Saturday, June 27, 2020

How a false hydroxychloroquine narrative was created, and more

It is remarkable that a large series of events taking place over the past months produced a unified message about hydroxychloroquine (HCQ), and produced similar policies about the drug in the US, Canada, Australia, NZ and western Europe.  The message is that generic, inexpensive hydroxychloroquine (costing only $1.00 to produce a full course) is dangerous and should not be used to treat a potentially fatal disease, Covid-19, for which there are no (other) reliable treatments. 

Hydroxychloroquine has been used safely for 65 years in many millions of patients.  And so the message was crafted that the drug is safe for its other uses, but dangerous when used for Covid-19.  It doesn't make sense, but it seems to have worked.

In the US, "Never Trump" morphed into "Never Hydroxychloroquine," and the result for the pandemic is "Never Over."  But while anti-Trump spin is what characterized suppression strategies in the US, the frauds perpetrated about hydroxychloroquine and the pandemic include most western countries.

Why do I say "Never Over"?  I am expanding on this claim with a), b), c) on August 30. Later in the paper additional evidence is provided.

a) Because if people were treated with HCQ at the onset of their illness, over 99% would quickly resolve the infection, avoiding progression to the late stage disease characterized by cytokine storm, thrombophilia and organ failure. Despite claims to the contrary, this treatment is very safe.  (Yet outpatient treatment is banned in many US states.) UPDATE Jan 15: The CDC forgot to rewrite its guidance on malaria and hydroxychloroquine during Covid.  CDC says hydroxychloroquine "can be safely taken by pregnant women and nursing mothers..."  Only "when it is used at higher doses for many years, a rare eye condition called retinopathy has occurred."

b) If people were treated prophylactically with this drug (using only 2 tablets weekly) as is done in some areas and in some occupational groups in India, there would probably be at least 50% fewer cases after exposure. (Such treatment is currently banned in much of the US, including in my state of Maine.)

c) Protocols for in-hospital treatment (that were unknown during the initial peak of illness in the US and Europe) using HCQ and individually selected blood thinners, steroids, vitamins, zinc and other drugs such as used at NYU, have significantly reduced mortality of the very small number of people who might still progress to a serious illness. (The FDA, however, recommends against the use of HCQ outside of clinical trials, and the CDC and NIH recommend against it.) 

If we followed a), b) and c) the result would be much briefer periods of infectiousness, lower viral loads, less severe illness and considerably less transmission.  The R zero (average number of people each case infects) would drop below one and the pandemic would soon die out.

Were acts to suppress the use of HCQ carefully orchestrated?  You decide.

Might these events have been planned to keep the pandemic going?  To sell expensive drugs and vaccines to a captive population?   Could these acts result in prolonged economic and social hardship, eventually transferring wealth from the middle class to the very rich?  Are these events evidence of a conspiracy?

Here is a list of what happened, in no special order. Please help add to this list if you know of other actions I should include.  This will be a living document, added to as new information becomes available. 

I have penned this as if it is the "To Do" list of items to be accomplished by those who pull the strings.  The items on the list have already been carried out.  One wonders what else might be on their list, yet to be carried out, for this pandemic.
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1.  You stop doctors from using the drug in ways it is most likely to be effective (in outpatients at onset of illness).  You prohibit use outside of situations you can control.  

Situations that were controlled to show no benefit included 3 large, randomized, multi-center clinical trials (Recovery, Solidarity and REMAP-Covid), the kind of trials that are generally believed to yield the most reliable evidence. However, each of them used excessive hydroxychloroquine doses that were known to be toxic and may have been fatal in some cases; see my previous articles here and here. And a 4th Chinese study that also used excessive doses (3.6 g HCQ in the first three days and 800mg/day thereafter, comparable to the above studies) also found no benefit from HCQ.

2.  You prevent or limit use in outpatients by controlling the supply of the drug, using different methods in different countries and states.  For example, in New York state, by order of the governor, hydroxychloroquine could only be prescribed for hospitalized patients.  In Nevada, the governor outright prohibited both prescribing and dispensing chloroquine drugs for a Covid-19 diagnosis. In New Jersey, the Department of Consumer Affairs required a positive test result before a chloroquine prescription could be dispensed or prescribed. Even back in March, pharmacy boards were coordinating to restrict its use.

France has issued a series of different regulations to limit prescribers from using it.  France's Health Minister also changed the drugs' status from over-the-counter (OTC) to a drug requiring a prescription on January 13.

3.  You play up the danger of the drug, emphasizing side effects that are very rare when the drug is used correctly. You make sure everyone has heard about the man who died after consuming hydroxychloroquine in the form of fish tank cleaner. Yet its toxicity at approved doses is minimal. Chloroquine was added to table salt in some regions in the 1950s as a malaria preventive, according to Professor Nicholas White in his study for the Recovery trial.

4.  You limit clinical trials to hospitalized patients, instead of testing the drug in outpatients, early in the illness, when it is predicted to be most effective.

Finally, but not until May, you have Fauci's NIAID conduct a trial in outpatients, using hydroxychloroquine plus azithromycin, but you only enroll 20 patients, after planning for 2,000. You reduce the duration of followup from 24 weeks to 13 days post treatment. You cancel the study after only 5 weeks, claiming inadequate enrollments, even though you have 11 study sites to enroll patients.

5.  You design a series of clinical trials to give much too high a dose, ensuring the drug will cause harm in some subjects, sufficient to mask any possible beneficial effect.  You make sure that trials in 400 hospitals in 35 countries (Solidarity) plus most hospitals in the UK (Recovery) use these dangerous doses, as well as additional sites in 13 countries (REMAP-Covid trial). There were additional Covid-19 trials that used similar excessive doses, such as PATCH, which I have not yet addressed.

6.  You design clinical trials to collect almost no safety data, so any cause of death due to drug toxicity will be attributed to the disease instead of the drug.

7.  You issue rules for use of the drug based on the results of the UK Recovery study, which overdosed patients. Of course the Recovery results showed more deaths in the hydroxychloroquine arm, since they gave patients 2.4 g in the first 24 hours, 800 mg/day thereafter. Furthermore, the UK has the 2nd highest death rate in the world for Covid-19 (Belgium is 1st), so simply conducting the trial in the UK may have contributed to the poor results. 

8.  You publish, in the world's most-read medical journal, the Lancet, an observational study from a massive worldwide database named Surgisphere (which includes 96,000 hospitalized Covid cases) that says use of chloroquine drugs caused significantly increased mortality.  This was said to be the paper to end all controversy about HCQ and Covid-19.  You make sure that all major media report on this result. This was to be the nail in the coffin for hydroxychloroquine. Then you quickly have 3 European countries announce they will not allow doctors to prescribe the drug. Soon additional countries ban its use for Covid.

9.  You do your best to ride out any controversy over the veracity of this paper, never admitting culpability. Even after hundreds of people criticized this Lancet observational study due to easily identified fabrications--the database used in the study did not exist, and the claimed numbers of cases did not agree with known numbers of cases--the Lancet held firm for two weeks, which served to muddy the waters about the trial, until finally 3 of the 4 coauthors (but not the Lancet nor the author who purportedly owned the database) retracted the study. Neither the authors nor the journal have admitted responsibility, let alone explained what it was that induced them to coauthor and publish such an obvious fraud.

You made sure very few media reported that the data were fabricated, the "study" was fraudulent, and the drugs were actually safe. Even though the story of the database company, Surgisphere, was full of scandalous details, most media ignored it.  The story of the study's retraction went largely unnoticed by the public.  You made sure most people remember the original (false) story: that chloroquine and hydroxychloroquine frequently kill patients.

10.  You ensure federal agencies like FDA and CDC hew to your desired policies.  Some examples:  a) FDA advised use only in hospitalized patients (too late) and later advised use restricted to only clinical trials (which are limited, are difficult to enroll in, have been halted prematurely, or may use excessive doses). 

b) you have FDA make unsubstantiated and false claims, such as:  "Hospitalized patients were likely to have greater prospect of benefit (compared to ambulatory patients with mild illness)" and claim the chloroquine drugs have a slow onset of action. If that were really true, they would not be used for acute attacks of malaria or in critically ill patients with Covid. (Disclosure:  I once dosed myself with chloroquine for an acute attack of P. vivax malaria, and it worked very fast.).

c) although providing treatment advice is a large part of its mission, CDC instead refers clinicians to the NIH guidelines, discussed below.

d) Despite the fact that Belgium's COVID treatment guidelines repeatedly mention that the doses of HCQ in the Recovery and Solidarity trials were 4 times the cumulative dose used in Belgium, you make sure the Belgian guidelines, paradoxically, only recommend use of HCQ within clinical trials.

11.  You make sure to avoid funding/encouraging clinical trials that test drug combinations like hydroxychloroquine with zinc, with azithromycin, or with both, although there is ample clinical evidence that such combinations provide a cumulative benefit to patients. For example, one study that did look at this combination had no funding.

