Dr. Pierre Kory to major U.S. media: “We do not have months. Thousands are dying every day.”
Hello, major U.S.media.
My name is Joyce Kamen. I am the Co-Coordinator of the Communications and Education Team for the Frontline Covide19 Critical Care Alliance. (FLCCC). FLCCC.net
I am writing to you with unprecedented urgency. If, after you review the below communication, you agree with its conclusions that the current clinical trials evidence supporting the use of ivermectin in COVID-19 meets the criteria for an A1 level recommendation from the NIH, we would ask that you consider urgently authoring an article or presenting a television story articulating the overwhelming scientific evidence supporting the need for Ivermectin to receive an “A1” rating from the NIH.
Now, it is my understanding that you and your editors believe that the evidence supporting the use of Ivermectin for the prevention and treatment of COVID19 is “inconclusive.”
While there have been a couple of small studies with benefits that have not met statistical significance, there are now trial results from 11 large Randomized Controlled Trials (RCTs) from different centers and countries around the world which, in almost every case, reach not only high levels of statistical significance but do so showing large magnitudes of benefit in transmission rates, need for hospitalization, and death.
Ivermectin is a safe, low-cost, widely available drug. We encourage you to read our manuscript (link below) which details almost all existing studies. Our Critical Care physician team, as close readers of the medical literature and having contributed over 2,000 peer-reviewed publications to the medical evidence base, report that they have never encountered an intervention with a totality of trials data supporting a drug as they have uncovered for the prevention and treatment of COVID-19 with ivermectin. Never. In no other disease model or drug or intervention (noting that antibiotics have never really been tested in an RCT). And they have been studying interventions and novel therapies their entire careers. They now have data from 23 controlled trials studying ivermectin which include a total of over 7,200 patients showing consistent, reproducible, large magnitude benefits. This is the only medicine they have seen with reproducible and large impacts on mortality in COVID-19 as well as transmission in COVID-19.
To be unconvinced at this point after a close read of our manuscript is unconscionably biased. We ask why this same level of skepticism was not directed towards all the other failed therapies before they were adopted widely. None ever showed a mortality benefit yet have been widely supported by NIH, pharma, academia, and the mass media, i.e. remdesivir, convalescent plasma, tocilizumab, monoclonal antibodies, and vaccines. With the exception of the vaccines, all these therapies have been marched out and widely used on some of the weakest evidence bases we have seen supporting a therapeutic intervention. Perhaps one could argue that these therapeutic efforts are forgivable in a pandemic but to deny the same “benefit of the doubt” to a safe and cheap drug with such a supportive evidence base while thousands are dying every day in America and around the world will be a historically unforgivable act.
Further, why are the epidemiologic data presented in our manuscript being ignored? The massive and increasing amounts of data showing many regions and countries and states and cities that have initiated ivermectin distribution campaigns have essentially controlled COVID-19 in those areas. You would have to read our scientific manuscript. You would also need to visit our website (FLCCC.net)with growing numbers of these examples from India and multiple regions of South America.
Let’s now analyze those arguments that might lead you and your editors to be “unconvinced” . Here are the arguments verbatim from our Dr. Pierre Kory, who testified to all of this on Tuesday morning at the Senate Committee on Homeland Security and Governmental Affairs. His testimony has been viewed nearly 3 million times on YouTube. Our phones and email boxes are overflowing with thousands of people desperate to get their hands on Ivermectin because they heard Dr. Kory’s message, went on our website, read the science, and are outraged that the NIH has failed to protect them and that major media outlets like yours have also inexplicably remained mum.
During his testimony, Dr. Kory presented the massive evidence base our Critical Care team has compiled. Here are his words and the irrefutable answers he wrote this morning. He has asked me to convey them to you, Major U.S. Media:
FROM DR. PIERRE KORY
Here is a list of criticisms of the existing medical evidence-base supporting ivermectin as a prophylactic and early treatment agent in COVID19:
“The data primarily come from uncontrolled observational trials.” ANSWER: FALSE
Every observational trial (ignoring the massive case series for a moment) that has studied ivermectin in COVID-19 have matched control groups for comparison, with some controlled using a technique called propensity-matching and others simply using contemporaneous, well-matched control groups of patients who did not receive ivermectin by their treating doctor (one would need a close reading of each study to see how well matched they are)
Observational controlled trials are generally equivalent to randomized controlled trials in their conclusions. They are highly valid, and thus represent a valuable trial design, especially in a pandemic. Throughout the history of evidence-based medicine, it has been shown repeatedly that findings from observational trials with control groups and findings from trials with randomized controls reach the same conclusion, on average, in almost all circumstances. This fact has been published in systematic reviews published in the Cochrane database multiple times. It is a fact and a truth about evidence based medicine that is both neither taught nor emphasized by most of academia who have recently been described, for this reason, as “RCT fundamentalists” -coined by the author of a recent essay on evidence based medicine (can provide essay and the systematic reviews if desired)
The consistency of findings among the observational trials is both profound and unique in clinical trials. The reason for this statement is that almost every therapy that has been studied in large numbers of trials tend to produce, at least in a minority, “conflicting results”, especially when the intervention is not particularly potent and/or simply leads to small differences in outcomes and/or some of the trials are poorly designed. If they are science editors, they should recognize how difficult it is within science to reproduce experimental results. Thus, the remarkable consistency of these supposedly inferior observational trials must be emphasized. That consistency is unique and persuasive given the diverse set of centers and countries and sizes and designs and phases of illness. Finally, it was exactly this consistency that first alerted us to ivermectin’s efficacy, we as a group were struck from the consistent efficacy data emerging from the first emerging trials. That consistency has been getting stronger and stronger as the number of trial results have passed 30.
