Analysis of a small subset of 12 ivermectin trials showing a relationship with efficacy and strongyloides prevalence. This analysis is confounded by treatment delay, dose, conflicts of interest, and other factors, and the effect disappears when analyzing all studies, all RCTs, or all mortality results, as detailed in [ivmmeta.com]
Although the first author has responded to the confounders on Twitter, we do not see mention of them in the paper. Author is also aware that the larger sets of all trials, all RCTs, or all mortality results do not show the effect, however we also do not see this mentioned in the paper. These omissions suggest investigator bias. Author claims they could not discuss these issues due to publication delays, however the paper was accepted Jan 31, 2022, and author was aware of the issues months before, for example discussing treatment delay and dose in Nov 2021. These confounders are also basic and not really possible to miss.
The meta analysis for [Hashim]
includes critical patients, however these patients were always allocated to the treatment arm for ethical reasons, therefore including them is not logical and introduces substantial bias. According to the author response, this appears to have been known, suggesting investigator bias. Authors include [Shahbaznejad]
where the only death was a critical patient that died within 24 hours of admission.
Although authors note following PRISMA guidelines, we do not see registration of the protocol or discussion thereof. We note that the current protocol is the result of multiple changes to the original methodology as posted on Twitter: from 3 groups to 2 groups, altering the included studies, and switching from using one source for prevalence estimates to selecting estimate sources on a per study basis, which allows potential bias in the selection. Notably, this resulted in moving the Together Trial (Brazil) into the low prevalence category.
Author's results rely on trials with a very small number of mortality events — the high stronglyoides prevalance group has trials with 1, 3, 4, and 13 events. Authors do mention limitations due to the small number of events and the reliability of strongyloides estimates.
Authors changed from taking all prevalence estimates from the same source, to using a separate source for the two Brazilian studies. This moved those trials to the low prevalence group, which was required to show the effect. However, according to 
, authors have mixed adjusted and unadjusted prevalence estimates, and after adjustment the new source would also place these studies in the high prevalence group.
Authors indicate no conflicts of interest, however the first author has been an investigator on a Pfizer trial, which may be NCT04092452
, showing completion in January 2022 [clinicaltrials.gov, openpaymentsdata.cms.gov]
For other issues see [medicospelavidacovid19.com.br, ]