12.  You have federal and UN agencies make false, illogical claims based on models (or invention) rather than human data.  For example, you have the FDA state on June 15 that the dose required to treat Covid is so high it is toxic, after the Recovery and Solidarity trials have been exposed for toxic dosing.  This scientific double-speak gives some legal cover to the clinical trials that overdosed their patients. According to Denise Hinton, RN, the FDA's Chief Scientist (yes, a registered nurse without scientific qualifications is the Chief Scientist at FDA), or perhaps a clumsy FDA wordsmith: 

"Under the assumption that in vivo cellular accumulation is similar to that from the in vitro cell-based assays, the calculated free lung concentrations that would result from the EUA suggested dosing regimens are well below the in vitro EC50/EC90 values, making the antiviral effect against SARS-CoV-2 not likely achievable with the dosing regimens recommended in the EUA. The substantial increase in dosing that would be needed to increase the likelihood of an antiviral effect would not be acceptable due to toxicity concerns."

You have a WHO report claim toxic doses are needed. This is nonsense since:
  • In 2005, CDC researchers showed strong effects against SARS-1 at safely achievable concentrations.  Here is the relevant quote, "The infectivity of coronaviruses other than SARS-CoV are also affected by chloroquine, as exemplified by the human CoV-229E [15]. The inhibitory effects observed on SARS-CoV infectivity and cell spread occurred in the presence of 1–10 μM chloroquine, which are plasma concentrations achievable during the prophylaxis and treatment of malaria (varying from 1.6–12.5 μM) [26] and hence are well tolerated by patients.” A reader asked me to note that this study was done in tissue culture.
  • the drug at normal doses is being tested in over 30 different medical conditions (see clinicaltrials.gov), and 
  • reports from many different countries say that the drug is effective for Covid-19 at normal doses, while a high dose chloroquine treatment trial was halted in Brazil and a preprint of the study was posted April 11, or perhaps April 7, after finding that drug effects were causing ventricular arrhythmias and deaths. JAMA published the results in their April 24 edition.
  • Toxicity in the Brazilian study was seen after only 3 days of treatment, during which 3.6 grams of chloroquine were administered. But the Solidarity (3.2 grams of hydroxychloroquine in 3 days), Recovery (3.6 grams of hydroxychloroquine in 3 days) and REMAP-Covid trials (3.6 grams of hydroxychloroquine in 3 days) continued overdosing patients until June, or probably longer in the case of REMAP-Covid, despite Brazil's evidence of deaths by overdose.

Tellingly, JAMA editor Gordon Rubenfeld wrote in April, after the Brazilian study came out in JAMA, "if you are prescribing HCQ after these JAMA results, do yourself and your defense lawyer a favor. Document in your medical record that you informed the patient of the potential risks of HCQ including sudden death and its benefits (???)." 

13.  You create an NIH Guidelines committee for Covid treatment recommendations, in which 16 members have or had financial entanglements with Gilead, maker of Remdesivir. The members were appointed by the Co-Chairs.  Two of the three Co-Chairs are themselves financially entangled with Gilead.  Are you surprised that their guidelines recommend specifically against the use of hydroxychloroquine and in favor of Remdesivir, despite a Chinese Phase III study showing no benefit, which was mistakenly posted on the WHO website, then taken down?  The guidelines authors deem their recommendations the new "standard of care." Additional remdesivir studies have shown no clear mortality benefit.

You create an NIH treatment guidelines summary that cherry picks the literature to claim HCQ provides no benefit.

14.  You frighten doctors so they don't prescribe hydroxychloroquine, if prescribing it is even allowed in their jurisdiction, because prescribing outside the new NIH "standard of care" leaves them open to both malpractice lawsuits and potential loss of license.  For example, Michigan's Medical Licensing Board issued the following:

"Prescribing hydroxychloroquine or chloroquine without further proof of efficacy for treating COVID-19 or with the intent to stockpile the drug may create a shortage for patients with lupus, rheumatoid arthritis, or other ailments for which chloroquine and hydroxychloroquine are proven treatments. Reports of this conduct will be evaluated and may be further investigated for administrative action... It is also important to be mindful that licensed health professionals are required to report inappropriate prescribing practices." 

In other words, Michigan pharmacists are required to snitch on doctors prescribing the drugs for Covid.

You further tell doctors (through the FDA) they need to monitor a variety of lab parameters and EKGs when using the drug, although this was never advised before, which makes it very difficult to use the drug in outpatients. You have the European Medicines Agency issue similar warnings. In Australia only physicians in certain specialties are allowed to prescribe the drug for Covid. And in Queensland, physicians or pharmacists who do not comply (for example, by prescribing the drug for prevention of Covid) face up to 6 months' imprisonment and a fine up to $13,000 Australian dollars.

15.  You manage to control the conduct of most trials around the world by specially designing the WHO-managed Solidarity trials, currently conducted in 35 countries. WHO halted hydroxychloroquine clinical trials around the world, twice. The first time, May 25, WHO claimed it was in response to the (fraudulent) Lancet study.  The second time, June 17, WHO claimed the stop was in response to the Recovery trial results.  Recovery used highly toxic doses of hydroxychloroquine in over 1500 patients, of whom 396 died.  You stop the trial before the data safety monitoring board has looked at your data, a move that is unlikely to be consistent with trial protocol. WHO's trial in over 400 hospitals overdosed patients with 2.0 g hydroxychloroquine in the first 24 hours.  The trial was halted 3 days after the toxic doses were exposed (by me). The trial involved doctors around the world typing minimal patient information into an online WHO platform, which assigned the patient a treatment.

The only "safety" information collected during the trial was whether patients required oxygen, required a ventilator, or died. This effectively masked the adverse effects of the drugs tested.  

I should mention that WHO's initial plan for its Solidarity trial entirely omitted the chloroquine drugs, but they were added at the urging of participating nations. WHO's fallback position appears to have been to use toxic doses.

16.  You have the WHO pressure governments to stop doctors prescribing hydroxychloroquine. 

17.  You have the WHO pressure professional societies to stop doctors prescribing hydroxychloroquine.

18.  You make sure that the most-consulted US medical encyclopedia, UptoDate, advises physicians to restrict hydroxychloroquine to only clinical trials, citing the FDA.

19.  You have the head of the Coronavirus Task Force, Dr. Tony Fauci, insist the drug cannot be used in the absence of strong evidence...while he insisted exactly the opposite in the case of the MERS coronavirus outbreak several years ago, when he recommended an untested drug combination for use...which had been developed for that purpose by his agency.  And while he was bemoaning the lack of evidence, he was refusing to pay for trials to study hydroxychloroquine, and cancelled two NIAID-sponsored trials of outpatient HCQ before completion. And he changed the goalposts on the Remdesivir trial, not once but twice, to make Remdesivir show a tiny bit of benefit, but no mortality benefit. Yet don't forget, Fauci was thrilled to sponsor a trial of a Covid vaccine (partly owned by his agency) in humans, before there were any data from animal studies.  So much for Fauci's requirement for high quality evidence, before risking use of drugs and vaccines in humans.

20.  You convince the population that the crisis will be long-lasting. You have the 2nd richest man in the world, and biggest funder of the WHO, Bill Gates, keep repeating to the media megaphone that we cannot go back to normal until everyone has been vaccinated or there is a perfect drug.  (The Gates Foundation helped design the WHO Solidarity trial, which says only that it has multiple funders,  helped fund the Recovery trial, and Gates is heavily invested in Covid pharmaceuticals and vaccines.)

21.  You have CDC (with help from FDA) prevent the purchase of coronavirus test kits from Germany, China, WHO, etc, and fail to produce a valid test kit themselves. The result was that during January and February, US cases could not be tested, and for months thereafter insufficient and unreliable test kits made it impossible to track the epidemic and stop the spread.

22.  You have trusted medical spokesmen lie to the public about the pandemic's severity, so precautions weren't taken when they might have been more effective and less long-lasting.  Congress was repeatedly briefed about the pandemic in January and February, which scared several Congress members enough that they sold off large amounts of stock, risking insider trading charges.  Senator Burr is one of them, currently under investigation for major stock sales on February 13.

Yet Dr. Fauci told USA Today on February 17 that Americans should worry more about the flu than about coronavirus, the danger of which was "just miniscule." Then on February 28, Drs. Fauci and Robert Redfield (CDC Director) wrote in the New England Journal:

"...the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%) or a pandemic influenza (similar to those in 1957 and 1968) rather than a disease similar to SARS or MERS, which have had case fatality rates of 9 to 10% and 36%, respectively."

23.  You destroy the reputation of respected physicians who stand in your way.  Professor Didier Raoult and his team in Marseille have used hydroxychloroquine on over 4,000 patients, reporting a mortality rate of about 0.8%.  (The mortality rate of patients given hydroxychloroquine in the Recovery trial was 25.7%.) Raoult is very famous for discovering over 100 different microorganisms, and finding the long-sought cause of Whipple's Disease.  With this reputation, Raoult apparently thought he could treat patients as he saw fit, which he has done, under great duress.  Raoult was featured in a New York Times Magazine article, with his face on the magazine cover, on May 12, 2020.  After describing his considerable accomplishments, the Times very unfavorably discussed his personality, implied he conducted unethical trials without approval, and using anonymous sourcing produced a detailed hit piece. Raoult is now considered an unreliable crank in the US.
UPDATE:  Raoult has now (November 13) been legally charged with ethics violations in France for propounding and using HCQ in Covid patients.

