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H’mm, Remdesivir may be promising . . .

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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

47 Replies to “H’mm, Remdesivir may be promising . . .

  1. 1
    kairosfocus says:

    H’mm, Remdesivir may be promising . .

  2. 2
    jerry says:

    The more the better

    Is it an Intravenous treatment? I believe the stock market responded to it yesterday.

  3. 3
    Bob O'H says:

    Be careful – by the sounds of it, this doesn’t have a control group either. Hopefully some of the other trials have control groups.

  4. 4
    kairosfocus says:

    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. KF

  5. 5
    jerry says:

    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.

  6. 6
    kairosfocus says:

    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.

    KF

  7. 7
    Bob O'H says:

    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.

  8. 8
    Bob O'H says:

    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!

  9. 9
  10. 10
    kairosfocus says:

    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

  11. 11
    kairosfocus says:

    BO’H, to see where this trial may be coming from, kindly see 6 above; which is also relevant to Raoult et al. KF

  12. 12
  13. 13
    jerry says:

    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

  14. 14
    jerry says:

    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.

  15. 15
    kairosfocus says:

    JVL, see the gold standard thinking? KF

  16. 16
    Ed George says:

    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.

  17. 17
    Truthfreedom says:

    @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.

  18. 18
    jerry says:

    Zelenko is up to 1450 C19 patients and only 2 dying. One from cancer.

  19. 19
    jerry says:

    There is nothing unethical about this process as the patients enrolled in a trial must give informed consent.

    Do you think anyone would sign up if they were specifically told there is a much higher chance of dying if they got the placebo?

    I think you should read my sarcastic comments from above. Actually we are witnessing a new standard for ignorance and cynicism. Thank you for validating that assessment.

    The campaign against the drug is working with Democrats as only 18% say they would take it. Already New York City area and Los Angeles have lost nearly 20,000 anti-Trump voters.

  20. 20
    Truthfreedom says:

    @19 Jerry

    Do you think anyone would sign up if they were specifically told there is a much higher chance of dying if they got the placebo?

    Remember that under naturalism, we have no free will, so ‘informed consent’ is an oxymoron.
    Naturalism = non-sense.

  21. 21
    kairosfocus says:

    EG, really! I cited some typical results from using placebos — “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.” — then gave a quick and dirty summary — “belief kills and belief cures” — and you take that as proving my ignorance of the placebo effect. That tells me all I need to know. KF

    PS: For the information of the serious-minded, here is some of what I am summarising:

    . . . That placebos work is well documented. Aaron Carroll has summarized the placebo effect of fake surgeries. Austin Frakt gives additional examples taken from David Newman’s book, Hippocrates’ Shadow:

    Taking two placebo pills (e.g., sugar pills) relieves more pain or provides a greater stimulative effect or is more sedating or heals stomach ulcers more quickly (depending on the study) than taking just one.
    Placebo pills with a brand name printed on them are more effective at pain reduction than the same pills without the brand name.
    Patients who faithfully take placebo medication for cholesterol reduction survive longer than those who skip doses.
    Though sham acupuncture reduces migraines as much as real acupuncture, both reduce migraines far more than no treatment at all.
    Measurements of increased endorphins — our bodies’ natural pain relievers — have been associated with placebos’ ability to reduce pain.

  22. 22
    Ed George says:

    KF

    … and you take that as proving my ignorance of the placebo effect. That tells me all I need to know. KF

    No, I said that you were demonstrating your ignorance of how and why clinical trials are important. You haven’t said anything to disprove this.

