A continuation of a timeline of ivermectin-related events in theCOVID-19 pandemic

Abstract This review presents a continuation of a previous timeline that described ivermectin-related events in the COVID-19 pandemic from April 2020 to the end of March 2021. The new timeline covers a period from the beginning of April 2021 to the end of June 2021. In April 2021, the US National Institutes of Health (NIH) announced a new, large clinical trial including ivermectin, with an estimated study completion date is March 2023. A large national trial was also announced in the Philippines, a 1,160-patient trial in the US, and another trial in Ireland. Trial results published in the period resembled those of previous trials, not producing clinically meaningful changes to the results of existing meta-analyses. Mainstream press of the high-income countries mostly repeated the same arguments as in the previous period, including the warnings against ivermectin by the European Medicine Agency (EMA) and the World Health Organization (WHO). The sparse and one-sided coverage of ivermectin in the press appeared to result from a program called Trusted News Initiative (TNI). The censorship practices of the social media companies, with policies disallowing expression of views differing from the guidelines of the WHO, continued unchanged, apparently organized under a program called International Fact-Checking Network (IFCN). In contrast to the previous period – during which groups such as the Front Line COVID-19 Critical Care Alliance (FLCCC) and the British Ivermectin Recommendation Development (BIRD) group attempted to influence the decisions of government agencies – in this period these groups began to bypass the agencies and turn directly to clinicians and the public. FLCCC also published two new protocols, IMASS for mass immunization, and I-RECOVER for long haul COVID-19 syndrome (LHCS), and a review article which by the end of the period had reached a position in the top 120 of 18 million articles tracked by Altmetric. The BIRD group organized two online conferences on ivermectin and published a meta-analysis which had reached a position in the top 60, respectively. One of the authors of the in vitro study that initiated the international interest in ivermectin explained that due to, for example, the lack of adaptive immune responses in the cell model, their study was unsuitable for making conclusions about in vivo dosing in humans. A review described 20 mechanisms of action of ivermectin in COVID-19. The parties against and in favor of ivermectin remained in deeply conflicting positions, presenting opposite conclusions on the existing research. The WHO, along with regulatory agencies and national governments of high-income countries, appeared to aim at preserving the value of existing investments in vaccine and investigational therapeutics development, as well as questioning the efficacy and safety of repurposed medicines. Criticism towards the excessive influence of Bill Gates in the WHO emerged during the period, as the largest funder of the WHO appeared to be a group of vaccine promotion and intellectual property rights enforcement-oriented organizations founded by Gates. There was a noticeable centralization of power, with the pandemic response largely directed by a few public-private partnerships working on commercializable technologies.



Introduction

Ivermectin is a multifaceted medication invented in collaboration between Japanese professor emeritus Satoshi Omura from Kitasato University and US researcher William Campbell from Merck & Co/MSD ¯ between 1973 and 1979 [1]; [2]. Each of them received one-quarter of the 2015 Nobel Prize in physiology or medicine for their discoveries [3]. Ivermectin is best known as an antiparasitic agent, with approximately four billion doses having been administered since 1981, predominantly in Africa. Merck & Co/MSD’s patent expired in most countries in 1996, and ivermectin preparations are currently available internationally from many sources, with the production cost of a single dose estimated to be less than 0.1 US dollars [4]. This article extends the timeline of ivermectin related-events described in a previous preprint available in two versions, March 30, 2021, and April 3, 2021 [5]; [6]. The latter preprint covered the period from April 1, 2020, to March 31, 2021. This preprint extends the timeline to cover April–June 2021, as well as adding a few earlier events. Some caveats of the review are described in the previous preprint. Due to resource limitations, details of many developments are not covered in detail but only mentioned briefly, and omissions have been unavoidable. The focus of this review entails the social, organizational, financial, and legal aspects of the situation with ivermectin, with less emphasis placed on presenting clinical trial results and biomedical research. Some of the main events in the previously covered period from April 2020 to March 2021 were an Australian in vitro study which initiated the interest in ivermectin [7]. This was followed by the adoption of ivermectin in several South and Central American countries, the state of Uttar Pradesh in India, and Bangladesh in the second and third quarters of 2020. In late October 2020, the Front Line COVID-19 Critical Care Alliance (FLCCC) published its ivermectin-based outpatient protocol called I-MASK+ [8]; [9]; [10].