You gather a group of Yale professors to dispute their Yale professor colleague Harvey Risch, an MD, PhD epidemiologist, on his publications and vocal support of the benefits of HCQ for Covid. Their first argument is that he is not an infectious disease doctor.  Notably, the first signer of the statement opposing Dr. Risch is an economist.

Physician and state senator Scott Jensen of Minnesota is being investigated by his state medical board due to anonymous complaints about 'spreading misinformation' and giving 'reckless advice' about COVID in interviews. Jensen was previously selected as "Family Physician of the Year" in his state. Now his medical license is at risk, not because of how he treated a patient, but for what he said outside of the office. Unprecedented.
UPDATE:  Jensen was exonerated.

24.  You have social media platforms ban content that does not agree with the desired narrative.  As YouTube CEO and ex-wife of Google founder Sergey Brin, Susan Wojcicki said,

“YouTube will ban any content containing medical advice that contradicts World Health Organisation (WHO) coronavirus recommendations. Anything that would go against World Health Organisation recommendations would be a violation of our policy.”

25.  When your clinical trials are criticized for overdosing patients, you quickly have Oxford-affiliated, Wellcome Trust-supported scientists at Mahidol University publish papers (a literature review with modeling and a modeling study) purporting to show that the doses used were not toxic. You develop a new method to measure hydroxychloroquine in a handful of Recovery patients who were not poisoned.  However, there are 2 problems you forgot with this approach: 
  • The Brazilian data, including 16 deaths, extensive clinical information and documented ventricular arrhythmias, are much more persuasive than a theoretical model of hydroxychloroquine pharmacokinetics.
  • Either the drug is too toxic to use, even at normal doses, for a life-threatening disease, or even extremely high doses are safe.  You can't have it both ways.

Oxford is the institution running the Recovery trial, and invented a Covid vaccine that already has 400 million doses on order.  The Wellcome Trust funded the Recovery trial.

26.  You change your trial's primary outcome measures after the trials have started, in order to prevent detection of drug-induced deaths (Recovery) or to make your drug appear to have efficacy (NIAID Remdesivir trial).

27.  You stop manufacturers from supplying the drug. Shortly after the fraudulent Lancet paper came out, Sanofi announced it would no longer supply the drug for use with Covid, and would halt its two hydroxychloroquine clinical trials. One of the cancelled Sanofi trials was expected to test 210 outpatients early in the course of disease. The trial remains suspended at the time of writing, while the Lancet paper was retracted 13 days after publication.  You surely don't want a trial of hydroxychloroquine treatment early in the disease, since it might show an excellent effect.

Sanofi (a pharma company) began acting like a regulator.  From the Australian DOH's Therapeutic Goods Administration website:

Sanofi, the supplier of one of the hydroxychloroquine products marketed in Australia (Plaquenil), has also written to health professionals reinforcing that hydroxychloroquine is not approved for use in Australia for treatment of COVID-19 outside the confines of a clinical trial. Sanofi also reinforced some of the known risks of prescribing hydroxychloroquine, in particular potentially serious cardiac issues. Globally, Sanofi has received an increased number of reports of serious cardiac issues, including deaths, in patients treated with hydroxychloroquine, This appears to be more common in patients also treated with other medicines that can affect the heart.

Then Sanofi started collecting information on all off-label use of hydroxychloroquine in New Zealand and Australia.  Why is Sanofi, a drug manufacturing company, becoming a surveillance/enforcement mechanism intended to frighten medical providers from using the drug for Covid, which use is by definition "off label." Sanofi alternatively suggests one may report (anonymously or not) others' off-label use to New Zealand's Pharmacovigilance Center or the Australian equivalent.

And see this: Novartis will supply HCQ only under certain conditions, and halted its HCQ trial due to lack of enrollments, although enrollment was not an issue for its other COVID trials.

28. You attempt to retract published papers that provide evidence to support use of hydroxychloroquine for COVID.

29. You have your 'bought' scientists conceal their financial conflicts of interest in their HCQ clinical trials and publications as well as in the guidelines they produce.

30. You can get your experimental, unlicensed drugs tested, much more expeditiously and cheaply than under ordinary circumstances, on Covid patients in large clinical trials, but only as long as no drug is designated effective for the condition. This opportunity only lasts while the "standard of care" for early Covid disease is nothing more than supportive measures, since no drug is deemed effective.

31. You have a research organization with big Pharma members (A.O.K.I.) pressure the Russian Ministry of Health to remove hydroxychloroquine from its treatment guidelines.

32. You stopped use of hydroxychloroquine, allegedly in response to the fabricated Lancet study, in France, Italy and Belgium (countries with very high COVID mortality rates) then Portugal then Switzerland. But Switzerland restarted using HCQ 15 days later. This created a natural experiment in Switzerland. About 2 weeks after hydroxychloroquine use was halted, death rates approximately tripled, for about 15 days. Then, after its use was allowed again, two weeks later death rates from Covid fell back to their baseline. (Thanks to FranceSoir:

33.  You reverse an old trick of clinical trials, to mask benefit of hydroxychloroquine.  The trick was to replace the saline placebo with a substance that is being used by many clinicians and in many trials against Covid, thus by comparison likely to reduce the positive effect of your tested medication. This was done in trials both at NYU and at University of Washington, using vitamin C or vitamin C plus folate respectively as placebos.

34. You have the chief medical officers of Wales, England, Scotland and Northern Ireland, and the director of the UK's National Health Service, write to UK doctors, a) urging them to enroll their Covid patients in one of 3 national clinical trials, two of which greatly overdosed patients with hydroxychloroquine, and b) stopping their use of "off license treatments" outside of a trial. Yet again, we encounter a veiled threat against clinicians actually attempting to treat the primary SARS-Cov-2 infection. The chief doctors wrote:

While it is for every individual clinician to make prescribing decisions, we strongly discourage the use of off-licence treatments outside of a trial, where participation in a trial is possible... Any treatment given for coronavirus other than general supportive care, treatment for underlying conditions, and antibiotics for secondary bacterial complications, should currently be as part of a trial, where that is possible."

35.   You have a state Pharmacy Board refuse to dispense hydroxychloroquine outside of clinical trials on June 15, citing the FDA recommendation for use only in trials.  You issue this new regulation on the same day that FDA publishes its recommendation, indicating prior coordination. But when your regulation is exposed on July 14, you immediately rescind it. 

36.  You have the IMF offer rapid financing to Belarus, but only if it follows the recommended model of Covid response and imposes quarantines, isolation and curfews.

37.  A group of doctors went to Washington DC July 27-28.  They called themselves "America's Frontline Doctors" and gave a press conference and livestream talks about the Covid-19 pandemic as well as about the need for physicians to be able to prescribe HCQ freely.  While the media sparsely attended the press conference, the livestream got millions of views. And within hours, their livestream was banned by Google, YouTube, Facebook and Twitter.  Twitter was said to additionally ban comments about its ban. Then Squarespace took down the Frontline Doctors' website. 

38. After the HCQ issue got so much attention on social media, you impose another ban on July 29 on the prescribing of HCQ for Covid, starting July 30 in Ohio, using its Pharmacy Board to dictate to physicians what they may not prescribe. (A repeat of #35 in a different state.) Ohio, with the governor's approval, had first limited hydroxychloroquine dispensing on March 22. At least 3 other states limited its dispensing at the same time.

This ban got so much attention that Republican Governor Mike DeWine rescinded it the next morning. DeWine claimed to agree with FDA Commissioner Stephen Hahn, who said in a July 30 TV interview that the prescribing of HCQ is between a doctor and patient. This is in accord with FDA law; but then, why was FDA silent when pharmacy boards, governors and other state entities prevented the prescribing of this FDA-approved drug in their jurisdictions?

39.  After having Google take down physician James Todaro's article on hydroxychloroquine for 4 months, you allow it to resurface right before Google's (and Facebook's and Amazon's and Apple's) CEOs testify before Congress on July 29 on censorship and abuse of power. You have Twitter warn that Todaro's article is at an unsafe link.

40.  After massive attention to the banning of the videos posted by the physician group 'America's Frontline Physicians' and its website, you make intense efforts to discredit the physicians involved. 

MedPageToday claimed it
 "could find no evidence that any of the speakers worked in hospitals with significant numbers of COVID-19 patients." But the doctors claimed they used the drug early and prevented hospitalizations and deaths.  With over 4.4 million Americans diagnosed with Covid, what doctor hasn't seen a Covid patient? 

USAToday blared the headline: 
'America's Frontline Doctors' may be real doctors, but experts say they don't know what they're talking about.

You have USA Today review and publish detailed information on the licenses, practice locations and malpractice histories of the doctors who spoke out. USAT reporters claim these doctors are not experts and lack knowledge about the use of HCQ in Covid-19, despite the fact that most work in primary care, urgent care or emergency medicine and report using the drug for Covid. Yet no one asks how many years ago 'expert' Tony Fauci last treated a patient? 'Expert' Deborah Birx' medical license expired in 2014, so she hasn't treated a Covid patient either.  BTW, she worked in Fauci's lab between 1983 and 1986.

