— versus centralized, organized control [which would inhibit immediate, imaginative and effective responses] .
By Howard Laitin
A. My thoughts
1. Do more than 1,200 positive anecdotal reports from practicing physicians on their successful use of Hydroxychloroquine/
2.. Will the proposed coordination procedures now being promoted by NIH a) substantially reduce the the probability for the rapid exploration of potential advances, and b) increase the time lag for the introduction to practice for those techniques/medications that appear to offer promise as potential effective advances…
My experience says “the bureaucratic mentality of in group selected panels of experts ( choosing the winners and the losers and putting everything on the table before anything is tried) a) increases the length of time for any test and/or exploratory action at all to be taken and , b) substantially decreases the probability of the introduction, testing and first applications of the imaginative breakthroughs that most frequently come from outside of the gridlocked the bureaucracies.”
My experience indicates that frontline practitioner communication networks ( some illustrative examples include EMCrit, EMrap, Medcram — ER doctors sharing information with each other) is one of the most effective techniques for the most rapid identification of, and transfusion and widespread application of medical advances.
B. Reports from frontline practitioners
1. From: Dr. Michael Hirt email@example.com>
So far in my clinical experience, I can tell you that Hydroxychloroquine/
2. From Dr. Zelenko
Since 3/15/20, my team has seen approximately 1354 patients in Monroe, New York with either test proven or clinically suspected coronavirus infection. The majority of the patients were treated with only supportive care. The patients with shortness of breath or who are in the high
risk category were treated with the above regimen (approximately 405 patients at this point)..
Of this group and the information provided to me by affiliated medical teams, we have had two deaths, six hospitalizations for pneumonia, and four intubations (all extubated now). In addition, I have not heard of any negative side effects other than approximately 10% of patients with
temporary nausea and diarrhea. In sum, my urgent recommendation is to initiate treatment in the outpatient setting as soon as possible in accordance with the above. Based on my direct experience, it prevents acute respiratory distress syndrome (ARDS), prevents the need for hospitalization and saves lives.
Conclusion: TREAT AS EARLY AND AS AGGRESSIVELY AS POSSIBLE IN THE OUTPATIENT SETTING
1- hydroxychloroquine 200mg twice a day for 5 days
2- azithromycin 500mg once a day for five days
3- zinc sulfate 220mg once a day for five days
Respectfully, Dr. Vladimir (Zev) Zelenko Special thanks to President Trump Mark Meadows – Chief of Staff Sean Hannity Rudy Guliani Dr. William R. Grace Dr. Rosy Joseph Dr. Avery Knapp
3. From the more than 2,300 physicians who are currently successfully treating patients infected with Covid-19 reported their “anecdotal evidence” of their success with their patients using hydroxychlorquine
“Hydroxychloroquine rated ‘most effective therapy’ by doctors for coronavirus: Global survey” (by Valerie Richardson Washington Tmes 4-2-20)
An international poll of more than 6,000 doctors released Thursday found that the antimalarial drug hydroxychloroquine was the most highly rated treatment for the novel coronavirus.
The survey conducted by Sermo, a global health care polling company, of 6,227 physicians in 30 countries found that 37% of those treating COVID-19 patients rated hydroxychloroquine as the “most effective therapy” from a list of 15 options.
The U.S. Food and Drug Administration gave chloroquine and its next-generation derivative, hydroxychloroquine, emergency-use authorization Monday for treating the novel coronavirus, although the drug was already being used off-label by some doctors and hospitals for COVID-19 patients.
The survey also found that the most commonly prescribed treatments are analgesics (56%), azithromycin (41%) and hydroxychloroquine (33%).
Azithromycin, known by the brand name Zithromax or Z-Pak, was rated the second-most effective therapy at 32%, followed by “nothing,” analgesics (including acetaminophen), anti-HIV drugs and cough medicine.
Hydroxychloroquine, which is sold under the brand name Plaquenil, was prescribed mainly in the United States for the most severe cases, but not so in other countries.
“Outside the U.S., hydroxychloroquine was equally used for diagnosed patients with mild to severe symptoms whereas in the U.S. it was most commonly used for high risk diagnosed patients,” the survey found.
