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Apr 27, 2021 29 tweets 9 min read Read on X
This is one of the larger trials of hydroxychloroquine, ivermectin, povidone-iodine and zinc for prevention of COVID-19

At first, it appears positive, but there are some worrying issues

Some peer-review on twitter 1/n
2/n The study is here, and it's a cluster-randomized controlled trial, where people living in dorms of Singapore were given one of the 4 treatments or a vitamin C control during large COVID-19 outbreaks in the dorms ijidonline.com/article/S1201-…
3/n The results seem to show that people who take HCQ or P-I have fewer infections than those who only have vitamin C, with a really impressive risk reduction
4/n If these reductions are true, either HCQ or P-I would be a massive, world-changing reduction in risk for the prevention of COVID-19 (although zinc and ivermectin would be largely useless)
5/n But reading the methodology, some things immediately spring out. Firstly, this was a cluster-randomized trial, where participants were randomized to the intervention by the floor of their dorm
6/n ...but this was NOT what the study was originally designed for. The sample sizes, statistical analysis, and other protocols were designed for a parallel-arm clinical trial

This is not ideal
7/ While cluster-randomized trials are not my forte, all of the statisticians I've asked so far have said that turning a 5-arm study into a cluster RCT in this way leaves you with quite a lot of issues
7.5/n In particular, by clustering at the floor level the researchers essentially reduced their effective sample size from 3,000 patients to 40 floors. You have to take this into account in the statistical analysis, which the study does not seem to have done
8/n There's also an issue with how COVID-19 was ascertained in the study. Patients gave a blood sample at day 1 and 42, and then medical records were searched to see if they'd had a positive PCR between those two dates
9/n So, firstly, that is an issue because there's a bias in the PCR testing - only those who had a test (for whatever reason) AND had it entered into whichever medical records system would show up as positive
10/n On top of that, the serology isn't great. Serology often misses people who are tested early in their infection, so the estimates of infection rates for all the groups are probably too low
11/n If you correct for this, instead of the percentages given in the results, you get much higher values for all the treatments, and a potentially reduced protective effect
12/n Also, the study excluded people who already had COVID-19 antibodies at the start, but there isn't much information about these people, which is an issue given that they were excluded after already being randomized (and treated?)
13/n Moreover, a full 20% of the sample was excluded because they were not from randomized floors, which is bizarre. How were they recruited, randomized, and apparently treated if they were not on randomized floors?
14/n It seems very much like this trial was conceived, planned, AND RUN as a randomized parallel-arm trial and then halfway through switched to a cluster RCT
15/n Ok, so that's all pretty worrying. The results may not be statistically viable, the methodology has quite a few flaws

But there's actually a potentially bigger issue
16/n The primary outcome reported in the trial was laboratory-confirmed (through either PCR or serology) COVID-19. This is the measure that the headline results is based on
17/n But if we go to the pre-registration for the study (which, incidentally, doesn't talk about controlling for a clustered design), there's something a bit weird

The primary outcome was originally "acute respiratory illness"
18/n So when the study was registered, in June 2020, the primary outcome was acute illness. A month after the final results came in, the primary outcome was changed to laboratory-confirmed COVID-19
19/n Moreover, the outcome that was registered in advance as the primary outcome has completely different results, showing a statistically significant effect for ivermectin but nothing else
20/n Now, there's nothing inherently wrong about switching outcomes, and the authors do mention a reason for changing it, but the fact that it was only changed after the study was finished is very strange
21/n The explanation in the text also doesn't quite make sense. The paper reports excluding people who had a positive serological test at baseline - how can these people have been tested if there were no serological tests when the study started?
22/n So what does this all mean?

Well, overall, it's quite hard to trust the trial's results
23/n The study does not appear to follow the guidelines for implementation and analysis for cluster RCTs, which means that it's hard to know what to make of the analysis ncbi.nlm.nih.gov/pmc/articles/P…
24/n The primary outcome was also switched, with a bunch of other odd inconsistencies in the research that make it a bit hard to know if the conclusions hold water
25/n To their credit, the authors talk about some of these things in the limitations section of the study, but not all of them and I'm not sure they really explain why these are not issues
26/n Anyway, I'm not sure I would rely on this study as evidence for much, despite the large size
27/n Apologies, one of the above tweets is wrong. The authors did indeed take into account the clustering in their statistical analysis
28/n The more I read this paper, the weirder it sounds. So they randomized ineligible people (how?) from two floors that were not clustered, and then assigned them to vitamin C if the other medications were contraindicated?