41.  Hydroxychloroquine use is truly the wedge issue for understanding and turning around the pandemic.  If hydroxychloroquine works reasonably well as a prophylactic and treatment for Covid-19, it could potentially end the severity of the pandemic, greatly reduce transmission, and return us to life as we knew it.  You must make use of the levers of government, plus mainstream media and social media, to stop that from happening.

So, just in case doctors thought the Frontline Doctors' video, or a new study from Spain showing the drug's usefulness meant they should use hydroxychloroquine to treat Covid, you must act fast. You use Representatives at a Congressional health subcommittee hearing on July 29 to threaten doctors about one use of the drug last April, in veterans who were nursing home patients.  Per the Washington Post:

"doctors at the 238-bed nursing home dosed [30] patients with what came to be called a “covid cocktail” for more than two weeks in April, often over the objections of nurses and without the full knowledge of residents’ families. At least 11 residents received the drug even though they had not been tested for covid-19, The Post found."

I have treated patients in nursing homes, and one rarely discusses medication changes with family, unless the patient is seriously ill.  When nursing home residents were dying like flies last April, when tests were hard to come by, and confirmed diagnoses few and far between, doctors used this medicine to try to prevent nursing home deaths during a pandemic. And now they are being scapegoated for doing so.

The WaPo article does not even tell us whether the patients survived, thrived or were harmed. The article hardly makes sense. Its only purpose is to blacken the drug and the physicians who use it.

Yet on August 27, with respect to HCQ's use in nursing homes, Senators Warren, Wyden and Casey demanded that FDA and Medicare/Medicaid explain how they are tracking it, and also demanded an Inspector General investigation into its recent use in nursing homes. "The Trump Administration owes us answers on the use of an ineffective drug like hydroxychloroquine in nursing homes — the epicenter of the pandemic,” Elizabeth Warren said in a statement. 

42.  You use state Medical Licensing Boards to threaten doctors who claim there is a cure for Covid-19. 

43.  You have Dr. Fauci discredit published observational studies that show benefit during a Congressional hearing, demanding randomized controlled trials.  Fauci never tells the Committee he has cancelled the one randomized controlled trial of HCQ that his agency, NIAID, had promised to conduct on HCQ.  NIAID claimed that it could not enroll enough subjects, and the study was cancelled after only 20 were enrolled.  However, Fauci told the Committee that 250,000 Americans have shown interest in participating in trials of a Covid vaccine. It is difficult to reconcile such extreme lack of interest in a treatment trial, and such massive interest in a vaccine trial.  

Doctors who wrote studies showing HCQ benefit, even when used late (50% mortality reduction) have defended their work from Fauci's criticism of it to Congress.

44.  You erode the doctor's primary responsibility to the patient, replacing it with the need to perform clinical research. This is the first time I have ever heard such a thing in the US: research physicians are pressuring frontline doctors not to veer from protocol-determined treatment, even when patients enrolled in treatment trials are at risk of death. 'Helping future patients' is the rationale provided. 

Need I say this was the justification for the Nazi doctors' experiments? It was not accepted at Nuremberg and it shouldn't be accepted now. Medical ethics are no mystery. As published in the JAMA, and accepted worldwide, the World Medical Association's Declaration of Helsinki, a.k.a. "Ethical Principles for Medical Research Involving Human Subjects" states,

While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects.

One of the Nuremberg Principles says essentially the same thing.

45. You use the term "stellar" to describe the Recovery trial in the August 5, 2020 NY Times, but avoid any hint that the Recovery trial's hydroxychloroquine arm gave 1500 patients a toxic, potentially lethal dose, of whom over 25% died.

46.  You censure and oust from the Detroit Democrats a state legislator because she credited HCQ for saving her life when she had Covid-19, and she publicly thanked President Trump for bringing the drug to her attention. It had been extremely difficult for her to obtain the drug, because her governor, Gretchen Whitmer, had banned use of the drug for Covid.

47.  Despite assuring you control the outcome of the vast majority of randomized clinical trials of the chloroquine drugs, you have been thwarted by physician researchers in Detroit, Spain, Italy, France, Saudi Arabia who publish their observational results with hydroxychloroquine, showing the drug dramatically reduces mortality from Covid.  

Doctors in Turkey, the US and Canada, and the US show that HCQ's cardiac toxicity is negligible. So you have frontman Tony Fauci repeatedly dismiss this evidence from thousands of patients, since it did not come from randomized controlled trials.  See c19study.com for a compilation of 99 (58 peer reviewed) studies of the chloroquine drugs in Covid-19, and convince yourself what the overall data truly show.

48.  You have Wikipedia write the following about Covid and HCQ:  "all clinical trials conducted during 2020 found it is ineffective and may cause dangerous side effects."  The footnotes refer to only a handful of trials, while a compilation of all 99 studies (of different types, including meta-analyses and observational studies) on the drug in Covid-19 tells a completely different story. 

49.  You electronically disappear articles favorable to HCQ. A meta-analysis preprint of 41 studies of EARLY HCQ use, written by US physicians, is posted at this link on the ResearchGate site, 
which hosts a collection of academic papers. The article rapidly disappeared from the link.  Here is a brief description of the article:

Prodromos et al., Preprint, doi:10.13140/RG.2.2.29781.65765 (meta analysis)

Hydroxychloroquine is Effective and Safe for the Treatment of COVID-19, and May be Universally Effective When Used Early Before Hospitalization: A Systematic Review

Meta analysis of 41 studies concluding: "HCQ has been shown to have consistent clinical efficacy for COVID-19 when it is used early in the outpatient setting, and in general would appear to work better the earlier it is used. Overall HCQ is effective against COVID-19. There is no credible evidence that HCQ results in worsening of COVID-19. HCQ has been shown to be safe for the treatment of COVID-19 when responsibly used."

A reader (later) sent me another working link for the full text here.

50.  Can we begin to connect the dots between those who fraudulently suppressed effective treatments for Covid-19, and those who wish to maintain the pandemic crisis to remake the world? Today, on 9/11, Oxford epidemiologist Dr. Peter Horby, a principal investigator for the Recovery trial in which 396 people who were overdosed with hydroxychloroquine died, retweeted a tweet from the World Economic Forum about the environmental benefits of using bicycles.  Horby added, "This is where we need to be headed."

51.  From Anthony Fauci, who has perhaps done more than any other person to besmirch the value of HCQ and prevent Covid patients being treated effectively, comes a statement that seems to hearken to the World Economic Forum sentiment in #50 above.  Fauci blames the pandemic (which his actions prolong) on humans damaging nature.  And he suggests we must learn to live differently, in harmony with nature.  

And now, suddenly, I understand why it is so important to claim the pandemic came from human encroachment on bat territory, and not from a lab accident. Because human encroachment is being positioned to take the blame for Covid-19. (SARS-1, Ebola and SARS-2 are claimed to have arisen from humans living too close to bats, eating them and getting infected, starting epidemics--but this has not been proven for either SARS epidemic, nor proven for the Ebola epidemics.). This is not Fauci waxing eloquent about nature. This is Fauci, America’s Doctor, starting the conversation about how the human population, not the bat virus, is the real underlying problem.

The quote below was published in the journal Cell, in the final paragraph, on September 3 by Fauci and Morens:
"The COVID-19 pandemic is yet another reminder, added to the rapidly growing archive of historical reminders, that in a human-dominated world, in which our human activities represent aggressive, damaging, and unbalanced interactions with nature, we will increasingly provoke new disease emergences. We remain at risk for the foreseeable future. COVID-19 is among the most vivid wake-up calls in over a century. It should force us to begin to think in earnest and collectively about living in more thoughtful and creative harmony with nature, even as we plan for nature’s inevitable, and always unexpected, surprises."
Are they hinting that a reduced human population will be less susceptible to pandemics? Or that rural populations need to move?

52.  Even though the famous Mehra/Desai Lancet paper claiming HCQ and CQ caused hugely increased deaths was exposed as a total fabrication by the Lancet editor and retracted on June 4, the Washington Post today, on September 11, links to its favorable May 22 story about the Mehra/Desai paper--using it as the sole evidence for yet another false claim of the danger of hydroxychloroquine. 

This despite the fact that the WaPo reported on June 2  about concerns regarding the paper's authenticity. The New York Times ran at least 3 articles about the fabricated Mehra/Desai paper here, here and here, and you know the WaPo reads what the NYT reports.

You neuter criticism electronically by making it hard to read.  I commented on the 9/11 article in the WaPo, and its gratuitous slur against HCQ, in which WaPo cited as authority a fabricated paper.  I used the online comment form.  I am a subscriber. The WaPo printed my comment, but my comment seems to be the only comment whose words extend beyond the right margin, and are chopped off. How odd. 

53.  When all else fails, would you really try to blow up much of the world supply of hydroxychloroquine? 
According to the Taiwan English News:

An explosion at a pharmaceutical factory in Taoyuan City left two injured and caused a fire early this afternoon, December 20...

Liberty Times reported that the factory produces hydroxychloroquine APIs, and is the world’s second largest HCQ raw material supplier.