The 30 nations surveyed included those in Europe, Asia, North America and South America, as well as Australia. No incentives were provided to participate in the poll, conducted March 25-27, according to Sermo.
Hydroxychloroquine usage was most widespread in Spain, where 72% of physicians surveyed said they had prescribed it, followed by Italy at 49%, and least popular in Japan, where 7% had used it to treat COVID-19.
The poll found 23% of U.S. medical professionals had prescribed the drug, which has been FDA-approved for malaria, lupus and rheumatoid arthritis.
Debate about hydroxychloroquine has raged in the United States since President Trump touted it two weeks ago as a potential “game-changer” in the fight against the deadly pandemic, prompting critics to accuse him of peddling unproven remedies, or “snake oil,” as USA Today put it.
Sermo CEO Peter Kirk called the polling results a “treasure trove of global insights for policy makers.”
“Physicians should have more of a voice in how we deal with this pandemic and be able to quickly share information with one another and the world,” he said. “With censorship of the media and the medical community in some countries, along with biased and poorly designed studies, solutions to the pandemic are being delayed.”
4. From a physician on the frontlines of this covid Pandemic…I( am sharing my thoughts how to immediately end the epidemic and the quarantine protocols, [from a board-certified physician with 30 years of experience in treating infectious diseases, including current Corona virus cases)
I can confirm that the vast majority of patients infected with Covid19 have minimal, mild or modest cold and flu-like symptoms, requiring little to no medical intervention. The planet is being systematically shut down because a very small percentage of those infected may have serious or grave reactions to the viral infection. When these seriously ill patients contract the disease over a short period of time, the healthcare system can become overwhelmed as was the experience in China, Korea and Italy.
The Chinese have largely completed their Covid19 experience and some significant science has come from their doctors and researchers as to the virology, epidemiology and treatment of Covid19. The most important of which is the recent study showing a 100% cure rate for Covid19 patients (n = 20) treated with the combination of chloroquine and azithromycin.
Now that a cure has been established (and is being confirmed in other areas hard hit with Covid19 — to my understanding), this new finding should be the antidote for public and political panic regarding any significant downside human costs (grave illness, casualties) of the pandemic.
As we no longer have the domestic capacity to manufacture these medications in the quantities needed on the timeline required, the Federal government should immediately work to re-tool US chemical factories that are capable of retrofitting to manufacture these two drugs. The raw materials of these medicines can then be shipped directly to vitamin manufacturers who have the capacity to conservatively and collectively make 5 – 10 millions pills daily. As a contract manufacturer of vitamins, I know first hand that these facilities follow strict FDA guidelines that are equivalent to the regulations of Big Pharma. Therefore, quality control will not be a concern. Compound pharmacies are also capable of participating in this effort.
If this protocol were to be adopted, some 150M doses of these life-saving medications would be available in the next two weeks to treat all patients in need and any first responder/front line healthcare worker.
While not scientifically proven, it has also been anecdotally observed that chloroquine may offer significant prophylaxis so that those most at risk (the vulnerable patients and front-line healthcare workers) may never develop a primary infection during the epidemic. This preventive intervention should be immediately offered to vulnerable populations and healthcare workers in an open-label, observational study.
With the cure in the hands of pharmacies, hospitals and first responders, the concern for the health and wellness of the vulnerable population (whose characteristics have been well described) can be assured. By treating these vulnerable patients in the early part of the 5 day prodrome (when mild symptoms begin), demands on hospital resources will be effectively countered.
Governmental authorities can then begin to immediately prepare the population for a systematic roll out of return-to-work orders while releasing the healthy, general public from quarantine.
It is my opinion, the vulnerable populations should remain quarantined for the next one month while the treatments are used and proven on a mass scale.
The concern of patients (and their providers) with an infectious disease is always the success and availability of the treatment for their condition. Now that a treatment has been Now that a treatment has been identified and can be made widely available at minimal cost (but with considerable public-private coordination issues) the End Game for this pandemic is within our collective reach.
