Daily review 08/03/2021

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1. RedLogix 1

   8 March 2021 at 6:01 pm

   First the Vitamin D debacle – now the Ivermectin denial. How much blood on their hands?

   Study link.

   Conclusions.

   Ivermectin is an essential drug to reduce morbidity and mortality from COVID-19 infection.

   Placebo-controlled trials of ivermectin treatment among people with COVID-19 infection are no longer ethical and active placebo-controlled trials should be closed.

   https://www.youtube.com/watch?v=ix8i7dfsCJg
   • Drowsy M. Kram 1.1

     8 March 2021 at 6:49 pm

     How much blood on their hands?

     On WHOse hands? The USFDA's? The editors of Frontiers in Pharmacology?

     Why You Should Not Use Ivermectin to Treat or Prevent COVID-19

     Frontiers Removes Controversial Ivermectin Paper Pre-Publication

     After being contacted by The Scientist, the journal posted a statement from Frontiers’s chief executive editor, Frederick Fenter, saying that “Frontiers takes no position on the efficacy of ivermectin as a treatment of patients with COVID-19, however, we do take a very firm stance against unbalanced or unsupported scientific conclusions.”

     This isn’t the first time that Kory and his colleagues at FLCCC have been accused of making unsubstantiated claims about ivermectin.

     Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19
     Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.

     How Covid-sceptics were duped by the “wonder drug” ivermectin

     Dr. Roach: Ivermectin for COVID is still in trial phase

     I think I understand where you're coming from RL. We all want this global pandemic to be "over" sooner rather than later – that's only natural. But the ‘medical jury‘ is still out on the utility of imvermectin as a treatment for COVID-19, and claiming that unspecified people have blood on their hands is unhelpful, imho.

     https://pharmaceutical-journal.com/article/feature/everything-you-need-to-know-about-the-covid-19-therapy-trials#Ivermectin
     • RedLogix 1.1.1

       8 March 2021 at 6:58 pm

       Did you bother to read the actual study or even watch the relatively short summary video? If not then I'll do your homework for you:

       Dr. Tess Lawrie is a specialist medical researcher. In essence she has taken raw data from a number of ivermectin studies around the world and using a sophisticated software tool designed for this purpose, she has essentially synthesised one very large one.

       The results are quite conclusive. For a start – an 83% reduction in deaths.
       • Drowsy M. Kram 1.1.1.1

         8 March 2021 at 7:08 pm

         Yes RL, I did bother to read the actual study (didn’t watch the video), and I agree that the results are quite conclusive. Have you never been wrong? I know I have.

         But the ivermectin proponents have been duped – not by a specific person, necessarily, but by their own desire for a simple answer to the pandemic. It could easily be that, once the high-quality trial data comes in, we discover that ivermectin is useful under some circumstances. But there’s simply no basis for saying that at present. Until that evidence appears, the advocacy for ivermectin tells you more about the psychology of its proponents than it does about any effects of the drug.

         The ivermectin proponents may well be right, and I genuinely hope that they are.

         https://trialsitenews.com/bird-evidence-to-decision-framework-meeting-for-ivermectins-efficacy/
         • RedLogix 1.1.1.1.1

           8 March 2021 at 7:13 pm

           Yes I read that – the guy is a psychologist ffs.

           On what evidential basis has he made this diagnosis when writing this article do you imagine? Or was he just interviewing his keyboard?

           As for the wider medical industry – it has this fundamental problem around a massive loss of credibility (and potential liability) if it reverses it’s stance now.
           • Drowsy M. Kram 1.1.1.1.1.1

             8 March 2021 at 7:29 pm

             Or was he just interviewing his keyboard?

             Ritchie wrote “Science Fictions: How Fraud, Bias, Negligence and Hype Undermine the Search for Truth” – you might have more in common than you think!

             Providentially there's no need for New Zealanders or Australians to start taking ivermectin (one of the concerns mentioned by the FDA) – we're in the fortunately situation of being able wait for COVID-19 vaccine roll-outs.

             Amazingly lucky really – a year ago I wouldn't have thought it possible.
             • RedLogix …

               8 March 2021 at 7:56 pm

               Again on what evidential basis did our pyschologist use to make his diagnosis when writing that article? Essentially his arguments are so broad brush and generic they can be used to discredit absolutely anything.
               • Drowsy M. Kram …

                 8 March 2021 at 8:15 pm

                 Again on what evidential basis did our pyschologist use to make his diagnosis when writing that article?

                 RL, I don't have a pyschologist, although if I felt the need for one then I could do worse than Ritchie.

                 As for ‘evidential basis‘, Ritchie's brief article contains at least 17 links; I reckon a couple might direct to the "evidential basis" for his opinion.

                 Btw, it's quite intriguing that one of the ivermectin proponents mentioned in Ritchie's article apparently claimed that ivermectin “should render lockdowns redundant” – the pandemic would effectively be over – a quite ‘fantastical‘ claim, don’t you think?
           • McFlock 1.1.1.1.1.2

             8 March 2021 at 7:37 pm

             A "retired Nurse Teacher" beats a psychologist when it comes to analysing population research?

             Curious.
             • RedLogix …

               8 March 2021 at 7:49 pm

               Again an obvious sneering ploy. You're on a roll here tonight.
               • Drowsy M. Kram …

                 8 March 2021 at 7:53 pm

                 “…the guy is a psychologist ffs.” “Or was he just interviewing his keyboard?”

                 Again an obvious sneering ploy
               • McFlock …

                 8 March 2021 at 7:54 pm

                 As obvious as your "the guy is a psychologist ffs."

                 🙄
       • Andre 1.1.1.2

         8 March 2021 at 7:19 pm

         Lawrie's study bears a remarkable resemblance to a copy and paste job on the (now withdrawn by Frontiers in Pharmacology) FLCCC review, with a few embellishments.

         The grounds for withdrawal include:

         During review of the article in what the journal refers to as “the provisional acceptance phase,” Fenter says in the statement, members of Frontiers’s research integrity team identified “a series of strong, unsupported claims based on studies with insufficient statistical significance, and at times, without the use of control groups.”

