British Ivermectin Recommendation Development Panel – Response to EMA Statement on Ivermectin for Covid-19 https://www.e-bmc.co.uk On 22 March, the European Medicines Agency (EMA) issued a statement [0] that, after reviewing the evidence, they recommend against the use of ivermectin for the prevention and treatment of covid-19, outside of ‘well-designed’ clinical trials. The EMA claims evidence from laboratory studies, clinical trials, observational studies, and meta-analysis, but provides no sources, specifics or citations. We fill these omissions below. The British Ivermectin Recommendation Development (BIRD) panel was set up in January 2021 by Dr Tess Lawrie of the Evidence-Based Medicine Consultancy Ltd (E-BMC), an independent medical research company based in Bath, UK. A systematic review and meta-analysis of ivermectin for covid-19 was recently conducted by Dr Lawrie, the director, with a team of expert systematic reviewers. A preliminary report was released in the public domain on 3 January [1]. A comprehensive paper including 21 RCTs has been submitted to a peer-reviewed journal, and meanwhile is available on two pre-print servers [2 ,3]. Moreover, on 20 February 2021, a panel of 65 clinicians, researchers and patient representatives from 16 countries attended the BIRD panel meeting, convened by Dr. Lawrie and her team, to evaluate the evidence on ivermectin for covid19. Following the standard “DECIDE” Evidence-to-Decision framework [4] for clinical recommendations, BIRD concluded that there was enough evidence to recommend the rapid implementation of ivermectin for covid-19 [5, 6]. This recommendation is by implication global and not restricted to the UK or the EU. Indeed, the low cost and widespread use make ivermectin uniquely placed to tackle covid-19 worldwide, including very low income countries. BIRD provides a detailed response to the EMA statement, with citations to the evidence. EMA advice against ivermectin for the prevention or treatment of COVID-19: 1. Review of the evidence EMA has reviewed the latest evidence on the use of ivermectin for the prevention and treatment of COVID-19 and concluded that the available data do not support its use for COVID-19 outside welldesigned clinical trials. … Results from clinical studies were varied, with some studies showing no benefit and others reporting a potential benefit. Most studies EMA reviewed were small and had additional limitations, including different dosing regimens and use of concomitant medications. EMA therefore concluded that the currently available evidence is not sufficient to support the use of ivermectin in COVID-19 outside clinical trials. 2 Ivermectin's potential therapeutic utility has expanded over the last decade as broad-spectrum anti-viral and even anti-neoplastic properties have been discovered [7, 8]. Since April 2020, the evidence base of observational and randomised trials of ivermectin for covid-19 has accumulated. A review [9, 10] by the Front Line Covid-19 Critical Care Alliance (FLCCC) summarised findings from 27 randomised controlled trials (RCTs) and 16 observational studies on ivermectin both for prevention and treatment of covid-19. They conclude that ivermectin “demonstrates a strong signal of therapeutic efficacy.” Moreover, ivermectin is the sole therapeutic so far to have demonstrated efficacy at all stages of the very complex clinical course of the covid-19 disease, from prophylaxis through to critical care. A systematic review and meta-analysis [2, 3] was subsequently conducted by Dr Lawrie and a team of experts. Twenty-one RCTs involving 2741 participants met review inclusion, according to strict criteria, and subsequent meta-analysis of 13 trials found that ivermectin reduced risk of death (compared to no ivermectin) with an average Risk Ratio 0.32 [ 95% confidence interval (CI) 0.14 to 0.72; n=1892; I 2 =57% ] with “low to moderate-certainty.” Low certainty evidence found ivermectin prophylaxis reduced the risk of covid-19 infection by an average of 86% [95% CI 79% to 91%]. Adverse events were rare and usually attributable to other adjunct medications. In practical terms this means that ivermectin reduces the risk of death from covid-19 to about one-third of the risk of death without using this medication. In the long run, of every nine patients who would otherwise die from covid-19, six can now be saved by using ivermectin. Similarly the risk of contracting covid-19 is reduced to one-seventh of the risk faced by other healthy people with similar exposure, when using ivermectin as prophylaxis. For every seven people who would catch covid-19 from an infected person, only one is likely to catch the illness, when using ivermectin.
