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Covid vaccine safety: how correct are these allegations?

See a reproduction of Lawrie's metastudy here.
Even without both of those constributions the result doesn't meaningfully change.

How do the ivermectin meta-reviews come to so different conclusions?

I have not managed to see Hariyanto et al reproduced yet (any help welcome), so I don't know what effect removing Elgazzar from it would have on that specific meta-study.

For Bryant et al though this is the result with both Elgazzar's in:

This is the result with both Elgazzar's out:

RR moved, but the result is fundamentally the same.
Do you think it would change the result for Hariyanto et al?

How do the ivermectin meta-reviews come to so different conclusions?

A recent preprint compares Roman et al and Bryant et al: Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease

The two studies find similar RR (risk reduction as )

Bryant found RR = 0.38 [CI 95%: (0.19, 0.73)]
Roman found RR = 0.37 [CI 95%: (0.12, 1.13)]

Roman et al should conclude there's not enough evidence because they can't rule out RR >= 1 at 95% confidence. Instead they conclude:

In comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay or viral clearance in RCTs in COVID-19 patients with mostly mild disease. IVM did not have effect on AEs or SAEs. IVM is not a viable option to treat COVID-19 patients.

Bryant and Roman use similar methods, the difference in the confidence interval is because they picked different studies.

Bryant has different estimates for mild vs severe vs all cases. 0.38 is for all-cases to allow comparison with Roman batched all-cases together and has no breakdowns.

This third Bayesian (meta-?)meta-analysis concludes:

This Bayesian meta-analysis has shown that the posterior probability for the hypothesis of a causal link between, Covid-19 severity ivermectin and mortality is over 99%. From the Bayesian meta-analysis estimates the mean probability of death of patients with severe Covid19 to be 11.7% (CI 12.6 – 34.75%) for those given ivermectin compared to 22.9% (CI 1.83 – 27.62%) for those not given ivermectin. For the severe Covid-19 cases the probability of the 7 risk ratio being less than one is 90.7% while for mild/moderate cases this probability it is 84.1%.

In our view this Bayesian analysis, based on the statistical study data, provides sufficient confidence that ivermectin is an effective treatment for Covid-19 and this belief supports the conclusions of (Bryant et al., 2021) over those of (Roman et al., 2021).

The paper has also highlighted the advantages of using Bayesian methods over classical statistical methods for meta-analysis, which is especially persuasive in providing a transparent marginal probability distribution for both risk ratio 𝑅𝑅 and risk difference, 𝑅𝐷. Furthermore, we show that using 𝑅𝐷 avoids the estimation and computational issues encountered using 𝑅𝑅 , thus making full and more efficient use of all evidence.

How would you run the statistics on whether Ivermectin helped India reduce COVID-19 cases?
Answer by ndrJul 04, 20212

India's situation is messy because of the different states policies.
To properly do this one would need to control for incidence and lockdown policy state-by-state. Also some states have no approval for Ivermectin yet it gets used.

My best bet is that we'll get the cleaner data on whether it works from Europe, in particular from Slovakia and Czechia.
Even if EMA advises against Ivermectin, Slovakia approved it for both prophylaxis and treatment in late January 2021.

I could not find how widespread the slovak usage of Ivermectin is, but there are few points:

  • Mobility report shows that Slovakia is not locking down, not effectively at least
  • Bratislava airport has arrivals from all places (including UK), seemingly no closed borders
  • Less than <40% of Slovakia population is vaccinated (vs >65% in UK, 47% in CZ)
  • Cases in Slovakia keep going down, but Czechia seems to start going up

I've not found data on the delta variant incidence in Slovakia, maybe it didn't reach there yet. It's 98% of cases in UK, 30% in CZ.

If Slovakia sees a ramp up in delta cases the Ivermectin proponents will likely say it wasn't used enough/correctly, and the detractors will keep saying it was useless from the start.

On the other hand, if Slovakia does not see a ramp up in delta cases whilst keeping a low vaccination rate and no effective lockdown in place it'd suggest something else must be at work.
Saying it's Ivermectin will come off as reasoning from exclusion but it'd be my best-bet hypothesis.

How do the ivermectin meta-reviews come to so different conclusions?

The Medina study received some methodological complains, see the JAMA letter.

Ivermectin proponents seem to consistently push for a regimen of:

  • high dosage (0.2mg/kg once-a-week for prevention)
  • early usage, ideally as prevention
  • usage with/after meals

If they're right one can imagine studies that see no effects either because of low dosage, late administration or administering it on empty stomach (the anti-parasite regimen), which the Medina study does.

How do the ivermectin meta-reviews come to so different conclusions?
Answer by ndrJul 02, 20215

Another meta-analysis (Bryant et al) has a very similar title but positive claims Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines.

The authors have put out an official rebuttal of the negative meta-analysis which is an interesting read and point to many of their perceived flaws.

The comments on the preprint of the negative study (Roman et al) are also interesting.

For instance:

Hi, I'm Dr.Niaee and I was surprised that even basic data from our RCT is completely mispresented and is WRONG. We had 60 indivisuals in control groups and 120 in intervention groups and even this simple thing is mispresented.


after your "mistake" inverting the control and IVM arm of the Niaee study, the RR goes from 1.11 to 0.37 yet you dare to not change a single word in your conclusion

My current impression is that the negative study is not very high quality at the moment, for any reason among rush to publish, incompetence or malice.
For sake of argument I still have to look at what studies Roman et al did include that was omitted by Bryant et al and Hariyanto et al as that would reveal any pro-ivm biases.

Covid vaccine safety: how correct are these allegations?
  1. seriously, what are the chances that all three vaccines are both dangerous and equally so?

Malone/Weinstein say they seem to have minor differences, at least in mechanism/effect. Their point being that if you get the S p circulating you're in trouble. All the three seem to produce that effect.

  1. One must also consider the reaction of other experts [...] When experts in high places thought there was a risk of rare blood clots, they were often willing to halt [...]

Well done, this is a very well put and good point. I don't know what drove the craze on blood clot (very few instances too?) against AZ and J&J. It's weirdly inconsistent with the reaction on myocarditis for mRNA vaccines, they only (reasonably?) halted on young population? It looks like a different standard than for AZ/J&J.

Covid vaccine safety: how correct are these allegations?

There's also criticism of the Bryant and Lawrie paper.

What's an actual criticism of that paper from that article? That meta-studies are garbage-in-garbage-out? That's weak at best, the author seems to have spent no time in spot checking any of the papers included to check whether this actually happened.

The Japanese data is at the center of Byram Bridle's claims, which is systematically debunked ...

... by a nameless "Concerned Scientist". I don't want to play ranking authorities, but it's obvious someone is mad at Bridle enough to steal his name to put up that website. It's hard to read that website assuming good faith, at least Bridle seems courageous enough to argue his points in the open under his own name, like any "Scientist" should do, especially "Concerned" ones.

Regarding the spike protein toxicity, my understanding is that the claim is a bit more nuanced. A recent tweet from Malone says:

The SARS-CoV-2 spike protein is cytotoxic. That is a fact. Who says so? Multiple peer reviewed references. The Salk Institute.
It is the responsibility of the vaccine developers to demonstrate that their expressed version is not toxic. Show us.

And then links to this Salk article.
Basically claiming that we know SARS-CoV-2 spike protein is cytotoxic and unless proven otherwise it's fair to assume the version expressed by vaccines is similarly cytotoxic.

All the "fact-checker" linked from that website are "we have no evidence that [...]", and this is very much a case in which absence of evidence is not evidence of absence.

Covid vaccine safety: how correct are these allegations?

Thy disagree, but in which direction? The second chart seem to report numbers higher than the first chart but I'm not sure they are about the same data. What's your read? Can you put some links for the second graph source?

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