  23. 23
    kairosfocus says:

    EG, You are still refusing to acknowledge that valid clinical trials don’t just come in the form, placebo controlled trials. This is the gold standard fallacy, using one type of evidence to try to disqualify other legitimate forms. While I take your point, you are making the same error Guardian did and which I pointed out already. FYI, control designs for experiments are a legitimate form, but they can run into serious ethical trouble with human subjects under certain circumstances. When that is compounded by insisting on using such studies to disqualify other evidence, that is selective hyperskepticism. Here, in the face of a fast moving deadly pandemic. KF

  24. 24
    kairosfocus says:

    EG, Let me take the exchange in steps, so we can fully clear accounts:

    BO’H, 8: >> . . . There are also many more who are alive and got the placebo. Therefore the placebo works!>>

    KF, 10: >>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.>>

    –> Notice, at 9, I pointed to a discussion: https://uncommondescent.com/ethics/on-scientific-methods-and-alternatives-to-the-placebo-control-is-the-gold-standard-view-in-the-face-of-pandemics/

    EG, 16: Quotes 10 [not 9], then comments >>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.>>

    — Note, unresponsive to a discussion on why there are legitimate concerns on the ethics of Placebo trials in certain cases, and to why there is a further concern, that we recognise that there are many alternative ways to garner valid and credible clinical evidence. (NB: Cf here on clinical trial design)

    — I think this is what confused me.

    >> Clinical trials with placebos are used to demonstrate whether the drug has a real beneficial effect.>>

    — No one said they are not so used. Concerns exist on their limitations requiring elaboration, there are concerns about ethics of deception of patients [how “hope” and faith arise as is manifested in some details of their impact such as brand or 2 vs 1 pills or how ignorance of lack of activity enhances effect, etc]

    — Similarly, the gold standard fallacy forgets, there’s more than one way to skin a catfish. That is, there are other legitimate ways to garner evidence of effectiveness, which in context is how Prof Raoult’s study of 2759 patients and counting etc garnered official approval of protocol in France.

    — Let me remind [courtesy Google Translate], as there has been unresponsiveness to that official approval:

    Research protocol approved by the ANSM [= “Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM)”, i.e. National Agency for the Safety of Medicines and Health Products] and the Île-de-France CPP [= “COMITE DE PROTECTION DES PERSONNES ILE DE FRANCE,” i.e. ILE DE FRANCE PERSONAL PROTECTION COMMITTEE] in progress at the IHU Méditerranée Infection: Treatment of respiratory infections with Coronavirus SARS-Cov2 by hydroxychloroquine Acronym: SARS-CoV2quine.”

    >>There is nothing unethical about this process as the patients enrolled in a trial must give informed consent>>

    — On the contrary, deception is manifest in the use of ineffective materials such that people have hope of success in the face of a deadly disease while a significant number are exposed further to a fast moving deadly disease without credible treatment.

    — Such is compounded by and reinforces the gold standard fallacy that imagines there is no credible alternative. In effect, some must unknowingly risk serious harm or death in this case in the wider hope that we can certify a drug as passing the alleged gold standard.

    — Meanwhile, we suppress, dismiss or ignore other reasonable means of garnering evidence.

    KF

  25. 25
    Bob O'H says:

    kf @ 24 –

    — Note, unresponsive to a discussion on why there are legitimate concerns on the ethics of Placebo trials in certain cases, and to why there is a further concern, that we recognise that there are many alternative ways to garner valid and credible clinical evidence. (NB: Cf here on clinical trial design)

    When you gave some links to these concerns, I read them. The main concerns were over giving placebos when there is already a standard treatment.

    As far as alternatives go, you still need to make a comparison between with and without your treatment, and the alternative methods have lower power or are liable to have bias. So you either delay getting a decision (because you need to generate more data) or you produce results which are worthless because of biases that can’t be corrected.

  26. 26
    kairosfocus says:

    BO’H, kindly read here on https://uncommondescent.com/ethics/on-scientific-methods-and-alternatives-to-the-placebo-control-is-the-gold-standard-view-in-the-face-of-pandemics/#comment-699045 to Jerry and Ortho. There is a de facto, near business as usual baseline here [flu with complications as modified], with a clear pattern of results. Thus, DR et al are perfectly in order to explore a credible alternative without resort to ineffective placebos given to patients facing a fast moving deadly disease. KF

  27. 27
    kairosfocus says:

    PS: Let me excerpt and comment on an article that may help clarify my concerns, using an example from an actual study:

    >> . . . some examples of PCTs [= Placebo controlled trials] have triggered serious concerns about their use.>>

    — What kind of concerns? Lessee . . .

