It is clear that we need to re-think how we go about doing science to warrant approaches to the pandemic. So, allow me to headline a comment from the double-blind thread:
KF, 16: >> I am also thinking back to the old “Scientific Method” summary we were taught in schools and its roots in Newton’s Opticks, Query 31:
As in Mathematicks, so in Natural Philosophy, the Investigation of difficult Things by the Method of Analysis, ought ever to precede the Method of Composition. This Analysis consists in making Experiments and Observations, and in drawing general Conclusions from them by Induction, and admitting of no Objections against the Conclusions, but such as are taken from Experiments, or other certain Truths. For [speculative, empirically ungrounded] Hypotheses are not to be regarded in experimental Philosophy. And although the arguing from Experiments and Observations by Induction be no Demonstration of general Conclusions; yet it is the best way of arguing which the Nature of Things admits of, and may be looked upon as so much the stronger, by how much the Induction is more general. And if no Exception occur from Phaenomena, the Conclusion may be pronounced generally. But if at any time afterwards any Exception shall occur from Experiments, it may then begin to be pronounced with such Exceptions as occur. [–> this for instance speaks to how Newtonian Dynamics works well for the large, slow moving bodies case, but is now limited by relativity and quantum findings] By this way of Analysis we may proceed from Compounds to Ingredients, and from Motions to the Forces producing them; and in general, from Effects to their Causes, and from particular Causes to more general ones, till the Argument end in the most general. This is the Method of Analysis: And the Synthesis consists in assuming the Causes discover’d, and establish’d as Principles, and by them explaining the Phaenomena proceeding from them, and proving [= testing, the older sense of “prove” . . . i.e. he anticipates Lakatos on progressive vs degenerative research programmes and the pivotal importance of predictive success of the dynamic models in our theories in establishing empirical reliability, thus trustworthiness and utility] the Explanations. [Newton in Opticks, 1704, Query 31, emphases and notes added]
Now, obviously, case-based, reliability driven, insightful inference to best current explanation oriented inductive investigations and reasoning are much broader than the conventionally labelled sciences. That’s a piece of why there is no one size fits all and only Big-S “Science” method. But it is undeniably powerful and when properly done, useful.
My favoured summary (honouring a favourite student) is O, HI PET:
O — OBSERVE a situation (looking at key factors, facts, trends, relationships, family resemblances etc, the intent being to accurately describe, effectively and reliably explain, reliably predict patterns, and use these to influence or control fresh situations)
H –HYPOTHESISE . . . infer an evident pattern (looking for reliable, best current explanatory frameworks)
I & P — INFER & PREDICT . . . what consequences would follow in fresh circumstances (an empirically reliable principle, rule, explanatory framework, law, model or theory — or entity embedding such — is highly valuable . . . including a new instrument, device, gadget, process, procedure or treatment embedding such)
ET — EMPIRICAL TESTING . . . we need to identify then disseminate successful, reliable, effective, insightful, fruitful results
Now, let’s state the needed obvious: nothing in this framework mandates double-blind, placebo control group procedure.
Indeed, it points to the underlying principle of case-based reliable inference. Where control groups can ethically and effectively be deliberately set up and used, fine. But that is by no means always the case, with Astronomy perhaps the capital example as a sub-discipline that uses case-based observational studies as a part of the hardest of the hard sciences, Physics. There is a reason why we speak of Astronomical OBSERV-atories, not LABOR-atories. (Ditto for Volcanology; and that was the pivot of my public warning here, 25 years ago. Looong story.)
In short, we must be humble enough to recognise that we cannot prescribe an investigative panacea.
Linked, we may ask, how does this work?
First, by applying the principle of distinct identity. A is A i/l/o its key characteristics, some in common with near and increasingly distant neighbours, some more specific to its class then ultimately to itself as a particular case. Where, core characteristics give rise to repeatable patterns of behaviour in sufficiently similar situations.
Thus, the art of scientific and broader empirical investigations is to seek sufficiently reliable candidate characteristics- in- common for a broad enough class of cases or entities. This then can be tested for reliability through further studies, whether experimental, observational, predictive or “retrodictive” etc. Such, can then be accepted as a provisional, promising explanatory model, which at the high end will be a theory [i.e. an explanatory model that is felt to be possibly true; models may be deliberately simplified . . . so necessarily false, but useful].
