The distribution of demographic factors is not consistent with what would be expected by random chance from a true double blinded RCT with allocation concealment. The extreme heterogeneity and differences in baseline characteristics between patients in control and treatment arms are very unlikely to occur by chance,
For example, the percentage of participants who were "PCR negative" covid patients in the control groups are 40-50%, while in the single high dose ivermectin (400mcg/Kg) arm just 3% of participants are PCR negative.
A simple Chi Square test gives a p value of approx 0.0008, suggesting these results are very unlikely to arise by random chance.
This raises serious questions about whether the trial was conducted as described, and whether random allocation with concealment genuinely occurred.
In the absence of a good explanation these results should be interpreted with extreme caution, this study should be considered at very high risk of bias, and, in my opinion, should not be included in meta-analyses. The authors should audit their concealment procedures and check for between centre differences in case this heterogeneity between enrolment centres.
Some of the baseline characteristics are indeed quite heterogeneous, but others look strangely homogeneous, e.g. diastolic BP (from bottom of Table 1):
Another thing which is unclear in the paper is whether hydroxychloroquine was prescribed to all patients, or only to the non-ivermectin groups. These two passages are somewhat contradictory:
The participants were randomly allocated to six arms including common regimen based on Iran health ministry (Hydroxychloroquine 200mg/kg twice per day), placebo plus common regime, single dose ivermectin (200mcg/Kg, 1 pill per day), three low interval doses of ivermectin (200, 200, 200 mcg/Kg , 3 pills in 1, 3 and 5 interval days ), single dose ivermectin (400mcg/Kg, 2 pills per day), and three high interval doses of ivermectin ( 400, 200, 200 mcg/Kg, 4 pills in 1, 3 and 5 interval days).
All patients were treated according to “Iranian guideline of hospitalized COVID-19 patients’ management (version 5)”. This comprised oral hydroxychloroquine (HCQ) 200mg/kg twice per day as standard regimen and a heparin prophylaxis in combination with supplemental oxygen. Tablet of ivermectin (14 mg) and placebo were formulated in Alborz Darou pharmaceutical Co., Tehran, Iran.
You have noted on your blog that Niaee et al. have agreed the the p-value for the proportion of positive PCR results in each arm was actually <0.001, not 0.421.
I’m wondering whether the Arm 4 died n=1 is also a typo and should actually be n=10.
For all arms except 4, FAS=allocated–died.
However Arm 4 allocated n=30, died n=1, FAS n=20.
If Arm 4 died n was actually 10:
Arm 4 FAS would=allocated–died, consistent with the other arms
the Fisher’s exact p-value for ivermectin vs no-ivermectin mortality would change from p=0.001 to p=0.171
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