    >> For example, in 1996, a patient was enrolled in a clinical trial for Parkinson’s disease which involved injection of embryonic cells into the brain. Prior to study participation, the subject was aware of the possibility of being allotted to the control group. A year after the study’s termination, the subject found that he had not received any beneficial treatment for his disease.>>

    — Ethical concerns, on do no harm, for one.

    — Epistemological and logical concerns may also be relevant. As we can see . . .

    >>During his neurosurgery, there were no embryonic cells injected into his brain since he was randomized to the control group.>>

    — Here, we have neurosurgery performed, with implications of the risks of surgery

    — Having gone through all the rituals, costumes and staging of surgery, deliberately ineffective surgery was performed

    >> In this trial, out of 40 study participants only 20 patients received actual treatment.{9}>>

    — The treatment, itself, was ethically questionable [as in, abortion issues etc as we may recall from the debates and outcomes on pluripotent adult stem cells etc]

    — More directly, half the patients were not given any significantly credible treatment while being exposed to significant risk of harm

    — Already, a fortiori, what should we say of health care professionals and researchers charged to “first do no harm” who are contemplating giving sugar pills or the equivalent to patients suffering from a fast-moving deadly, highly contagious disease?

    — And yet more, are using such contemplations to belittle, deride and dismiss trials approved by regulatory agencies in France that are showing evidently significant results, through the gold standard fallacy . . .

    >>In the above example, it is clear that those 20 unfortunate Parkinson’s disease patients in the control group would have hoped and expected to receive some kind of treatment.>>

    — meaning, some kind of promising treatment, not known ineffective treatments, never mind that the injections would have been labelled so the surgeons, nurses etc could not tell the difference. SOMEBODY did know, and the health care and research people involved were compromising the first do no harm principle of professionalism.

    — this brings out the irreducible element of deception and exposure to unacceptable risk of harm by deliberately useless treatment.

    >> This situation raises several questions: In general, under which medical conditions and circumstances are the use of placebos acceptable in clinical trials, and what are the physicians’ responsibilities in this regard?>>

    — indeed, and those questions directly apply to our circumstances.

    >> Further, in a new interventional treatment trial of critical illnesses or irreversible diseases, should a placebo arm be considered as a part of treatment?{9}>>

    — Here, we come to a truly core question.

    — In our situation, we face pandemic with a disease known to kill within a matter of days. In addition, it damages lungs and credibly heart, kidneys, while opening the way for secondary infections etc that may do much wider damage as well as potentially triggering catastrophic immune system over-reactions.

    — It should be manifest that in that situation, the baseline is a modified flu with complications approach. Hence, the debates on ventilators and testing, etc. That is in place globally.

    — The issue is, there are no generally approved antivirals and cocktails etc. However, there are drugs that are known anti-inflammatories, anti-bacterials, and at least in vitro antivirals with some significant clinical track record of success. So, there is a serious candidate alternative.

    — In this context, for cause, I cannot see why that evidence is belittled and dismissed i/l/o the gold standard fallacy. Including, that regulatory agency approved trials and results are being dismissed because they fail to include placebos.

    — That is why I think something is seriously wrong and needs to be faced and fixed.

    KF

  28. 28
    Bob O'H says:

    kf @ 26 – I read that link. It doesn’t seem to relate to the necessity of being able to make a comparison. The resat of your comment seems to make the point that some people have not been treated with HCQ, so a comparison could be made. But it doesn’t discuss any problems with the detail, e.g. differences between the two groups that are not due to HCQ (e.g. they may be different populations, or other aspects of care might be different) and might have an effect on outcome.

  29. 29
    kairosfocus says:

    F/N2: Let’s do a bit of tea-blend component extraction, on the assumption that in the other thread the IPHM/IHU number is a blend of those treated specially and those getting the near-BAU flu with possible complications baseline.

    Now, 4420 – 2759 = 1661, and 85 – 11 = 74, so 74/1661 = 4.46 % deaths. That would make the 0.399% rate for the alternative treatment group even more dramatically different, a better than 10:1 ratio.

