The news headlines proclaimed: “Ivermectin doesn’t prevent severe disease from Covid-19, new study finds”. But an examination of the study in question shows that the headline is not accurate. The study showed a trend toward benefits in the secondary endpoints with use of ivermectin and a borderline statistically significant result of lower 28-day in-hospital deaths. Yet the news reports and the study itself failed to note these benefits in the results.
Here is a link to the study at JAMA. And all quotes are from that study. “The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021.”
Note that new reports claiming that a placebo was used, or that the study was “placebo controlled” are false. This was an open label study, meaning that the intervention group knew they were getting ivermectin. The control group received standard of care at those public hospitals and at the one quarantine center in Malaysia. The study attempted to recruit 500 patients. However, some patients (as usually happens in studies) dropped out.
The study authors wrote that “This trial required 462 patients to be adequately powered.” And 481 patients completed the study, which means the study had barely enough patients to possibly reach statistical significance. There were 249 in the control group, while “232 patients (96.3%) in the intervention group completed 5 doses of ivermectin.” The only result to achieve statistical significance was this: “Post hoc analyses on clinical outcomes by vaccination status showed that fully vaccinated patients in the control group had a significantly lower rate of severe disease” (P = .002). So vaccination is useful in reducing risk of progression to severe disease, if a vaccinated person becomes ill with Covid-19.
But none of the results for ivermectin or the standard of care were statistically significant. So the study did not prove that ivermectin is better than standard of care, but it also did not prove that standard of care is better than ivermectin. The lack of statistical significance may be due to the low number of patients. Here are the results:
“Results Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all pre-specified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).”
Note that of the 241 patients in the ivermectin group, only 232 completed all 5 doses. In the ivermectin group, 9 more patients progressed to severe disease, for a p-value of 0.25, which is not statistically significant. However, ivermectin patients had a lower rate of needing mechanical ventilation, 1.7% to 4.0% compared to the control; a lower rate of ICU admission, 2.4% to 3.2%, and a lower rate of 28-day in-hospital death, 1.2% to 4.0%. The latter result had borderline statistical significance at p=.09.
In medical studies, authors usually note when an intervention shows a trend toward benefiting patients, despite a lack of statistical significance, as ivermectin did. Moreover, authors almost always point out when an intervention has a substantial benefit with borderline statistical significance, in this case reducing death. But this study did not point out those potential benefits. The above noted clear trend toward reduction of the need for mechanical ventilation (only 4 in the ivermectin group versus 10 in the control) and the borderline significant reduction of 28-day in-hospital deaths (only 3 for ivermectin and 10 for the control) should have been pointed out by authors, and by news reports covering the study. But it was not. There is a bias against ivermectin in media, a bias that puts pressure on researchers not to point out the benefits of ivermectin in their own study.
Would you rather be in the ivermectin group where 3 persons died (1.2%), or the “standard of care” control where 10 persons died (4.0%)? And with borderline significance, the result clearly suggests that a larger study might achieve statistical significance, as other studies discussed here have done.
The dosing used in this study was 0.4 mg/kg, rounded to the nearest 6 or 12 mg dose. This means that a 60 kg (132 lb) patient would receive a 24 mg per day dose, rather than the much lower 12 mg/day dose that has been used in several successful studies. See this analysis of all ivermectin clinical trials. Most studies favored ivermectin.
Ronald L. Conte Jr.
“an author, not a doctor”