Despite the rapidly increasing and diverse amounts of medical evidence supporting ivermectin as a life-saving therapy in COVID, multiple national and international health agencies – including but not limited to the World Health Organization, the European Medicines Agency, and the regulatory health agencies of all of North America and Europe – have continued to issue negative recommendations against use of ivermectin in COVID-19.

The FLCCC is one of several groups researching the use of ivermectin in COVID-19, and along with many such groups, we have become increasingly concerned regarding unprecedented, highly irregular, and poorly defended public health agency (PHA) decisions regarding multiple therapeutic agents including that of ivermectin. Many providers, patients, and citizens now openly speculate that these behaviors are consistent with suppression and distortion of the scientific data in order to meet non-scientific (financial and other) objectives. We remind all health care providers and patients that policy decisions must derive from the science with a primary interest in improving public health and not from a predetermined, non-scientific objective. What follows is a detailed and objective analysis of these numerous PHA recommendations.
Agency Concerns: “Because most of these studies have significant limitations, we cannot draw definitive conclusions on the clinical efficacy of ivermectin for the treatment of COVID-19.”

FLCCC Response: Guideline officials of numerous leading PHA’s in the US (NIH), UK, Canada, Europe, and the WHO were sent the proceedings of the recent British Ivermectin Recommendation Development effort (BIRD) whereby on February 20, 2021, the results of a comprehensive assessment of the quality of the existing ivermectin trials – conducted according to a widely accepted protocol consistent with WHO Guideline standard– was presented by the BIRD Technical Working Group to their Recommendation Development Panel.1 The presentation consisted of the details and results of a systematic review and meta-analysis of 21 randomized controlled trials (RCTs) including over 2,500 patients. The Panel was made up of over 65 general practitioners, specialists, researchers and patient representatives representing over 15 countries from all regions of the world. Following a guideline development process consistent with the WHO standard, the BIRD Panel reviewed not only the RCT data, but also a summary of the observational controlled trials (OCT) and the numerous examples of epidemiologic analyses showing the effects of ivermectin distribution campaigns and/or widespread treatment adoption on population-wide rates of excess death.1 The majority of Panel members (75%) found that the overall certainty of this comprehensive evidence base was overall moderate to high. Importantly, no apparent conflicts of interest were identified amongst the trials. Finally, the Panel consensus gave the strongest recommendation option for ivermectin to be adopted in both the prevention and treatment of COVID-19.

We are severely troubled by the multiple examples of PHA’s failing to openly address the reasons for their discordant conclusions from the now widely known BIRD recommendation as well as to undertake as extensive and proactive an effort as the BIRD or Unitaid research teams. For instance, the Unitaid team identified and established communication with the principal investigators of all 59 active registered, randomized, controlled treatment trials of ivermectin in COVID-19. In this fashion, they were able to receive not only trial results immediately upon completion of each trial, but all the critical details required to accurately assess the quality of the trials. The Unitaid team has also repeatedly offered to share the data they have compiled in their “active” review with any regulatory agency. We have been informed that, as of April 1, 2021, the Unitaid team had results from approximately 24 RCT’s of ivermectin treatment in COVID-19, yet no recent PHA recommendation reflects the data from this number of trial results. The WHO recommendation of March 31, 2021 is most troubling given that they referenced only 16 of the approximately 24 available trial results compiled by the Unitaid team they directly collaborate with.
Further, and perhaps as a direct result of the above, all such PHA recommendations conflict with the findings of benefit reported in multiple published independent expert reviews and meta-analyses from across the world including a recent report co-authored by the Nobel Prize winning discoverer of ivermectin, Professor Satoshi Omura. These include:

1. UK -British Ivermectin Recommendation Development Panel[1] 2. Spain – Cabo-Campos et al, Bioaraba Health Research Institute[2] 3. Italy – Nardelli et al. San Raffaele Scientific Institute, Milan, Italy[3] 4. US – Kory P et al. Front Line COVID-19 Critical Care Alliance[4] 5. Japan – Yagisawa, M et al. Kitasato Institute, Japan[5]

In particular, the FLCCC’s comprehensive narrative review of ivermectin by Kory et al passed a rigorous peer review performed by 2 career FDA scientists, an expert ICU clinician, and a Senior Scientist/Subject Matter Expert for the Therapeutics Branch of Translational Medicine Division of the Defense Threat Reduction Agency (DTRA) of the Department of Defense. This recently published manuscript, along with the publications from Spain, Italy, Japan, and the UK, and in contrast to all major PHA’s, concluded that the existing evidence base fully supports the immediate global adoption and deployment of ivermectin in the prevention and treatment of COVID-19.

