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Inference Review devotes issue to COVID-19

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Here. Special Reports

SARS-CoV-2 and COVID-19

Hat tip: Philip Cunningham

52 Replies to “Inference Review devotes issue to COVID-19

  1. 1
    kairosfocus says:

    News, some first class commentary is there. KF

  2. 2
    jerry says:

    The best thing about this is that it is a site that provides some liberal view points. So here we have site that is definitely not conservative espousing HCQ and CQ. Maybe they haven’t gotten the memo yet.

    One of the articles mentions the value of zinc and why.

  3. 3
    Jim Thibodeau says:

    More small molecule clinical data against COVID-19. I was going to cut and paste it here but there are lots of links so you should just go over there and read the whole thing. It might help some commenters understand why people who have done science have different opinions than people who haven’t.

    https://blogs.sciencemag.org/pipeline/archives/2020/04/16/more-small-molecule-clinical-data-against-covid-19-as-of-april-16

  4. 4
    kairosfocus says:

    JT,

    I took a look at your link. It leads with Chinese randomized, double-blinded, and placebo-controlled trials for moderate and severe cases of Covid-19 using Gilead’s Remdesivir being suspended, i/l/o stringent controls on clinical studies. Specifically, “[t]he epidemic of COVID-19 has been controlled well at present, no eligible patients can be recruited.” Mr Lowe then goes on, in an update: “I’m told that one big issue was the stringent inclusion criteria for the trials – apparently patients had to have no previous therapy with any other experimental agent to enroll, and that eliminates a *lot* of people.”

    Directly, that tends to suggest that OTHER treatments are commonly used and could confound trial outcomes . . . as they are effective. No prizes for guessing what such treatments likely include, given China’s approval of HCQ and the relatively low cost of this drug and of other components in suggested cocktails.

    Indirectly, we here see some sausage factory details that point to the credibility of regulatory process for such testing in China.

    Similarly, while clearly Chinese data on the epidemic will be proxies [as is common], this supports the pattern that the disease is under control there.

    When we transfer such findings to background considerations for the reported HCQ tests there for the same disease when it was NOT under control, in absence of specific reason to doubt the quality, such should increase our willingness to take the earlier studies on HCQ seriously.

    Studies, which obviously contributed to the approval. Where also, Raoult’s work etc should factor into our evaluations. As is notoriously so for economics, there is no end of debates, but policy makers facing crisis have to make decisions today not a year from now. Decisions where, not using something reasonably credible now could cost so much in loss of life and economic dislocation — which implies a wave of deaths from other causes — that such factors are material.

    KF

  5. 5
    Bob O'H says:

    kf – you clearly didn’t read the whole piece Jim linked to. Particularly the paragraphs after “And while we’re on the topic of updating one’s expectations, there are more studies of hydroxychloroquine to review.”

  6. 6
    kairosfocus says:

    BO’H: Nope, the decisive part was the prior. On the latter, the issue is the overall pattern of cumulative evidence. When the impact of literally thousands of patently relevant cases is left out [along with the facts regarding official decisions as I already reported], for cause I become dubious of the true balance on merits of claims being made. What was highly material, then, becomes what is admitted or implied against evident interest. Which is, as I just noted. First, that something “experimental” is evidently effective enough and in sufficiently common use in China as to prejudice testing of other candidate drugs. What that is, is obvious given context. Further inference, what is now “moderate” or “severe” is in the context of likely being resistant to other treatments, so these are going to be particularly hard cases. Such cases will typically be hard for any drug. Where also, the window into how trials are being regulated lends credence to earlier trials. In which context, the outcome of those trials in a country with the no 2 economy in the world . . . clearly, including the 75 patient test being put up as example no 2 . . . is that HCQ etc were approved and seem to have gone into fairly routine use. In that context, the pattern of wider approvals [including by the US FDA and by France, post Raoult stage 2] counts as an index of the balance on the merits. Yes, there is conflict of evidence, yes further testing is desirable and underway, but equally yes, there is sufficient of a balance that in an emergency, HCQ seems a good place to go, especially in a cocktail . . . which per Raoult et al [notice, you have never responded to the Raoult chart on relative impacts of three treatments] is what is on the table as giving dramatic results. And, the 75 patient test per report, did not study cocktails. KF

  7. 7
    kairosfocus says:

    PS: I note, again, the actual status of Raoult’s protocol, in regards to procedure:

    Research protocol approved by the ANSM and the Île-de-France CPP in progress at the IHU Méditerranée Infection: Treatment of respiratory infections with Coronavirus SARS-Cov2 by hydroxychloroquine Acronym: SARS-CoV2quine.”

