AAPS News June 2020 – AAPS Sues FDA

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Volume 76, no. 6  June 2020

While more than 100,000 American deaths have been attributed to COVID-19, 150 million doses of hydroxychloroquine, donated by manufacturers, are deteriorating in government warehouses. There is an aggressive campaign to portray HCQ at first as “unproven” and now as also “unsafe.” Following the lead of the Food and Drug Administration’s Emergency Use Authorization (EUA), which prohibits use of HCQ being stored in the Strategic National Stockpile (SNS) outside of hospitals, most states have placed unprecedented restrictions on physicians’ ability to prescribe HCQ “off-label” for COVID-19 (tinyurl.com/y7oc65gn).

In its lawsuit (http://aapsonline.org/hcqsuit), filed in June in federal court in the Western District of Michigan, AAPS asks the court to enjoin the enforcement of the restrictions in the Mar 28 EUA; to make available and distribute promptly, for the benefit of the public, HCQ from the SNS; and to enjoin FDA, the Biomedical Advance Research & Development Authority (BARDA), and HHS from impeding the distribution, sale, or purchase of HCQ by members of the public during the COVID-19 pandemic.

Through a biased, improper process, FDA officials from prior administrations acted contrary to the wishes of President Donald Trump by arbitrarily limiting use of HCQ. Rick Bright, Ph.D., former head of BARDA, who is an outspoken critic of President Trump and is personally opposed to making HCQ widely available, distorted the agency process to unjustifiably limit access.

Bright is also biased by his pre-conceived opinion in favor of an expensive, proprietary antiviral medication developed by Gilead Sciences, remdesivir. He repeatedly advised HHS officials to acquire the existing doses, to secure future doses as they were produced, and to “on-shore” all steps of the remdesivir supply chain.  These actions should have caused his recusal from the decision-making process about HCQ.

According to Bright’s whistleblower complaint against the Trump Administration, Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, also played a pivotal role in pushing for the EUA. Woodcock simultaneously occupied a top position in a public-private operation designed to approve new vaccines for COVID-19, and she reportedly communicated with a Wall Street analyst concerning such development.

A safe, inexpensive treatment or prophylactic would diminish demand for a new drug or vaccine.

Safety

HCQ has been approved as safe by the FDA for 65 years, and is safer than numerous medications that are widely available over-the-counter (OTC), including anti-depressants, sleeping pills, bronchodilators, Tylenol, and even aspirin.

The “safety profile” with respect to new uses of a medication previously approved by the FDA is virtually never studied, and there is no rational basis for delaying new uses of previously approved medication by requiring such studies.

Harvey A. Risch, professor of epidemiology at the Yale School of Public Health and Yale School of Medicine, stated: “Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users.” He noted that 10,000 Americans are dying each week from COVID-19. Five studies,  he writes, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. He concluded that “these medications need to be widely available and promoted immediately for physicians” (Am J Epidemiol, May 27, 2020, https://tinyurl.com/y9yfb2h9).

Dr. Jon Giles, an epidemiologist and rheumatologist at Columbia University Department of Medicine, told National Public Radio (NPR) that HCQ is a “very, very safe drug; it’s been used for over 75 years. When I give someone [HCQ], I don’t get an ECG or do blood monitoring” (tinyurl.com/y7enya9w).

More than 25 articles since 1982 published in peer-reviewed medical journals have reported on the safety of HCQ, and these articles are included in the PubMed database.

Harms of Restricting Access to Prevention

Dr. Risch states that “an outpatient treatment that prevents hospitalization is desperately needed [for COVID-19].”

In addition to the preventable mortality and morbidity, devastating harm results from lockdowns and fear of acquiring an untreatable illness. The AAPS complaint states that irrational interference with the use of HCQ as a prophylaxis interferes with the political process, for example, national political conventions, and with rights to associate, assemble, and attend religious services.

Defendants violate the equal protection guarantee implicit in the Due Process Clause of the Fifth Amendment to the U.S. Constitution by discriminating based on a patient’s hospitalization status, illness status, and access to clinical trials.

Defendants lack the authority to override the discretion of a  medical professional to prescribe off-label uses of FDA-approved drugs. The decision-making underlying the EUA was tainted by bias, and thus it is arbitrary and capricious. The Administrative Procedure Act directs courts to “hold unlawful and set aside agency action…found to be … contrary to constitutional right, power, privilege or immunity.” 5 U.S.C. § 706(2)(B).


Misinformation Keeps COVID-19 Alive

In countries that started using HCQ for prophylaxis and early treatment, death rates soon began to decrease, and the ratio of recoveries to deaths increased dramatically, e.g. in Cyprus, Costa Rica, Russia, Monaco, Algeria, Turkey, Israel, Italy, Peru, Honduras, Indonesia, United Arab Emirates, South Africa, and Portugal. See graphs on twitter.com; search @Covid19Crusher.

But WHO has now recommended that use of chloroquine (CQ) and HCQ for COVID-19 be suspended, and is also suspending their use in a global clinical trial called Solidarity (tinyurl.com/y935al4c). “What a difference one week makes in medical practice,” opined Milton Packer, M.D., a consultant for many drug companies, who argues in MedPage Today that prescribing HCQ is “practicing politics” (tinyurl.com/yajxf9bx).