    However, there may be self-selection. Perhaps, younger, more adventurous and hopeful people opted for alternative treatment, or the like? Leaving older, more prone to die people on the n-BAU list? Or, the like?

    Does that reduce the credibility to nil?

    No, as even with that as a possible defeater for averaging, in the other thread — this one SHOULD be about Remdesivir, but at UD objections are often cross-threaded — we have tracking charts showing proportions clearing up after X-days of n-BAU, HCL only, Cocktail. Also, we know that as would be typical, DR’s treatment group deaths are biased to the elderly, which is what is expected.

    Where,too, let us recall, mere objection does not remove the mutual reinforcement of components of a composite, accumulative case. HCL is longstanding as reasonably safe and as an anti-inflammatory, implying it gets into the body and is active in tissues and cells etc. In vitro in relevant concentrations it somehow attacks corona viruses etc, including SARS-2 and SARS-1. We have the overall statistics and have extracted the groups somewhat. Where, too, a full disclosure placebo study group would be subject to the same questions of self-selection bias, given presumed willingness to be taking sugar pills or the like in the face of a fast-acting potentially deadly plague. The objections on self-selection bias cancel out.

    What is left, is to study the day by day clearing statistics. These show the n-BAU baseline hardly has people clearing within 6 or so days, with maybe some relapsing. The HCL only group has up to 40% clearing, while the cocktail group clears in 5 – 6 days. That suggests, strongly, that it is not natural immunity that is at work and that hitting secondary bacterial infections in parallel is synergistic. Where the multiple, time tracked data points across three blocks indicates that this is unlikely to be a mere artifact of chance or a matter of luck of the draw causing the most likely to recover very fast to be in the cocktail group or the HCL only group, with the cocktail group being even more unusual.

    Such synergises with the known in vitro result at plausible somatic concentrations and with the known ability of HCL to act in the body, its tissues and cells. Indeed, we have various candidate mechanisms, several of which may be acting in concert.

    In that context, it seems clear that we need to take the 80 patient and near 3000 patient results seriously instead of belittling and dismissing them through a gold standard test fallacy. Which is what is going on in the teeth of for instance, two tiers of FDA emergency use approval.

    KF

  30. 30
    Bob O'H says:

    kf @ 27 –

    >>In the above example, it is clear that those 20 unfortunate Parkinson’s disease patients in the control group would have hoped and expected to receive some kind of treatment.>>

    Indeed, but a basic standard of RCTs is informed consent. if the trial was run to the standard, they would have been told that this was an experimental treatment, and that they might have ended up in either arm of the trial. If they had decided that they didn’t want to take part, they could have declined.

  31. 31
    kairosfocus says:

    BO’H, you will see my further note just now, which specifically anticipates and discusses such objections. They do not undermine a cumulative case: short, weak fibres twist together to form long strands which lock through counter twisting to form a long, strong rope . Pardon, but I do need to sleep, for the clarity of my head and good of my blood pressure if nothing else. KF

  32. 32
    kairosfocus says:

    BO’H: It seems clear that you fail to see the obvious objection and its ethical seriousness. No, signing a consent form in no way can justify deception, manipulation of expectations and exposure to serious degradation of health or loss of life. In fact, the very presence of manipulation undermines claims of informed consent. It matters not, the specific words used, the circumstances create the sorts of issues mentioned, and more. Let us do harm that good may come simply does not work. If you are blind to that, I cannot help you further. But the next point remains, that there are alternatives that produce credible evidence which should not be belittled and dismissed through a gold standard test fallacy. I am reminded of Hitler’s reaction to seeing a roughly finished, captured T-34: it couldn’t be any good as it was not up to the standards of German engineering and workmanship . . . and indeed, they were rather crude. But in fact, where precision was needed, it was there and it was more than good enough. KF

  33. 33
    Bob O'H says:

    No, signing a consent form in no way can justify deception, manipulation of expectations and exposure to serious degradation of health or loss of life

    Where’s the deception? The people who enter the trial know they might or might not get a treatment.

    But the next point remains, that there are alternatives that produce credible evidence which should not be belittled and dismissed through a gold standard test fallacy.