Again, nothing in this imposes placebo control groups as a necessary criterion of validity or reliability. And, contrasted cases studied in matched pairs or clusters with variances points to a broad framework for statistical studies, ANOVA and its various extensions.
But even that is not a straightjacket, various forms of exploratory data analysis and scientific visualisation have often been powerful. Modelling- and- simulation exercises (often with computer animations and Monte Carlo explorations of contingencies) have joined such in recent years. Taxonomical studies have been fruitful, e.g. in Biology. So can be simple tabulation, with the periodic table being perhaps the classic case in point. That brings up, familiarity with epochal cases, the paradigms that set up new schools of thought and launch research programmes.
But, such programmes are almost never “proved” — in Lakatos’ terms, they are born, live and die “refuted” by anomalies, counter-examples, challenges, exceptions, open questions etc. But a progressive research programme advances through successive predictive success, and a regressive one falters and wanders off into becoming increasingly ad hoc and/or simplistic and restricted. If institutionalised in power centres, a degenerative programme can stave off competitors for many years, but eventually, the bills come due with nothing to cover them.
All of this sounds rather political and ideological, doubtless. (Economics is perhaps the capital example.)
Yes.
We are social creatures and power- with- linked- wealth is always a consideration. Which is why issues of corruption are always lurking as a dirty secret in Science; including, on what may go on behind the scenes of peer review. Likewise, we see the challenge . . . or, is that now, crisis? . . . of testing and reliable replicability.
Coming back to our immediate focus, it is obvious that urgency here undermines the relevance of placebo controlled studies, even were one to set aside the issue that first the physician must do no harm. Where, sugar pills deliberately administered to patients facing a fast acting, potentially deadly disease pose fairly obvious ethical challenges. So, we need to go to deeper investigatory principles, to identify what is a more relevant approach to a pandemic in progress.
The answer comes back, repeated, case based clinical studies using suitable candidates reflecting the state of our knowledge. Which is precisely what Prof Raoult has been doing. 2759 cases reflects Stalin’s principle: sufficiently massive quantity has a quality all of its own.*
KF
*PS: That’s so here because in this context, beyond a certain mass of cases that sufficiently contrast with the general background, errors of coincidence are not a credible candidate null explanation. If there is a 10 percent chance of error, and, we see 100 independent cases that trend is unlikely to be chance. The chance that a string of errors that long falls exponentially. 0.1^100 is 10^-100. If the die keeps coming up sixes 100 times, or the coin comes up H 100 times in a row, loading becomes the best explanation. Which is of course the basic point in classic hypothesis testing in statistics. >>
Such gains further strength in light of a further comment in the Remdesivir thread, in response to BO’H and Jerry; which I now augment as OP’s allow insertion of images:
BO’H, 3: >> Be careful – by the sounds of it, this [leak on a Chicago study on Remdesivir] doesn’t have a control group either. Hopefully some of the other trials have control groups. >>
KF, 4: >> 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. >>
Jerry, 5: >> There is a control group of several thousand dead people from the virus. They got the placebo. >>
KF, 6: >>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]. [I insert, an image:]
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.)
[I add, for existential, crisis situations:]
[Then, there is the old lemmings story — let’s connect a few dots:]
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.>>
In short, no, we are not locked up to human patient, placebo control testing as a gold standard, implying that in the face of a fast moving deadly pandemic, we can only hope for credible treatments a year from now. END
On Scientific Methods and alternatives to the “Placebo Control is the gold standard” view, in the face of pandemics (–> Logic & First Principles, 38)
KF,
Is there evidence showing that using these alternative approaches will result in a net benefit? Fewer deaths, smaller economic impact, etc?