    Until the implication of such is acknowledged, remarks like “when you look over the actual controlled data that we have so far” simply become excuses for suppressing what does not fit a preferred narrative. As in, no true Sassenach.

    KF

  8. 8
    kairosfocus says:

    PPS: A NIH paper on the ethics of Placebo control studies:

    Abstract

    The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling.

    Here is an article in Psych Today, drawing out how some of those ethical issues undermine the claimed power of placebo studies:

    The Trouble With Double-Blind Placebo Studies
    There are two flaws in double-blind placebo studies.
    Posted Nov 23, 2010

    Jefferson M Fish Ph.D.

    . . . there are significant problems with double-blind placebo studies. These have long been known in the research world, but for some reason, word hasn’t gotten out to the public. Here are two important ones.
    1. In real life, when patients receive a prescription, they are implicitly told: “This is real medicine.” In double-blind placebo studies, subjects are explicitly told: “This pill might be real medicine, or it might be a placebo.” Obviously, these lead to different sets of expectations, with different effects.
    The solution to this shortcoming is the balanced placebo design. In addition to a control group, it has two placebo groups and two treatment groups. People in both placebo groups receive a placebo, but one group is told that it is a placebo, and the other group is told that it is real medicine. And people in both treatment groups receive the medicine, but one group is told that it is a placebo, and the other group is told that it is real medicine.
    The difficulty with the balanced placebo design is an ethical one—it involves deceiving participants and violating the principle of informed consent. The fact that such studies cannot be done ethically, however, leaves the problem of effectively controlling for expectancies unresolved.
    2. The other problem is the active placebos. Double-blind studies respond to the objection of experimenters unintentionally communicating whether or not a pill is a placebo. But they don’t respond to the objection of the pill communicating that information.
    While the placebo pill and real pill look identical, the placebo pill is inert, but the real pill has real biological effects. Therefore, even though the real pill may not improve the condition it is supposed to treat, people taking it may be able to feel those effects. This could lead them to conclude: “I must be in the treatment group.” This is a more positive expectancy than: “I don’t know if I’m in the treatment group or the placebo group.” As a result, placebo effects could be misinterpreted as treatment effects.
    A partial solution would be to use active placebos instead of inert placebos. For example, nicotinic acid (niacin) causes skin flushing and itching. However, since the real pill and the active placebo pill would have different bodily effects, there is still the possibility that this difference rather than the medication in the real pill is responsible for any greater improvement in the treatment group.
    Maybe instead of calling double-blind placebo studies the gold standard, we should call them the brass standard—far from perfect, but unfortunately the best practical solution available.

    Let me add, Sherman Silverstein, Attorney at Law, in this ambulance-chasing world, regarding a potentially lurking tort or worse:

    For research to be ethical in design, what is known as “clinical equipoise” must exist between the two arms of the study. This means that the researchers must not believe that the subjects in one arm of the study are getting any better or worse therapy than the subjects in the other arm. Thus, where standard therapy exists, the researchers must believe that the subjects in both arms are getting therapy at least equal to standard best therapy. Obviously, no state of clinical equipoise can exist where one arm of the study receives a nontherapeutic placebo unless no therapy considered standard exists for the disease or ailment.

    The Declaration of Helsinki speaks directly to this issue. The World Medical Association had adopted a resolution on human experimentation in 1954 based largely on the Nuremberg Code. In 1964, after several revisions, the World Medical Assembly in Helsinki adopted the document now known as the Declaration of Helsinki. Like the Nuremberg Code out of which it arose, the Declaration of Helsinki recommended a worldwide minimal standard for human subject research. It has since been revised not only to include a requirement for ethical review committees, such as IRBs, but also to expressly preclude the use of a placebo when a proven therapeutic method exists and where the absence of therapy poses a risk to the subject. It states in relevant part:

    29. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists. See footnote.