    Yes, but the alternatives still rely on having groups with an without the treatment. It’s just that they need more in each group. So if the treatment is effective, then even more people are denied an effective treatment. if it’s not effective, then even more people are subjected to a treatment that doesn’t work, and can (and in the case of HCQ does) have side effects.

  34. 34
    kairosfocus says:

    BO’H: does the term, fine print mean anything to you? Does, the concept, that non-verbal circumstances shape and may dominate meaning? Does the very nature of placebo action, that one has faith in the treatment and the one doing the treatment in order to trigger psycho-somatic effects not tell you something? In that context, lo and behold, you are still refusing to acknowledge that there is a body of evidence that cumulatively points to HCL esp with a cocktail, being reasonably credibly effective. Why is that? Precisely because of the impact of the gold standard fallacy. KF

    PS: As to the attempted comeback, oh more people need to be tested to be credible, first there is a world of difference between what obtains naturally and what obtains by our deliberate, morally governed action. Second, you are dismissing the cumulative evidence principle. Then, the disease had to be recognised and in that process, nBAU, an adjusted Flu with complications treatment would be applied. Statistics naturally come from case records. A Corona virus was identified, SARS2. This raised the question of known in vitro effective action and subsequent off label use. As I noted but you have not interacted with, animal analogue studies are another level of evidence [with much less restrictive ethical issues], and indeed the very presence of bats is significant here. So, the obvious setup that allows ranking of performance emerges, through n-BAU vs credible alternatives. In that general context, we have research under approved protocols . . . you haven’t even acknowledged that much . . . which has yielded results that are indicative of effective action. So we see a natural nBAU, access to credible alternatives, reasonable protocols and accumulating results. Only, to consistently meet the Gold Standard trial fallacy. To that, I retort, there’s more than one way to skin a catfish.

  35. 35
    Truthfreedom says:

    @32 Kairosfocus

    No, signing a consent form

    Now our naturalist friends explain how you can sign a consent form with the appearance of free will.
    Oh, wait. 🙂

  36. 36
    jerry says:

    It seems clear that you fail to see the obvious objection and its ethical seriousness.

    No, the objections must be coming from some other motivation than seeking the truth. Nobody with education could fail to see the obvious. But similar objections are coming from all over the world. That is the real crisis in our d.ay. There are a lot of fellow travelers that are raising similar nonsense.

    Evidence and reasoning will have no effect. There is something internal that prevents admitting the obvious. They know the truth but reject it outwardly. That is what we are witnessing.

    And the irony is that some will refer to the obvious as ignorance.

  37. 37
    Truthfreedom says:

    ___

    Another big disadvantage of the RCT supremacy is the gap – i.e., loss of time and information – between research and practice, as illustrated by the ‘pipeline fallacy’ metaphor. In short, RCT may be the gold standard of study design in (bio) medical research,
    but it is often not feasible, ethical, or generalizable in the context of practice-based or practically-oriented research. In recent years, the appreciation and use of alternative research designs and data sources
    – that will overcome the disadvantages and limitations of RCTs – have increased.
    https://dare.uva.nl/search?identifier=d0af45af-27c4-40a5-9b91-32fc780eb1bf

    I’d recommend more real philosophy to our naturalist friends.
    Have a rested sleep, Kairosfocus. 🙂

  38. 38
    jerry says:

    A relevant tweet

    The cost of politicizing a disease is that it locks one into a position. In fact dealing with an epidemic is an exercise in adaptability

  39. 39
    kairosfocus says:

    Jerry,

    it has not escaped my attention that we are in the midst of the worst, ongoing, holocaust in history. We are killing our living posterity in the womb at up to a million further victims per week; which makes the global panic over a disease that in several months has killed about 1/8 of that, sound like making an uproar over a relatively minor event.

    To sustain that holocaust, our seven mountain institutions have been corrupted, especially media, education and government. Part of that has been the effect of indoctrination in evolutionary materialist scientism and/or fellow travellers, which we know is self-referentially incoherent, undermining of rationality and utterly wanting in ability to bridge IS and OUGHT in the roots of reality.