DS, sustainability principles and a wider understanding of credible empirically grounded warrant are justified in their own right, even were they to make no practical difference in this case — soundness and prudence count in decision-making. However, the evidence on the ground is, that something is wrong with epistemology and ethics, leading to hyperskeptical dismissal of research findings and results that would otherwise receive a fairer hearing and shift the balance on what can be done now. For example, ponder the tabulation in the OP here on Raoult’s results: 4420:85 vs 2759:11. That evidence is widely being trashed and dismissed by appeal to a flawed golden standard, warping decision-making, reducing treatment options and contributing to a panic that will be hard to climb back down from, even on the brink of recession. Setting aside the flawed yardstick used to dismiss mounting evidence, we probably would be more willing to accept that there are treatments effective enough to be worth trying. As it is, the two tiers of FDA approval have been widely ignored or buried under a needless controversy, and evidence from other countries has been similarly buried. Given that the US Economy is still the leading one, the economic implications of the needless panic and polarisation should not be underestimated. Where, of course, that carries with it its own toll of lives. We need to return to prudence. KF
What is the purpose of the placebo? The main reason to have a placebo is to be sure that any effects that happen are actually caused by the treatment and not by some other factor. They are used for new medical procedures on already well known diseases or injuries that have well known trajectories and currently accepted treatments.
They are never used in a study when there is the possibility of death due to no known effective treatment. The COVID 19 disease is such an example. The insanity of insisting on a double blind study with no effective treatment for a disease that has a high immediate death rate is incredibly callous.
Those proclaiming that such a study is needed do not really understand medical testing and are insisting that some people have to die for a drug to be validly tested. This is not a disease with a well understood trajectory and that has a usual treatment. This is completely new and is known to kill a significant part of the population quickly. To suggest that anyone will submit to such an experiment because they are given a consent form that says they may be given the placebo is nonsense. No one in. their right mind would sign such an agreement.
Double blind studies are ludicrous for testing HCQ for COVID 19. Those suggesting they be done know full well the madness of what they are saying. So why are they making these comments?
Not usually. If there is already demonstrated treatment then trials for a new treatment are compared to the standard one. Long experience of promising early study has shown us randomised controlled studies are out best way of finding real treatments. Placebo trials are the only way to do this for a new disease with no established treatment. (Compassionate use and case studies can go on, of course, but taken together HCQ isn’t looking very good).
Jerry, while of course your never is in the sense, one ought not, it seems that routinely, people are being exposed to serious risk of harm or death in order to use what is regarded as such a gold standard test procedure that other legitimate approaches to trials and building up empirical evidence such as used by Dr Raoult, are disregarded, denigrated, dismissed. That speaks sobering volumes on where we have reached as a civilisation and it is why I made then headlined the comments above. Notice, unresponsiveness to the concern, driven by the gold standard fallacy I have highlighted. KF
PS: As this is consistently ignored by objectors, I again highlight the GT rendering of Dr Raoult’s approval of protocol, here with expansion on the regulatory agencies in France involved:
Notice, these regulatory agencies are charged with safety of medicines and medical products and protection of people. Observe, too, the code for Raoult’s HCQ-oriented trials. The suggestion that no legitimate or credible trials and resulting cogent evidence have been provided to date, is groundless but driven by a gold standard ethical, epistemological and logical fallacy.
Ortho:
See the fallacy of a gold standard procedure of testing used to dismiss credibility and results of other approaches? Kindly, see my response to Jerry just above and the concerns in the OP. My concerns are ethical, epistemological and logical. We must never forget, “”first, do no harm.”
Next, let us go to a fortiori logic.
Our situation is, there is a novel, fast spreading, deadly pandemic and full regulatory procedure trials using placebos, animal analogues and in vitro studies etc, development of vaccines and the like are expected to take a year and more. What are we to do now, beyond social distancing, to deal with patients? We see emergence of a standard procedure to use flu with complications approaches to treat, ending up with ventilators or the like.
That means, there is in fact a de facto standard approach, starting with referral or ER procedures and moving through the ward to the ICU. Often, it works and people recover. Regrettably, too often, it does not. Indeed, it is a cluster of odd cases of apparent flu with high deadliness that led to recognition of a new disease, in Wuhan. The doctor making the discovery, regrettably, has died.
So, now, we do not have a baseline of zero but of the standard or somewhat modified flu with complications approach. Therefore, we have a business as usual or as slightly modified baseline. That is what provides an automatic comparison for testing new interventions such as HCQ in a cocktail or Remdesivir, etc. These are there, on in vitro studies going back to SARS1 etc. over the past two decades. There may be animal analogue studies, as the bats seem to suggest.
In that light, the resort to placebos seems even less warranted.
