“The obfuscation of mortality results can be viewed as a crime against humanity” – Prof Aldous on recent Ivermectin trials

When Covid-19 emerged in 2020, Ivermectin, a word that prior to the pandemic had not formed part of many people’s vocabularies, became a hot and very controversial topic. Throughout the pandemic, Professor Colleen Aldous, a healthcare scientist at UKZN’s College of Health Sciences, argued that the placement of our trust in a small group of experts who advocate against Ivermectin was being done at the potential cost of human life. In this article, while Aldous puts forth that “with the pandemic having passed, the opportunity for a proper well-funded trial for Ivermectin to treat Covid-19 has been lost”, she argues that preparation of a protocol for future pandemics is required. Aldous sets out the ways in which the analysis of recent pro-Ivermectin trials has been unsound “which shows how evidence-based medicine has been distorted to suit the agendas of corporate interests, failed regulation, and the commercialisation of academia”. – Nadya Swart

An outright propaganda war against Ivermectin in two latest trials

By Professor Colleen Aldous* 

The Ivermectin saga is becoming an HC Bosman’s ‘Bekkersdal Marathon’. If only we had a Bosman to make it interesting.

Professor Colleen Aldous

Last week, a colleague tweeted, “As we enter the next wave of Covid-19, please stay away from Ivermectin if you trust science. It’s no longer a scientific debate, the weight of evidence is clear, a repeated scientific No No No!”

He has based this statement on the publication of the TOGETHER Trial results released last week, a paper preceded by an extensive and coincidental press campaign beginning with the Wall Street Journal a few weeks earlier.

There are three points that my learned colleague gets wrong in his tweet…

Firstly, he places his own interpretation of science as the “settled science”. I have seen this throughout the pandemic, where a specific group of scientists repeats this without looking at the totality of evidence. If the public were to believe the ‘science’ regurgitated by these ‘scientists’ – who are either too busy to analytically engage with the published body of literature and unquestioningly echo what their colleagues say or have huge conflicts of interest – we would be in trouble. Luckily, many in the public remember a bit of natural science from their school days and realise that science is truth-seeking, and they can wade through what the mainstream media feed us and discern real science from spurious propaganda disguised as science.

Much of the mainstream media has signed up to the Trusted News Initiative, a partnership that includes several organisations such as Google/YouTube, Twitter, Reuters and the BBC. This initiative has taken it upon itself to decide what is disinformation. According to them, anything positive about Ivermectin is disinformation, and they vigorously counter it with misinformation campaigns such as the defective Ivermectin toxicity narrative, which was splashed across newspapers worldwide but squashed when proven to be totally false and unsubstantiated.

The second point my colleague makes is that there is no longer a debate on the efficacy of Ivermectin. This is only true for those who will not engage with the totality of evidence. Of the 247 published articles I had in my database a fortnight ago on the use of Ivermectin in Covid-19, only 10% of the studies were negative; yet, these are the only studies they myopically focus on. Earlier on they argued that the positive results came from countries where the results could not be trusted, which borders on a form of scientific xenophobia against developing world countries, that is becoming all too common of late. But now, apparently the fact that the trials are conducted in developing countries is no longer an issue because the two studies which have “decisively ended the debate” in the last few weeks are from Malaysia and Brazil!

Both the Malaysian and the Brazilian studies pose soft outcomes as their primary outcomes, outcomes that can be impacted by researcher perception such as when a patient needs hospitalisation. Hard outcomes, those that are indisputable such as numbers of research participants who die are subtly hidden as secondary outcomes. The Malaysian trial shows Ivermectin is effective against mortality with a certainty of 91%; with three people dying in the Ivermectin arm and 10 in the control arm. The Brazilian trial is such a mess I cannot wait to see the corrected statistics; but in the Ivermectin arm, 21 people died out of the 624 who completed the study, and 24 people died out of the 288 (or 228 because the figures are sloppy) who completed the study in the control arm. Primary school mathematics will show a result that clears Ivermectin for efficacy against death.

My colleague is correct that this is no longer a debate; it’s an outright propaganda war against the use of Ivermectin and other repurposed drugs.

The last point made by my colleague is about the weight of evidence. We have kept a rough and ready database of all published academic articles on Ivermectin use in Covid-19 using Scholar.google alerts. We have been careful to seek out every publication that shows Ivermectin is not effective. Fewer than 20 of the 247 articles from all levels of evidence-based medicine we have are negative. The rest show efficacy. The weight of the published data clearly is not how my colleague sees it.

