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.
And:
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.
Summary:
The two studies find similar RR (risk reduction as
RR=riskivermectinriskcontrol)
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.
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:
And:
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.
Well worth reading the linked material—quite damning.
Update:
A recent preprint compares Roman et al and Bryant et al: Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease
Summary:
The two studies find similar
RR(risk reduction as RR=riskivermectinriskcontrol)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:
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: