I had a quick look and essentially it seems the latter found fewer studies (10 vs 19) and therefore fewer patients (1173 vs 2768)*
They have similar central estimates for RR of all cause mortality (0.37 vs 0.31) but due to having more patients the former has tighter CI (0.15 to 0.62) and concludes that there is an effect but the latter has wider CI (0.12 to 1.13) and concludes that there isn’t an effect.
The latter could claim that there is as yet insufficient evidence of an effect based on the studies in their analysis but not that these isn’t an effect. I especially take issue with the claim that “IVM is not a viable option for treating COVID-19 patients” when they themselves take such pains to talk about how low quality much of the evidence is!
The two meta-analyses also differ on their ratings of different papers—for instance the largest study (n=400, Lopez-Medina et al.) is rated as High quality (7 out of 7) in the former but at high risk of bias in the latter (due to deviations from intended interventions).
Scanning the paper there are a few issues. For the most part the problems are mitigated but there could still be issues:
There was a period of 17 days where the placebo group were receiving ivermectin(!)
The people from these 17 days were excluded from the primary analysis and additional subjects were enrolled
The primary outcome was changed during the study
This occurred ~30% through the study.
The reasoning for changing from the old outcome seems reasonable
It’s hard to comment on whether the selection of the new outcome could have seen bias
Placebo was changed during the study from dextrose water to something tasting more like ivermectin
This was ~25% through the study
Results did not differ much between the 2 placebo groups
I don’t feel like this would make a massive difference but I’m not sure
This paper is fairly typical of the quality of the studies (according to meta-analysis 2) or on the top end of study quality (according to meta-analysis 1) which causes me some concern.
In conclusion, if I was offered Ivermectin I would take it at this point (side effects seem to be small) and might even look to sign up to a trial if I had COVID—in the UK some people would be eligible for this one.
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.
I had a quick look and essentially it seems the latter found fewer studies (10 vs 19) and therefore fewer patients (1173 vs 2768)*
It seems like one of the reasons they found fewer studies was that they only searched till March 22, 2021 which is odd for a review paper published 28 June 2021.
The pro-Ivermectin was published earlier and went till May 10th.
Yes, I think this definitely had some effect (I misread 10th May as 10th March originally!).
I also think the fundamental search must have been better in #1. Of the 13 present in #1 but missing in #2 6 were from 2020, 7 from 2021 (I haven’t looked at specific dates for the 2021 ones but I’d guess some of them are from before March 22nd).
For #1 the original search turned up 1237 articles then 95 full text analysed leading to the 19 included. Corresponding numbers for #2 are 256, 12 & 10.
I had a quick look and essentially it seems the latter found fewer studies (10 vs 19) and therefore fewer patients (1173 vs 2768)*
They have similar central estimates for RR of all cause mortality (0.37 vs 0.31) but due to having more patients the former has tighter CI (0.15 to 0.62) and concludes that there is an effect but the latter has wider CI (0.12 to 1.13) and concludes that there isn’t an effect.
The latter could claim that there is as yet insufficient evidence of an effect based on the studies in their analysis but not that these isn’t an effect. I especially take issue with the claim that “IVM is not a viable option for treating COVID-19 patients” when they themselves take such pains to talk about how low quality much of the evidence is!
The two meta-analyses also differ on their ratings of different papers—for instance the largest study (n=400, Lopez-Medina et al.) is rated as High quality (7 out of 7) in the former but at high risk of bias in the latter (due to deviations from intended interventions).
Scanning the paper there are a few issues. For the most part the problems are mitigated but there could still be issues:
There was a period of 17 days where the placebo group were receiving ivermectin(!)
The people from these 17 days were excluded from the primary analysis and additional subjects were enrolled
The primary outcome was changed during the study
This occurred ~30% through the study.
The reasoning for changing from the old outcome seems reasonable
It’s hard to comment on whether the selection of the new outcome could have seen bias
Placebo was changed during the study from dextrose water to something tasting more like ivermectin
This was ~25% through the study
Results did not differ much between the 2 placebo groups
I don’t feel like this would make a massive difference but I’m not sure
This paper is fairly typical of the quality of the studies (according to meta-analysis 2) or on the top end of study quality (according to meta-analysis 1) which causes me some concern.
In conclusion, if I was offered Ivermectin I would take it at this point (side effects seem to be small) and might even look to sign up to a trial if I had COVID—in the UK some people would be eligible for this one.
* 6 studies were common to both analyses.
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.
That’s super-helpful—thanks!
One thing the negative meta-study noted was the variation in doses between studies (12 − 210mg).
It seems like one of the reasons they found fewer studies was that they only searched till March 22, 2021 which is odd for a review paper published 28 June 2021.
The pro-Ivermectin was published earlier and went till May 10th.
Yes, I think this definitely had some effect (I misread 10th May as 10th March originally!).
I also think the fundamental search must have been better in #1. Of the 13 present in #1 but missing in #2 6 were from 2020, 7 from 2021 (I haven’t looked at specific dates for the 2021 ones but I’d guess some of them are from before March 22nd).
For #1 the original search turned up 1237 articles then 95 full text analysed leading to the 19 included. Corresponding numbers for #2 are 256, 12 & 10.