Appendix to Petition - "Give Ivermectin To Vulnerable Group. Not Discrimination"
1. Ivermectin For Prevention and Treatment of Covid-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines (https://ivmmeta.com/).
This is an extensive and comprehensive meta-analysis report dated 16 July 2021, written by a group of researchers and scientists who selected and analysed 60 studies of ivermectin including 38 peer reviewed trials.
The 60 studies were grouped into 4 categories in order to offer different perspectives of study outcomes for cross-checking: (1) All 60 Studies (2) Exclusions of sensitivity biases (3) Peer reviewed studies (4) RCTS.
a. Ivermectin As Prophylaxis
According to the above table "Peer-reviewed" study of 38 trials involving 11,464 patients, the efficacy of Ivermectin as a prophylaxis is comparable, if not better, than the mRNA vaccines and Sinovac. The prophylaxis rate of Ivermectin is 88%
Ivermectin : 88% (https://ivmmeta.com/#fig_fpp) - works against all variants
Pfizer mRNA : 95% * ( dropped to 39% against Delta variant in Israel )
Moderna mRNA : 94.1% * ( similar drop against Delta variant as Pfizer)
Sinovac : 65.9% ( NEJM 7 July 2021 re Chile study)
Sinovac: 83.5% ( Lancet 17 July 2021 re Turkey study)
* The Lancet 17 July 2021 re Turkey Study
The Meta-analysis of Ivermectin 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.
b. Ivermectin's efficacy For Early Treatment To Prevent Disease Severity
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.
c. 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).
d. 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.
e. While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 28% of ivermectin studies show zero events in the treatment arm.
f. The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.
g. 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.
2. Meta-analysis of 24 RCTS Involving 3,406 participants
This is by far the most professionally done meta-analysis of peer reviewed RCTs. It was published on July/Aug 2021 in the American Journal of Therapeutics ( click on link). Quality and certainty of the evidence was assessed using the GRADE approach ( Grading of Recommendations, Assessment, Development and Evaluations). Authors used Cochrane Effective Practice and Organisation of Care guidance to interpret the evidence.
Summary of Findings
a. Moderate certainty evidence of 49% reduction of deaths compared with no ivermectin
b. Low certainty evidence of 86% reduction in infection (as prophylaxis). Three trials involving 738 participants among health care workers Covid-19 contacts, evaluated Ivermectin for Covid-19 prophylaxis. Although low certainty evidence, the studies strongly indicate that using Ivermectin early in the clinical course may reduce numbers progressing to severe disease.
c. The apparent safety and low cost suggest that Ivermectin is likely to have a significant impact on the Sars-CoV-2 pandemic globally.
3. Ivermectin Safety Profile
(a) For nearly 40 years with 3.7 billion doses administered, there were only 20 reports of deaths related to the use of Ivermectin
(b) Ivermectin is safe for humans in spite of doses higher than normal.
" Safety of high-dose Ivermectin: a systematic review and meta-analysis"
Ivermectin's 40-year record of safety is astounding when compared to vaccine deaths and injuries!
4. Real World Studies
When certain states and cities of Argentina, Peru, Slovakia, Mexico, India, Paraguay and Brazil, experienced outbreaks of Covid cases, the mayors or state governments widely distributed Ivermectin to its residents. Within a month, the cases fell dramatically and millions were saved.
Below are stunning data visualizations of dramatic falls
a. India Case Study - Desperate to bring down the 2nd wave of infections in India, the 4 states of Goa, Uttar Pradesh, Kerala, Karnataka, Uttarakhand and the city of Delhi distributed Ivermectin Home Treatment Kits to their residents. Within a month, infections dropped dramatically ("Ivermectin obliterated 97% of Covid cases in Delhi, India", 1 June 2021 )
b. Peru Case Study: " Ivermectin for Covid-19 in Peru: 14-fold reduction in nationwide excess deaths, then 13-fold increase after ivermectin use restricted" (https://osf.io/9egh4/)
Excerpt from paper: "In these eight Peruvian State analyses, Ivermectin distributions preceded sound reductions in excess deaths and case fatality rate (CFR). The variation in the number of detected cases nor the vulnerable population decrease can explain this reduction. Other possible explanations, such as cross-immunity with dengue, or mere causality, have been discarded due to their lack of consistency in this study.
Treatment with ivermectin is the most reasonable explanation for the decrease in number of deaths and fatality rate in Peru. Its implementation in public policies is a highly effective measure to reduce the excess deaths and IFR of COVID-19."
c. Argentina Case Study
e. Zimbadwee Case Study
Ivermectin is now used in 34
countries to prevent and treat Covid-19, and the list is growing. Of these, 15 countries have adopted
Ivermectin, nation-wide. Among first
world countries, Ivermectin is used in certain states of USA, Germany and Japan
( source: https://ivmstatus.com/)
5. Critics & Biased Treatment Towards Use of Ivermectin for Covid-19
a. The WHO study There are numerous flaws (about 12) in the study that WHO commissioned to recommend the use of Ivermectin in clinical trials. Some of the flaws are related to limitations of the studies used (e.g. 7 studies with 1,419 patients, not specifying which trials, the forest plot shows 4 studies with mortality results, they excluded all 13 prophylaxis studies ), no protocol for data exclusion etc ). They do not specify which trials they included. The report is inconsistent, with a forest plot that only shows 4 studies with mortality results), their risk of bias assessments does not match the actual risk of bias in studies etc ( source: https://ivmmeta.com/#who )
b· Higher standards of approving criteria are being applied to Ivermectin
The evidence supporting ivermectin for COVID-19 far exceeds the typical amount of evidence used for the approval of treatments. [Lee] shows that only 14% of the guidelines of the Infectious Diseases Society of America were based on RCTs.
Table 3 and Table 4 compare the amount of evidence for ivermectin compared to that used for other COVID-19 approvals, and that used by WHO for the approval of ivermectin for scabies and strongyloidiasis. Table 5 compares US CDC recommendations for ibuprofen and ivermectin.
Ivermectin is a well-known, FDA-approved anti-parasite drug that has been used successfully for 40 years to treat onchocerciasis "river blindness" and other parasitic diseases. It is one of the safest drugs known. It won the Nobel prize for its discoverer and is listed in the WHO list of essential drugs.
Since the pandemic started 1.5 years ago, out of desperation, many critical care doctors tried many antiviral drugs to treat severe Covid-190 to save their patients. Ivermectin was one of the most efficacious drugs. Human trials then begin.
To-date, many meta-analyses have been done. Here is a list of 100+ studies done on Ivermectin ( https://c19ivermectin.com/).
Ivermectin lost its patent status in the late 1990s and its sales income became less lucrative for Merck, its former patent holder. This means that any manufacturer can produce Ivermectin, making it a generic drug that is cheap and easily available