    Footnote: Note of clarification on paragraph 29 of the WMA Declaration of Helsinki

    The WMA hereby reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances:

    – Where for compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or

    – Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm.

    All other provisions of the Declaration of Helsinki must be adhered to, especially the need for appropriate ethical and scientific review.

    In short, with human life, health and well-being on the table, we need to do a lot more than suggest that anything “less” than a placebo test is not good enough. That is going to require considerable rethinking, involving recognising that hyperskepticism is not a virtue [as opposed to prudence], and requiring fairly serious thought in light of inductive logic, cumulative force arguments, linked issues on cogency and our understanding of epistemology, informed by the concept of moral certainty.

  9. 9
    kairosfocus says:

    Later, I will develop, DV.

  10. 10
    Jim Thibodeau says:

    @Bob O’H he obviously missed that part and will now go back and try to diminish it.

    We’re all hoping it’s some kind of miracle cure. I know I could use it, I have a very lucrative sales job(1) and customers have been much reduced in the last month. But I suspect that if the evidence comes in that it’s not effective, we’ll get HCQ Truthers who insist years from now that it really did work and it was a conspiracy and so forth, rather than admit they immediately fell for some poor evidence despite being warned by people who understand science.

    (1) Science paid less than the engineering that I switched to, and engineering was tedious and unrewarding, when I can make literally twice as much shaking hands and chatting people up. If I had known this 30 years ago I would’ve studied science and medicine on my own time and done sales right out of high school and been retired by now. 🙂

  11. 11
    Jim Thibodeau says:

    AFP news agency
    @AFP

    #UPDATE Wuhan, China’s #coronavirus ground-zero, has abruptly raised its death toll by 50% to a total of 3,869, admitting many cases were “mistakenly reported” or missed.

    China kind of sorta admitting they were lying and the death toll is higher than they said. But these are just baby steps, everybody knows the real death toll is higher than reported everywhere.

  12. 12
    Bob O'H says:

    kf –

    On the latter, the issue is the overall pattern of cumulative evidence.

    Indeed. And the piece discusses several studies that suggest no beneficial effects of HCQ, compared to other treatments. You keep on citing Raoult, but you need to be able to provide evidence, not just that a lot of his patients survived (or did better by another endpoint), but that they wouldn’t have done as well without HCQ. His first study was, as I’ve acknowledged several times, suggestive that follow-up studies were worth doing. But now the results of such studies are coming out, and they don’t look good. As the piece on Science concludes:

    Now, there are many more trials underway, and I very much look forward to their readouts. But when you look over the actual controlled data that we have so far for hydroxychloroquine, those previous links plus what we have today, the case for the drug is not encouraging at all. There is one small trial (from China) that showed some positive results, and data from China, Brazil, and France that show no benefit for either hydroxychloroquine or chloroquine itself and (in some cases) evidence of actual harm. The trials that are yet to report are going to have to start showing some strong positive effects if this story is going to have a good ending.

  13. 13
    kairosfocus says:

    JT, nope, and you are again resorting to hyperskepticism. I have explained the reason why, in a context where the general case is defective, the key issue is what is implied or admitted against interest. Getting out the door momentarily. KF

  14. 14
    kairosfocus says:

    BO’H: again, you overlook material evidence and the issue that undermines the whole framework of using placebos as if that were a gold standard. Nope. Where, again, you neatly side-step a la Wilson’s Arte of Rhetorique, the chart showing three options on treatment, with strongly divergent results in a trend that implies a clear dynamic at work, and the approval of protocol by France. Raoult’s work is not dismissible. There is a lot more here than you are admitting. KF

  15. 15
    Truthfreedom says:

    @Bob O’H
    So according to you, we need to wait until the trials are done.
    But meanwhile you can speculate, obfuscate and equivocate.
    Am I wrong?

  16. 16
    Jim Thibodeau says:

    The people here who have actually done science are properly skeptical. In the next week or two we will see if they were right. Although I don’t expect people who were wrong to admit it.

  17. 17
    Truthfreedom says:

    @16 JT
    Yawn. So obfuscation, equivocation and wild speculation are ‘scientific’. You always make me laugh. 🙂

  18. 18

    #16
    The people here who have “done science” and who are “properly skeptical” in this instance are the same people who already know that the living cell simultaneously requires a discontinuous symbol system, a spatial-oriented language structure, and semantic closure in order to begin to function, and yet none of them will admit it (i.e. they can’t even speak the words). Since you appear to want to be the scorekeeper, you might want to write that down.

  19. 19
    Truthfreedom says:

    JT is a clairvoyant. He already knows the results of the clinical trials. No need to wait then.
    JT has all answers.
    Dust off the crystal ball, baby.

  20. 20
    Truthfreedom says:

    JT is the typical darwinian:
    -‘I know I am right’
    -‘Experiments will only confirm it’
    The problem here is that that’s dogma, not real science.

  21. 21
    Jim Thibodeau says:

    I didn’t say it wouldn’t work, I said I hoped it worked but I’m skeptical. If you want somebody who’s clairvoyant, find the person here who called Hydrochloroquine a “cure” a few days ago.

    Oh, and when I said that ~600 sailors from the USS Theodore Roosevelt had tested positive for COVID-19, someone asked how many are asymptomatic. The answer is apparently 60%. ~236 are sick out of 589 infected. 2 or 3 are in the ICU.

  22. 22
    kairosfocus says:

    JT, you are not “skeptical.” You are selectively HYPER-skeptical (and UB is dead right to highlight your evident compensating credulity). There is on the table a study by the leading relevant researcher in France, with an officially approved protocol now not at 30 or 80 but 2759 (with 11 dead). There are the reports by other clinicians (Raoult is a medical doctor and microbiologist) and there is a pattern of approvals including by the US FDA. Obviously, all of this is incremental and subject to change on further evidence and analysis, as is so for any empirical result. When we see no true Sassenach games with the balance of evidence, that tells us something, as I noted above. Then, there are the significant problems, ethical and psychological [as the placebo is psychological] with the type of testing posed as gold standard and used to effectively discount other empirical evidence to zero . . . which is where selective hyperskepticism walks in the door. Having come back just now (the line was short and I was only stopped by police twice), I will turn to that next. KF

  23. 23
    daveS says:

    KF,

    Briefly, what specific steps do you think should be taken immediately, in terms of treatment? If you had the proverbial magic wand, what would happen today?

  24. 24
    Truthfreedom says:

    @ DaveS
    Briefly: is having sex with a dead person ‘wrong’?
    -Yes?
    – or No?
    (Last time you tried to avoid the question).

  25. 25
  26. 26
    jerry says:

    Briefly, what specific steps do you think should be taken immediately, in terms of treatment?

    A teaching medical university (Eastern Virginia Medical School) has recommendations – https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

    Prevention

    • Vitamin C 500 mg BID and Quercetin 250-500 mg BID
    • Zinc 75-100 mg/day (acetate, gluconate or picolinate). Zinc lozenges are preferred. After 1-2 months, reduce the dose to 30-50 mg/day.
    • Melatonin (slow release): Begin with 0.3mg and increase as tolerated to 1-2 mg at night
    • Vitamin D3 1000-4000 u/day (optimal dose unknown).

    Mildly Symptomatic patients (at home)
    • Vitamin C 500mg BID and Quercetin 250-500 mg BID (if available)
    • Zinc 75-100 mg/day
    • Melatonin 6-12 mg at night (the optimal dose is unknown)
    • Vitamin D3 1000-4000 u/day
    • Optional: Hydroxychloroquine 400mg BID day 1 followed by 200mg BID for 4 days

    Mildly Symptomatic patients on floor)

    • Vitamin C 500mg BID and Quercetin 250-500 mg BID (if available)
    • Zinc 75-100 mg/day
    • Melatonin 6-12 mg at night (the optimal dose is unknown)
    • Vitamin D3 1000-4000 u/day
    • Methylprednisolone 40 mg daily
    • Enoxaparin 40-60 mg daily
    • Optional: Hydroxychloroquine 400mg BID day 1 followed by 200mg BID for 4 days
    • Vitamin C 500mg BID and Quercetin 250-500 mg BID (if available)
    • Zinc 75-100 mg/day
    • Melatonin 6-12 mg at night (the optimal dose is unknown)
    • Vitamin D3 1000-4000 u/day
    • Optional: Hydroxychloroquine 400mg BID day 1 followed by 200mg BID for 4 days
    • N/C 2L /min if required (max 4 L/min; consider early t/f to ICU for escalation of care).
    • Avoid Nebulization and Respiratory treatments. Use “Spinhaler” or MDI and spacer if required.
    • Avoid non-invasive ventilation
    • T/f EARLY to the ICU for increasing respiratory signs/symptoms.