         The statement continues: “Further, the authors promoted their own specific ivermectin-based treatment which is inappropriate for a review article and against our editorial policies. In our view, this paper does not offer an objective nor balanced scientific contribution to the evaluation of ivermectin as a potential treatment for COVID-19.”

         https://www.the-scientist.com/news-opinion/frontiers-removes-controversial-ivermectin-paper-pre-publication-68505

         Those flaws mostly apply equally to Lawrie's review, since it is based on the same flawed studies the FLCCC review used.

         The idea that there might be common cheap drugs out there that could be repurposed against covid but are being ignored because … reasons … is debunked by the ready acceptance of using dexamethasone. After it had been robustly shown to be beneficial to specific groups of patients.
         • McFlock 1.1.1.2.1

           8 March 2021 at 7:27 pm

           It's a check of the FLCCC data, not a review of the actual methodology.

           Frankly, it simply reinforces my initial assumption that [edit: my bad, rl had a link. Still crap, though].
           • RedLogix 1.1.1.2.1.1

             8 March 2021 at 8:01 pm

             It's a check of the FLCCC data, not a review of the actual methodology.

             Here is Lawrie's own statement on p2 of her report:

             The FLCCC review summarizes the findings of 27 studies evaluating ivermectin for prophylaxis and treatment of COVID-19 infection; however, it does not include metaanalyses for the majority of outcomes. The FLCCC has called upon national and international health care agencies to devote the necessary resources to checking and confirming this groundbreaking evidence.

             Given the urgency of the situation, I undertook this rapid systematic review and metaanalysis of studies included in the FLCCC paper to validate the FLCCC’s conclusions

             In other words she took their raw data, used her own methodology and expertise as a medical researcher, and has published her own conclusions. Which on the face of it are an independent validation of FLCCC's work.
             • Andre …

               8 March 2021 at 8:07 pm

               If the studies the FLCCC piece used were unreliable because of serious methodological flaws, thereby invalidating FLCCC's conclusions, that same 'garbage in, garbage out' flaw equally applies to Lawrie's piece.
               • RedLogix …

                 8 March 2021 at 8:47 pm

                 that same 'garbage in, garbage out' flaw equally applies to Lawrie's piece.

                 Not necessarily. If you bothered to listen to Lawrie's explanation you would see how she overcomes these challenges.

                 Real life medical data is very rarely clean and conclusive – it's almost always necessary to apply analytical tools to produce useful information. It's worth a quick review of what evidence based medicine is about, and how various levels of evidence are used to guide the clinicians.

                 Fully gold plated RCT's are by no means the sole basis on which progress is made.
                 • McFlock …

                   8 March 2021 at 8:56 pm

                   If you want to talk about "wonder drugs" in senate hearings RCT's are the bare minimum, let alone a gold standard.
                   • RedLogix …

                     8 March 2021 at 9:07 pm

                     In which case we would never have been allowed to make the connection between say smoking and lung cancer.
                   • McFlock …

                     8 March 2021 at 9:18 pm

                     Smoking had loads of RCTs. Sure, in animals, but they supplemented decades and billions of dollars put into other research.

                     Ivermectin & covid? not so much when Kory was talking "wonder drug".
                   • RedLogix …

                     8 March 2021 at 9:25 pm

                     Not one single human RCT trial was ever performed to adequately establish the smoking/lung cancer connection. Instead:

                     The association between cigarettes and lung cancer has been proven by large cohort studies.

                     Evidence based medicine =\= RCT
                   • McFlock …

                     8 March 2021 at 9:48 pm

                     "wonder drug"

                     That requires a shedload of evidence that still doesn't exist.

                     "in humans"

                     Because that's what I said? Nope. But all them rats rabbits and monkeys served an important purpose.
             • McFlock …

               8 March 2021 at 8:13 pm

               Leaving out the core validation step of seeing if the review gathered all relevant studies.

               She checked their math. This is not validation or review.
               • RedLogix …

                 8 March 2021 at 8:23 pm

                 She checked their math. This is not validation or review.

                 Taking the raw data, confirming and clarifying it to the extent possible by contacting the originating researchers in multiple countries, and then applying your own independent methodology is the very definition of a validation.

                 After all this sort of specialised work seems to be pretty much Lawrie’s day job. I’m merely reporting on her work, it rather astounds me there are so many other people here who consider themselves so much smarter and more experienced they can tear her work down without even listening to her.
                 • McFlock …

                   8 March 2021 at 8:41 pm

                   It's the very definition of checking their math, it's not a validation of the paper.

                   The other thing about science is that you put the important information in the article, not in a youtube video.
                   • RedLogix …

                     8 March 2021 at 8:53 pm

                     What you're effectively demanding is that Lawrie should have conducted her own independent clinical research and generated her own raw data before doing her own analysis of it. That's something quite different and would be called an independent replication.

                     A validation takes someone else’s raw input data and subjects it to your own independent analysis. (This is what Lawrie has done.)

                     A review takes the someone else’s data and their analysis – and then checks it for mistakes. This is what the vast majority of ‘peer reviews’ constitute so it’s by no means a weak method either.
                   • McFlock …

                     8 March 2021 at 9:01 pm

                     Totes. Reviewers never state "why wasn't this paper/study included". /sarc

                     In real life, they're usually talking about research published after your paper was submitted (if you're lucky).

                     Edit: as for validation only checking the math when the main determinant of any review is the methodology behind selecting which research to include, regardless of semantics a purely quant approach seems pretty damned inadequate given the subject matter and snake-oil sales frenzy around covid.
                   • RedLogix …

                     8 March 2021 at 9:18 pm

                     If you have any questions on the difference between replication, validation and review feel free to ask. I'll do my best to clarify.
                   • McFlock …

                     8 March 2021 at 9:43 pm

                     Save your youtube links. If the paper was any good, you wouldn't need to waste time on semantics. You would say any of the following:

                     Why yes, they did actually control for incredibly obvious factors such as smoking in all the studies that looked at a treatment for a respiratory illness, look that's mentioned on page xxx of the article

                     Why, yes, they did cover all the applicable research, the Lawrie paper outlined their lit review process on page yyy and, barring a couple of papers published after the FLCCC paper, all major studies were there.