Another source tells the same tale.  The Pharmaceutical company is named Sci Pharmtech Inc. The explosion was huge and spread to five other companies.

54.  Big mistake. You meant to expunge all official information about the safety of hydroxychloroquine.  But you forgot to remove CDC's malaria treatment guidance, which still tells the truth about the drug. A 2 page information sheet is available online on the CDC website.  It might disappear after I post this. CDC's guidance states, 

"Who can take hydroxychloroquine? Hydroxychloroquine can be prescribed to adults and children of all ages. It can also be safely taken by pregnant women and nursing mothers.

What are the potential side effects of hydroxychloroquine? Hydroxychloroquine is a relatively well tolerated medicine. The most common adverse reactions reported are stomach pain, nausea, vomiting, and headache. These side effects can often be lessened by taking hydroxychloroquine with food. Hydroxychloroquine may also cause itching in some people. All medicines may have some side effects. Minor side effects such as nausea, occasional vomiting, or diarrhea usually do not require stopping the antimalarial drug. If you cannot tolerate your antimalarial drug, see your health care provider; other antimalarial drugs are available. 

How long is it safe to use hydroxychloroquine? CDC has no limits on the use of hydroxychloroquine for the prevention of malaria. When hydroxychloroquine is used at higher doses for many years, a rare eye condition called retinopathy has occurred. People who take hydroxychloroquine for more than five years should get regular eye exams.

  • Overdose of antimalarial drugs, particularly hydroxychloroquine, can be fatal.

55.  Twitter censored the Brazilian Ministry of Health for tweeting to citizens that they should seek early treatment for Covid, as the sooner they get treated, the better the result. (The harmful US recommendation is to stay home and do nothing until you require hospitalization.)
https://twitter.com/estardepresso/status/1350596931295338509

Image
Quote Tweet
This Tweet violated the Twitter Rules about spreading misleading and potentially harmful information related to COVID-19. However, Twitter has determined that it may be in the public’s interest for the Tweet to remain accessible. Learn more

56.  You have the WHO issue guidance that HCQ should not be used for Covid, based on 6 multicenter trials that included over 6,000 patients. Six!  Scores of trials using much larger numbers of patients demonstrated benefit, but these were omitted from the WHO review.

Of course, included in these six trials (and accounting for about half the patients in WHO's review) are the Recovery and Solidarity trials that overdosed subjects on hydroxychloroquine and caused 10-20% higher mortality than in the placebo subjects who received no treatment! 
 
If effect, WHO is confirming that when you poison patients with excessive doses they do not do well. I concur that poisonous doses of HCQ  or anything else should never be used in patients.
 
Will WHO comment on the only real question, which is the value of using therapeutic doses early in the course of illness? The results of over 200 studies speak for themselves.

Why aren't the families of subjects who died in these trials bringing charges? Was information on which drugs their family members received withheld from them to prevent that from happening?

57.  The Bill and Melinda Gates Foundation is still up to their dirty tricks smearing hydroxychloroquine. Yet another paper has come out of U. Washington, paid for by BMGF, that claims HCQ isn't helpful for early treatment (despite dozens of studies to the contrary). If you read the new paper carefully, you learn that HCQ actually did help, but the authors massaged the data to remove statistical significance... and shut the trial down prematurely.  My analysis is here.

58.  It is important to keep banging the drum that says, not only don't the drugs work, but they are dangerous, to boot. And so we have a new meta-analysis designed to do just that.
Here's how:

1. Never admit there was anything wrong with the trials that overdosed patients with hydroxychloroquine or chloroquine.  In fact, these authors called the Recovery and Solidarity trials that gave patients 4 times the normal dose of HCQ at first, "pragmatic." Odd use of verbiage.
2.  Cherry pick a small number of studies from which to perform your meta-analysis, so that the number of subjects in the overdose studies outweighs the number in all the other trials. In this case 67% of all subjects in this meta-analysis (which included about 14 of 233 total trials) had been enrolled in the Recovery and Solidarity overdose trials. Two other overdose studies were included, PATCH and Remap-CAP. (PATCH abruptly ended after only 5 subjects were enrolled, once the other overdose trials were exposed.)
3.  Because the 3 overdose studies (except PATCH, in which none of the 5 died) had a higher proportion of deaths in the hydroxychloroquine arms than in the placebo arms, and provided more than two thirds of the subjects for this meta-analysis, the authors of the meta-analysis were able to conclude that using HCQ is associated with higher death rates than using nothing at all.  
4.  Incredible that the toxic doses used in 4 of the trials selected are whitewashed by calling them "relatively high doses" and never linking these doses to the increased death rates.
5.  Another odd thing is that investigators from the included trials, whose data were used in this study, are listed as coauthors.  There are 94 coauthors, all of whom signed off on the final paper (i.e., the overdose investigators had the opportunity to craft the language of this paper to cover their butts regarding their overdose trials).
6.  Many of these investigators have financial interests in products and/or companies making new products for which hydroxychloroquine would be a cheap competitor.

Here is the new paper.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trialsvolume 12, Article number: 2349 (2021)  
https://www.nature.com/articles/s41467-021-22446-z
"Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20)..."
 ------------------------

Remember:  the system would not be going to these lengths if hydroxychloroquine didn't work. Please think about that.

------------------------

The People and the Professionals Fight Back

I am starting a new "live" list of ways in which the people are pushing back against the abrogation of our rights, the propagation of lies, and our ability to access the medical care we choose. Please help contribute to it.

1.  A huge Thank You goes to FranceSoir, which has covered the hydroxychloroquine restrictions in a long series of articles, has done the digging that the mainstream media refuses to do, and has brought the issue before a judge.  The judge ruled that a Press Release issued on May 27 by France's Minister of Solidarity and Health, informing doctors they cannot use hydroxychloroquine for Covid, has no legal meaning, and cannot restrict the prescribing of medicines by France's medical providers.

2. Italian citizens take their government to court over the handling of the pandemic and the lockdown.

3.  Skye News Australia presents information on the effective responses to the pandemic in Sweden and Switzerland.  The pandemic is over in Sweden.  Switzerland proved (again) the benefits of HCQ used at the proper dose, in conjunction with other drugs/supplements.  "The destruction of our economies was completely pointless."

4.  The statistical methods of 3 major, randomized controlled trials of hydroxychloroquine efficacy in Covid have been questioned by a large group of statisticians, researchers and clinicians.  All 3 trials were inadequately powered, with large p values. In fact, evaluated differently, "the evidence from all these trials points to [HCQ] treatment effectiveness" according to the group of professionals providing the critique.

5.  The assertion that antibodies only last a few months, and therefore immunity wanes rapidly, seems to be another misleading claim from the fake-science influencers.  As with many other viruses, T and B lymphocytes are critical for coronavirus immunity, and a lot more durable than antibodies. From a U. Washington study, "the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies."

6.  The governor of Minnesota on August 12 rescinded his state's ban on the use of hydroxychloroquine and chloroquine for Covid.

7.  Three US Senators demand answers from the FDA on what evidence it used to recommend against outpatient treatment with HCQ, whether states have the right to regulate what drugs can be used, etc.  Very powerful letter that cuts to the heart of the legal confusion regarding HCQ restrictions.

8. Marchers from Germany and beyond planned a huge demonstration against Covid restrictions in Berlin on August 29.  Thousands of police will line the streets. As reported in The Hill on August 26, "
Officials in Berlin are banning demonstrations against coronavirus prevention measures, calling the protests themselves a breach of social distancing rules." However, at the eleventh hour, the German courts ruled against the government, and the demonstration will proceed legally.

Perhaps it is notable that anti-restriction demonstrators are said to be on the left in Germany, but said to be on the right in the US.  Maybe these distinctions lack actual meaning?

9. Panamanian physician and government advisor Sanchez Cardenas notes that when HCQ was banned in Panama, deaths shot up, and when it was allowed again, deaths were reduced. He is working to change their treatment protocol and provide a legal basis for HCQ's use.

10. Australian Member of Parliament Craig Kelly repeatedly speaks out against the banning of HCQ, including in Parliament. Attempts to censure him have so far failed.

11.  Guyana's Ministry of Health goes public with an announcement that frontline healthcare workers in Guyana have been receiving HCQ as prophylaxis against Covid-19. According to Dr. Anthony, the feedback received from doctors suggests that the drug has been effective.

12.  Attorneys in Ohio file suit over the lockdown measures and other rules put into place as a result of Covid-19.  Psychiatrist Peter Breggin has posted all the case documents and his affidavit here, along with links to many other papers and documents relevant to  SARS-C0V-2.

13.  @ArtLeroux has connected the Remdesivir manufacturer, Gilead, with anti-HCQ propaganda.  In a Gilead-sponsored symposium, every speaker except one has written that HCQ does not work.  "
During the National Days of Infectious Disease organized by the famous SPILF, sponsored symposia take place, including one by Gilead. Among the speakers, ALL those who have spoken or written on the subject have pleaded the ineffectiveness of hydroxychloroquine. All except De Truchis."


14. Ivermectin has not been smacked down like HCQ, and is being used successfully in Australia, Brazil and some other places as an anti-Covid drug.  This paper out of Australia explains why.  

