Chaos and covid

The last 19-20 months of pandemic have taken a toll on everyone in one way or the other. We all have stories, anecdotes, experiences, and have participated in “have you heard” conversations. The beginnings of the pandemic were just devoid of information. It was chaos in the normal and the mathematical sense. It is the mathematical sense that always interests me. People confuse chaos with randomness. Actually mathematical chaos is quite predictable – if you understand the initial conditions. Of course, there’s the rub. When I think about the early days of the pandemic we have the initial conditions of (a) a population used to ferreting out information from the internet with relative ease and (b) a situation when there wasn’t information. Into the void…nature hates a vacuum… let loose the dogs of war… take your pick. The milieu was ripe for the lowest denominator of accuracy to provide fuel for conversations from water cooler to talk radio, Facebook to “in the know” sites, and all the existing and emerging channels of information and disinformation.

Late to the game, but soon into the mix is the antiparasitic drug, Ivermectin. If you are infected with the roundworms that cause river blindness or the parasitic mites that cause scabies, it is wonderfully effective. It is cheap; it is accessible; and its discoverers won the Nobel Prize in 2015. Lately it has also been widely promoted as a coronavirus prophylactic and treatment. That’s not to say off-label use is not a common practice, but it’s a long way from virus to parasite. But hey, at least we can hold studies to see if it can be part of the toolset in the fight against the coronavirus. Perhaps 70 to 100 studies have been conducted on the use of ivermectin for treating or preventing COVID-19. What did the studies show? Several dozen of them support the hypothesis that the drug is a coronavirus mitigant. Two studies looked at data aggregated across subsets of these studies. They concluded that the drug has value in the fight against the pandemic.

Are the studies enough to try the drug? Initiate a second round of studies? As is, would such studies convince you to join the supporters of ivermectin – or at least withhold objection even if it is not something you would consider ingesting. One immediate problem is what about the other 50 to 80 studies? What did they reveal?

And then a question for all the studies: (a) which are peer reviewed and (b) what was the quality of the peer reviews. In the world of scientific study publication there is something called the “preprint” which releases the study into the public domain prior to review and publishing. Then there is the underlying publish or perish dynamic. Add to that the accelerant of the pandemic and you have created a difficult environment for scientific publishing. In early 2020, a hunger for high-quality information arose immediately. How scared of the coronavirus should we be, and how should we behave? How does the virus spread? How dangerous is it? What decisions should governments make? To answer those questions, scientific studies were produced at record pace, peer-reviewed almost immediately after they were submitted or else put into the public domain via preprint as soon as they had been completed.

James Heather writes: “Publishing science is slow; highly contagious diseases are fast.  It’s not that, under such conditions, a few bad studies were bound to slip through the net. Rather, there is no net. Peer review, especially when conducted at pandemic speed, does not exert the rather boring scientific scrutiny needed to identify the problems described above.”

There have always been forensic research scientists whose work is to scrutinize published studies. Added to the pandemic-fueled research milieu of accessible grant money, there is a large collection of journals that are not The Lancet or The New England Journal of Medicine – nor close to it. In parallel to reliable clinical research journals, there is a market of questionable or outright for-the-profit journals that will publish almost anything for money. There are not a few researchers with a modest ambition: get published, add the credit to their resumes, and produce volumes of work that are fundamentally designed to be “written but not read.”

Returning to the 80-100 studies, there is the question of not only the process and quality of the study, but also the quality of the peer review (which is not forensic by any means), and the quality of the publishing journal. It raises the question of when “following the science” is the science worth following.

James Heathers is a forensic research scientist who undertook a look at the body of Ivermectin research. He and his colleagues examined 30 studies of the drug’s use for treating or preventing COVID-19, focusing on randomized studies, or nonrandomized ones that have been influential, with at least 100 participants. The results were five studies were so misconceived or flawed that ultimately the studies were withdrawn. That doesn’t mean they are not floating across the internet, just that the publishing company published a notice of withdrawal.

What does that mean? As Heathers writes: “If five out of 30 trials have serious problems, perhaps that means the other 25 are up to snuff. That’s 83 percent! You might be tempted to think of these papers as being like cheaply made light bulbs: Once we’ve discarded the duds with broken filaments, we can just use the “good” ones.” He offers that a better metaphor is that if five out of 30 new production cars were guaranteed to explode as soon as they entered a freeway on-ramp, you draw a different conclusion: “you would prefer to take the bus.”

Another problem is that the forensic review shows the studies that are most unreliable are the very ones that show Ivermectin as most effective. Studies that show inconclusive results are the ones to have been adequately conducted. The studies of reasonable size with spectacular results leading folks to assert miraculous effects of the drug, garnering public attention and digital notoriety, were not adequately conducted.

How does this happen? Much of this research is simply ignored by other scientists because it either looks “off” or is published in the gray market journal whose history of publishing is already questioned. The scientists you’d hope to weigh in fulfilled the author’s original intent to produce a study  “written but not read.”  The internet ignores the difference between prestigious journals and gray publications. Heather writes, “Everything is a magnet for immediate attention and misunderstanding. An unbelievable, inaccurate study no longer has to linger in obscurity; it may bubble over into the public consciousness as soon as it appears online, and get passed around the internet like a lost kitten in a preschool. An instantly forgettable preprint, which would once have been read by only a few pedantic experts, can now be widely shared among hundreds of thousands on social media.”

Is Ivermectin the “silver bullet?” Take a cruise through the internet (a trip down the rabbit hole of Alice’s nightmare). A meta-analysis study published that I read was (a) produced by a software sales and services company under the moniker of what sounded to be a very official group, (b) used studies from very small sized studies, (c) had many studies that were preprint only, and had (d) almost 25% of its findings based on a  study was rapidly withdrawn in July this year, and (d) no surprise here – overall found miraculous results. The study had been viewed 150,000 times and re-posted from preprint countless times on the usual social media channels. It is the go study to justify use of Ivermectin. The paper’s irregularities came to light when Jack Lawrence, a master’s student at the University of London, was reading it for a class assignment and realized there was no way the study could be valid. Given the prominence of the article, Mr. Lawrence reached out to the forensic researchers. Things unravel. One of the lead scientists on the meta-analysis study remarked that there was no reason to doubt the original study. A masters-level student disagreed, but then he actually took a hard look at the source information.

Is Ivermetic a viable drug for the covid-19 virus? The jury is still out. Any claims otherwise, especially as a preventive, are simply bogus. I am sure there is a more suitable scientific phrase. As James Heathers writes, the real scandal about ivermectin claims are based on shoddy science—but that science is entirely unremarkable in its shoddiness. And therein lies a more deeply rooted problem.

It is a problem of uncertain initial conditions in mathematical chaos. Let us hope the butterfly in China takes a break from wing flapping. Kansas could use the break.

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