                     Why, yes, they did have more than a few thousand participants in total

                     gosh, no, not at all, the author of the original study does not have a history of hyperbolic and unsubstantiated claims that their research conveniently substantiates

                     why yes, I do get my information about epidemiology from a trained scientific researcher, even one trained in epidemiology . I carefully vet all my youtube sources to make sure they know what they're talking about even if it's not my main area of publication history, thank you for asking.

                     But you can't say any of that in truth.
                   • RedLogix …

                     8 March 2021 at 9:50 pm

                     That makes no sense.

                     Is this the link you meant to include
                   • McFlock …

                     8 March 2021 at 10:00 pm

                     Again, you're not doing the case for ignoring comorbidities much favour. Unless your argument is "yes, the current evidence is shit, but it works I promise".

                     The comment was pretty solid: if your links were any good, you wouldn’t be debating semantics.
                   • RedLogix …

                     8 March 2021 at 10:19 pm

                     Semantics = the meaning of words.

                     In this context the words replication, validation and review each have specific meanings that I attempted to outline above. Pretending otherwise is a deliberate derail.
                   • McFlock …

                     8 March 2021 at 10:28 pm

                     That's the shizzle.

                     If the actual research was meaningful, you wouldn't be getting all huffy about semantics.

                     Rather than lecturing me in what checking the math should actually be labelled, maybe you should address why checking the math applied to the data (while not checking the methodology for selecting the particular papers from which that data came) adds anything at all to the significance or reliability of the withdrawn FLCCC paper?
                   • RedLogix …

                     9 March 2021 at 12:08 am

                     You miss the point completely – it doesn't matter what grounds the FLCCC group used to select their research data, by going back to their originating source data to confirm it, and using her own independent analysis to generate her own conclusions – then Lawrie has performed a validation of the work FLCCC have done within it's original parameters.

                     Denigrating this process as merely ‘checking the math’ is more of your usual underhand playing the man.
                   • McFlock …

                     9 March 2021 at 10:00 am

                     I thought that the main point was that the FLCCC paper had serious methodological errors and made claims that its data did not support, and that by ignoring all of those issues Lawrie's paper does nothing to change that.

                     Even if the math adds up.

                     If you're doing a review of publications to judge the effectiveness of a treatment, the criteria and thoroughness by which you include or exclude publications for your review is absolutely fundamental to the quality of your outputs.
                   • RedLogix …

                     9 March 2021 at 10:56 am

                     If you want to take apart Lawrie's work it would be best to have some sense of what she actually did. Campbell has two videos that deep dive on this. (Each one is about an hour long and I have minimal expectation anyone here will watch.)

                     In a nutshell my understanding goes like this. It's entirely likely that most smaller studies, where n is typically in the range of 100 – 500, and conducted in clinical settings under severe stress, will have 'serious technical flaws' in their design or implementation. (It's worth keeping in mind we're talking about clinician's who have to daily face a massive human toll of suffering here – and I'm of no mind to play keyboard warrior with their motives or integrity.)

                     In each research event there are three broad things to consider, the design of the study, it's actual implementation and the data analysis used to turn the raw data into a actionable information. All three aspects need to be evaluated in order to judge the 'quality' of the conclusion. Absent the funding and resources available to Big Pharma, clinician directed research will likely fall short on at least one aspect.

                     However when you have the raw data from multiple such studies then you not only have the opportunity to dramatically increase the n count, but more importantly evaluate the data according to a single consistent rule set. Done properly it's entirely possible to take a dozen or more 'flawed' studies and synthesise a single much larger one of much better quality. It's my understanding that this kind of work is pretty much Lawrie's day job.

                     As an aside the basic concept here is very similar to something I've worked with myself in an industrial process control setting – virtual sensors. Often there are good reasons why a direct physical measurement of a process parameter is not available, but with careful modelling and some clever data analysis, it's possible to synthesise an indirect software 'virtual' model of the measurement you want from otherwise indirect, weak and usually noisy data. In principle the direct physical measurement would always be better, but practice it's amazing just how good the virtual version can be. It's the exact opposite of the popular old saw 'garbage in, garbage out' – we can take garbage and make gold of it.

                     A similar idea is at work here – take multiple sources of low quality data, clean them up, get them aligned properly – and out falls a conclusion that can be of much higher quality than what could be drawn from any single one of the original sources. Reducing this process to just 'checking the math' is like saying your cellphone is nothing more than a fancy crystal radio.
                   • McFlock …

                     9 March 2021 at 1:24 pm

                     Saying a study has methodological issues indicates nothing about the integrity of the original researcher. It does, however, say a lot about the reliability of the research.

                     However when you have the raw data from multiple such studies then you not only have the opportunity to dramatically increase the n count, but more importantly evaluate the data according to a single consistent rule set. Done properly it's entirely possible to take a dozen or more 'flawed' studies and synthesise a single much larger one of much better quality. It's my understanding that this kind of work is pretty much Lawrie's day job.

                     If the studies are flawed in a systematic way, then no, conflating the systematically-biased datasets does not result in better quality.

                     If no work has been done to examine whether the source studies were selected with an accidental systematic bias, then one might merely be repeating a systemic error.

                     Think of it this way: that modelling process you're using to indirectly monitor a variable. How would that work if a third of the variables being measured were essentially null values, and only three of the 17 remaining directly measured your selected variables with reliable precision, while the others were possibly measuring something else entirely?

                     The short version is this: ivermectin might have some benefit to covid patients, or it might not. The data at bests suggests further research of a robust and much larger scale might be useful, along with further research into every other youtube (nonclinical) doctor's "wonder drug".