5. From Doctors Are Improvising Coronavirus Treatments, Then Quickly Sharing Them Rebecca Davis O’Brien Wall Street Journal 4-10-20
In mid-March, as U.S. hospitals scrambled for ventilators to treat a surge of coronavirus cases, a Vermont pulmonologist proposed a different treatment on a blog popular with emergency-medicine doctors.
Joshua Farkas observed in the post on the EMCrit blog that many Covid-19 patients seemed to benefit from less-invasive alternatives to help their breathing, including pressure therapy used to treat sleep apnea—sometimes referred to as CPAP, for continuous positive airway pressure. Soon, a Milan doctor weighed in, offering encouraging statistics on CPAP use from his hard-hit hospital. U.S. health-care workers sought guidance and a physiotherapist in Denmark gave tips for securing CPAP equipment.
C. PROPOSAL FROM NIH WHICH IN FACT CENTRALIZES CONTROL AND WOULD EXPLICITLY LIMIT “NONCONVENTIONAL” APPROACHES
[Chaotic search for coronavirus treatments reveals another shortcoming in pandemic preparation By CarolynJohnson
Development of effective treatments for covid-19, the disease the virus causes, would be one of the most significant milestones in returning the United States to normalcy. But the massive effort is disorganized and scattershot, harming its prospects for success, according to multiple researchers and health experts. Researchers working around-the-clock describe a lack of a centralized national strategy, overlapping efforts, an array of small-scale trials that will not lead to definitive answers and no standards for how to prioritize efforts, what data to collect or how to share it to get to answers faster.
“It’s a cacophony — it’s not an orchestra. There’s no conductor,” said Derek Angus, chair of the department of critical care medicine at University of Pittsburgh School of Medicine, who is leading a covid-19 trial that will test multiple therapies. “My heart aches over the complete chaos in the response.”
The global biomedical research establishment could be one of most powerful assets in the campaign against the new virus, with experts all over the world — and especially the scientific and medical powerhouse of the United States — in rare alignment in their focus on a single enemy. Some large trials designed to be definitive have launched. But with more than 500 human clinical trials worldwide, the lack of coordination puts the world at risk of ending up with a raft of inconclusive and conflicting studies and little idea of what interventions work for the next wave of illness.
Francis Collins, director of the National Institutes of Health, the nation’s largest biomedical research agency, acknowledged researchers’ frustrations but said in an interview Wednesday he has been working behind the scenes to launch an unprecedented public-private partnership to address the problems. He said the framework involves top pharmaceutical companies such as Pfizer and Johnson & Johnson, domestic and international government agencies including the European Medicines Agency, and academic research centers.
Collins said the month-long discussions have been kept under wraps to ensure buy-in for an approach likely to require sacrifices of personal recognition, scientific credit and profit — a centralized decision, for example, not to proceed with tests of one company’s drug to move faster on a competitor’s.
“I think we have the necessary clout to steer this whole complicated ecosystem,” he said. “When you look at some of the things that are happening sporadically, we may be unlikely to learn what we need to from such disconnected, small trials. The whole point is to replace that with a coherent, evidence-based approach. … I want to know what works, and I want to have it answered by June or July.”
Agency officials said further details would be released in coming days.
Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said in an email Tuesday that the partnership led by Collins is the “functional equivalent of a National Strategy.”
While Collins was working on developing that strategy, hospitals, drug companies, government labs and individual doctors were flooding the system with proposals for drugs and other interventions to test against the virus — an outpouring that reveals how siloed and fragmented the research enterprise remains. For example, there are 26 separate U.S. trials listed for the anti-malarial drug hydroxychloroquine, all with different designs. Some use the drug as a preventive, others as a treatment. Some use it alone, some with other drugs or vitamins, and some have no comparison group to tell if the drug was responsible for the outcome. That will make it more difficult to conclude whether, or in what circumstances, the drug may work. [NOT TRUE… rapid communications is the key, see section B. REPORTS FROM FRONTLINE PRACTITIONERS, above.]
