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Dec 16, 2021 24 tweets 7 min read
Another new ivermectin study out recently. Apparently it is quasi-randomized and proof that suppressing ivermectin is a "crime against humanity"

Let's do some twitter peer-review 1/n
2/n The preprint is here, and it's a retrospective analysis of routinely collected clinical registry data from the city of Itajai in Brazil

researchgate.net/publication/35…
3/n The design was very simple - take routine data on people who either had or had not elected to be part of an ivermectin distribution program, and controlled for a small number of confounding variables using either a propensity-score or regression model ImageImageImageImage
4/n They authors found a very modest benefit for ivermectin on the risk of having a recorded infection, but a very large relative benefit for mortality from COVID-19 Image
5/n So, on to the problems. There are quite a few.

Firstly, the author group. While this is not disclosed in the paper, several authors are members of the FLCCC, an ivermectin promotion organisation who we might expect to have some interest in the outcome of the research
6/n The corresponding author, Dr. Cadegiani, has been accused of, and I kid you not, "crimes against humanity" due to ethics breaches in his previous research on COVID-19 bmj.com/content/375/bm…
7/n On top of this, two of the authors report a direct financial conflict of interest, in that they say they work for a pharmaceutical company that makes money off ivermectin Image
8/n So, on to the study itself. In general, it's a fairly simple example of observational research that you'd do on routine medical data. The authors took an intervention (primary care doctor giving ivermectin), divided people into 2 groups based on this, and compared them
9/n The controls for confounding are obviously pretty inadequate given the purpose. The paper aims to see whether ivermectin has an impact on COVID-19 risk, but they don't control for any confounders that might increase your risk of catching COVID
10/n For example, there's no control for occupation, nothing about income, no analysis of the results looking at many well-known risk factors for COVID-19 infection and death
11/n To their credit, the authors do control for some major comorbidities, but since these are rarely related to the risk of CATCHING the disease (as opposed to dying from it if you get it), the causal chain is quite messy Image
12/n So the potential for uncontrolled confounding is high, and this cannot possibly be described as "quasi-randomized". Quasi-randomized studies are usually either natural experiments with some randomness to them, or prospective studies where randomization was done poorly
13/n Moreover, there are some pretty obvious challenges with ascertaining causality here. The intervention was a doctor prescribing ivermectin at some point, but as far as I can tell that's not followed up on at all in the paper
14/n We do not know, for example, how many in either group were taking ivermectin BEFORE the study took place (given the heavy use of the drug in Brazil, it is likely to be a non-zero figure)
15/n There's also quite strong evidence that many of the "ivermectin" group did not pick up the medication, and stopped taking it almost immediately
16/n This means that there may have been a large proportion of people in the control group taking ivermectin, and a similar proportion in the intervention group NOT taking ivermectin. There's no analysis of this issue in the paper that I can see
17/n There are other issues with the document, although to be fair here it's only a preprint so you expect some mistakes. For example, the main result presented is the unadjusted risk ratio, but for the adjustments the authors just give a p-value Image
18/n But overall, it's just not a very convincing paper. There is a huge potential for uncontrolled confounding, there are issues with the delineation of intervention vs control groups, and it's generally just a very weak observational study
19/ All of this makes the "limitations" and conclusions sections absolutely bizarre. Turns out you can just declare things are causal as long as you believe it hard enough I suppose? Image
20/n Ultimately, this newest piece of research is a very weak paper. It might be useful as the very first piece of research into a medication, but it gives us no useful information at this point in the ivermectin literature
21/n It's also worth noting that the people who've been complaining about low ivermectin doses, people not taking drugs etc in NEGATIVE trials are very happy to ignore these issues when it comes to a POSITIVE result

I wonder why that is 🤔🤔🤔
22/n Turns out there are even more issues with the study. Very worrying stuff
23/n In an rather astonishing move, the paper is now only available from the preprint server "on request", after being promoted heavily for weeks by the authors after numeric errors were discovered Image
24/n I spoke too soon! The paper is up, with more concerning issues yet again

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More from @GidMK

Jun 29
For a blog I'm writing - something that's not COVID-19

I can see at least 5 serious issues with this trial. Who can tell me what they are?

ncbi.nlm.nih.gov/pmc/articles/P…
Well spotted! The authors call it randomized but actually they just allocated people alternately to intervention and control
Dr Tim is on fire! Yes, it's called blinded but there's no description of blinding and the placebo is not described either
Read 6 tweets
Jun 26
In case you weren't aware, there are many countries fudging their COVID-19 numbers in some way. China, for example, basically just stopped reporting any deaths after their initial surge in Jan 2020
Is it plausible that China has had no deaths due to COVID-19 in the last 2 years?

No. Not even a little
This is not quite as fake as Belarus, which just makes up numbers that look good, but it is extremely unlikely that China has had no deaths at all from COVID-19 this year
Read 4 tweets
Jun 20
I have no particular expertise in this area, but from a scientific perspective I find the banning of transgender/intersex athletes with these vague arguments to be problematic
The thing to remember is that no one cares whether elite athletes have an advantage. Every elite athlete has advantages over their peers to some extent (there's a reason short people rarely play basketball)

We care about UNFAIR advantages
So, for example - without debating whether this is true or not - we consider doping to be unfair for a variety of reasons while using expensive and difficult to obtain training methods are usually considered to be fair
Read 25 tweets
Jun 16
Another fairly large RCT from Iran fails to find a benefit for ivermectin in the treatment of COVID-19. People taking ivermectin no less likely to deteriorate, non-sig less likely to die, and more likely to need hospital care than placebo frontiersin.org/articles/10.33…
So that's 3 more trials with no meaningful benefits for ivermectin, with a total of about 3,000 patients, reported this week. The updated meta-analysis for mortality looks less and less positive
Another fascinating note - the new Iranian trial which found no benefit was completed nearly a year ago. The same team published positive results from their pilot in April 2021 sciencedirect.com/science/articl…
Read 6 tweets
Jun 16
It almost certainly isn't - the study found that pre/post drinking either alcoholic or non-alcoholic beer increased gut microbiome diversity by <10% as recorded by the Shannon diversity index
There were no meaningful changes to any clinical marker, and also this didn't compare to a non-beer control so there's no possible way you can infer anything about the impact of beer, specifically
I've got no idea how increasing the Shannon index of gut microbiome from 2.7 to 2.9 might relate to overall health, but technically this study didn't even show that was caused by beer per se pubs.acs.org/doi/full/10.10…
Read 4 tweets
Jun 15
Often people ask "where's the harm?" for low-risk treatments like vitamin C

A new RCT rather answers that question. In ICU, patients given IV vitamin C had a higher risk of death or major organ dysfunction than placebo nejm.org/doi/full/10.10…
This is also a fantastic teaching tool for science and evidence appraisal - the initial study indicating a possible benefit for vitamin C in the treatment of sepsis in ICU was a poorly-controlled observational trial with <100 patients
Objectively, this should not have changed treatment anywhere. But it was published in a big journal to great acclaim, and a lot of doctors took notice
Read 4 tweets

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