The Cochrane Review is certainly credible but they are NOT the final authority. I would put the work of Dr. Pierre Kory and Paul Marik of covid19criticalcare.com above anything The Cochrane Review would say as Dr. Kory and Marik are actually treating patients.
What exactly would put Kory and Marik above the Cochrane Review? Their meta-analysis with some seriously questionable studies (Elgazzar 2020)? Or, is it
just their unpublished data (anecdotes and observations) from treating patients?
You are correct in that the final authority will come from clinical trials recruiting thousands of patients. However, the Cochrane Review
is the most accurate assessment of the data and evidence available
right now. The review by Kory et al. is not equatorial, and you can even find where Cochrane compares their analysis to other meta-analyses. Treating patients gives them observational data and anecdotes that are subject to bias and are not randomized. There is no shortage of treatments that looked great in observational studies, and then the efficacy signal vanishes or demonstrates harm in the large RCTs. Off the top of my head, that was the case for drugs like colchicine for COVID early on, and famously, HRT in post-menopausal women.
As far as Kory et al.:
"
Kory 2021 identified seven RCTs on the efficacy of ivermectin in outpatients with mild COVID‐19 and six RCTs in hospitalized people with COVID‐19. The review was published in the
American Journal of Therapeutics and did not provide any search date or other methodological details used for meta‐analyses.
Kory 2021 concluded there was a mortality benefit based on the inclusion of six of the 13 studies (odds ratio (OR) 0.13, 95% CI 0.07 to 0.28), which was not a valid inclusion because
Elgazzar 2020,
Hashim 2020,
Mahmud 2021, and
Niaee 2020 were not eligible for the reasons described above, and
Cadegiani 2020 was not an RCT. As described for
Hill 2021, there remains only one small study (
Kirti 2021), and a high degree of uncertainty for a mortality benefit."
The "reasons described above" for study ineligibility:
"We did not include five of the six studies in our meta‐analysis on mortality of people with moderate COVID‐19, including
Elgazzar 2020,
Hashim 2020,
Mahmud 2021,
Niaee 2020, and
Okumuş 2021.
Hashim 2020 and
Mahmud 2021 combined ivermectin with doxycycline, which makes it impossible to isolate any potential effect to the individual drugs used.
Elgazzar 2020 compared ivermectin to hydroxychloroquine. The latter is not effective for the treatment of COVID‐19 and has resulted in clinical adverse effects (
Singh 2021). We did not consider hydroxychloroquine an eligible comparator to investigate the efficacy and safety profile of ivermectin for the treatment of COVID‐19.
Niaee 2020 included a population of about 30% of people who were SARS‐CoV‐2‐negative, which we did not consider appropriate to investigate SARS‐CoV‐2‐specific antiviral effect of ivermectin."
Have you read the Elgazzar 2020 study or its criticisms? There is strong evidence of fraud! There were also widespread errors in data reporting and blatant plagiarism. Best part yet? Elgazzar 2020 was by far one of the most convincing studies on ivermectin based on size and was the centerpiece of a lot of the positive evidence reported by meta-analyses.
"The main error is that at least 79 of the patient records are obvious clones of other records,” Brown told the Guardian. “It’s certainly the hardest to explain away as innocent error, especially since the clones aren’t even pure copies. There are signs that they have tried to change one or two fields to make them look more natural."
Add in that Kory et al. also includes Niaee 2020, which, according to the discrepancies in the PCR positivity between the groups, brings the study randomization into question.
Evidenced here:
"Even if not eligible for the Cochrane Review, two studies in
Bryant 2021 and all the other meta‐analyses were notable because of the size of the effect reported and the narrow CIs:
Elgazzar 2020 and
Niaee 2020 help drive the large effects seen in the random‐effects analysis.
Elgazzar 2020, for example, reported among people with severe disease two deaths out of 100 in the ivermectin group and 20 deaths out of 100 in the chloroquine group; and
Niaee 2020 reported two deaths out of 100 in the ivermectin group and 11 deaths out of 60 in the control group. These effect sizes are extreme. A recent press release claimed that the large trial by
Elgazzar 2020 showed clear signs of fraudulence and should be withdrawn over ethical concerns (
The Guardian 2021). Research Square withdrew this preprint on 14 July 2021 due to an expression of concern (
Elgazzar 2020)."
Criticism of methodology for websites like ivmmeta:
"The website
ivmmeta.com provides several meta‐analyses of pooled effects including up to 60 studies. This website shows pooled estimates suggesting significant benefits with ivermectin, which has resulted in confusion for clinicians, patients, and decision‐makers (
Garegnani 2021). The analyses are misleading and have several limitations. As described for the other reviews, several ineligible interventions and comparators were pooled. Additionally, different outcomes were pooled and reported as percentage improvement with ivermectin studied in RCTs ranging from 40% improvement when used as late treatment to 83% improvement when used as prophylaxis. However, there is no full prospective protocol available describing the relevant review methodology, and there is no assessment of the risk of bias or the certainty of evidence."