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Inference Review devotes issue to COVID-19

Denyse O'Leary
April 15, 2020
Culture, Intelligent Design, Naturalism
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Here. Special Reports

SARS-CoV-2 and COVID-19

Hat tip: Philip Cunningham

Comments
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. KFkairosfocus
April 17, 2020
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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.Jim Thibodeau
April 17, 2020
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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.Truthfreedom
April 17, 2020
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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. Truthfreedom
April 17, 2020
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#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.Upright BiPed
April 17, 2020
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@16 JT Yawn. So obfuscation, equivocation and wild speculation are 'scientific'. You always make me laugh. :)Truthfreedom
April 17, 2020
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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.Jim Thibodeau
April 17, 2020
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@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?Truthfreedom
April 17, 2020
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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. KFkairosfocus
April 17, 2020
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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. KFkairosfocus
April 17, 2020
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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.
Bob O'H
April 17, 2020
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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.Jim Thibodeau
April 17, 2020
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@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. :-)Jim Thibodeau
April 17, 2020
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Later, I will develop, DV.kairosfocus
April 17, 2020
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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.kairosfocus
April 17, 2020
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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. KFkairosfocus
April 17, 2020
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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. KFkairosfocus
April 17, 2020
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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."Bob O'H
April 17, 2020
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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. KFkairosfocus
April 17, 2020
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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-16Jim Thibodeau
April 16, 2020
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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.jerry
April 16, 2020
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News, some first class commentary is there. KFkairosfocus
April 16, 2020
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