KF
PS: I had a further thought. With the de facto approach being used for many thousands of cases and yielding statistically identifiable patterns of outcomes, what does adding sugar pills or the like add to the near business as usual baseline? Nothing directly physiological, though arguably, hope and confidence [= faith] may help the body’s natural defences. That hope and confidence would be far better placed in physicians willing to be truthful and to use treatments under test with significant reason to hope in their promise. This again underscores the legitimacy of Dr Raoult’s approach and Dr Zelenko’s approach. It also makes the placebo approach even more questionable under these circumstances.
I mean, the placebo patients in a tiral are getting the standard best-practice treatment, so I’m not sure this is relevant to my point.
If you mean case studies can compare some HCQ patients to others not treated with the drug (retrospective of case-study designs), then yes, you can do that. Most of the published results of these studies suggest HCQ has no significant effect. Randomised controlled studies are our best way to know if a treatment really works, and many, many putative cures (for other illnesses) have looked much better than HCQ does in preliminary trials and proved useless in RCTs.
So, I think the balance of evidence suggess HCQ isn’t up to much, but RCTs will help us learn precisely how good or bad it is.
kf – the data are becoming available now, but only now. If Raoult and Zelenko had started proper trials, they would already have results. If Raoult has treated ~3000 patients, then he could already have actual real results. Instead we still have to wait. If HCQ is effective, is it really ethical to let more people die because you didn’t want to find out whether your treatment was effective? Conversely, if your treatment isn’t effective, isn’t it ethical to prevent a waste of time and resources by finding out that it doesn’t work, and thus not sending a lot of doctors down a blind alley?
Either way, how can it be legitimate to not try to provide evidence that would be convincing to health professionals on the efficacy of your work?
Absolute nonsense. We already knew the treatment was effective. Especially with the incredible results of Zelenko. Nearly 100% vs people dying all over the world. There were previous medical studies from 10 years ago explaining why it should work
We already knew this was a disease they had never seen before as the New York doctor said they didn’t know what they were doing. Meanwhile there are doctors having incredible success. New diseases that are killing people in large numbers never get a placebo. The thousands of dead with no effective treatment are your control group.
No it’s attitudes similar to what’s expressed on this site that is letting people die. Did the New York Times help? No they did a hit piece on Zelenko. Did the Washington Post help? No they provided misinformation on hydroxychloroquine.
In research done in France, hydroxychloroquine reduced neither deaths nor admissions to intensive care units among patients who received it. In a study conducted in China and another in Brazil, the two drugs failed to help patients clear the coronavirus faster.
“My own impression so far is that these medications are a colossal ‘Maybe,’” said Dr. Michael H. Pillinger, a professor of medicine at New York University and chief of rheumatology at the Veterans Affairs’ New York Harbor Healthcare System.
But researchers in the United States cautioned that the small number of patients in the studies, their hurried execution and the difficulty of assessing any drug during a medical crisis made all of the findings far from definitive. And it doesn’t help that the drugs have become political footballs, they added.
When COVID-19 patients are hospitalized, they will typically be given oxygen, as well as intravenous fluids to prevent dehydration and maintain electrolyte levels. Medical staff may also start blood tests for markers of inflammation, to track the severity of disease.
In many cases, with patient consent, physicians will administer experimental treatments that may attack the virus or reduce the harmful inflammation that is triggered by COVID-19 infection. Treatments that have been used so far include: the antimalarial drug hydroxychloroquine; the antiviral drug remdesivir; infusions of antibody-laden blood serum from recovered patients; and anti-inflammatory treatments called IL-6 inhibitors.
RH7, we will see. KF
No, Jerry, we don’t.
It’s nearly 100% all over the world. And didn’t Zelenko himself admit that ~ 40% of his cases didn’t have covid-19?
Not on covid-19, of course. And they weren’t trials on real-world patients were they?
BO’H:
What is actually manifest is that despite the label on the tin, we do NOT have “evidence-based Medicine.”
Instead, we have an imposed hierarchy of evidence that institutionalises the Gold Standard fallacy, disqualifying that which might not fit the agenda of the establishment power factions. In a technocratic era, that implies, we are back at the deep state, implying that big decisions are made and implemented based on manipulation across the seven mountains.