                     Throwing even apparently-harmless medications at people on the off-chance it'll have a positive effect, done on the frequency that youtube videos recommend, is at significant risk of violating the principle "first, do no harm" via unintended consequences. Did we learn nothing from antibiotic resistance?
                   • RedLogix …

                     9 March 2021 at 2:05 pm

                     If the studies are flawed in a systematic way, then no, conflating the systematically-biased datasets does not result in better quality.

                     I took some time to try and explain to you why this is not always the case, just repeating your misunderstanding doesn't progress anything. The fact that medical researchers like Lawrie do this kind of work all the time – and get paid for it – is a big fat clue that this kind of analysis can and does yield valuable results.

                     that modelling process you're using to indirectly monitor a variable. How would that work if a third of the variables being measured were essentially null values, and only three of the 17 remaining directly measured your selected variables with reliable precision, while the others were possibly measuring something else entirely?

                     That's precisely the kind of problem I've seen solved reliably with virtual sensors. They're a subset of a much larger disciple called advanced process control – and while I came to it too late in my working life to become an expert on it, I've done enough with it to understand broadly what it's capable of. Frankly when you get it going correctly – it's capable of things that look a bit like magic.
                   • Drowsy M. Kram …

                     9 March 2021 at 2:46 pm

                     The fact that medical researchers like Lawrie do this kind of work all the time – and get paid for it – is a big fat clue that this kind of analysis can and does yield valuable results.

                     And in the fullness of time we will probably have a better idea of just how valuable Lawrie's analysis is. At present, however, that ‘value’ is a matter of debate, wouldn't you agree RL?

                     The unprecented speed of development of several effective COVID-19 vaccines is "a big fat clue" that pharmaceutical companies have been taking the pandemic threat seriously, but the precautionary principle still applies. My vitamin D levels are good, and I'm operating at (a personal) level 2 pretty much all the time, so (in NZ) I reckon I can wait a few more months for my jab.

                     If my GP started advocating ivermectin for COVID I'd run a mile, figuratively of course.
                   • McFlock …

                     9 March 2021 at 3:21 pm

                     RL, if the FLCCC study was persuasive enough to say "How much blood on their hands?", you wouldn't have to try to convince people magic exists.
                   • RedLogix …

                     9 March 2021 at 3:28 pm

                     At present, however, that ‘value’ is a matter of debate, wouldn't you agree RL?

                     Depends on what exactly you're debating here. Seems to me there's a bunch of people acting like gatekeepers, determined to limit the allowable conversation more than anything else.

                     And of course while I've highlighted Lawrie's work here, she's by no means alone. Dr Andrew Hill has also recently gone public with very similar results. This guy comes from a very conservative position – relying only on good RCT evidence.
                   • Andre …

                     9 March 2021 at 4:03 pm

                     At first glance, Hill's study appears to be based on many of the same studies with serious methodological problems that FLCCC and Lawrie used. Ahmed:Bangladesh, Elgazzar:Egypt, Niaee:Iran, are just the first three I checked, and they're common to both Hill and Lawrie/FLCCC. And therefore Hill’s piece suffers the same 'garbage in, garbage out' problem.

                     Meanwhile, a much more robustly designed study with fewer flaws finds

                     Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.

                     https://jamanetwork.com/journals/jama/fullarticle/2777389?guestAccessKey=ab31cadb-b516-469a-be55-bbbf6b2c7b11&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=030421

                     So hmmmm, a pile of deeply flawed studies on one side gathered up by someone that way overhypes ivermectin to the point of calling it a wonder drug, versus a well-designed carefully conducted study that finds no benefit?

                     It may still be that ivermectin provides a limited benefit to specific patients under specific conditions, but "wonder drug" it definitely ain't. Nor is there blood on anyone's hands for not falling all over themselves to push it onto people in advance of there being good evidence for using it.
                   • arkie …

                     9 March 2021 at 4:05 pm

                     Zain Chagla, MD, an infectious diseases physician at McMaster University in Hamilton, Ontario, reviewed each of the trials in Hill's review in a Twitter thread. He called the overall evidence "very low grade" and was also unhappy that Hill disseminated it as a video.

                     "We always want to see these things published, rather than me walking through a video, pulling these studies myself," Chagla told MedPage Today.

                     He said if there was indeed a signal for efficacy, he would have expected ivermectin to be rolled into the SOLIDARITY or RECOVERY study by now.

                     https://www.medpagetoday.com/infectiousdisease/covid19/90552

                     Those pesky scientists gatekeeping the scientific method and analysis…
                   • McFlock …

                     9 March 2021 at 4:08 pm

                     Hill seems a lot more reserved in his conclusions than Kory.

                     In fact, his ppt comment "We need more clinical trials data to confirm the clinical benefits observed in the first 11 randomized clinical trials" is much closer to "The short version is this: ivermectin might have some benefit to covid patients, or it might not. The data at bests suggests further research of a robust and much larger scale might be useful" rather than "wonder drug".

                     So I'm much closer to Hill's position than Kory's.
                   • RedLogix …

                     9 March 2021 at 4:17 pm

                     And therefore Hill’s piece suffers the same 'garbage in, garbage out' problem.

                     As I've taken sometime to explain above to McFlock this is not necessarily the case. Just repeating a slogan without making the effort to understand exactly how the meta analysis process works is lazy and low grade imo. Meta analysis exists because done properly it can and does yield results not readily available otherwise.

                     As for you Colombian study – how about quoting the limitations section for balance?

                     @arkie

                     Frankly I don't do Twitter – garbage in garbage out.
                   • McFlock …

                     9 March 2021 at 4:30 pm

                     @Andre:
                     you mean it's possible to conduct an ivermectin ICT that even excludes a respiratory comorbidity in its sample selection, as well as reporting the proportions of known comobidities in study participants by intervention and placebo groups?

                     Gosh, maybe we should have more of them. I'd been reliably informed that such a study would be absolutely unethical, but I guess if this rct can get through several ethics committees, maybe that was a slight overstatement.

                     @RL: meta analysis might be able to produce more than the sum of its parts. But the sum of this one’s parts are small, and have significant methodological errors.
                   • arkie …

                     9 March 2021 at 5:26 pm

                     @RL

                     I didn't link to twitter, I linked to an article by MedPageToday.com that interviewed a clinician who uses twitter, expressing concerns about why these 'experts' feel the best way to communicate with medical professionals is through youtube videos.

