•100% of the 35 studies to date report positive effects. Early treatment is more successful, with an estimated reduction of 84% in the effect measured using a random effects meta-analysis, RR 0.16 [0.08-0.33]. Prophylactic use also shows high effectiveness.
•100% of the 17 Randomized Controlled Trials (RCTs) report positive effects, with an estimated reduction of 71%, RR 0.29 [0.17-0.51].
•The probability that an ineffective treatment generated results as positive as the 35 studies to date is estimated to be 1 in 34 billion (p = 0.000000000029).
Introduction
We analyze all significant studies concerning the use of ivermectin for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for mortality results only, and for Randomized Controlled Trials (RCTs) only.
We also perform a simple analysis of the distribution of study effects. If treatment was not effective, the observed effects would be randomly distributed (or more likely to be negative if treatment is harmful). We can compute the probability that the observed percentage of positive results (or higher) could occur due to chance with an ineffective treatment (the probability of >= k heads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias is important and adjustments may be needed if there is a bias toward publishing positive results.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.Figure 3, 4, and 5 show results by treatment stage. Figure 6 and 7 show forest plots for a random effects meta-analysis of all studies with pooled effects, and for studies reporting mortality results only. Table 1 summarizes the results.
| Treatment time | Number of studies reporting positive results | Total number of studies | Percentage of studies reporting positive results | Probability of an equal or greater percentage of positive results from an ineffective treatment | Random effects meta-analysis results | ||
| Early treatment | 10 | 10 | 100% | 0.00098 0.00098 1 in 1 thousand | 84% improvement RR 0.16 [0.08‑0.33] p < 0.0001 | ||
| Late treatment | 15 | 15 | 100% | 0.000031 3.1e-05 1 in 33 thousand | 39% improvement RR 0.61 [0.47‑0.79] p = 0.0002 | ||
| Prophylaxis | 10 | 10 | 100% | 0.00098 0.00098 1 in 1 thousand | 90% improvement RR 0.10 [0.05‑0.23] p < 0.0001 | ||
| All studies | 35 | 35 | 100% | 0.000000000029 2.9e-11 1 in 34 billion | 74% improvement RR 0.26 [0.19‑0.36] p < 0.0001 |