Agency Concerns: The Infectious Disease Society of America (IDSA), a professional society of infectious disease specialists within the US, “recommend against use outside of clinical trials”. Most disturbing, beyond the limited evidence base they included for review, were their “concerns about publication bias, as the available evidence consisted mostly of positive trials of smaller size.” Despite this concern, no mention of any effort to assess for publication bias was done by the IDSA, nor did the IDSA consult with the Unitaid team that had performed the sophisticated “Harbord test for small study effects” and found “no significant risk of publication bias.” Thus, the IDSA erroneously and tragically dismissed an evidence base consisting “mostly of positive trials.”

Agency Concerns: Agencies continue to state the need for “adequately powered, well-designed, and well-conducted clinical trials”

FLCCC Response: The recent non-evidence-based practice by many PHA’s of consistently dismissing all findings from observational controlled trials (OCT’s) is increasingly described and almost universally accepted. The excessive concerns over possible misinterpretation of such trials due to worries over unmeasured confounders or imbalanced comparison groups has fueled the recent near universal reliance on RCT data alone to inform treatment recommendations. What is shocking is that now, in an almost identical manner, the quality and findings of a large body of prospective, randomized, controlled trials are being questioned. This is occurring even though RCT’s have long been considered the gold standard of scientific investigation and thus the PHA’s refusal to accept these findings are indefensible given that, among the almost two dozen RCTs studying ivermectin in COVID-19, the results from double-blind, single-blind, open label, quasi-randomized, placebo-controlled, or standard of care comparison designs all report consistently similar benefits in clinical outcomes. The known bias against OCT data is exactly why Unitaid/WHO restricted its ivermectin research team to studying results of RCT trials only. Yet, despite their team’s compilation of results from almost 24 RCT’s, only 16 were referenced in the WHO recommendation and most concerning, only 5 were considered in their estimation of ivermectin’s mortality benefit.

The repeated actions by PHA’s whereby they include only a limited sample of the existing, publicly available evidence base has led to the ignoring of massive amounts of trials data including thousands of patients. If any and every purported design shortfall of the RCT’s is used for either dismissal or weakening of consideration, this “raises the bar” such that almost no studied therapeutic could ever be considered to have proven efficacy. A possible exception appears to be that of a single, massive, impeccably designed and conducted trial performed by a pharmaceutical company or major academic medical center within North America or Europe. Unfortunately, and for increasingly suspect reasons, no such study has yet been completed on ivermectin 16 months into the pandemic. However, even if such a trial had been completed by now, the strength of its findings would not outweigh the current evidence base, given that it derives from a summary of data from many RCTs (“systematic review and meta-analysis data”), long considered the highest form of medical evidence in support of an intervention, more so than any single—even large—RCT.

FLCCC Response: The persistent PHA practices of selecting only a subset of available medical evidence for ivermectin is common. The last NIH Panel recommendation update on February 12th , where 9 of the 17 RCT results with data on almost 1,100 patients were excluded without explanation, despite having received the results of these trials during an FLCCC/Unitaid presentation to the Panel on January 6, 2021.[6]

• 3 excluded RCTs reported statistically significant reductions in mortality
• 4 additional excluded RCTs reported statistically significant reductions in viral clearance
• One included RCT was mischaracterized as unblinded when it employed a single-blind design
Further, of the agencies that do consider OCT trials data to be of value, many also selectively include only a minority. Using the NIH recommendation from February 12th again as an example;
• 3 excluded OCT’s reported statistically significant reductions in mortality or viral clearance
• 1 “negative” OCT was included despite numerous and widely criticized design, conduct, and interpretation flaws and the firing of multiple authors and supervisors of the study [1],[2] • 1 cited OCT (the “ICON” trial published in the high impact journal Chest by the Amer