                     Also that the evidence isn't good.

                     No need to 'do twitter'.
                 • Drowsy M. Kram …

                   9 March 2021 at 5:34 pm

                   Depends on what exactly you're debating here.

                   Apologies RL (@3:28 pm) if I what I wrote @2:46 pm wasn't clear to you; I was referring to the current debate about the value of Lawrie's analysis, a debate not confined to this page of The Standard. Can we perhaps agree that the value of Lawrie's analysis in settling the matter of the effectiveness of ivermectin for the clinical treatment of COVID-19 infections is a matter of on-going debate, i.e. the value of the analysis is debatable (for now), and so the matter is not settled (for now.)

                   Seems to me there's a bunch of people acting like gatekeepers, determined to limit the allowable conversation more than anything else.

                   Does that include me? I wasn't aware that I was trying to limit allowable conversation, and apologise (again) if I have given you that impression. I'm simply not as certain as you are about the utility of ivermectin treatments and/or (for that matter) vitamin D supplementation to protect against or alleviate the symptoms of COVID-19 infections.

                   To be honest, if you hadn't appended the "How much blood on their [?] hands?" comment I probably wouldn't have replied, but that type of shock jock hyperbole is objectionable, imho.
         • RedLogix 1.1.1.2.2

           8 March 2021 at 7:34 pm

           Do you have any evidence that Lawrie's study is a copy and paste job – ie a plagarised study? Or are you accusing her of being a fraud? If so then just come out and say so. Otherwise all you're attempting here is a rather obvious smear by association by skating on some rather thin ice.

           As for the withdrawal of the FLCCC's paper, how about putting up their response for balance:

           The paper’s removal has drawn anger from members of the FLCCC and its followers. In comments on Twitter and in an interview with The Scientist, the organization’s president, Pierre Kory, describes the move as “censorship.” He adds in the interview that the paper had already successfully passed through multiple rounds of review. In reversing the paper’s acceptance, the journal is “allowing some sort of external peer reviewer to comment on our paper,” he says. “I find that very abnormal.”

           The paper was clearly not withdrawn by the authors or rejected by reviewers, but by some unknown external party.
           • Andre 1.1.1.2.2.1

             8 March 2021 at 7:49 pm

             Lawrie herself acknowledged the dependence of her piece on what the FLCCC produced.

             Frontiers in Pharmacology decision-makers withdrew the paper. These are experts that need to consider the credibility and reputation of their publication. Seems to me that carries a lot of weight. Much more weight than a few people pushing a dubious barrow trying to get a publication.
             • RedLogix …

               8 March 2021 at 8:17 pm

               Nope – she used their raw data and contacted the originating research teams to confirm and clarify it.

               She confirms this in two much longer interviews with Campbell that I won't bother linking to because I know how short your attention span is.
             • RedLogix …

               8 March 2021 at 8:36 pm

               And I'm not sure exactly how much 'weight' I would put on an editorial decision made like this:

               Responding to the Frontiers statement’s invitation to the authors to submit a revised version of the paper, Kory says that while he would have been open to removing mentions of his own team’s treatment protocol, he doesn’t want to work with the journal again. “There was no communication with us, no telling us of their concerns, no discussion” during this process, he says. “The idea that I would resubmit to that journal is fairly preposterous, don’t you think?”

               It seems to me that if the Frontier's management were genuinely concerned about the paper then good faith would require at least some communication on exactly why they were going to withdraw it.

               This strongly suggests they don't want to defend their decision in public, or have it put under too much scrutiny.
               • Incognito …

                 8 March 2021 at 11:11 pm

                 That seems to directly contradict the statement by the journal:

                 “Our concerns were discussed by the handling editor and myself, and then further investigated by an external expert. The decision was made to reject the paper prior to publication, which was communicated to the authors via the normal channels. We note that last week the authors offered a revised version of their paper for consideration, based on the concerns discussed with the Handling Editor. Should the authors formally submit the revised manuscript, and should our concerns be addressed in this new version, the updated paper will be assessed for publication according to our standard review process. The original version has been published by the authors on their website and is available for all to read and to judge for themselves.”

                 https://blog.frontiersin.org/2021/03/02/2-march-2021-media-statement/
       • McFlock 1.1.1.3

         8 March 2021 at 7:26 pm

         17 studies. 3 excluded comorbs, 8 included (and I'll include parasitic worms as a comorbidity, although this isn't mentioned in the review). The rest did not report comorbity. Ivermectin is a worming medication.

         So there's a decent chance that all it reports is that undiagnosed parasitic worm infections might increase covid-related mortality (in a sample size of ~4k, ffs).

         Of the fifteen studies, FOUR reported the prevalence of smoking. One might imagine smoking could have an effect on the outcome for a patient with a respiratory condition so controlling for it could help with the reliability of one's research, but hey, I don't have a youtube channel.
         • RedLogix 1.1.1.3.1

           8 March 2021 at 7:47 pm

           Ivermectin is a worming medication.

           It's widely regarded as one of the most valuable medications the human race has ever discovered, effective against a remarkable range of parasites. Sneering at it as a 'worming medication' is an obvious ploy.
           • McFlock 1.1.1.3.1.1

             8 March 2021 at 7:57 pm

             …

             Doesn't that make the failure of the majority of studies in the review to exclude comorbidities even worse?

             You just expanded the list of comorbidities upon which ivermectin has a demonstrable effect into "a remarkable range".

             Confounding, much? We cannot know from this review.
             • RedLogix …

               8 March 2021 at 8:14 pm

               By that amazing logic, if hypothetically we discovered a magic bullet that really did cure everything – we wouldn't be allowed to use it because co-morbidities.
               • McFlock …

                 8 March 2021 at 8:37 pm

                 What you do is a multivariate analysis.

                 Depending on how deep you want to dive (which is affected to some degree by your sample size and the size of the effect you observe in previous research papers), you look at each comorbidity controlled for all the other factors.