“The majority of the existing studies are not peer-reviewed”
13 of the 23 controlled trial results have been peer reviewed, along with two of the 5 case series.
Manuscripts of trial methods and full results posted on pre-print servers have been a standard in many of the sciences, including medicine, especially during the pandemic. Everyone should be reminded that every single novel therapeutic that we have widely adopted in actual medical practice during COVID-19 happened before the peer-reviewed manuscript was available for analysis by the medical community, with the exception of hydroxychloroquine which was widely adopted without any clinical evidence base. Examples of pre-print adopted therapeutics are remdesivir, corticsteroids, monoclonal antibodies, convalescent plasma.. and the vaccines. All were adopted before passing through peer-review. Note the vaccines began even before a pre-print manuscript was made available. To dismiss the value of ivermectin study results because they have only been accepted by medical pre-print servers creates a new higher level criteria that the former pharmaceutical sponsored agents were not required to meet. Thus, to do so with ivermectin departs from this now-standard in the pandemic and is thus egregiously biased and also ignorant of the extreme importance that pre-prints play in the rapid dissemination of medical knowledge. That is why they exist. Peer-review takes months. We do not have months. Thousands are dying every day.
“Trials were done in foreign countries and are not generalizable to our patients here.”
This is a shocking, but documented criticism made by the COVID-19 therapeutics committee of a large hospital health care system in the Midwest after they recently reviewed the existing trials data for ivermectin approximately 3 weeks ago. The belief that a potent anti-viral medicine only works in foreigners and not in Americans is ludicrously racist and ignorant and deserves no further comment or explanation except for noting that it is likely the most extreme that biased skepticism can reach in the minds of physicians who simply “do not believe” in the efficacy of ivermectin.
“We need randomized controlled trials.” ANSWER — FALSE.
14 of the 23 controlled trials results are prospective and randomized and include almost 3,000 patients. Note that the RECOVERY trial which overnight made corticosteroids the standard of care in COVID-19 was a randomized controlled trial which included an identical amount of treated patients as we now have treated with ivermectin in the existing randomized controlled trials. Again, corticosteroid in late phase disease was adopted worldwide based on that one large randomized controlled trial. We have numerous randomized controlled trials of ivermectin.Further, the number of patients in the 9 observational controlled trials also total over 4,000 patients. Thus, after 7,000 patients and 23 trials of ivermectin in varying sizes and designs and countries, with nearly all resulting in consistent, reproducible, large magnitude, statistically significant findings of efficacy as a prophylactic, early and late phase disease agent leading to marked reductions in transmission, hospitalizations, and death, any further studies using a placebo would…unethical, particularly in a pandemic. For any who require more clinical trials data prior to adopting ivermectin as standard of care in COVID-19, we suggest that you simply conduct well-designed observational controlled trials as they are a perfectly valid alternative.
“We are concerned regarding the safety of Ivermectin.”
It is one of the safest drugs known. It is on the WHO’s list of essential medicines, has been given 3.7 billion times around the globe, and won the Nobel prize for its global and historic impacts in eradicating endemic parasitic infections in many parts of the world
Further, in the 7,000 trial patients, no differences in side-effects were reported, millions of doses have been distributed among many cities and regions in South America, the Middle East, and India. We are aware of no important side effects or reactions.
“The NIH recommends against the use of ivermectin outside of clinical trials.”
That recommendation is from August 27th, is graded IIIA, which means that it was expert opinion only and reflecteda “strong” opinion against use.
Given the amount of data available as of today, December 13, 2020, we must ask the question, “What should the strength and level of recommendation for Ivermectin be updated to by the NIH?
First, one must understand how recommendations for medical therapies are created by the NIH. Table 1 below explains the NIH recommendation rating scheme which provides an assessment of both the strength of the recommendation and the quality of evidence to support that recommendation.