In short, the pandemic crisis is in key part symptomatic of a deeper governance crisis in our civilisation. One which, in the US, is at the level of low end 4th generation civil war. One, multiplied by the corruption implicit in enabling the ongoing holocaust of our living posterity in the womb. One, in which key institutions across the board are now increasingly untrustworthy and manipulative [“NEVER let a crisis go to waste . . .”], leading for cause to the rise of populism as people, sensing that something is deeply wrong, seek a champion.
We see how integrated, fragile and brittle things are, from signs in different quarters, such as how oil futures for WTI just hit -$40/bbl yesterday afternoon. Such reflects a glut due to locked in contracts to deliver oil facing a collapse in demand due to a lockdown. Recession and just possibly, depression loom. A pandemic that so far is comparable to the annual flu, has us on a brink of collapse. (And you can bet that in their hidden labs, the bio-war plotters are watching.)
We need ways forward, and in that context it is clear that reasonable treatment for viruses is now a geostrategic issue. After SARS1, that should have been put high on the priority list: broad spectrum, cost-effective antivirals.
It seems plausible that that is why bats were being studied at Wuhan, and the rapid convergence on HCQ suggests that it was likely being used with animal physiological analogues, which are far better suited for placebo or no treatment control studies with deadly plagues than are people.
Of course, it is now plausible that lab containment failed and an epidemic broke out. In that context, HCQ’s rising to the short list would be unsurprising. And in any case, we have a background chatter that it was identified 15 years ago as a candidate broad spectrum antiviral, post SARS1.
Whether or not you are inclined to acknowledge it, several jurisdictions including India, China, Russia, S Korea, The US and Brazil have given emergency approvals of some sort on evidence that is there. Unfortunately, this has got tangled up in the US political and media chaos.
In the case of Dr Raoult and others including Dr Zelenko, it is clear that all empirical evidence is just that, evidence. Including, case records and studies using approved protocols that pivot on cases and compare to the de facto standard near-flu with complications model. Raoult’s now just under 3,000 cases speak. So do the Zelenko cases [and as HCQ is broad spectrum, if vulnerable groups are being cleared of flu too, that is relevant; especially, as it is a good question that the general statistics may be tainted with flu cases and other cases: dying OF Covid-19 is different from dying WITH CV19.]
And, more.
In this context, it is highly relevant to note that after you made serial objections, dismissals and demands for details, you have yet to acknowledge that in fact Dr Raoult’s study at IHU in Marseilles, was in fact done under an officially approved protocol, qualifying it as drug trials. That speaks.
Let me cite again, thanks to GT:
KF
It may well be evidence, but it’s poor evidence.
You can whine and complain, but there are good reasons for not accepting any sort of evidence – it’s easy to reach dangerous and wrong conclusions from them.
You keep on saying that Raoult and Zelenko have successfully treated lots of patients with HCQ. But unless you can show that fewer would have had a successful outcome if they hadn’t been treated with HCQ, this is useless information.
Jerry will probably now chime in saying that the thousands of people who died are the comparison, but he ignores the larger number of people who have recovered.
BO’H, Gold standard fallacy again. KF
The death toll is far higher than being confirmed. In every major country there are thousands more deaths than usual. https://www.nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.html
Nope, I never do. Why do you misrepresent what I say? Search for the comments that say 100% or only 1-2 dead.
I have a question. Have you ever studied statistics? You really should. It is the basis for correct inferential reasoning.
It could explain all the nonsense or trivial comments you make. But actually I claim you make them on purpose because you actually support ID and in this case actually support Zelenko.
Zelenko now has over 60 doctors supporting his approach. I guess because of his amazing statistics and previous studies supporting his treatment.
@20 Jerry:
You’ve opened the can of worms. Bob O’H says he is a statiscian.
Grabbing my popcorn.
Oh, I know. His wife also has a PhD in biology.
That just reinforces my point on the nature of his comments. Have you ever seen a comment by Bob that actually undermines ID or Zelenko’s approach.?
Here is my speculation on this virus. And it’s just that speculation based on a lot of reports by doctors
Most who get it will not even know it and their immune system will defeat it early. Nearly all young people are in this category.
Anecdote: a good friend of my daughter said she got a cold and she lost her taste sensation and sense of smell for a few days. Didn’t think anything of it till she read about symptoms.
