• Meta analysis using the most serious outcome reported shows 74% and 85% improvement for early treatment and prophylaxis (RR 0.26 [0.16-0.43] and 0.15 [0.08-0.25]), with similar results after exclusion based sensitivity analysis, restriction to peer-reviewed studies, and restriction to Randomized Controlled Trials.• 64% and 96% lower mortality is observed for early treatment and prophylaxis (RR 0.36 [0.15-0.85] and 0.04 [0.00-0.59]). Statistically significant improvements are seen for mortality, hospitalization, cases, and viral clearance. 26 studies show statistically significant improvements in isolation.

	Studies	Prophylaxis	Early treatment	Late treatment	Patients	Authors
All studies	60	85% [75‑92%]	74% [57‑84%]	43% [26‑56%]	21,838	574
With exclusions	50	88% [75‑94%]	76% [66‑83%]	50% [28‑65%]	17,437	513
Peer-reviewed	39	88% [70‑95%]	75% [59‑84%]	43% [21‑59%]	11,593	408
Randomized Controlled Trials	30	84% [25‑96%]	67% [54‑76%]	30% [2‑50%]	5,206	358
Mortality results	23	96% [41‑100%]	64% [15‑85%]	59% [35‑74%]	10,797	236
Percentage improvement with ivermectin treatment

• The probability that an ineffective treatment generated results as positive as the 60 studies to date is estimated to be 1 in 193 billion (p = 0.0000000000052).• Heterogeneity arises from many factors including treatment delay, population, effect measured, variants, and regimens. The consistency of positive results is remarkable. Heterogeneity is low in specific cases, for example early treatment mortality.• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 30% of ivermectin studies show zero events in the treatment arm.• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Those denying the efficacy of treatments share responsibility for the increased risk of COVID-19 becoming endemic; and the increased mortality, morbidity, and collateral damage.• Administration with food, often not specified, may significantly increase plasma and tissue concentration.• The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.• All data to reproduce this paper and sources are in the appendix. See [Bryant, Hariyanto, Hill, Kory, Lawrie, Nardelli] for other meta analyses, all with similar results confirming effectiveness.

Evidence base used for other COVID-19 approvals
Medication	Studies	Patients	Improvement
Budesonide (UK)	1	1,779	17%
Remdesivir (USA)	1	1,063	31%
Casiri/imdevimab (USA)	1	799	66%
Ivermectin evidence	60	21,814	70% [61‑76%]