    Respiratory symptoms (SOB; hypoxia- requiring N/C ? 4 L min: admit to ICU):

    1. Methylprednisolone 80 mg loading dose then 40mg q 12 hourly for at least 7 days and until transferred out of ICU. Alterative approach: Hydrocortisone 50 mg q 6 hourly.
    2. Ascorbic acid (Vitamin C) 3g IV q 6 hourly for at least 7 days and/or until transferred out of ICU. Note caution with POC glucose testing (see below).
    3. Full anticoagulation: Unless contraindicated we suggest FULL anticoagulation (on admission to the ICU) with enoxaparin, i.e 1 mg kg s/c q 12 hourly (dose adjust with Cr Cl < 30mls/min). Heparin is suggested with CrCl < 15 ml/min. Alternative approach: Half-dose rTPA: 25mg of tPA over 2 hours followed by a 25mg tPA infusion administered over the subsequent 22 hours, with a dose not to exceed 0.9 mg/kg followed by full anticoagulation. On transfer to floor, consider reducing enoxaparin to 40-60 mg /day.

    I’m sure many will laser in on optional use of HCQ. But with the success with others out there I would think it would be foolish to not take it in the doses recommended.

  27. 27
    jerry says:

    From recommended reading list above – https://inference-review.com/report/therapeutic-options-for-covid-19

    When the disease is detected early, there are now many other medicines that may be useful. The antimalarial and Lupus drug chloroquine, and its more potent form hydroxychloroquine (Plaquenil), have shown some efficacy. A significant number of patients that were given hydroxychloroquine, either alone or with a supplementary Z-Pak (azithromycin) to fight bacterial pneumonia, made a quick recovery. Because no sick patients were refused treatment as a control, an inhuman action by any standard, critics argue that the results were worthless. Those critics are in fact people who do not have the coronavirus. The truth is that the entire infected world of people who were not given this drug were the control. Their lengthy recovery times are the data.

    Hydroxychloroquine is a pleiotropic drug, a fancy way of saying it works in many mysterious ways. One primary action is that it increases the pH of lysosomes inside cells from around 4 to 6. This inhibits acidic proteases and decreases intracellular processing, glycosylation, and protein secretions. In antigen-presenting cells, this leads to a decrease in inflammatory activities. Perhaps more importantly, in other cells infected with the coronavirus, this leads to a decrease in viral loads.

    Hydroxychloroquine also binds to specific zinc transporters, or zinc ionophores, and keeps them open. If excess zinc is available, this presumably lets more zinc enter the cell. Zinc appears to alter the membrane permeability of lysosomes, but it has another important function. It can block the unique RNA-dependent RNA polymerase (RdRP) of the coronavirus. Although the literature calls hydroxychloroquine itself an ionophore, it only binds to the real zinc ionophores in the cell. This term is at best awkward and at worst misapplied.

  28. 28
  29. 29
    kairosfocus says:

    BTW, notice, the difference between HCL alone and in cocktails.

  30. 30
    daveS says:

    Jerry,

    Thanks for that background.

  31. 31
    bornagain77 says:

    JT states,

    The people here who have actually done science are properly skeptical.

    Says the man who believes, without real time empirical evidence, in Darwinian evolution.
    https://uncommondescent.com/intelligent-design/if-even-genes-are-into-special-creation-whats-left-for-darwinism-now/#comment-698652
    Being a Darwinist is the antithesis of being ‘properly skeptical’!

  32. 32
    daveS says:

    KF,

    I worded my original question poorly, but here’s what I intended: What is not currently happening that should be happening? In other words, what specific changes should immediately be implemented?

  33. 33
    Ed George says:

    JT@25, you would almost think that Falwell did it for the money.

    Amid those struggles, a Liberty student on Monday filed a class-action lawsuit in a federal court in Virginia, saying that Liberty and Mr. Falwell had “placed students at severe physical risk and refused to refund thousands of dollars in fees owed to them for the Spring 2020 semester,” according to a statement from the law firm filing the suit.

  34. 34
    kairosfocus says:

    DS,

    please see the new OP and onward discussion, JT brought to my attention a Guardian article that is almost a caricature of the concerns I have. What we first need to do is to realise we have seriously blundered in logic, epistemology and ethics, turning selective hyperskepticism into a fallacious substitute for prudence. In that context, we need to rethink how we assess empirical observation, evidence and reasoning, thus context-relevant degree of warrant towards necessarily risky decisions.

    We need to bring back the principle of moral certainty, and recognise when errors are acceptable or affordable.

    As applied to this situation, it would be nice to see reasonableness in response to Dr Raoult et al, and some willingness to recognise that he is not shilling for snake oil, with gullible masses running along behind.

    It would be nice to see recognition of the two stages of FDA approval to date, and recognition that each physician is a qualified ethically governed agent who on relevant evidence with disclosure, can make reasonable off label use of drugs, supplements etc. (I am right now having serious second thoughts on some of the dismissals I took at far too much of face value regarding supplements, neutraceuticals and superfoods generally. Eatcher veggies etc makes even more sense.)

    As public policy, we need to recognise that large scale trials may be more limited and more ethically challenged than we may like to think. There are no “gold standard” yardsticks. Next, we must recognise that vaccines, the favoured trials and so forth may be too late for the full impact of this epidemic.

    And so we gotta fight this war with what we got in hand now. Maybe, for a decade now we should have been doing as security matters, serious investigations on antivirals and further antibiotics etc. And more.

    KF

  35. 35
    daveS says:

    KF,

    Maybe you and I don’t have any disagreement on policy (in the US, which is all I am vaguely familiar with) around the drugs Raoult studied? I don’t think either of us is suggesting any specific changes to current policy.

  36. 36
    kairosfocus says:

    DS, policy is wider than declared state policy — the point of defining governance as: how the big decisions are made and are made to stick. (Hence, BTW, my reference to the idea of using “seven mountains” as a handy model of key centres of influence.) There is, on paper, a reasonable policy by the US FDA, though the amount of bureaucracy seems dubious. Looking from a wider viewpoint, I am seeing serious signs of intellectual and ethical breakdown leading to serious trouble in the face of an ongoing deadly pandemic. KF

  37. 37
    Bob O'H says:

    BO’H: again, you overlook material evidence and the issue that undermines the whole framework of using placebos as if that were a gold standard.

    I don’t think I’ve even mentioned placebos.

    Of the three links you give, the first outlines when placebos can be ethically problematic, but I don’t see that any apply here (particularly as there is no “standard treatment”).
    The second raises some interesting ideas, but it’s speculative so I wonder if any research has been done since to see whether they are actually a problem. FWIW I don’t think the first will influence the results of a trial (because all arms get the same information). The second might have an effect, but presumably only in cases where the active drug has side effects.
    The third link is explicitly about when there is a standard therapy, which is not relevant here.

  38. 38
    kairosfocus says:

    BO’H, placebo driven studies are the manifest context. There is a de facto standard treatment, that given to most cases, leading up to the last ditch ventilators lately the subject of much media huffing and puffing. Next, you duck the basic challenge of knowingly mislabelling sugar pills or the like [Niacin to promote skin itching and perception of active treatment], deceiving patients, and in this case exposing patients to a fast acting deadly disease. Something is wrong with how we approach empirical investigations, as I went on to discuss here. KF

  39. 39
    Jim Thibodeau says:

    One of the sailors on the USS Teddy Roosevelt has died from COVID-19. RIP Chief Petty Officer.

  40. 40
    Bob O'H says:

    kf – nobody is suggesting “exposing patients to a fast acting deadly disease” in these large trials.

  41. 41
    kairosfocus says:

    BO’H, that is the direct implication of using sugar pills or the like in this case. KF

  42. 42
    kairosfocus says:

    JT, RIP indeed. KF

  43. 43
    Bob O'H says:

    kf, no. The trials are for people who already have the disease.

  44. 44
    ET says:

    Umm, that sailor died 5 days ago…

  45. 45
    Ed George says:

    KF

    Next, you duck the basic challenge of knowingly mislabelling sugar pills or the like [snip ], deceiving patients, and in this case exposing patients to a fast acting deadly disease.