Collins said a working group is addressing this problem by sifting through about 100 possible covid-19 treatments to decide which are the six to eight most promising drugs to move forward in large-scale trials. Those will be deployed in large clinical trial networks.
The new federal effort is motivated in part by what happened in China. Clifford Lane, deputy director for clinical research and special projects at NIAID, traveled to the origin of the outbreak in February as part of an international delegation to help the world learn from the Chinese experience. He was troubled by the lack of a strategic plan to prioritize and fast-track the most promising treatments, leading to a mosaic of inconclusive findings. [ This very rapid implementation of the Mosaic of studies resulted in a very rapid sifting of various approaches and a very quick second stage of additional studies and analyses.]
“We do have to have a bigger strategy than every university, every institute and — to be blunt — every country” working on their own research efforts, Lane said in an interview.
At the heart of the problem is the basic question of whether a drug really works. Typically, drugs and medical interventions are first tested in small clinical trials that establish safety before the most promising ones are funneled into bigger trials, in an iterative and years-long process. These trials, which typically randomly assign patients to receive either a drug or a placebo, prove that medicines, vaccines and medical procedures are effective and safe. But with the urgency of the coronavirus threat, timelines have been squeezed, doctors are doing uncontrolled experiments as they administer regular care,[ promising approaches and developing concerns should be promptly shared for the maximum speed of introduction and generalization to widespread practice of the most promising results ] and the typical model for research is too slow.[ it is the Fauci / Collins et/al approach that is too slow]
David Boulware, an infectious-disease physician and scientist at the University of Minnesota, has gotten at least 50 emails from companies and researchers with treatments they want to test. The urgency to find something — anything — for patients who have nothing other than supportive care has led researchers to pull everything off the shelf: a mix of existing drugs that show promise, stem cell treatments and brand new compounds designed specifically against covid-19.
The energy is remarkable, but it needs to be channeled. Clinical trials, whether for an HIV drug or a brand new medicine, compete for many of the same patients. If there are too many trials at a hospital, none of them may enroll enough patients to get clear results. If there are too many similar small trials running in parallel, their results individually may be inconclusive and the data could have so many differences they may not be able to be pooled.
“There’s all sorts of people wanting to try anything, because people are desperate,” Boulware said.
He and others who were unaware of Collins’s plans argue that national leadership — whether guidance on how to prioritize trials, a central body coordinating efforts, This would be the most helpfulor a mechanism to play matchmaker among institutions working on similar ideas [This would be the most helpful]— could help channel the ubiquitous scientific desire to make a bigger, faster impact.
Some large-scale efforts are already underway: The World Health Organization has organized a massive trial in 90 countries of four promising therapies. The National Institutes of Health is conducting a test of the antiviral medication remdesivir at more than 50 institutions and last week launched a large trial for an anti-malarial medication. A $50 million effort at the Duke Clinical Research Institute will test hydroxychloroquine in 15,000 health-care workers and create a registry that can be tapped to speed up future trials, such as for a vaccine.
“People should not be fatalistic that we’re going to have a paucity of evidence for things that provide benefit,” Collins said. “I hope we’ll have three to four of those [treatments] by the summer.”
But as the federal effort has proceeded largely in secret, individual institutions have scrambled to set up committees of experts who evaluate which trials make sense to move forward. At the University of Pennsylvania, a weeks-old committee gives priority scores to trials based on criteria such as whether they will compete with existing efforts and how they are to enroll all the patients needed to get a result. A task force at Duke University does a similar review. about
“There’s a lot of stuff bubbling up. It would seem like a sensible thing to do would be to align everyone around the same trials, not one trial for each context and not have each institution do its own thing and at the end of the day everyone has done a small trial … and we don’t know what to make of it,” said Steven Joffe, a bioethicist at the University of Pennsylvania. “Let’s get to an answer.”
Many proposed trials overlap — using the same drug, such as the anti-malaria treatment hydroxychloroquine that has been touted by President Trump, his personal lawyer Rudolph W. Giuliani and conservative talk show host Laura Ingraham.
Boulware is halfway through one such hydroxychloroquine trial, which examines whether the drug is effective at preventing the disease or in treating people with mild cases. People who participate will receive either the drug or a vitamin in the mail.