                 You have some rationale of biological plausibility in the confounding comorbidities to avoid datamining every 95% "significant" result, but given covid is largely a respiratory condition one would expect other respiratory-affecting comorbidities (such as, oh, I dunno, smoking and parasitic infections that can affect the lungs let alone ones your intervention actually treats) to be controlled for in the analyses. Probably narrowing down the list with the guidance of a research clinician because they actually know how the body works.

                 And never, never, wikipedia the conditions to see if there's biological plausibility. It's probably not too far off accuracy-wise, but the pictures are usually disgusting.
                 • RedLogix …

                   8 March 2021 at 9:14 pm

                   What you do is a multivariate analysis.

                   Which you can reasonably do with very large data sets, but with each co-morbidity (variable) you introduce, the numbers necessary to generate strong results just become more and more daunting.

                   In a fast moving pandemic demanding perfection, and conducting massive RCT trials in which you have every reason to expect that large numbers of your placebo control group are going to be harmed or die unnecessarily is absolutely unethical. As Lawrie points out, quite a few RCT trials are terminated early for this reason.
                   • McFlock …

                     8 March 2021 at 9:21 pm

                     Yet the vaccine producers managed to log comorbs and get tens of thousands of participants for their RCTs.
                   • RedLogix …

                     8 March 2021 at 9:44 pm

                     So a quick search throws up this on the Moderna vaccine trials:

                     The Phase III randomized controlled trial accrued the number of cases needed to meet the primary endpoint of vaccine efficacy against symptomatic COVID-19 and the secondary endpoint of vaccine efficacy against severe COVID-19, based on a protocol definition that did not require hospitalization. Hospitalizations due to COVID-19 and deaths are less common, thus, Phase III trials may not be designed or statistically powered to evaluate differences between vaccine and placebo arms for these outcomes. However, for hospitalization due to COVID-19, a statistical difference was observed based on only 10 cases in the Phase III trial. Since robust direct evidence is not expected from early results from Phase III studies, vaccine efficacy in preventing hospitalizations due to COVID-19 and deaths may also be inferred from observed efficacy against symptomatic COVID-19. Preliminary data from one study suggested possible short-term efficacy against asymptomatic SARS-CoV-2 infection after one vaccine dose, but no data were available to assess long-term efficacy or efficacy after two-dose vaccination series completion. No data were available for assessment of SARS-CoV-2 seroconversion.

                     And this is on a trial that if I read the report correctly had over 14,000 participants – yet still they don't have robust evidence on their effectiveness to prevent death. Instead they're "inferred from observed efficacy against symptomatic COVID-19" which seems a perfectly reasonable approach.

                     The point being that if we had demanded absolute gold standard proof, the rollout of these vaccines could have been delayed many more months. Instead we went with a reasonable inference.

                     Look at what else they cannot robustly conclude – yet these Phase 3 trials have been reasonably used to approve the use of a vaccine type never used before.

                     And here we are debating whether or not ivermectin, an exceptionally safe and cheap medicine that literally billions of people (and even more animals) have taken with no harm whatsoever, should be used in clinical settings or not.
                   • McFlock …

                     8 March 2021 at 9:56 pm

                     " accrued the number of cases needed to meet the primary endpoint of vaccine efficacy against symptomatic COVID-19 and the secondary endpoint of vaccine efficacy against severe COVID-19, "

                     Where's the equivalent evaluation for ivermectin?

                     And do you really want to be part of a panic rush for a so-far likely ineffective covid treatment that millions of people might need to treat the infections it actually works on? Were you on the bandwagon for an earlier one?
                   • RedLogix …

                     8 March 2021 at 10:12 pm

                     Nope – I've never suggested HCQ was going to be particularly useful.

                     It did irk me that the issue got so grossly politicised, and resulted in all manner of contradictory statements and official warnings about it's safety, when in fact it's been used by extensively for many decades to treat malaria with no such concerns.

                     When I was working in Latin America our own travel doctor handed it out to the team like aspirin.
                   • McFlock …

                     8 March 2021 at 10:19 pm

                     Company doctor? Main priority that none of the workers were immobilised while on the job?

                     Never did you any harm, must be fine then.
                   • RedLogix …

                     8 March 2021 at 10:39 pm

                     Company doctor?

                     In Australia some doctors and clinics specialise in 'travel medicine', a city the size of Ballarat with about 100,000 people had two. They're open to the general public, and ordinary people would constitute most of their clients. You don't have to be 'on their books' to see them as you would your GP, and I found the consultation quite helpful as he made me aware of hazards I had never thought about before.

                     They also specialise in necessary vaccinations for things like yellow fever, typhus, rabies and the like, and issue a vaccination record booklet. I still have mine as it’s necessary to produce it at border control whenever you return from certain countries.

                     Your cynical implication that they allow harm to come to their clients because employers pay them to is … fucked in the head.
                   • McFlock …

                     8 March 2021 at 10:54 pm

                     Yeah. ACC say the same thing about their doctors, too.
                   • Treetop []

                     9 March 2021 at 9:02 am

                     Some of the ACC doctors need to be investigated for the harm they do. Initially a doctor signs an injury form. Then ACC process it. When it comes to back pain and a mental injury (speaking from experience) ACC have a harmful process when it comes to sticking to the facts.

                     It has always struck me as being odd that ACC accept cover for an injury and then they change their interpretation down the track for the covered injury.
                   • RedLogix …

                     8 March 2021 at 11:43 pm

                     Are you claiming that Australian travel doctors routinely give bad advice they know will harm their clients?

                     You might want to produce some direct evidence of this or withdraw.
                   • Treetop []

                     9 March 2021 at 2:24 pm

                     I am not sure of the numbering. I am saying this about ACC doctors who do assessments.

                     The link from McFlock (their doctors) raised Judge Beattie. In the early 2000's Beattie gave me a reserved judgement for a back injury.

                     I have found the Aussie judicial system to not be as thick as the NZ system. Mesothelioma in Australia was thrased out in the courts and this helped to shut up some ACC specialists.