Now, let’s assess the last NIH recommendation on ivermectin from August 27th which was graded AIII, as per above table. This means that it was based on “expert opinion only” and was graded as “strongly” against the use of ivermectin, which is interesting given that ivermectin is one of the worlds safest, cheapest and most widely available drugs. We must call attention to the fact that no rationale or supporting evidence was given underneath that one sentence recommendation against its use. Further, this recommendation, given that it was graded “expert opinion”, implies that there was no available clinical evidence at the time to make an “evidence-based” grading. We have recently received a report that ten trial results were available at the time of that recommendation in August. If true, to invoke such a strength and level of recommendation against ivermectin was not only erroneous, but influenced by an unconscionable and conservative bias that potentially borders on the corrupt.
So what should the recommendation for ivermectin be updated to as of today, December 13, 2020? The strongest recommendation possible would be an A1 in support of ivermectin. To to obtain an A1 recommendation, as per above NIH published grading system, it would require “one or more randomized trials with clinical outcomes and/or laboratory endpoints”. In many medical guidelines, it is often very difficult to obtain an A1 recommendation due to the fact that, in practice, some reserve A1 for drugs with multiple, large randomized, controlled trials showing the same important benefits to some clinical outcome, a feat which usually requires immense financial resources and infrastructure to achieve, and with a cheap, safe, and widely available drug there is very little financial incentive to conduct them. Despite this, we were fortunate that researchers from academic and non-academic medical centers decided to conduct such trials. In fact, as of this writing, we now have data from 14 randomized controlled trials (RCT’s) with nearly all demonstrating both improvements in “clinical outcomes” and in a minority, laboratory endpoints consisting of reduced time to viral clearance. Note that the 14 RCT’s consist of trials studying ivermectin as a prophylactic agent (3), early outpatient treatment (5), and in hospitalized patients (6). In each phase of illness, the majority find statistically significant reductions in rates of transmission, need for hospitalization and mechanical ventilation, and mortality. Thus, it would appear that ivermectin more than fulfills the criteria for a Level A1 recommendation in support of its use as a prophylactic and treatment agent for COVID-19 and thus this country’s heath care providers can immediately adopt ivermectin for those indications.
However, if somehow there remains sufficient, ingrained skepticism such that skeptics manage to minimize the importance or even dismiss these numerous trial results entirely, such skeptics would still be left with having to answer whether ivermectin meets Level AII evidence. It should be noted that level AII evidence, in the face of the pandemic and in the context of a cheap, safe and widely available drug, would effectively translate into the same level of action and adoption as level AI evidence. Now, for Level AII evidence, as above, all that is required are supportive findings from “one of more well-designed non-randomized, or observational cohort studies”. Again, fortunately, there are many such studies on ivermectin in COVID-19, with the largest and strongest being Dr. Rijter’s study from Florida, published in the major medical journal Chest several weeks ago, where they used propensity matching, a technique accorded by many to be as valid a design as a well-designed RCT’s. His and many other well-designed OCT’s exist, all reproducing the findings from all the above mentioned RCT’s. Thus at a minimum, an AII recommendation is met, which would and should lead to immediate and widespread adoption. I will not even begin to entertain how ivermectin, given the available trial results we have as of today, could ever even be considered worthy of a moderate strength (B), or weak strength © or be given a quality grade of III, or remain as an AIII against.That would require a complete dismissal of the near entirety of the evidence available and thus does not deserve further exploration or discussion. So, it would appear that ivermectin clearly meets an AI level recommendation in favor. And that is without the epidemiologic data we have compiled which is presented below.
“The epidemiologic data presented is unconvincing”
The epidemiologic data presented in our manuscript essentially provides the strongest level of medical evidence attainable as they consist of findings from large, real-word “natural experiments” which spontaneously occurred among many cities and regions of the world where health ministries decided to initiate widespread ivermectin distribution to their citizen populations. All these areas show large and temporally associated decreases in case counts and fatalities. Again, the magnitude and reproducibility from city to city, region to region and country to country is unassailable. All data were sourced from universally used, publicly available COVID-19 epidemiologic databases. The manuscript by Chamie et al which focuses solely on these data, is currently near submission for publication, and has been co-authored by PhD researchers after having been refined and reviewed by scientists and researchers under the direction of a dean at a major medical research university.”
Pierre Kory, MD, MPA
President, Front-Line Covid-19 Critical Care Alliance
Pulmonary and Critical Care Specialist
So, major media, may I hear back from you please? And swiftly? Ivermectin has already saved hundreds of thousands around the world. If we fail to do the same in America right now, we will be party to tens of thousands of unnecessary deaths. Thank you, Joyce
LINK TO SCIENTIFIC MANUSCRIPT: https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-Ivermectin-in-the-prophylaxis-and-treatment-of-COVID-19.pdf