He said he is motivated by his experience working on Ebola, when by the time a well-designed trial was up and running, the outbreak was dying down. He plowed ahead with his hydroxychloroquine trial weeks before he heard — last Friday — the National Institutes of Health had declined to fund it. He found international collaborators through chance and social media when some Canadian researchers emailed to ask if he would share his trial design with them. He ended up connecting the Canadians with each other and is now working on overcoming the complex legal requirements to share data.
But now, his trial is potentially competing with a bunch of others that also test hydroxychloroquine all across the country — and enrollment has slowed in recent days.
Risks of inconclusive evidence in the social media age
Small trials and even anecdotal reports of treatments that appear to have worked on small groups of patients already are being shared, sowing both hope and confusion about the evidence.
A study published Friday in the New England Journal of Medicine reported on 53 people who took remdesivir, a failed Ebola drug Trump has praised and many families have tried to access outside of trials. The results were impossible to interpret, though, since some of those patients might have gotten better on their own and there was no comparison group of patients who did not receive the drug. Hydroxychloroquine, the cheap and readily available anti-malarial drug, also already has been widely used in patients despite only suggestive evidence it might work.
As more small-scale studies are designed, the risks of inconclusive but suggestive results multiply — and paradoxically, they could make it harder to conduct well-designed clinical trials that get to the bottom of whether a treatment works. Well-designed clinical trials require patients to be willing to be randomly assigned to receive the treatment — or a placebo.
Emma Meagher, chief clinical research officer at the University of Pennsylvania’s Perelman School of Medicine, said her institution’s study of the malaria drug in severely ill patients does not have a comparison group that receives a placebo because the media around the drug has made it the standard of care despite the lack of evidence. Every meeting, she said, begins with a discussion about how to prevent the next experimental therapy from becoming like hydroxychloroquine.
In some ways, designing research studies when clinicians have an imperative to give their patients the best care possible is an inherently tricky situation. Outside of top-tier research hospitals, patients may not have access to trials, so clinicians may have little option but to give them drugs in what amounts to an uncontrolled experiment. The Infectious Diseases Society of America released guidelines last week that clinicians should give experimental drugs only in trials, but safety-net and rural hospitals are less to have access to those.
“Do we really want to have [some] people trying new different things and the rest of you sit and wait?” asked Benjamin Linas, an infectious-disease physician working on oversight of clinical trial protocols at Boston Medical Center.
Many researchers have said they are hopeful a national strategy will help unify and speed up the search but lament the time already lost. The United States did not have a pandemic clinical trials network ready to be activated, but existing clinical trials networks, such as those used to test HIV treatments, are now being repurposed. Collins said he had never seen research move faster, but in a pandemic that can still feel slow.
“We have imperfect networks. I mean, there are some there, but they’ve never been tested in this way,” said Adrian Hernandez, vice dean for clinical research at Duke University School of Medicine. “Having a common infrastructure that can do rapid-cycle trials — that would be beneficial.”
Collins said he began partnering with private companies, research institutions and other agencies in mid-March. Had he started sooner, he said, the urgency of the situation might not have been clear to those groups he had to convince to work together. He disagrees significant time has been lost and noted the efforts were able to piggyback on an existing framework for pursuing drugs with industry collaboration called the Accelerating Medicines Partnership.
Partnerships that previously took a year and a half to build were put together in a week, he said.
“I think it is a world record for anything of this sort. It might have been difficult to get full unanimous agreement to what is clearly unprecedented — for a willingness to give up control,” Collins said.
As with other areas of pandemic planning, many hope the United States will learn from this lesson, that it needs a preparedness plan not only for allocating essential supplies and scaling up testing but also in plotting research.
“The problem is we need to remember to invest in preparedness, at times when we’re not affected with a pandemic or epidemic,” said Barbara Bierer, director of the regulatory foundations, ethics and the law program of the Harvard Clinical and Translational Science Center. “And it’s hard to repurpose or commit resources to something that doesn’t appear immediate on the horizon.”