Whether they are protected against another bout is uncertain.
A large percentage of those who develop symptoms will defeat it in a week or two as their immune system defeats it. Mostly young people again but probably a high percentage of old people. Can be defeated by Zelenko’s treatment more quickly.
Of the remainder a high percentage if left untreated will be hospitalized. By this time the virus or secondary processes are attacking more than one bodily process. So there are more than one pathological condition. Probably overwhelming immune system.
An unknown number will recover after using a myriad of treatments of which none including HCQ will have a determinate outcome. But it may help a lot of people at this stage but so might other treatments.
Of these a high percentage will need some form of oxygen support as the disease is attacking oxygen delivery and CO2 removal. Of these a high percentage will die.
The question then becomes could these deaths have been prevented if Zelenko’s treatment was administered early on. Or some other treatment if one can be found. We are at minimum talking hundreds of thousands of unnecessary deaths probably several million worldwide. For that outcome some are wed to a questionable research technique.
Not wed tp Zelenko’s treatment but to saving lives and lowering demand on hospital resources.
Again uncertain about ongoing immunity.
Always the possibility of Zelenko making up his results. But even NY Times didn’t go there. And they investigated him.
@22 Jerry:
Are you saying he is our particular Mata Hari?
My homepage. So yes, I have studied it. Quite a lot.
Can you provide a link to a list of them?
This is sarcasm, right?
According to Dr. Zelenko himself, he has only treated 405 patients, and his inclusion criteria were “shortness of breath or who are in the high risk category”. So, he’s not even saying his patients have covid-19, just (at most) one symptom.
No on Zelenko. Yes on you.
I have links. But on iPad at moment. Zelenko is up to 1450 now. I have a list of the doctors on my computer and was on a link provided by DLH a few days ago. I then made the comment that no one was commenting on this update.
They have all been posted. Zelenko first showed up here over three weeks ago. Things have been moving along.
Is that 1450 the number he has treated with HCQ et al. or is it the number he has seen (which was 1354 on the 12th of April)?
Do we have any independent confirmation of Zelenko’s claims yet?
Don’t know but he only uses his treatment on those who are vulnerable (no one under 60) and those showing symptoms (all ages) mainly shortness of breath. But it is at least several hundred and he reported 2 deaths, one due to cancer.
The key ingredient is apparently zinc and HCQ is just an ionophore. There may be other ionophores but HCQ has been shown to facilitate zinc getting into cell and preventing virus from replicating. For example, my wife and I are taking zinc but unless it can get into cells it won’t be effective. Using quercetin in hope it is an ionophore. First heard about this by ET on this site. Which is the reason I am here since the ID people are a good source for science without a political motivation.
Do I know quercetin works for sure. No, but there are reports it has this effect. Now this would be an excellent case for a double blind study. No one has to die in the non-quercetin group.
I pointed to the research at McGill by two research scientists on quercetin. Probably doing double blind studies.
You asked that before and I pointed you to the NY Times.
Here is a link to the doctors using Zelenko’s treatment. Article appeared here about 10 days ago, updated by DLH and ignored. There is a tab for doctors who have endorsed the treatment.
https://coda.io/@covid-19-initiative/immediate-treatment-early-stage-sars-cov-2
Jerry @ 30 – but the NYT only reported what Zelenko said, didn’t it? I don’t think they actually checked his figures.
How negligent of the NY Times not to look into the details.
Can you imagine that if Zelenko was somehow cooking his books even a little that the NY Times, the biggest purveyor of Trump Hate in the US, would not have been all over it. They would have been interviewing everyone in the place about Zelenko’s lies. They would have made the nitpickers here look like amateurs. Still could happen but until it does, have to go with his word.
First came across zinc argument on MedCram, a US medical site aimed at doctors and medical professionals. Posted links here which references past studies providing support for the relevance of zinc. Another medical site in Austria made the same argument. Are these professional sites in collusion?
I have a background in science, physics and math major undergraduate, and was in a PhD program in math where I learned the proof by heart of the Theorem for the Law of Large Numbers, the underpinning of statistics. Changed my whole image of statistics as a technique for reasoning.