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More from @GidMK

Mar 4
The final large published trial on ivermectin for COVID-19, PRINCIPLE, is now out. Main findings:

1. Clinically unimportant (~1-2day reduction) in time to resolution of symptoms.
2. No benefit for hospitalization/death. Image
Now, you may be asking "why does anyone care at all any more about ivermectin for COVID?" to which I would respond "yes"

We already knew pretty much everything this study shows. That being said, always good to have more data!
The study is here:

For me, the main finding is pretty simple - ivermectin didn't impact the likelihood of people going to hospital or dying from COVID-19. This has now been shown in every high-quality study out there.pubmed.ncbi.nlm.nih.gov/38431155/
Read 8 tweets
Feb 20
Fascinating study.

What's particularly interesting is a finding that the authors don't really discuss in their conclusion. These results appear to show that gender affirming care is associated with a reduction in suicide risk 1/n
2/n The paper is a retrospective cohort study that compares young adults and some teens who were referred for gender related services in Finland with a cohort that was matched using age and sex. The median age in the study was 19, so the majority of the population are adults. Image
3/n The study is very limited. The authors had access to the Finnish registries which include a wide range of data, but chose to only correct their cohorts for age, sex, and number of psychiatric appointments prior to their inclusion in the cohort.
Read 11 tweets
Oct 26, 2023
These headlines have to be some of the most ridiculous I've seen in a while

The study tested 18 different PFAS in a tiny sample of 176 people. Of those, one had a barely significant association with thyroid cancer

This is genuinely just not news at all Image
Here's the study. I'm somewhat surprised it even got published if I'm honest. A tiny case-control study, they looked at 88 people with thyroid cancer and 88 controls thelancet.com/journals/ebiom…
Here are the main results. There was a single measured PFAS which had a 'significant' association with the cancer, the others just look a bit like noise to me Image
Read 7 tweets
Oct 11, 2023
A new study has gone viral for purportedly showing that running therapy had similar efficacy to medication for depression

Which is weird, because a) it's not a very good study and b) seems not to show that at all 1/n
Image
Image
2/n The study is here. The authors describe it as a "partially randomized patient preference design", which is a wildly misleading term. In practice, this is simply a cohort study, where ~90% of the patients self-selected into their preferred treatment sciencedirect.com/science/articl…
3/n This is a big problem, because it means that there are likely confounding factors between the two groups (i.e. who is likely to choose running therapy over meds?). Instead of a useful, randomized trial, this is a very small (n=141) non-randomized paper
Read 15 tweets
Oct 6, 2023
This is SO MISLEADING

The study showed that COVID-19 had, if anything, very few long-term issues for children! As a new father, I find this data very reassuring regarding #LongCovid in kids 1/n Image
2/n The study is here, it's a retrospective cohort comparing children aged 0-14 who had COVID-19 to a matched control using a database of primary care visits in Italy
onlinelibrary.wiley.com/doi/10.1111/ap…
3/ The authors found that there was an increased risk of a range of diagnoses for the kids with COVID-19 after their acute disease, including things like runny noses, anxiety/depression, diarrhoea, etc Image
Read 13 tweets
Sep 20, 2023
This study has recently gone viral, with people saying that it shows that nearly 20% of highly vaccinated people get Long COVID

I don't think it's reasonable to draw these conclusions based on this research. Let's talk about bias 1/n Image
2/n The study is here. It is a survey of people who tested positive to COVID-19 in Western Australia from July-Aug 2022 medrxiv.org/content/10.110…
3/n This immediately gives us our first source of bias

We KNOW that most cases of COVID-19 were missed at this point in the pandemic, so we're only getting the sample of those people who were sick enough to go and get tested
Read 12 tweets

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