• Meta analysis using the most serious outcome reported shows 76% and 85% improvement for early treatment and prophylaxis (RR 0.24 [0.14-0.41] and 0.15 [0.09-0.25]), with similar results after exclusion based sensitivity analysis, restriction to peer-reviewed studies, and restriction to Randomized Controlled Trials.• 81% and 96% lower mortality is observed for early treatment and prophylaxis (RR 0.19 [0.07-0.54] and 0.04 [0.00-0.58]). Statistically significant improvements are seen for mortality, ventilation, hospitalization, cases, and viral clearance. 28 studies show statistically significant improvements in isolation.

	Studies	Prophylaxis	Early treatment	Late treatment	Patients	Authors
All studies	60	85% [75‑91%]	76% [59‑86%]	46% [29‑59%]	18,931	549
With exclusions	51	87% [75‑93%]	78% [69‑84%]	54% [33‑68%]	14,554	495
Peer-reviewed	35	88% [70‑95%]	77% [62‑86%]	42% [19‑58%]	7,611	357
Randomized Controlled Trials	31	83% [39‑95%]	69% [57‑77%]	40% [11‑60%]	5,316	340
Mortality results	22	96% [42‑100%]	81% [46‑93%]	61% [38‑76%]	7,690	205
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 2 trillion (p = 0.00000000000045).• 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 27% 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	18,931	71% [62‑77%]