Left PhD program to go into US Navy since I realized math was not what I wanted to do. After getting out of Navy got an MBA from Stanford. Also I have learned biology for my business and am grateful for the evolution debate as I learned a lot of cellular biology to understand the arguments. So for a non scientist know a fair amount of science.
What I find interesting about the evolution debate, economics and politics is not the evidence of which there is lots and most clearly leaning in certain directions but the human reaction to these and many other debates. It is all emotional, much of if based on a dislike for positions others are taking or who they are or what they do and nothing to do with evidence or reasoning. The same reactions are taking place on medicine and this virus and especially on one drug.
JT, As has been repeatedly noted here at UD, we are dealing with proxies that are good enough to track with the epidemiological models. We thus see that we are at global peak of spreading and as the driving force that broke exponential growth is still acting, we are headed to decline. China is telling us, we will likely go down several orders of magnitude but will have a pool of fresh infections and fast, secondary etc peaks at a lower level. It is plausible that we will see a major wave in the upcoming flu season. That is a concern, in tension with indications of recession including a sharp drop in oil prices reflecting emerging glut due to lower economic activity. If that begins to hit businesses hard, we could see an induced recession. I note, that the major countries fit into a common pattern on the tracking plots, so there is no good reason to infer that there was a way to avert pandemic once the disease broke out of initial containment. We also need to acknowledge that while models give a reasonable general pattern, they are not as good as was hoped for quantitatively. But then, that is a commonplace in decision theory. KF
BO’H:
I follow up, now that I am back home.
>>You can whine and complain,>>
— belittling ad hominem. What I am doing is speaking i/l/o decision theory [as is commonly taught in, say MBA courses] as further informed by ethical, epistemological and logical considerations, bearing in mind the common sustainability challenge of BAU vs a sustainable ALT. (That last I learned from the Bariloche Foundation of Argentina, years ago. Integrated with SWOT, it is powerful for strategic decisions.)
— There is no good hierarchy of evidence, the question is materiality and credibility constrained by bounded rationality and too often faction or political dynamics and polarisation.
— I suspect you are familiar with the garbage can organisation model, and I am saying we need to find a way out of that vortex.
>>but there are good reasons for not accepting any sort of evidence>>
— On the contrary, there is good reason to evaluate credibility of all serious candidate evidence, including the most empirical of all, summaries of cases including observations. If one automatically relegates that to the garbage bin, one injects self-referential incoherence as one is always making observations and inferences at some level.
— Note, my discussion: https://uncommondescent.com/medicine/hmm-remdesivir-may-be-promising/#comment-699088
>> – it’s easy to reach dangerous and wrong conclusions from them.>>
— that is a general danger of reasoning, hence the importance of first principles and duties of reason, associated logic of being, logic of structure and quantity, etc.
>>You keep on saying that Raoult and Zelenko have successfully treated lots of patients with HCQ. >>
— strawman. I keep pointing out that Raoult undertook a study based on cases, also on in vitro analysis. As I again pointed out today, the umpteenth time, Raoult’s work as distinguished researcher and head of one of France’s IHU’s, in a centre with FOUR hospitals disposing of 3500 beds [and associated with a University has the following approval:
— Dr Zelenko is taking Raoult’s work and that of others to create a treatment regimen that seems to be having considerable success. Where, as he is not really a public figure, NYT and others of like ilk have to be on tip toe with slander tactics, in the aftermath of how Mrs Trump was able to hit those who slandered her, hard. (Much of the bird cage liner level stuff in the media in the US reflects a sad state of defamation law.)
— My basic point is, evidence is evidence.
>>But unless you can show that fewer would have had a successful outcome if they hadn’t been treated with HCQ, this is useless information. >>
— You seem to forget that no inductive investigation [modern sense] is capable of demonstrative proof, only of pistis, which may amount to sufficient to guide a prudent person. And, one can always imagine outcomes in a neighbouring world where instead of X, ~X was the case and the outcome was oh so different or not different at all as suits one’s case.
— What we have is something else, an extension to the BAU vs ALT framework. For, naturally, there is a baseline, near-BAU treatment that extends usual flu and complications treatments. That is yielding a pattern of development of the disease and a branching pattern on resolutions, especially as regards death rates etc.