    For 2360 years, Plato has been on record as to consequences, evidently i/l/o impacts of the Athenian Plague from 430 on: rise of manipulative, amoral factions leading to moral ruin and shipwreck. All of this adds up, and so we are seeing yet another warning sign.

    Yes, we cannot escape first duties of reason, but we can end up in a self-referentially incoherent manipulative chaos with balance of factions leading over the cliff. Do you think it is coincidence that on recovery a decade after the plague, Athens; first serious offensive made no strategic sense and ended in disaster? Beginning, the spiral to utter defeat?

    I think not. And, I think it is no coincidence that we are largely ignorant of that history of the failure of the first Democracy or its echo in Ac 27.

    Lessons, bought with blood and tears, but not heeded.

    KF

  40. 40
    Truthfreedom says:

    Jerry

    Evidence and reasoning

    Reasoning = neurochemicals.
    Day 1: you secrete lots of those neurochemicals — you are very reasonable.
    Day 2: you secret a lesser amount of those neurochemicals — your reason poof, disappears.
    Naturalists use their valid reasoning processes to reach the conclusion that reasoning should not be trusted and is autonomously controlled.
    Pathetic. 🙂

  41. 41
    kairosfocus says:

    TF, thanks. Will follow up. KF

  42. 42
    daveS says:

    KF,

    As you know, there are people participating in randomized, blinded, placebo-controlled experiments involving HCQ right now. I would probably be willing to volunteer, but I’d want to speak with my doctor about the side-effects of the treatment. I think I’m at very low risk of serious illness or death, so it’s not a great risk for me. It would be an opportunity to help out my fellow woman/man, and perhaps get things back to normal more quickly, thus improving my own circumstances.

    Would you also consent to participate in such an experiment? Would have any concerns that the researchers were trying to “deceive” you by giving you “mislabeled” pills?

  43. 43
    kairosfocus says:

    DS, If I were suffering with Covid-19, I would go to a physician willing to prescribe a cocktail, immediately. I would test for falloff in viral load and if it was not working, I would go for bigger guns if available. I would happily sign off to allow the data to be used for research. If I had reason to not trust my doctor, I would not be there. KF

  44. 44
    Truthfreedom says:

    @Kairosfocus:

    It has not escaped my attention that we are in the midst of the worst, ongoing, holocaust in history.

    Yes. We are a corrupt society that feels proud of killing its innocent members.
    [SNIP] dressed in glitter.

  45. 45
    kairosfocus says:

    F/N: I have found some discussion on research designs and hierarchies of research evidence that hints at the problems I have been highlighting. Let me clip and comment:

    https://www.healthknowledge.org.uk/public-health-textbook/research-methods/1a-epidemiology/hierarchy-research-evidence

    The hierarchy of research evidence – from well conducted meta-analysis down to small case series

    . . .

    >>Evidence-based medicine>>

    — loaded language title, is it that before this school of thought came along, medical practice was not observation and evidence based? I think the ghost of Hippocrates is knocking at the door.

    >> has been described as ‘the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.’1>>

    — best vs credible and material is a world of difference, lending to the gold standard fallacy that imprudently rejects reasonable warrant in a given situation.

    — some lessons need to be drawn from decision theory

    >> This involves evaluating the quality of the best available clinical research>>

    — better, credible and material findings and fresh observations or results as well as the body of credible knowledge

    >>, by critically assessing techniques reported by researchers in their publications,>>

    — This sets up the fallacy

    >> and integrating this with clinical expertise.>>

    — In what way, if the fallacy is brought in, it undermines the quality of judgement.

    >>Although it has provoked controversy, the hierarchy of evidence lies at the heart of the appraisal process.>>

    — and, i/l/o bounded rationality, provisionality of empirical evidence and inductive reasoning etc, why might it be controversial?

    — an inherently fallacy prone process does not lend itself to sound decisions.

    >>Ranking of trial designs

    The hierarchy indicates the relative weight that can be attributed to a particular study design.>>

    — should we not rather be bringing to bear all credible, material evidence and analysis?