The last couple of weeks has seen three important papers published for the case of Ivermectin – the Malaysian I-Tech trial in JAMA, the Brazilian TOGETHER trial in NEJM and a BMJ op-ed – which show how evidence-based medicine has been distorted to suit the agendas of corporate interests, failed regulation and the commercialisation of academia.

I have clinical colleagues across the globe who are able to demonstrate more issues with the analysis of the TOGETHER trial, which is being touted as the definitive paper on Ivermectin efficacy, than I can, but here is my list:

More than half of the participants from the placebo arm of the trial did not complete the trial, whereas only 50 from the Ivermectin arm did not finish. This causes the trial to no longer be a randomised control trial. But the data can be used as observational and, as I showed above, we observe that Ivermectin has a strong signal for efficacy against death. An outcome that is meaningful to most people.

Ivermectin was given on an empty stomach, which is the protocol for its use as an antiparasitic. It has been known that for antiviral activity, Ivermectin should be given with a fatty meal to aid systemic absorption.

The dose given was below the dose that many across the globe have used successfully; it was given at too low a dose, too late for many, and stopped too early.

Giving Ivermectin as a monotherapy, when it is known it is a zinc ionophore and thus is more effective given with zinc, is poor design.

However, even with all these problems, Ivermectin still comes through as effective, particularly against mortality.

Interestingly, Dr Edward Mills, the senior author on the TOGETHER Trial, has stated (see substack reference below) that if more participants had been enrolled in the study, there would have been a statistical significance for Ivermectin efficacy. But this admission has not been seen anywhere in the mainstream media. And nor does it sit anywhere in the limitations of the research, which should be written into the paper. To quote Ed Mills, “I really don’t view our study as negative, and also in that talk you will hear me retract previous statements where I had been previously negative.” He had also said that, “I advocate that actually there is a clear signal that IVM works in Covid-19 patients, just that our study didn’t achieve significance.” What he means is that p > 0.05.

Let me just get my bit in here about p values. The p value of 0.05 is almost religiously used as a cut-off for statistical significance. Fisher, one of the great statisticians of the 20th century adopted this value and, when asked why, he responded that it just seemed like a good figure to go with. Which is brilliant for business and industry. Gosette was a brewery statistician for Guinness Stout, and a p > 0.05 might create scaled variances that would determine production. But when you see that an Ivermectin arm has an advantage for mortality with a p = 0.09 (as in the Malaysian trial), a figure thrown out by the regulatory authorities and other bigwig academics as being insignificant, would you consider it appropriate to use this figure?

Personally, I would not be dissatisfied with a p = 0.5 if it was a life or death situation and the intervention was as safe as Ivermectin has shown itself to be. Which arm would people choose? The arm with Ivermectin where there is a certainty of 91% that it reduces mortality as in the Malaysian trial, or would they play roulette in the control arm? Stats for beer brewing are not completely transferable to human life.

With the pandemic having passed, the opportunity for a proper well-funded trial for Ivermectin to treat Covid-19 has been lost. However, the totality of evidence shows that Ivermectin is effective. I am really only interested in how many lives Ivermectin can save, which should be enough for the public to demand clarity. The obfuscation of mortality results can be viewed as a crime against humanity. We need to prepare a protocol for future pandemics, those our children and grandchildren will experience, that will not allow this to happen again.

  • Professor Colleen Aldous is a healthcare scientist at UKZN’s College of Health Sciences where she runs the Doctoral Academy. She is  a member of the Academy of Science of South Africa. She has a PHD and has published over 140 peer-reviewed articles in rated journals.

References:

Jureidini J, McHenry LB. The illusion of evidence based medicine. bmj. 2022 Mar 16;376.

Lim SC, Hor CP, Tay KH, Jelani AM, Tan WH, Ker HB, Chow TS, Zaid M, Cheah WK, Lim HH, Khalid KE. Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomised Clinical Trial. JAMA Internal Medicine. 2022 Feb 18.

Reis G, Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, Dos Santos CV, Campos VH, Nogueira AM, de Almeida AP, Callegari ED. Effect of Early Treatment with Ivermectin among Patients with Covid-19. New England Journal of Medicine. 2022 Mar 30.

https://stevekirsch.substack.com/p/did-the-together-study-show-that?s=r

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