— The statistics on cases treated with HCQ cocktails (especially, early) can be reasonably evaluated against that, yielding a gap. That gap can then reasonably motivate strategic change.
— And, there is a gap, one credibly in favour of using HCQ + azithromycin [or a similar anti bacterial] + Zn supplements + Vits C and D. As civilian prophylaxis, before one gets to HCQ, we can look at other reasonable supplements. For frontline health workers, prophylaxis may justify HCQ and Azithro.
— Also, masks, social distancing and regular sanitising of hands, surfaces etc. In my case, I am wearing an industrial gas mask as I fit into vulnerable groups.
Now, if and as other evidence comes in we can shift but this looks like best current option on balance of evidence.
KF
F/N A first couple of reads on decision theory http://personal.lse.ac.uk/brad.....0(revised).pdf and https://people.kth.se/~soh/decisiontheory.pdf the ALT vs n-BAU approach to strategic change and critical mass building is built on scenario based planning approaches, informed by work done by the Bariloche foundation. I add, the three mutually interacting domains model — biophysical natural, sociocultural, — econ and policy — is fairly common in sustainability circles. I find that putting BP with PEST or PESTLE models may better communicate with managerial types: PESTLE + BP . . . stressing the biophysical aspects of the environment. Systems theory is also helpful and NASA has a great handbook. Good governance issues relate too. KF
Researchers analyzed medical records of 368 male veterans hospitalized with confirmed coronavirus infection at Veterans Health Administration medical centers who died or were discharged by April 11.
About 28% who were given hydroxychloroquine plus usual care died, versus 11% of those getting routine care alone. About 22% of those getting the drug plus azithromycin died too, but the difference between that group and usual care was not considered large enough to rule out other factors that could have affected survival.
Hydroxychloroquine made no difference in the need for a breathing machine, either.
Researchers did not track side effects, but noted hints that hydroxychloroquine might have damaged other organs.
The study was posted on an online site for researchers and has been submitted to the New England Journal of Medicine, but has not been reviewed by other scientists. Grants from the National Institutes of Health and the University of Virginia paid for the work.
Here is a link to study that RHampton referred to
https://www.nbcnewyork.com/news/coronavirus/more-deaths-no-benefit-from-malaria-drug-hydroxychloroquine-in-va-virus-study/2383680/
And another link
https://apnews.com/a5077c7227b8eb8b0dc23423c0bbe2b2
There is misinformation at end of each article as each article duly portrays the drug in a bad light. They are almost identical so one quoted the other
Most important information not available is how far along were these patients. HCQ might be less effective as the disease progresses. Might be less effective without zinc.
Jerry, there is an old saying, that a stitch in time saves nine. This is a fast-moving disease that as it progresses can do irreversible or fatal damage, directly or indirectly (cytokine storm). We are also familiar with how once synergy is at work, the whole exceeds the simple sum of the parts. For example, you get a virus, which opens the door for bacteria, which jointly do a number on your lungs, which amplifies the process then immune system goes haywire. The faster you hit that, the easier it is to stop. Kindly, explain to me why we should not think in these terms? Or, in terms that hitting the virus, going after the opportunistic secondary and going after the inflammatory response while boosting the Zn ions that feed the antiviral effect all at once makes sense? KF
Texas Republican Senator John Cornyn is calling for clinical trials of a malaria and lupus drug touted for weeks by President Donald Trump as a possible cure for coronavirus.
>> How about real clinical trials? “The nationwide study was not a rigorous experiment. But with 368 patients, it’s the largest look so far of hydroxychloroquine with or without the antibiotic azithromycin for COVID-19, which has killed more than 171,000 people as of Tuesday.”
>> The study was posted on an online site for researchers and has been submitted to the New England Journal of Medicine, but has not been reviewed by other scientists.
Jerry @ 37 –
Yes, this is a genuine concern. The preprint is here, and they discuss this specific issue:
So, even after controlling for the patients treated with HCQ being sicker, they find the same result.
The usual caveats should apply – this isn’t a randomised trial, so there might be confounders that aren’t being considered. But it isn’t looking promising for a HCQ or HCQ+AZ treatment. It’s certainly not a miracle cure.
Incidentally, for those using the in vitro activity of HCQ as evidence that it works in clinical practice, the authors of the preprint address that in their discussion: