Real world evidence (RWE) means medical evidence obtained from real world data (RWD), that is observational data, secured from outside the context of clinical trials and rather produced during routine clinical practice. The 21st Century Cures Act, enacted as law in 2016, heavily supported by the pharmaceutical industry, mandated the use of Real World Evidence (RWE). The intention of the Act largely was to expedite the approval process including easing the requirements placed on clinical trial sponsors seeking U.S. Food and Drug Administration (FDA) approval on new products or new indications on existing drugs. For example, the new ACT supported a company to provide “data summaries” and “real world evidence”, such as observational studies, insurance claims data, patient input, rather full clinical trial results, at least in certain situations. With its passing, the FDA embraced RWE, noting that RWE and RWD are playing an increasing role in health care decisions. With the onset of the COVID-19 pandemic, a collaboration in Australia led by Monash University identified in a lab that an approved FDA drug, one with a well-established safety record, Ivermectin, is actually an inhibitor of the causative virus (SARS-CoV-2). They reported that in vitro there was a ~5000 fold reduction in viral RNDA at 48 hours. The rest is history as TrialSite has chronicled now the many dozens of case series, observational studies, a couple completed studies with randomized components, and in the aggregate off-label use cases in many countries around the world. A couple Ivermectin studies have surfaced in reputable peer review medical journals. Why put so much attention into the topic? There is a deadly pandemic that isn’t slowing down. In addition to the critical research supported by the pharmaceutical industry and National Institutes of Health (NIH), physicians seek to save lives in the present moment. Given Ivermectin was already FDA approved and in fact does have a well-known safety profile, could it in fact fall under the Act for purposes of accelerating FDA approval as part of some combined therapy? As that question may soon be pondered, the pandemic worsens. Enter groups of physicians such as the Front Line COVID-19 Critical Care Alliance (FLCCC).
The FLCC is best known for its MATH+ COVID-19 treatment protocol. On October 14, TrialSite reported that this protocol included an Ivermectin option for prevention and early treatment of COVID-19. On October 31, the group formalized a new protocol for both prevention and early treatment of COVID-19, this time dubbed, I-MASK+. The “I” stands for Ivermectin, which is now the key ingredient in the protocol rather than an option. FLCCC was formed as a working group of doctors recognizing the emergency conditions of the early pandemic in reaction to many reports of COVID-19 patients with inexplicable need for ventilation and the high death rate of the prevailing “supportive care only” recommendations from major healthcare organizations. This “group of highly published leaders in critical care,” led by Dr. Paul Marik had expertise in severe infections including bacterial sepsis. Along with high patient-survival numbers of those following the FLCC’s protocols, “equally concerned and motivated colleagues from other specialties” reached out to join the efforts. The MATH+ Hospital Treatment Protocol was formulated in March, and it has been used successfully since then for the severely ill. For more on the background of the FLCCCC alliance, follow the link.
“The I-MASK+ protocol will revolutionize the treatment of COVID-19”
As noted, I-MASK+ is a new protocol for both prophylaxis and early outpatient treatment of COVID-19 patients. It is, “centered around the use of Ivermectin, the FDA approved, well-known anti-parasite drug with the discovered anti-viral and anti-inflammatory properties and a rapidly growing published medical evidence base demonstrating its unique and highly potent ability to inhibit SARS-CoV-2 replication.” I-MASK+ and MATH+ are complementary in that the former excludes hospitalized patients while the later focuses on them. According to the FLCCC, all of their recommended medicines are, “FDA-approved, inexpensive, readily available and have been used for decades with well-established safety profiles.”
And according to Dr. Marik, “the I-MASK protocol will revolutionize the treatment of COVID-19.” FLCCC notes that recent studies have been negative for many treatments. These include remdesivir, HCQ, lopinavir, interferon, plasma, and mono-clonal antibody therapy. At present, the only thing officially “proven” to work is corticosteroids for moderate to severe illness and remdesivir. Of course remdesivir has a mixed record; the FDA and EMA approved despite the results of the Solidarity trial. The new protocol is based on the accumulation of published and unpublished trials showing that, “the drug Ivermectin, an anti-parasitic drug with increasingly well-known anti-viral and anti-inflammatory properties has demonstrated profound activity against COVID-19.”
FLCCC: Ivermectin Can Deliver Population-Wide Protection
Per the FLCCC, the available evidence shows that Ivermectin: inhibits SARS-CoV-2 replication, prevents transmission within households, hastens recovery and stops deterioration in mild to moderate cases, hastens recovery/avoidance of ICU, and “leads to striking reductions in case-fatality rates in regions with population-wide distribution and use.” Perhaps most importantly, as little as one dose a week can, “lead to population-wide protection and reduced transmission in a manner that is easier to achieve, more effective, and less expensive than the still elusive and widely suspect vaccine.” One study FLCCC believes deserves special attention is by Dr. Juan Chamie; his study gives us an analysis of, “large amounts of real-world epidemiologic data in support of Ivermectin as an effective population-wide intervention in Peru.” By comparing and contrasting eight regions, some of which used population-wide prophylactic Ivermectin, Dr. Chamie was able to reach strong confidence in the drug. As to the new protocol’s name, as noted “I” is for Ivermectin, “MASK” simply means wear a mask, and the “+” is differing amounts of vitamin D3, vitamin C, Quercetin, melatonin, zinc, and aspirin.
Meet the Physicians
Founded by highly published critical care specialists employed at major academic medical centers with over 1,000 medical publications, the FLCCC physicians came together to help patients during the COVID-19 pandemic.
∙ Pierre Kory, MPA, MD, Associate Professor of Medicine, Aurora St. Luke’s Medical Center
∙ G. Umberto Meduri MD, Professor of Medicine, University of Tennessee
∙ Jose Iglesias, DO, Associate Professor of Medicine, Hackensack School of Medicine, Seton Hall
∙ Joseph Varon, MD, Professor of Medicine, University of Texas Health Science Center
∙ Keith Berkowitz, MD, Center for Balanced Health, New York
∙ Howard Kornfeld, MD, Medical Director, Recovery Without Walls
∙ Eivind Vinjevoll, MD Critical Care and Emergency Department Chief, Volda, Norway
∙ Scott Mitchell, MRCS, Associate Specialist, Princess Elizabeth Hospital, Guernsey
∙ Fred Wagshul, MD, Lung Center of America, Dayton, Ohio
∙ Paul E. Marik, MD, Professor of Medicine, Eastern Virginia Medical School
Call to Action: Why can’t the FLCCC and the NIH get together and figure out how to leverage RWE and research in agile and creative ways to produce more evidence while continuing to save lives? To contact the FLCCC, follow the link.