                     I have been put through hell by ACC and the health system. ACC is unworkable when it comes to complex and complicated cases. ACC get in it above their head and they know it is above the head of the complainant. Confusion arises and ACC then dump on the complainant. ACC need to acknowledge their behaviour, change it and then look at the cost the behaviour of ACC has had on the complainants life.
                   • Muttonbird …

                     8 March 2021 at 11:45 pm

                     Settle down, RL. Don't threaten people who stand up to your nonsense.
                   • RedLogix …

                     8 March 2021 at 11:51 pm

                     Are you too supporting McFlock's assertion that Australian travel doctors routinely give harmful advice because they're paid to by employers?

                     A simple yes or no will suffice.
                   • Muttonbird …

                     8 March 2021 at 11:53 pm

                     Nope. I'm just unimpressed by your Incredible Hulk impersonation.
                   • RedLogix …

                     8 March 2021 at 11:57 pm

                     So in other words McFlock is talking smack and can't back it up.
                   • Muttonbird …

                     8 March 2021 at 11:59 pm

                     Go to bed.
                   • McFlock …

                     9 March 2021 at 12:04 am

                     Are you claiming that Australian travel doctors routinely give bad advice they know will harm their clients?

                     Nope. Absolutely never said anything approaching that. Those are entirely your words and have no similarity to what I wrote.

                     I'm just suggesting that any doctors paid by employers or insurers (hence the ACC link because "ACC doctor NZ" is an easy way to find some pretty interesting examples) can appear to have loyalties divided between the best interests of the patient and the best interests of their customer. I'm not even suggesting that apparent contradiction is "routine". But it can happen, on occasion.

                     So now we've settled that wee matter, where's the CDC statement that ivermectin RCTs have "accrued the number of cases needed to meet the primary endpoint of vaccine efficacy against symptomatic COVID-19 and the secondary endpoint of vaccine efficacy against severe COVID-19", like the moderna vaccine has?

                     I’m off to bed.
     • mauī 1.1.2

       8 March 2021 at 7:37 pm

       Interesting that the Frontiers article manages to quote the NIH's current negative position on Ivermectin without mentioning that they've recently gone from advocating against it's use to neither for and against it. One would think that's quite big news and a step towards a positive view of the drug. Apparently the bigger news in the article was calling a doctor using it a liar.

       https://www.newswise.com/coronavirus/nih-revises-treatment-guidelines-for-ivermectin-for-the-treatment-of-covid-19
   • Andre 1.2

     8 March 2021 at 7:56 pm

     Oh, and on the topic of vitamin D and covid, it appears that giving covid patients massive doses of vitamin D as a treatment is not beneficial.

     https://sciencebasedmedicine.org/vitamin-d-shows-no-efficacy-against-moderate-to-severe-covid-19-infections/

     It still leaves an open question about whether vitamin D supplementation prior to infection reduces likelihood of infection and/or severity of disease.
     • RedLogix 1.2.1

       8 March 2021 at 8:11 pm

       There is one fairly obvious problem with that study – it was designed to fail.

       It took people who were already very ill, and the intervention was:

       Patients were randomly allocated (1:1 ratio) to receive either a single oral dose of 200,000 IU of vitamin D3 or placebo.

       I'm pretty sure it takes about two weeks for the body to metabolise D3 into the useful calcifediol form the body uses. Quite long enough for COVID to do it's thing.
       • Andre 1.2.1.1

         8 March 2021 at 9:08 pm

         Wasn't that pretty much the same as was done in the Spanish study that you and Dr. John Campbell were touting back in mid-February? With a few other substances like hydroxychloroquine thrown in as well?

         That paper's been withdrawn too, so the original link is no use, and I can't be bothered looking for one that's still live.
         • RedLogix 1.2.1.1.1

           8 March 2021 at 11:38 pm

           Wasn't that pretty much the same as was done in the Spanish study that you and Dr. John Campbell were touting back in mid-February?

           No the two Spanish trials used the calcifidiol directly which results in immediate action.

           Campbell also routinely reports on vaccine progress – on your logic are we to discount them because he 'touts' them?
           • Andre 1.2.1.1.1.1

             9 March 2021 at 7:29 am

             When assessing issues such as vitamin D, ivermectin, vaccine efficacy covid, it's important to look at the counterargument.

             In the cases of the studies promoting vitamin D and ivermectin touted by Campbell and yourself, the counterargument is that the studies have been examined by actual experts in the field and found to be seriously flawed. Furthermore, better designed and conducted studies find no benefit from the substances, but are ignored by those promoting them as wonder drugs.

             In the case of vaccines, actual experts generally don't find serious flaws in the actual studies (Astra-Zeneca's cock-ups with dosages excepted), and the criticisms are generally around where more information needs to be gathered. The counterarguments against the vaccines generally come from kooks shouting weird shit like 'Gates, nanochip tracking, genetic reprogramming …'.

             As for Campbell's views on vaccine development, his lack of judgement in touting these garbage huckster pieces on vitamin D and ivermectin means as far as I'm concerned, his opinions have zero value. He has failed to apply the fundamental step of simple skepticism, in the sense of trying to determine 'is this information genuinely reliable, or is there other more reliable information out there that refutes it?'.
       • Drowsy M. Kram 1.2.1.2

         8 March 2021 at 9:27 pm

         RL, prior to advocating for ivermectin to treat the symptoms of COVID-19 infections, and for vitamin D before that, wasn’t IV-VitC looking promising to you?

         I'd personally like to see credible trials of IV-VitC as some Chinese hospitals report success with.

         There’s a strange irony in watching the Covid-sceptics, who have been ultra-critical of any study that goes against their preconceived views, giving a free pass to reams of low-quality ivermectin research. But it raises the question: why would they want to seize on drugs such as ivermectin—as they previously did with the damp squib of hydroxychloroquine and the still-unproven effects of Vitamin D—and promote them to the high heavens? Why be so vehement about this, but be so dismissive of models, masks, tests, and sometimes even vaccines?
         https://www.newstatesman.com/science-tech/coronavirus/2021/03/how-covid-sceptics-were-duped-wonder-drug-ivermectin

         Re COVID-19 vaccines:

         And simply waiting for a decent vaccine is a fool's game; you have no idea just how long it will take to arrive if at all. We could get lucky and have one by the end of this year … or it could be the end of next year, or the one after. Such a profound unknown represents a massive strategic risk." [2 Oct. 2020]

         Phew – a risk no longer. 'Lucky' again!
         • Rosemary McDonald 1.2.1.2.1

           8 March 2021 at 10:22 pm

           …IV-VitC looking promising…

           Hop into my time machine DMK…read all about it!!!

           https://www.odt.co.nz/opinion/doctor-does-not-always-know-best

           We are, therefore, on disputed turf, medico-legally and ethically speaking. Current orthodoxy is against a relatively untried or unscientific treatment and seems to have a body of theory to back its disbelief. But there is some reason to think that in this patient, this disease process at this particular time was responding to a treatment in a way we do not understand.

           Only an arrogant and high-handed insistence on the rectitude of current medical dogma would dismiss the observations as, in principle, misleading.

           Here, at last, we come to something with medico-legal resonance because arrogant and high-handed treatment of patients is reprehensible in anybody's book.
           • Drowsy M. Kram 1.2.1.2.1.1

             8 March 2021 at 10:59 pm

             Doctor does not always know best

             Indeed Rosemary – "everyone makes mistakes" and "nobody's perfect".

             Still, if you, like me, entrust your 'illness care' to medical professionals, and find a good one (preferably one who's not too arrogant), then cherish them. They are, after all, just flesh and blood; over-worked and under-appreciated imho.

             Whangārei doctor Richard Harding's suicide reflective of tragic statistics

             Greig's report cited research from NHS Practitioner Health which stated mental illness was common among doctors with about 25 per cent at risk.

             " … suicide rates are between two and four times those of other professional groups, and in some specialities, there appears to be increased risk," the report said.

             The report also said the culture of medicine was not generally supportive, with stigma and prejudice exacerbating mental health conditions.
   • Andre 1.3

     8 March 2021 at 9:03 pm

     Just in case anyone's wondering what the bad Big Pharma company that actually produces ivermectin for human use has to say about ivermectin and covid:

     KENILWORTH, N.J., Feb. 4, 2021 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, today affirmed its position regarding use of ivermectin during the COVID-19 pandemic. Company scientists continue to carefully examine the findings of all available and emerging studies of ivermectin for the treatment of COVID-19 for evidence of efficacy and safety. It is important to note that, to-date, our analysis has identified:

     • No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies;
     • No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and;
     • A concerning lack of safety data in the majority of studies.

     We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information.

     https://www.merck.com/news/merck-statement-on-ivermectin-use-during-the-covid-19-pandemic/

     nb: Merck abandoned their efforts to develop their own vaccine in late January. So at the time of that February 4 statement, ivermectin would have been one of their main possibilities to profit from covid. Their agreement to help produce the Johnson and Johnson vaccine (after apparently some arm-twisting from Biden) came much more recently.
     • Rosemary McDonald 1.3.1

       8 March 2021 at 10:13 pm

       …bad Big Pharma…

       Read all about it!

       https://en.wikipedia.org/wiki/List_of_largest_pharmaceutical_settlements
     • RedLogix 1.3.2

       8 March 2021 at 10:28 pm

       ivermectin would have been one of their main possibilities to profit from covid.

       No-one was ever going to profit from ivermectin. It's been out of patent for a while now, is made generically in very large quantities (primarily for animal health) and is so cheap it's effectively free.

       A concerning lack of safety data in the majority of studies.

       This drug has been used for decades, over 30% of the human race has been given it and apparently there have been just 46 deaths ever associated with it's use. Muddying the water with 'safety concerns' over such an incredibly safe treatment is quite bizarre.
       • cricklewood 1.3.2.1

         9 March 2021 at 8:08 am

         Not that bizarre if you're big pharma, can almost smell than panic that an almost free treatment would cause them… imagine the lost profits… they'll discredit anything that threatens their new patented treatments
         • Andre 1.3.2.1.1

           9 March 2021 at 8:27 am

           If Big Bad Pharma would try to discredit an almost free effective treatment, then where's the campaign to discredit dexamethasone?

           When it comes to Big Bad Pharma's ability to extract huge profits from cheap medicines that are long out of patent, just consider insulin, EpiPens, Pharma-Bro Shkreli … If big profits from covid were the concern, it would be easier and better public-relations-wise to work out some way of doing that from an existing medicine that they already produce, rather than trying to falsely discredit something that actually works.
2. greywarshark 2

   8 March 2021 at 7:18 pm

   Today's news –

   Tīrau farmer fined $12,000 for neglecting calves
   https://www.rnz.co.nz/news/national/437913/tirau-farmer-fined-12-000-for-neglecting-calves

   and

   DHB fined $12,000 for neglecting mother and underweight, now dead, baby?
   No, but we may have to have a people's Court case to ensure proper treatment of vulnerable mothers.

   https://www.rnz.co.nz/news/national/437912/dhb-fails-in-care-of-pregnant-woman-and-underweight-baby
   The woman, in her 20s, was admitted to hospital multiple times during her 2017 pregnancy with severe morning sickness, malnutrition and gallstones. Her baby was born weighing only 2.5 kilograms and while it initially did well, blood results showed profound hypoglycaemia.

   Health and Disability deputy commissioner Rose Wall said the management of the woman during her pregnancy by her midwife and the DHB's policies after the birth were inadequate…

   The DHB acknowledged its care was not ideal, but said that each time the woman presented to hospital her condition was taken seriously. It said the mother may not have taken seriously enough the importance of diet advice she had been given and said she would not stay in hospital for long, discharging herself against medical advice.

   In a statement from the woman's family they strongly rejected that she did not take on the advice and said eating well was near impossible given her severe morning sickness. "Her mental health through this period should have been taken into consideration in particular the effects of being so unwell for such a long period of time."

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