    Nobody is deceiving patients or exposing them to a deadly disease. Patients must volunteer to be in a clinical trial, knowing that they may receive a placebo. In most trials, the patients still receive the standard level of care.

    If I had COVID-19, I probably wouldn’t volunteer for the trial because of the known risks of the drug and because I am in a low risk group for fatal complications. However, if I were a few years older, was obese, or had some underlying condition, I would volunteer in a flash. If the treatment is effective, I have significantly increased my odds of survival.

  46. 46
    daveS says:

    EG & KF,

    However, if I were a few years older, was obese, or had some underlying condition, I would volunteer in a flash. If the treatment is effective, I have significantly increased my odds of survival.

    To amplify this point a bit, I would want my participation in such an experiment to have as much value as possible, so I would prefer that the experiment be blinded and have randomized controls (given what I know about the current situation).

    This talk of “mislabeling” pills and “deceiving” patients is not appropriate here, assuming patients are informed how the experiment is conducted.

  47. 47
    kairosfocus says:

    BO’H: Do you wish for me to elaborate as, exposing people to the ravages of a deadly disease, having taken deliberately mis-labelled sugar pills? That is discussed in more detail, with links above, its meaning was never in serious doubt. KF

  48. 48
    kairosfocus says:

    EG, false, as the analysis cited and linked onward at 8 above draws out. That is over and above taking people credibly suffering a fast-acting deadly plague and giving them sugar pills (with false labels) under the solemn colours of medical treatment. KF

  49. 49
    Bob O'H says:

    kf – once more, because you don’t seem to understand how these trials work. No, we don’t get people to take “deliberately mis-labelled sugar pills” and then expose them to the disease. That would be unethical and evil.
    People who already have the disease are given the opportunity to enter the trial. They are told that they could be given a treatment, or a control (I assume a placebo here, but in other contexts it can be the standard treatment), and neither they or their doctor will know which it is. If they agree, i.e. if they give informed consent, then they will enter the trial.

  50. 50
    Ed George says:

    KF, you continue to display your complete ignorance on how clinical trials are run. You focus on the fact that placebos are falsely labelled but completely ignore the fact that they are informed in advance that they may be receiving a placebo and that neither the doctor nor the patient knows which are which. All pills could just as easily be labelled as sugar. And during the trial, all participants still receive the standard level of care.

    We are all hoping that this treatment is effective, but there is too much contradictory information to know if it is effective. But we do know that there are some significant risks associated with the drug. It is used for lupus and malaria because the risks associated with the disease far outweighs the risks associated with the drug.

    By all accounts, this treatment appears to be most effective early in the infection. But we also know that the vast majority of people infected recover without any need for medical intervention.

  51. 51
    kairosfocus says:

    BO’H & EG:

    In this case, ethical failure is precisely the issue at stake.

    Let me cite in its long form, a famous aphorism of Hippocrates of Cos, often clipped in Latin to Ars longa, vita brevis:

    Life is short, and Art long;
    the crisis fleeting;
    experience perilous,
    and decision difficult.

    The physician must
    not only be prepared
    to do what is right himself,
    but also to make
    the patient,
    the attendants,
    and externals
    cooperate.

    In the face of finitude, fallibility and the challenges of judgement, decision and action, the physician [and by extension other professionals] must be prepared to act aright. This famously includes, “first, do no harm.”

    It matters not what is said about how placebo designs avoid ethical failure as there is a consent sign-off, or that neither the one who administers nor the one who receives knows beyond that X may or may not be a drug. In dealing with “zits,” or the like, that might be enough. But that is precisely what is not the case before us. As is noted, in the solemn name, ceremonies and colours of the most honoured of professions [save, one] and in the face of a deadly fast acting, fast spreading disease known to rapidly cause organ damage and death, it is proposed to design test treatments that will subject significant numbers of patients to “treatment” with sugar pills or the like.

    There is a comparison, one that I used here when it became clear that authorities were trifling with the dangers of a volcano, eventually costing (by official count) nineteen, their lives. Namely, Russian Roulette.

    What is worse, in the name of the alleged excellence of such a test (one that it is admitted will take perhaps a year to complete) evidence from case studies and tracking reasonably credible candidate treatments is being trashed as though it were no evidence or grossly inadequate evidence or utterly lacking in probative value. The Guardian article is only one case in point.