It is interesting that Sapan S. Desai, the disgraced author and database conjuror of the fraudulent, retracted papers in NEJM and Lancet (his Lancet paper fabricated data from over 600 hospitals, and falsely claimed patients who received chloroquine or hydroxychloroquine died at a rate about 35% higher than those who did not) also wrote a paper about Ivermectin this year.  That paper was on the internet as a preprint, but was taken down when Desai's frauds were exposed.  It is interesting to me that Desai had early access to information about what drugs worked against Covid, and authored fabrications intended to stop the use of thechloroquine drugs, but he promoted the use of ivermectin (briefly). Surely he must have received some remuneration for his fabrications?  While he cannot be prosecuted for scientific misconduct, as no government funding was used for his "studies," could he be prosecuted for fraud, as well as any entity which paid him for his labors. 

15.  A very outspoken physician had to face malpractice charges for prescribing hydroxychloroquine to treat several coronavirus patients.  The case has now been dismissed.

The doctor, Richard Urso, a Houston ophthalmologist, has been an outspoken proponent of hydroxychloroquine and is a member of America's Frontline Doctors.  This is the group that gained attention this summer for airing what some in the more mainstream medical community regarded as "outrageous claims" about the virus and its treatment. The group was banned from social media and had their website pulled down after receiving millions of views.

16.  A Senate hearing on the use of hydroxychloroquine for early treatment of Covid-19 was held November 19.  Great testimony!  And, it was claimed that Rick Bright PhD (former head of BARDA) obtained the EUA from FDA on hydroxychloroquine in order to shut the drug down and restrict it to hospitalized patients.  This is the most passionate Congressional hearing I have ever witnessed, with a true debate.  Please watch, especially the last hour.

17.  France and Italy have officially approved the use of HCQ in outpatients.

18.  Apparently #17 was not quite right, because today (12/11/20) it was reported that Italy's Council of State approved the prescribing of HCQ, with a doctor's prescription and informed consent, for Covid-19.

19.  Ivermectin may well be even better than the chloroquine drugs to treat Covid-19. There are no restrictions on prescribing or dispensing of the drug in the US.  It was featured in a Senate hearing December 8 on early Covid treatment.

However, its importation has just been banned in South Africa, suggesting that other national authorities may try to prevent populations from accessing the drug for Covid. In a replay of what was done to scare people about hydroxychloroquine, South African health authorities are warning the drug can kill you.  According to the label, the drug (when given at 50 times the recommended dose) killed mice.

Currently doctors can legally prescribe this drug in advance of a Covid diagnosis.

I was surprised to learn that there had been a run on the drug in April from veterinary medicine suppliers, leading to an FDA warning not to use veterinary ivermectin.  (The drug is over-the-counter for pets and livestock.) Its use only recently began to catch on, and the literature supporting it is very impressive.

20.  How India beat Covid.  Mary Beth Pfeiffer tells the story.

21.  El Salvador, Guatemala and Bolivia gave out medication kits to their citizens who developed Covid.  The kits contain acetaminophen, acetylsalicylic acid,  loratadine (antihistamine), ivermectin, azithromycin (antibiotic), vitamin C, vitamin D and zinc.

Friday, June 19, 2020

Even worse than 'Recovery,' potentially lethal hydroxychloroquine study in patients near death

What could be worse than giving potentially lethal doses of hydroxychloroquine to Hospitalized Covid-19 patients?

The REMAP-Covid study is using the same HCQ dose as the Recovery trial for 6 days.  But it is even worse for the following reasons:

  1. You have to be close to death, either on a ventilator or in shock, on pressor medications, to be included in the trial, according to the trial documents.  However, in a talk by Professor Anthony Gordon, less invasive means of oxygenation: HFNO (high flow nasal oxygen), CPAP (continuous positive airway pressure) and NIV (noninvasive ventilation) are listed as inclusion criteria.
  2. You may receive HCQ alone, or HCQ in combination with 2 more drugs, lopinavir/ritonavir.  Yet lopinavir/ritonavir predisposes to QT prolongation, as does HCQ, and the L/R drug label states, "Avoid use in combination with QTc- or PR-interval prolonging drugs."
  3. Patients who are in shock or on a ventilator may be unable to give their consent to enroll in a clinical trial. But the trial investigators have deemed that consent may not be required:  "For patients who are not competent to consent, either prospective agreement or entry via waiver of consent or some form of deferred consent can be applied, as required by an appropriate ethical review body."
  4. For patients too sick to swallow a pill, the drug will be administered via a feeding tube. This might entail an extra procedure for patients.
From the REMAP-Covid protocol page 23:
Dosing will be hydroxychloroquine administered by the enteral route. A loading dose is important because of the large volume of distribution. The loading dose will be 800 mg, administered 6-hourly, until 2 doses have been administered. Subsequently, starting 12 hours after the first loading dose, the dose will be 400 mg administered 12-hourly for 12 doses. The preferred method of administration is tablets swallowed whole but, if a patient is unable to swallow, crushed tablets dispersed in water can be administered via an enteral tube (a large bore gastric tube is preferred). No dose adjustment is required when hydroxychloroquine is administered via a gastric tube. No dose adjustment is necessary for renal dysfunction or concomitant use of renal replacement therapy. Clinicians should consider a dose adjustment in the presence of liver failure, however no dose adjustment is necessary for abnormal liver function tests in the absence of liver failure.
This is 2400 mg hydroxychloroquine in the first 24 hrs, over 1.86 g of the "base," then 800 mg/day for 5 more days or until discharge from the ICU, up to 6.4 g total. Dosing fails to take into account weight, renal or hepatic function (unless the patient is in liver failure) although there are good reasons why each should be considered, especially when using such high doses. 

The ignorant doctors who justified toxic doses by invoking 'volume of distribution' (which is 40,000 liters) failed to notice that the high 'volume of distribution' is an artifact related to the drug accumulating in tissue as opposed to plasma.  Drug levels in lung tissue are 200-700 times higher than in plasma, explaining why standard doses are effective. Furthermore, "renal and hepatic insufficiency lead to higher plasma concentrations for a given daily dose and raise the risk of toxicity."

WHO's consultant Weniger reported in 1979 that a single dose of 1.5-2 g of chloroquine "base" "may be fatal." A detailed discussion of therapeutic and toxic doses of chloroquine and hydroxychloroquine can be found in my article of June 14. I acknowledge that hydroxychloroquine is a bit less toxic than chloroquine.  But this trial studies the most fragile human beings, who have a 49% mortality at baseline. If the trial investigators were unsure of the right dose, they could have started low and gone slow as they watched the effect on the patient, as clinicians do. They could have tested the dose in a variety of ways. They could have read a toxicology text.

The REMAP-Covid study protocol acknowledges that the combination of lopinavir/ritonavir and hydroxychloroquine increases the risk of ventricular arrhythmia, but states that the risk is mitigated because patients this sick will be on cardiac monitors, with QTc monitoring.  However, it fails to say that the most likely arrhythmia in this setting is torsade de pointes, which is very difficult to treat.  Patients who are already critically ill are unlikely to survive if it occurs.  So why use an excessive hydroxychloroquine dose on these patients and risk it?  That is not explained.


The REMAP clinical trial is said to be ongoing in 200 sites in 14 countries. They include: 
Australia,   Belgium,   Canada,   Croatia,   Germany,   Hungary,   Ireland,   Netherlands,   New Zealand,   Portugal,   Romania,   Spain,   United Kingdom, USA.

All the online protocols have been stamped "Not for IRB (Institutional Review Board) submission," which makes one wonder what was changed when the trial arms were put before IRBs for approval. 


Four UK chief medical officers and the NHS Medical Director wrote a "Dear Colleague" letter, begging physicians to enroll their Covid patients in clinical trials, including 'Recovery' and REMAP, and discouraging "off-label" treatments for Covid outside of trials.  Did they know they were asking treating physicians to increase the risk of death for their patients?  Are they aware that as of today, June 19, the UK has had more deaths from Covid-19 than any country in the world outside the US and Brazil, with 5 and 3 times the UK population, respectively.  In other words, although many thousands of hospitalized Covid patients in the UK have been enrolled in clinical trials to identify optimal treatments (over 11,000 in the Recovery study alone), the UK has instead achieved the 2nd highest mortality rate (Covid deaths per UK person) on the planet. Belgium is 1st. Have the 4 Chief Medical Officers and the Medical Director of the National Health Service failed to notice this?


Why is public health being turned on its head?  REMAP-Covid is the third major multicenter clinical trial of hydroxychloroquine to give toxic doses to Covid patients.  The Recovery and Solidarity trials (with almost identical HCQ doses as REMAP) abruptly ended their hydroxychloroquine studies in the past two weeks, coincidentally soon after people began noticing the excessive doses, especially on Twitter.  Who or what is behind this concerted effort to maim or kill patients in order to to kill any appearance of benefit from hydroxychloroquine in the treatment of Covid-19?


Disclosure:  I am a longtime board member of the Alliance for Human Research Protection (AHRP), and our organization is taking the design and conduct of these clinical trials very seriously. The AHRP principles, ignored by those who planned and have conducted these trials, are the basis for good medical practice:

1.  Freedom of choice, to choose or refuse therapy
2.  Honest disclosure of risk and conflicts of interest
3.  Informed consent for every medical intervention
4.  Truth and scientific integrity.  Uncensored, open debate about scientific and empirical evidence

Thursday, June 18, 2020

Quick explanation of FDA's Emergency Use Authorization/Retraction for hydroxychloroquine and chloroquine

The Trump administration arranged on March 28 for 30-60 million tablets of hydroxychloroquine and certain (unapproved, unlicensed) chloroquine tablets to be donated by manufacturers to the National Strategic Stockpile (NSS) under an Emergency Use Authorization (EUA).  The official who signed the EUA is the FDA's Chief Scientist, Denise M. Hinton.  Denise Hinton is a nurse with a master's degree, an Air Force retiree who has achieved the rank of Rear Admiral in the Public Health Service. While she is probably very accomplished, I can find no scientific credentials.  Chief scientist at FDA?

The FDA document that granted the EUA authorization made clear that the hydroxychloroquine products that entered the NSS under this authorization may have expired or not met "requirements regarding current good manufacturing practice (GMP) otherwise applicable..."  

In revoking the EUA, Admiral Hinton wrote,
While HCQ that has been distributed from SNS is no longer authorized under the EUA for the authorized use to treat hospitalized patients for COVID-19, FDA-approved HCQ can be distributed in interstate commerce. The CQ products covered by the EUA are not approved by FDA for any indication and therefore cannot be legally introduced into interstate commerce.
In other words, some of the hydroxychloroquine, and all of the chloroquine covered in the EUA could not legally be sold in the US:  it was adulterated, according to the FDA definition. Yet millions of doses were released to the states for use by hospitals, for patients who were not entered into clinical trials. One has to wonder if patients who received adulterated chloroquine or hydroxychloroquine drugs from the national stockpile got the same benefit expected from drug that was not adulterated?

Pandemic countermeasures covered and distributed under an EUA provide almost complete liability protection to their manufacturers in the event of injuries. DHHS assumes limited product liability  under the Countermeasures Injury Compensation Program. 

The retraction of the EUA, therefore, means that currently available chloroquine drugs, obtained through commercial channels and not the EUA, should be of expected quality (no known GMP or expiration issues) and subject to ordinary regulations regarding liability.  This is a big plus for consumers, as the product should be more reliable and manufacturers are liable if it isn't.  It is also a huge plus for DHHS, which will no longer be liable for injuries that might develop from the use of inferior drugs under an EUA.

Furthermore, according to a statement by DHHS Secretary Alex Azar, medical practitioners are permitted to prescribe these drugs, obtained commercially, just as they would any off-label pharmaceutical.  It is estimated that 20% of prescriptions are for off-label use of approved drugs in the US.

While the meaning of the FDA's issuing and retracting the EUA has been hailed by the media as evidence the drug does not work for Covid, I think there is an entirely different explanation for FDA's moves.

1.  Only hospitalized patients or those entered into clinical trials testing hydroxychloroquine were allowed by FDA to receive the drug from the NSS under the EUA.  Almost all clinical trials of treatment waited until patients were severely ill before starting the drug. This ensured that few patients would receive HCQ, and get none from the national stockpile, at the onset of illness, when the disease is most treatable and the drug most likely to demonstrate an effect.

The EUA did not permit supply of the drug to outpatients.

2.  Providing adulterated, non-approvable and sometimes expired drugs to patients makes you wonder whether the drugs are adequately potent and safe. Might supplying questionable drugs further muddy the water about the efficacy of the chloroquine drugs, in addition to providing them to patients too late?

3.  Whenever an EUA is issued for a drug, let the patient beware!  The reasons to issue an EUA are to remove manufacturer liability from the product, and to allow use of products that may be substandard, and lack FDA approval.  Accepting a drug under an EUA takes away the right to seek damages from the manufacturer for an injury.  So going back to standard ways of obtaining drugs protects consumers.

4.  The FDA actions were explained and reported in a manner that made medical providers frightened to prescribe the drugs, limiting access to patients. This made it much harder to learn if the drug worked well when used early, in mild cases, at preventing much more severe illness. 


Sunday, June 14, 2020

WHO and UK trials use potentially lethal hydroxychloroquine dose--according to WHO consultant


The Solidarity Trial is a WHO-led conglomeration of many national trials of treatments for Covid-19. In March alone, the WHO collected $108 million from donors to cover costs of Solidairy clinical trials. Per the WHO:
As of 3 June 2020, more than 3500 patients have been recruited in 35 countries, with over 400 hospitals actively recruiting patients. Overall, over 100 countries have joined or expressed an interest in joining the trial, and WHO is actively supporting 60 of them...
The hydroxychloroquine arm of the Solidarity trials restarted enrolling patients June 3, after being halted May 25 by WHO Director-General Dr. Tedros Adhanom Ghebreyesus and the Executive Group of the Solidarity Trial. The hydroxychloroquine (HCQ) arm of the trials had been stopped after publication of the Lancet Surgisphere study, which claimed that patients who received chloroquine or hydroxychloroquine had 35% higher death rates, but the Lancet study was retracted 13 days after publication, as its data turned out to be fabricated. The HCQ Solidarity trials are currently ongoing.

●       Remdesivir
●       Hydroxychloroquine
●       Lopinavir with Ritonavir
●       Lopinavir with Ritonavir plus Interferon beta-1a.

Initially, the WHO planned to use neither cloroquine in its trials.  But multiple countries requested chloroquines, so both chloroquine (CQ) and HCQ were then added to the trial plan.  However, HCQ was felt to be a little safer, countries preferred it, so WHO dropped CQ from its trials.  Other clinical trials continue to test both CQ and HCQ against Covid-19. 

The doses were not specified on WHO's list of the drugs to be trialed, nor were they specified, surprisingly, in WHO's April 8 four-person "consultation on chloroquine (CQ) dosing". 

The Introduction of the Report of that meeting notes, 

"The chloroquine or hydroxychloroquine schedule selected for the trial includes two oral loading doses (250 mg per tablet CQ or 200 mg per tablet HCQ), then oral twice-daily maintenance doses for ten days. This meeting convened to discuss the appropriateness of the selected doses for the trial."

Last week, I was alerted to the fact that India's ICMR, its official medical research agency, had written to the WHO, telling WHO that the hydroxychloroquine doses being used in the Solidarity trial were 4 times higher than the doses being used in India.  Then I learned that Singapore had been hesitant to participate in the WHO trial due to the hydroxychloroquine dose.  

The UK "Recovery" trial was very similar to, but not part of, the international Solidarity conglomeration of clinical trials.  The Recovery trial ended its HCQ arm on June 4, reporting no benefit. In-hospital mortality of the 1542 patients receiving hydroxychloroquine was 25.7%, or 396 deaths, about 10% higher than those receiving standard care, a non-significant difference.

The UK Recovery trial Study Protocol notes it is funded in part by the Wellcome Trust and the Bill and Melinda Gates Foundation, and by UK government agencies.  The Protocol provides the doses of hydroxychloroquine used, on page 22.  Twitter users began to notice a dosing problem, with hashtag #RecoveryGate.  

The HCQ dosing regimen used in the Recovery trial was 12 tablets during the first 24 hours (800mg initial dose, 800 mg six hours later, 400 mg 6 hrs later, 400 mg 6 hours later), then 400 mg every 12 hours for 9 more days.  This is 2.4 grams during the first 24 hours, and a cumulative dose of 9.2 grams over 10 days.

Even more disturbing than this, babies weighing 5 kg could be given a dose of 300 mg HCQ in the first 24 hours in the UK Recovery trial, which is 233 mg of the base (47 mg/kg), nearly 4 times the recommended maximum.  One to two pills (200-400 mg) is "potentially fatal in a toddler". And authors from George Washington University say:
"Ingestion of 1-2 tablets of chloroquine or hydroxychloroquine is thought to predispose children under 6 years of age to serious morbidity and mortality...ingestions of greater than 10 mg/kg of chloroquine base or unknown amounts require triage to the nearest health care facility for 4-6 h of observation. There is very limited data on pediatric hydroxychloroquine overdoses and no reports of toxicity from 1-2 pills, but given its similarity to chloroquine, it also should be considered potentially toxic at small doses. Thus, similar recommendations should be followed for triage after accidental hydroxychloroquine overdose."

UPDATE July 21: The American Association of Poison Control Centers said on March 25:  

"These medications have a narrow therapeutic window, meaning that accidental ingestion of amounts that exceed recommended dosing can be extremely dangerous with toxicity including coma, seizures, cardiac dysrhythmias, low potassium levels, cardiac arrest and death. Even a single pill can be potentially life threatening to a child."
The quote from the WHO report on dosing, provided 9 paragraphs ago, seems to be deliberately vague regarding the dose used in the Solidarity trial, stating the number of milligrams per tablet, but not the number of tablets to be used.  The Solidarity trial is registered but the registration fails to specify dosages.

The registration of the Canadian portion of the Solidarity trial informs us of its HCQ dose: ten 200 mg tablets during the first 24 hours (800 mg initial dose, 800 mg 12 hours later then 400 mg every 12 hours for 9 more days).  This is 2.0 grams during the first 24 hours, and a cumulative dose of 8.8 grams over 10 days, or only 0.4 grams less than what Recovery used. The Norwegian Solidarity trial uses dosing identical to Canada.

Co-Principal Investigators of the Recovery trial, Drs. Peter Horby and Martin Landray, said they followed the WHO dosing. This is what their trial document says as well, on page 23. Landray also claimed in an interview with Paris Soir that the maximum allowed HCQ dose was "6 or 10 times" the dose used in Recovery, and that he was using the hydroxychloroquine dose that is used for amebic dysentery.  However, the accepted use for HCQ in amebiasis is only for a liver abscess and only then in pregnancy, when other drugs cannot be used.  That dose is 600 mg per day for 2 days, then 300 mg per day, considerably less than half the Recovery dose.  Co-Principal Investigator Peter Horby said that Paris Soir misinterpreted Landray's comments, but Paris Soir said Landray had confirmed what he told them in an email prior to publication.  Landray is a very busy man, too busy, apparently, to look up the proper dose of a drug he gave to over 1500 subjects, who were randomized to the treatment and had no say in the matter.

We know that in Brazil, both a high CQ dose and a low CQ dose were trialed, and by April 17 the high dose arm was stopped prematurely due to an excess of deaths, with 39% mortality (16 deaths in 41 subjects).  The mean age in the high dose group was 54.7. The high dose arm used 600 mg CQ twice daily for ten days, with cumulative dose of 12 grams. EKG changes typical of toxicity were seen in 25% of high dose subjects. The low dose trial continues in Brazil.

How is the drug hydroxychloroquine normally used?  For chronic daily use in systemic lupus erythematosus, rheumatoid arthritis or Lyme disease, patients receive between 200 and 400 mg daily, or a maximum of 5 mg/kg.  In acute Q fever, 600 mg daily may be given at the start of treatment. For acute attacks of malaria, 1,500-2,000 mg may be given over 3 days.  Professor Didier Raoult's group in Marseille used 600 mg daily for up to ten days in 1061 Covid-19 patients, and reported 8 deaths, a mortality rate of 0.75%, all over 74 years of age.  The mortality rate reported by Landray and Horby in the Recovery trial is 34 times higher.

We know from WHO's March 13 Informal consultation on the potential role of chloroquine that the Gates Foundation had been studying the drug's complex pharmacokinetics, and of the 25 participants at this meeting, 5 were from the Gates Foundation.  

The only treatment dose mentioned in the March 13 Informal consultation report was in a paragraph about preventive doses.  It said, "Higher doses would be considered for treatment, i.e., 10mg/kg base, followed by 5mg/kg twice daily for seven days." 

What is the "base"?  A 200 mg dose of hydroxychloroquine contains 155 mg "base" drug. Generally, a loading dose refers only to a high first dose, not to several high additional doses. However, the trial protocol used in Solidarity employs the same dose for all, rather than weight-based dosing.

What is a toxic dose?  All experts agree on this: "... chloroquine has a small toxic to therapeutic margin," according to Goldfrank's Toxicologic Emergencies.  The drug is very safe when used correctly, but not a lot more can potentially kill.  Prof. Nicholas White, a Wellcome Trust Principal Research Fellow and expert in malaria treatment, who attended both WHO consultations on the chloroquines, has confirmed this.  Careful monitoring of electrolyte levels and an EKG can prevent most problems.

The WHO hired a consultant to explore the toxicity of chloroquine in 1979. The consultant, H. Weniger, looked at 335 episodes of adult poisoning by chloroquine drugs.  Weniger on page 5 notes that a single dose of 1.5-2 grams of chloroquine base "may be fatal." 

According to Browning and Goldfrank, the pharmacokinetics and potency of chloroquine and hydroxychloroquine are almost identical, while the maximum used chronic dose of chloroquine is 3.5 mg/kg. 

The Recovery trial used 1.86 grams hydroxychloroquine base (equal to 2400 mg of hydroxychloroquine) in the first 24 hours for treatment of already very ill, hospitalized Covid-19 patients.  The Canadian and Norwegian Solidarity trials used 2,000 mg of HCQ, or 1.55 grams of HCQ base in the first 24 hours. Each trial gave patients a cumulative dose during the first 24 hours that, when given as a single dose, has been documented to be lethal. (The drug's half-life is about a month, so the cumulative amount is important.)  

The doses used in these trials are not recommended for therapy of any medical condition, which I confirmed with Goodman and Gilman's Pharmacology textbook, the drug's US label, and the online subscription medical encyclopedia UptoDate. 

Excessive, dangerous HCQ dosing continues to be used in WHO's Solidarity trials. While the Solidarity trials have an "adaptive" design which allows midstream protocol changes, no lessons were learned from the Brazil or Recovery trials' experience with excessive dosages. Solidarity has not reduced its HCQ dosing, although it can do so at any time.  The Solidarity trials are not, in fact, testing the benefits of HCQ on Covid-19, but rather are testing whether patients survive toxic, non-therapeutic doses.

The WHO Solidarity trials, in order to rapidly enroll patients and spare clinicians a lot of paperwork, collect only limited information on side effects.  No information has yet been provided regarding causes of death in the completed hydroxychloroquine arm of the Recovery trial, in which 396 patients died, and may never be.  

The Solidarity trial design being employed by WHO obscures whether mortality is due to drug toxicity (in which case, one would expect death to be due to an arrhythmia, neuropsychiatric effects, or hypoglycemia) as opposed to death due to Covid-19.

In fact, the lack of safety data being collected is downright scary.  Here is a description of the data obtained on patients enrolled in Solidarity, as reported in Science magazine:
The participant has to sign an informed consent form that is scanned and sent to WHO electronically. After the physician states which drugs are available at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19.  
“After that, no more measurements or documentation are required,” says Ana Maria Henao Restrepo, a medical officer at WHO’s Emergencies Programme. Physicians will record the day the patient left the hospital or died, the duration of the hospital stay, and whether the patient required oxygen or ventilation, she says. “That’s all.”
Although the preponderance of opinion tilted towards a reasonable benefit risk profile for the intervention, there was some scepticism about what was considered a ‘minimalistic safety data collection’ currently included in the protocol. 
The high dose regimen being used in these trials has no medical justification.  The trial design, with its limited collection of safety data, makes it difficult or impossible to identify toxic drug effects, compared to a standard drug trial.  This is completely unethical.

Excessive dosing makes it impossible to assess therapeutic benefit, if any, of HCQ. Furthermore, because there are over 400 trial sites, and relatively few subjects in each, unexpectedly high trends in mortality are likely to be missed at individual trial sites.

Finally, testing the drug only in hospitalized patients means that the window of time during which HCQ would be expected to provide the most benefit, early in the illness when viral titers are rising, has passed.

Didier Raoult's group has recently published on the major differences in treatment and outcomes patients receive when placed in "big data" studies vs. receiving individualized care for Covid-19.

As I was completing this article, the FDA announced it was withdrawing its Emergency Use Authorization for hydroxychloroquine in Covid-19, because the "known and potential benefits" no longer outweigh the risks of the drug. The FDA cited data from the Recovery trial in its announcement. I discuss the implications here.

To sum up:
  1. 1.  In the UK Recovery trial, and in WHO Solidarity trials, HCQ is used in a non-therapeutic, toxic and potentially lethal dose.
  2. 2.  HCQ is furthermore being given, in clinical trials, too late in the disease course to determine its value against SARS-CoV-2.
  3. 3.  Collection of limited safety data in the Solidarity trials serves to protect trial investigators and sponsors from disclosures of expected adverse drug effects, including death.
  4. 4.  It appears that WHO has tried to hide information on the hydroxychloroquine doses used in its Solidarity trial.  Fortunately, the information is discoverable from registries of its national trials.
  5. 5.  The conclusions to be drawn are frightening:
   a)  WHO and other national health agencies, universities and charities have conducted large clinical trials that were designed so hydroxychloroquine would fail to show benefit in the treatment of Covid-19, perhaps to advantage much more expensive competitors and vaccines in development, which have been heavily supported by Solidarity and Recovery trial sponsors and WHO sponsors.

   b)  In so doing, these agencies and charities have de facto conspired to increase the number of deaths in these trials.

   c)   In so doing, they have conspired to deprive billions of people from potentially benefiting from a safe and inexpensive drug, when used properly, during a major pandemic.  This might contribute to prolongation of the pandemic, massive economic losses and many increased cases and deaths.


Update June 18:  I sent a tweet to WHO Director General Tedros informing him of these findings 3 days ago.  I also emailed WHO's Dr. Restrepo, inquiring about the doses used in the Solidarity trial.  I am very pleased to report that WHO stopped this deadly trial yesterday, with no fanfare.  WHO claimed the decision was made on the basis of the Recovery trial result and a Cochrane review, as well as WHO data.  One wonders if the DSMB was bypassed again, as occurred on May 25 when WHO halted its HCQ arm for the first time.

I had pointed out that if trial investigators had not disclosed to subjects the known risks associated with the high HCQ doses used, the investigators and WHO would be liable for damages. 

I like to think my investigation has helped save some lives.