Bigtex
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- Aug 14, 2012
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Does the truth finally emerge?
In the context of ivermectin's long-standing safety record, low cost, and wide availability along with the consistent, reproducible, large magnitude of findings on transmission rates, need for hospitalization, and mortality, widespread deployment in both prevention and treatment has been proposed. Although a subset of trials are of an observational design, it must be recognized that in the case of ivermectin (1) half of the trials used a randomized controlled trial design (12 of the 24 reviewed above) and (2) observational and randomized trial designs reach equivalent conclusions on average as reported in a large Cochrane review of the topic from 2014.81 In particular, OCTs that use propensity-matching techniques (as in the Rajter study from Florida) find near identical conclusions to later-conducted RCTs in many different disease states, including coronary syndromes, critical illness, and surgery.82–84 Similarly, as evidenced in the prophylaxis (Figure (Figure1)1) and treatment trial (Figures (Figures22 and and3)3) meta-analyses as well as the summary trials table (Table (Table3),3), the entirety of the benefits found in both OCT and RCT trial designs aligns in both direction and magnitude of benefit. Such a consistency of benefit among numerous trials of varying sizes designs from multiple different countries and centers around the world is unique and provides strong, additional support.
The continued challenges faced by health care providers in deciding on appropriate therapeutic interventions in patients with COVID-19 would be greatly eased if more updated and commensurate evidence-based guidance came from the leading governmental health care agencies. Currently, in the United States, the treatment guidelines for COVID-19 are issued by the National Institutes of Health. Their most recent recommendation on the use of ivermectin in patients with COVID-19 was last updated on February 11, 2021, where they found that “there was insufficient evidence to recommend for or against ivermectin in COVID-19.” For a more definitive recommendation to be issued by major leading public health agencies (PHA), it is apparent that even more data on both the quality and quantity of trials are needed, even during a global health care emergency, and in consideration of a safe, oral, low-cost, widely available and deployable intervention such as ivermectin.
Fortunately, large teams sponsored by 2 different organizations have embarked on this effort. One team, sponsored by the Unitaid/WHO's ACT Accelerator Program and led by the University of Liverpool Senior Research Fellow Dr. Andrew Hill, is performing a systematic review and meta-analysis focused solely on ivermectin treatment RCTs in COVID-19. Although a preliminary meta-analysis of 17 RCTs was posted to a preprint server in February, it is expected that by March 19, 2021, results from approximately 27–29 RCTs including almost 4500 patients will be presented to the WHO Guidelines Committee and that the epidemiologic studies reviewed above by Chamie et al were already presented to the committee in early March (personal communication with Dr. Andrew Hill). It is important to note that on February 5, the WHO Guidelines Committee announced that they had begun a review of the accumulating ivermectin data and expected to arrive at their own formal treatment recommendation within 4–6 weeks. If the above benefits in clinical outcomes continue to be reported in the remaining trials, it is hoped that this almost doubling of the current supportive evidence base would merit a recommendation for use by the WHO, NIH, and other PHA's would be forthcoming.
Because of the urgency of the pandemic, and in response to the surprising persistent inaction by the leading PHA's, the British Ivermectin Recommendation Development Panel was recently coordinated by the Evidence-Based Medicine Consultancy Ltd to more rapidly formulate an ivermectin treatment guideline using the standard guideline development process followed by the WHO. Made up of long-time research consultants to numerous national and international public health organizations including the WHO, they convened both a steering committee and a technical working group that then performed a systematic review and meta-analysis. On February 12, 2021, a meeting was held that included an international consortium of 75 practitioners, researchers, specialists, and patient representatives representing 16 countries and most regions of the world. This Recommendation Development Panel was presented the results of the meta-analysis of 18 treatment RCTs and 3 prophylaxis RCTs including more than 2500 patients along with a summary of the observational trials and the epidemiologic analyses related to regional ivermectin use. After a discussion period, a vote was held on multiple aspects of the data on ivermectin, according to standard WHO guideline development processes. The Panel found the certainty of evidence for ivermectin's effects on survival to be strong and they recommended unconditional adoption for use in the prophylaxis and treatment of COVID-19.
In summary, based on the totality of the trials and epidemiologic evidence presented in this review along with the preliminary findings of the Unitaid/WHO meta-analysis of treatment RCTs and the guideline recommendation from the international BIRD conference, ivermectin should be globally and systematically deployed in the prevention and treatment of COVID-19.
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents ...
www.ncbi.nlm.nih.gov
DISCUSSION
Currently, as of December 14, 2020, there is accumulating evidence that demonstrates both the safety and efficacy of ivermectin in the prevention and treatment of COVID-19. Large-scale epidemiologic analyses validate the findings of in vitro, animal, prophylaxis, and clinical studies. Epidemiologic data from regions of the world with widespread ivermectin use have demonstrated a temporally associated reduction in case counts, hospitalizations, and fatality rates.In the context of ivermectin's long-standing safety record, low cost, and wide availability along with the consistent, reproducible, large magnitude of findings on transmission rates, need for hospitalization, and mortality, widespread deployment in both prevention and treatment has been proposed. Although a subset of trials are of an observational design, it must be recognized that in the case of ivermectin (1) half of the trials used a randomized controlled trial design (12 of the 24 reviewed above) and (2) observational and randomized trial designs reach equivalent conclusions on average as reported in a large Cochrane review of the topic from 2014.81 In particular, OCTs that use propensity-matching techniques (as in the Rajter study from Florida) find near identical conclusions to later-conducted RCTs in many different disease states, including coronary syndromes, critical illness, and surgery.82–84 Similarly, as evidenced in the prophylaxis (Figure (Figure1)1) and treatment trial (Figures (Figures22 and and3)3) meta-analyses as well as the summary trials table (Table (Table3),3), the entirety of the benefits found in both OCT and RCT trial designs aligns in both direction and magnitude of benefit. Such a consistency of benefit among numerous trials of varying sizes designs from multiple different countries and centers around the world is unique and provides strong, additional support.
The continued challenges faced by health care providers in deciding on appropriate therapeutic interventions in patients with COVID-19 would be greatly eased if more updated and commensurate evidence-based guidance came from the leading governmental health care agencies. Currently, in the United States, the treatment guidelines for COVID-19 are issued by the National Institutes of Health. Their most recent recommendation on the use of ivermectin in patients with COVID-19 was last updated on February 11, 2021, where they found that “there was insufficient evidence to recommend for or against ivermectin in COVID-19.” For a more definitive recommendation to be issued by major leading public health agencies (PHA), it is apparent that even more data on both the quality and quantity of trials are needed, even during a global health care emergency, and in consideration of a safe, oral, low-cost, widely available and deployable intervention such as ivermectin.
Fortunately, large teams sponsored by 2 different organizations have embarked on this effort. One team, sponsored by the Unitaid/WHO's ACT Accelerator Program and led by the University of Liverpool Senior Research Fellow Dr. Andrew Hill, is performing a systematic review and meta-analysis focused solely on ivermectin treatment RCTs in COVID-19. Although a preliminary meta-analysis of 17 RCTs was posted to a preprint server in February, it is expected that by March 19, 2021, results from approximately 27–29 RCTs including almost 4500 patients will be presented to the WHO Guidelines Committee and that the epidemiologic studies reviewed above by Chamie et al were already presented to the committee in early March (personal communication with Dr. Andrew Hill). It is important to note that on February 5, the WHO Guidelines Committee announced that they had begun a review of the accumulating ivermectin data and expected to arrive at their own formal treatment recommendation within 4–6 weeks. If the above benefits in clinical outcomes continue to be reported in the remaining trials, it is hoped that this almost doubling of the current supportive evidence base would merit a recommendation for use by the WHO, NIH, and other PHA's would be forthcoming.
Because of the urgency of the pandemic, and in response to the surprising persistent inaction by the leading PHA's, the British Ivermectin Recommendation Development Panel was recently coordinated by the Evidence-Based Medicine Consultancy Ltd to more rapidly formulate an ivermectin treatment guideline using the standard guideline development process followed by the WHO. Made up of long-time research consultants to numerous national and international public health organizations including the WHO, they convened both a steering committee and a technical working group that then performed a systematic review and meta-analysis. On February 12, 2021, a meeting was held that included an international consortium of 75 practitioners, researchers, specialists, and patient representatives representing 16 countries and most regions of the world. This Recommendation Development Panel was presented the results of the meta-analysis of 18 treatment RCTs and 3 prophylaxis RCTs including more than 2500 patients along with a summary of the observational trials and the epidemiologic analyses related to regional ivermectin use. After a discussion period, a vote was held on multiple aspects of the data on ivermectin, according to standard WHO guideline development processes. The Panel found the certainty of evidence for ivermectin's effects on survival to be strong and they recommended unconditional adoption for use in the prophylaxis and treatment of COVID-19.
In summary, based on the totality of the trials and epidemiologic evidence presented in this review along with the preliminary findings of the Unitaid/WHO meta-analysis of treatment RCTs and the guideline recommendation from the international BIRD conference, ivermectin should be globally and systematically deployed in the prevention and treatment of COVID-19.