    >>Generally, the higher up a methodology is ranked, the more robust it is assumed to be.>>

    — If you use this to lock out material evidence, trouble

    >> At the top end lies the meta-analysis – synthesising the results of a number of similar trials to produce a result of higher statistical power.>>

    — If the substance fed into the synthesis locks out material evidence, the resulting biases predictably will undermine decisions.

    >> At the other end of the spectrum lie individual case reports, thought to provide the weakest level of evidence.>>

    — H’mm, actual observed facts in detail on the ground are the WEAKEST evidence? So, what then are we to make of the observations and record at alleged higher levels? For, those too are cases of a different sort.

    — The hierarchy is self-referentially incoherent, resolved through biased ranking.

    >>Several possible methods for ranking study designs have been proposed, but one of the most widely accepted is listed below.2 Information about the individual study designs can be found elsewhere in Section 1A.>>

    — okay, we now see the voice of the establishment, i.e. business as usual.

    — we are of course in a crisis that breaks business as usual

    >>1] Systematic reviews and meta-analyses
    2] Randomised controlled trials
    3] Cohort studies
    4] Case-control studies
    5] Cross-sectional surveys
    6] Case series and case reports>>

    — an open invitation is given to the gold standard fallacy

    >>Concerns and caveats>>

    — at least, this is mentioned.

    >>The hierarchy is widely accepted in the medical literature,>>

    — it is the voice of the establishment/BAU

    >> but concerns have been raised about the ranking of evidence, versus that which is most relevant to practice.>>

    — Decision theory has somewhat to say about risk of locking out material but inconvenient evidence.

    >>Particular concerns are highlighted below.

    Techniques lower down the ranking are not always superfluous.>>

    — BINGO, gold standard fallacy IS built-in. Of course if the lower evidence were supportive, it would be at least mentioned, but in case of conflict it will be locked out. That is precisely the problem.

    >> For example, the link between smoking and lung cancer was initially discovered via case-control studies carried out in the 1950s3.>>

    — it took decades before statistical links were generally accepted as pointing to real causal patterns

    >>Although randomised control trials (RCTs) are considered more robust, it would in many cases be unethical to perform an RCT. For example, if studying a risk factor exposure, you would need a cohort exposed to the risk factor by chance or personal choice.>>

    — sounds familiar? It should.

    >> The hierarchy is also not absolute.>>

    — telling admission against interest

    >> A well-conducted observational study may provide more compelling evidence about a treatment than a poorly conducted RCT.>>

    — So, the proper issue is to address credible material evidence, not a hierarchy prone to trouble.

    >>The hierarchy focuses largely on quantitative methodologies. However, it is again important to choose the most appropriate study design to answer the question. For example, it is often not possible to establish why individuals choose to pursue a course of action without using a qualitative technique, such as interviewing.>>

    — further problems

    >>Alternatives to the traditional hierarchy of evidence have been suggested. For example, the GRADE system (Grades of Recommendation, Assessment, Development and Evaluation) classifies the quality of evidence not only based on the study design, but also the potential limitations and, conversely, the positive effects found.>>

    — a beginning of balance

    >>For example, an observational study would start off as being defined as low-quality evidence. >>

    — why? With a competent observer, facts are facts credibly recorded. And at every level, observation and record of various types is built in, i.e. we are back to self-referential incoherence.

    >>However, they can be downgraded to “very low” quality if there are clear limitations in the study design, or can be upgraded to “moderate” or “high” quality if they show a large magnitude of effect or a dose-response gradient.>>

    — it is circumstances and quality of observation and record that count.

    Clearly, something has gone very wrong and it is deeply institutionalised.

    KF

  46. 46
    kairosfocus says:

    TF, while mr Trump et al have contributed to a much coarsened public discourse, let us refrain, please. That said, point taken. KF

  47. 47
    jerry says:

    Over 60 doctors have signed on to Zelenko’s protocol. My guess is that they have lots of information on how well it is doing. Zelenko is over 1450 patients with C19 and 2 have died, one from cancer. If anyone has contrary information, please post it.

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