Discussion In the United States and the European Union, most of the year 2020 appeared to have been characterized by an attempt to collect ivermectin-related data. The period from the beginning of November 2020 to the end of March 2021 appeared to be characterized by disputes about the interpretation of this data. The change of administration in the United States did not appear to significantly change its ivermectinrelated health policy, likely to the disappointment of ivermectin proponents. Beginning from the March 30 guideline decision by the WHO against ivermectin, a period of a kind of trench warfare appeared to emerge. Ivermectin proponents, especially the FLCCC, announced they had resigned their attempts to influence the US National Institutes of Health, the Food and Drugs Agency, the European Medicines Agency, and the World Health Organization. Similarly, the BIRD group turned directly to clinicians and the public. Changes to existing treatment protocols were mostly minor. Fluvoxamine emerged as an option and was added to many protocols including the FLCCC’s. The FLCCC introduced two new protocols: the I-MASS protocol for mass prophylaxis and the I-RECOVER for long haul COVID-19 syndrome (LHCS). An interesting new development was the recognition of the role of mast cell activation and histamine release in LHCS [456]. The US NIH announced a new trial, ACTIV-6, for repurposed medicines, estimated to finish in March 2023, almost two years in the future, rendering the trial practically irrelevant for handling the pandemic. Simultaneously, pharmaceutical companies continued their attempts to finish their trials of new outpatient treatment pharmaceuticals as swiftly as possible, and new projects for the development of such treatments were initiated in the US and the UK. A third concurrent process was the slower-than-expected progress of vaccination programs. A fourth concurrent process was the adoption of ivermectin in countries outside the US and EU. The countries who 36 had adopted ivermectin previously, including Slovakia, implicitly disregarded the March 2021 guideline set by the WHO [171]; [457]. India adopted ivermectin nationally after the announcement of the WHO guideline, then mostly dropped it, with the current situation being somewhat unclear. Legal action against the WHO was initiated in India. At the end of the period, Indonesia adopted ivermectin. About researchers and clinicians, medical professionals whose practices appeared to be predominantly based on following existing regulations and protocols appeared to feel criticism against them unjustified and unfair. Similarly, medical professionals whose interest was in the further development of the protocols felt criticism against them unjustified and unfair. The first group may have perceived the latter group as deviants, whereas the latter group may have perceived the first group as anti-innovative. Presumably, both groups saw each others’ practices as somewhat unethical and antisocial. The difference was possibly due to different perspectives on collegiality and the perception of the role of patients. The first group appeared to put more weight on collegial cohesion and rule-adherence, with less weight put on individual patient outcomes, assumedly perceiving that patient outcomes were predominantly the product of the inflexible regulations which lay beyond their responsibility. The second group appeared to put less weight on collegial cohesion and regulations, placing more weight on individual patient outcomes, assumedly perceiving that patient outcome superseded the rules and that validation of rules was the responsibility of individual clinicians. About COVID-19, knowledge about the mechanisms and treatments were somewhat scarce especially in the early phase of the pandemic. A recent study described that in such a situation, it would be adaptive to seek further information to resolve uncertainty and obtain a more accurate worldview but biases in such information-seeking behavior could contribute to the maintenance of inaccurate views [458]. The study indicated that more dogmatic individuals were less likely to seek out new information to refine an initial perceptual decision, leading to a reduction in overall belief accuracy despite similar initial decision performance. In addition, dogmatic participants placed less reliance on internal signals of uncertainty, rendering them less likely to seek additional information to update beliefs derived from weak or uncertain initial evidence. Dogmatism is often defined as a viewpoint or system of ideas based on insufficiently examined premises. Thus, differences in openness to research evidence may have been due to differences in personalities and habits which, in turn, may be seen as products of the life experiences (environments) of the individuals, including their medical education. At times, the views appeared to differ up to a point in which the existence of a shared reality could be questioned, and the practice of presenting opposite conclusions on the same, existing data was in effect making further research irrelevant.


Private philanthropy, society, and science

In his recent book, Callahan discussed the role of private philanthropy, noting the rising influence and political significance of elite philanthropy, asking who is making choices over public life and who benefits from those choices [531]. Callahan described “today’s era of austerity” as a result of an orchestration of the upper class to reduce its taxes and the size of government, even so, that in some US states, cuts to higher education specifically helped finance tax reductions for the wealthy and corporations. He noted that in a decade, Bill Gates and Warren Buffett, the main funders of the Bill and Melinda Gates Foundation, had added USD 25 billion and USD 80 billion, respectively, to their wealth, and that the Koch brothers had increased their wealth from USD 9 billion in 2005 to USD 85 billion in 2015. In a book review, Saunders-Hastings asked whether elite philanthropists are a counterweight to other, self-interested elites or to democracy itself, and noted that the distance between elite “charity” and elite political influence is small and shrinking and that donors’ motivations matter less than the results of their actions [532]. Broad wrote that due to cuts to public funding and increase in private donations, “American science, long a source of national power and pride, is increasingly becoming a private enterprise” and quoted a policy analyst commenting that “the practice of science in the 21st century is becoming shaped less by national priorities or by peer-review groups and more by the particular preferences of individuals with huge amounts of money” [533]. Callahan proposed putting some curbs in place against private philanthropy, yet noted that foundations and nonprofit trade groups are strongly against any new restrictions, partly due to their dependency on philanthropy. He noted that “rethinking philanthropic freedom is Pandora’s box that almost nobody wants to open”, saying the current situation was a result of “yesterday’s mantras about philanthropic freedom and the dated regulation upholding it”. buy ivermectin | buy ivermectin India | buy ivermectin | buy ivermectin India | ivermectin tablet for humans | ivermectin tablet price ||ivermectin 12 mg tablet price in India | ivermectin buy online | where to buy ivermectin for humans | ivermectin dosage | where to buy ivermectin UK | ivermectin uses | ivermectin | Stromectol |buy ivermectin online | buy ivermectin online UK | buy ivermectin online NZ | buy ivermectin online south Africa | buy ivermectin online Malaysia | Buy Stromectol (ivermectin) Online at Lowest Price | Buy Ivermectin for Covid 19 Over the Counter | Buy Ivermectin for Humans and Ivermectin 3mg | Ivermectin Online Prescription | Buy Ivermectin Online

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