animal analogue studies are first going to take too long in the face of a fast-moving pandemic. Similarly, there are vested interests and unwelcome truths are liable to be suppressed; so, we have to be discerning and prudent. Thirdly, we have an ethical-epistemological challenge that is an embedded part of an institutionalised problematique tied to entrenched BAU, as BAU will not only take too long but pivots bon deception and on mistreating patients dealing with/facing a fast-moving, deadly epidemic. This is not a slow moving cancer where we may try A, then B then C etc. In that context the strategic change framework rationalises a case based approach. And that is precisely what Raoult et al seem to have been doing. Further, the spotlight is put on animal analogue studies. Given the significance of bats here, why is this side of the issue missing in action, especially as the ethical issues are much less intense? I suspect, this reflects factional interests and political calculation; including by the usual media suspects. Material truth is the first casualty in a war. We can draw some conclusions:
First, that there is a reasonable, responsible framework in which a Case based approach is reasonable and epistemically plausible. Second, that relevant powers and their spokesmen must be aware of that, so rhetoric about no evidence and gold standard testing is unethical, indeed deceitful. Third, that media amplifiers of agit prop lines like this [Guardian, I am looking at you] are irresponsible in the face of a serious global threat, but are obviously effective in promoting BAU and the agendas of its backers. Fourth, in the face of a global crisis, that BAU is not in the general interest of the publics in the USA, UK, France, China and beyond across the world. Fifth, that a credible cluster of potential alternatives is on the table, warranting the pursuit of SWOT-Scenario exploration, BAU vs ALT gap analysis then creation of a change strategy to more robustly sustainable strategies with sounder governance. Sixth, that a struggle to do so is in progress, with S Korea, France, Britain and the US as key theatres of operation. Seventh, that we need to rethink how we consume media offerings and how we have been led to think about even statistics etc.
So, now, let us think afresh. KFkairosfocus_{April 19, 2020
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by the sounds of it, this doesn’t have a control group eithe There is a control group of several thousand dead people from the virus. They got the placebo.jerry_{April 18, 2020
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BBO'H, you need to ask yourself why there is a case based rather than placebo based design, and why gold standard dismissive rhetoric fails ethically and epistemologically. KFkairosfocus_{April 18, 2020
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Be careful - by the sounds of it, this doesn't have a control group either. Hopefully some of the other trials have control groups.Bob O'H_{April 18, 2020
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The more the better Is it an Intravenous treatment? I believe the stock market responded to it yesterday.jerry_{April 18, 2020
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H’mm, Remdesivir may be promising . .kairosfocus_{April 18, 2020
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