    As I have pointed out repeatedly, it is simply not in the gift of empirical studies and linked inductive reasoning, to deliver proof. At least, beyond what the Greeks termed pistis, rhetorical proof. Evidence of weight that in the best case may attain moral certainty, or is at least reasonable, reliable and responsible to act on. But that is precisely what case based reasoning also delivers [without need for Russian Roulette or deceit with life on the line] and that is what is routinely being trashed.

    Next, we face a fast-moving, fast spreading epidemic, where “wait until our gold standard study delivers results” is tantamount to discrediting results of significant worth that are in hand, grow with cases and point to something that can be tried right now, with reasonable hope of success and cost. Here are Zelenko’s words from his March 23 letter to the world’s physicians:

    Given the urgency of the situation, I developed the following treatment protocol in the pre-hospital setting and have seen only positive results:

    1. Any patient with shortness of breath regardless of age is treated.
    2. Any patient in the high-risk category even with just mild symptoms is treated.
    3. Young, healthy and low risk patients even with symptoms are not treated (unless their circumstances change and they fall into category 1 or 2).

    My out-patient treatment regimen is as follows:

    1. Hydroxychloroquine 200mg twice a day for 5 days
    2. Azithromycin 500mg once a day for 5 days
    3. Zinc sulfate 220mg once a day for 5 days

    The rationale for my treatment plan is as follows. I combined the data available from China and South Korea with the recent study published from France (sites available on request). We know that hydroxychloroquine helps Zinc enter the cell. We know that Zinc slows viral replication within the cell. Regarding the use of azithromycin, I postulate it prevents secondary bacterial infections. These three drugs are well known and usually well tolerated, hence the risk to the patient is low . . . . In sum, my urgent recommendation is to initiate treatment in the outpatient setting as soon as possible in accordance with the above. Based on my direct experience, it prevents acute respiratory distress syndrome (ARDS), prevents the need for hospitalization and saves lives.

    It is of course a matter of record, that Dr Raoult, a distinguished researcher, has undertaken studies, which at the 80 patient stage led France to a measure of approval, and shortly thereafter the US FDA moved to a second level FDA approval. A significant cluster of countries including the two largest by population in the world and the two largest by population in this hemisphere, have given some degree of approval. All that is asked is to recognise that and that it is not without warrant; though obviously further warrant, exploration of other treatments and more are highly desirable, especially vaccinations. Unfortunately, the best bet on that is, a year out.

    Coming back to use of placebos, we need to recognise what a placebo is and that there is no responsible justification to dismiss other evidence or to subject patients in the face of a fast acting deadly plague to something comparable to Russian Roulette when there is evidence [which needs to be recognised not trashed] that there are possibilities that do not depend on frankly, deception. However disguised.

    We need to seriously rethink what we are doing, proposing to do or advocating.

    KF

    PS: BO’H, kindly, stop wrenching plain enough words into strawmannish pretzels. Patients obviously have something that makes them be cases, and are facing consequences of a fast acting, deadly disease in the relevant situation. Subjecting them to a regime where pills are given [for example] that bear the same label but in some cases are sugar pills rather than a credibly active agent, is exactly where the issues lie. Especially in a context where gold standard rhetoric is being used to dismiss other evidence that is material. Hence why in cases of serious and fast acting peril, I have to seriously question the ethics and epistemology at work.

  52. 52
    jerry says:

    you continue to display your complete ignorance on how clinical trials are run.

    We all know how studies are done. Control groups are done when you expect small differences due to the intervention or you expect that there are psychological factors involved or you expect rigging the results is an issue.

    The ignorance on display here and elsewhere is that a control group is needed to see an effect. Just assume the control group is the thousands who died from a different treatment. If you have 99% success with a certain treatment than who needs a control group. Only an idiot would think that isn’t a successful intervention.

    If you could find amongst the thousands who entered hospitalization that there was one or two treatments that led to some being quickly released in a few days, then you would have a natural experiment. That is what we have. We have a treatment by several doctors leading to quick release. That should be celebrated not nitpicked with irrelevancies. Otherwise we have to suspect the motives of the nitpickers.

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