The  sudden focus on safety stems largely from a heavily publicized Lancet article (https://tinyurl.com/ydg4j2td) that failed to confirm benefit and claimed decreased in-hospital survival and increased ventricular arrhythmias with CQ or HCQ.

Does Lancet practice politics? One can point to about 40 tweets by editor Richard Horton that appear to be anti-Trump, pro-China, or pro-WHO (twitter.com/richardhorton1).

From Apr 14, when the last patient was hospitalized, until May 22, when Trump pushed for lifting shutdowns, there were only 5 weeks for warp-speed publication. More than 120 researchers and medical professionals from around the world signed an open letter to the four coauthors and the editor with questions concerning the statistical analysis and data integrity (tinyurl.com/ycp94psp), including refusal to release codes or data and the lack of an ethics review (tinyurl.com/y82pw9c8). Lancet issued an “expression of concern” (tinyurl.com/y9zlw8fp), as did NEJM regarding the database used in an article that had three of the same authors as the Lancet article (tinyurl.com/yc6x6z9d).

The Lancet article cited an influential Brazilian study that found higher mortality together with more instances of QTc interval greater than 500 milliseconds in the “high-dosage” group of severely ill COVID-19 patients treated with CQ (JAMA 4/24/20, https://tinyurl.com/y98yv3ho). An open letter signed by about 25 Brazilian scientists, whose work has been cited more than 69,000 times, noted that lethal doses of CQ were given to “debilitated patients, many in severe conditions and with comorbidities.” They criticized methodologic errors in this and other studies in prestigious journals, such as “randomizing” higher-risk patients to higher doses (https://tinyurl.com/yc8kjrgq).

“These studies indicate that some scientists either forgot how ‘science’ is done or that there is a huge effort to disprove, whatever it takes, that HCQ works,” they conclude.

The study’s disregard of ethical standards is under judicial investigation by the Ministério Público Federal (Portaria Nº40 de 20 de Abril de 2020), and is being followed by other branches of the Brazilian Government, states Prof. Paolo Marinho de Andrade Zanotto of the University of São Paulo in a letter to JAMA editor-in-chief Howard Bauchner, demanding retraction of the article.


“The…texts were not only the fount of professional knowledge but an insurance policy against possible failure…. Diodorus saw this clearly. ‘If they follow the rules of the law…from the sacred book and yet are unable to save their patient, they are absolved from any charge: but if they go contrary to the law’s prescriptions, they must submit to a trial with death as the penalty.’”

Eugen Strouhal, Life of the Ancient Egyptians


Nations Respond to WHO on CQ and HCQ

Indonesia, the world’s fourth most populous nation, is considering how to react. It had told doctors to use the drugs to treat all COVID-19 patients with symptoms from mild to severe. The country has ramped up production of HCQ since March, granting two dozen licenses to local manufacturers, who have churned out millions of doses (https://tinyurl.com/yaq5edq2).

France, Italy, and Belgium moved to halt the use of HCQ (tinyurl.com/ybkpm3a5). Spain will not, and Germany is at this time undecided (tinyurl.com/y7ssdxmu). The Indian Council of Medical Research (ICMR) backed the use of HCQ as a preventive against coronavirus, after the WHO action (tinyurl.com/yba5g7uh). Seeing success with CQ or HCQ, Niger (tinyurl.com/y7as9vud), Algeria (tinyurl.com/yd2acram), and Morocco (tinyurl.com/y7dm4m9j) will not stop using them.

President Trump announced that he is ending U.S. membership in WHO. The U.S. has sent Brazil 2 million doses of HCQ to be used as a prophylactic and early treatment for medical workers who are infected with COVID-19 (tinyurl.com/y92rh4t8).


LancetGate?

The second  of the four coauthors on the Lancet study, Sapan Desai, is CEO and owner of Surgisphere, source of much of the data and subject of an investigative report published May 29 (https://tinyurl.com/ychr2e9f). Lancet and NEJM retracted the articles at the request of other authors, who stated that Surgisphere was not cooperating with an independent data review (https://tinyurl.com/y8n8asqp).


NEJM vs. HCQ Prophylaxis

 In an RCT trial of HCQ for post-exposure prophylaxis of COVID-19, researchers concluded that “after high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure” (https://tinyurl.com/y92dpqyk). Points to note:

17% fewer illnesses with HCQ: A new illness compatible with COVID-19 developed within 14 days in 49 of 414 (11.8%) of subjects receiving HCQ and 58 of 407 (14.3%) getting placebo. The difference was not statistically significant.

Underpowered: To detect a 50% difference with 90% probability would have required 750 subjects in each group. Recruitment was stopped early for “futility.”

No arrhythmias or serious adverse effects: There was one hospitalization in each group and no deaths.


AAPS Calendar

Sep 30-Oct 3. 77th Annual Meeting, San Antonio, TX

Sep 29-Oct 2. 78th Annual Meeting, Pittsburgh, PA


No FDA Authority to Regulate Medical Practice

FDA has expressly recognized the freedom that medical professionals possess to use and prescribe approved drugs off-label: “[O]nce a [drug] product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens of patient populations that are not included in approved labeling.” 59 Fed. Reg. 59, 820, 59, 821-22 (Nov. 18, 1994).

“FDA regulations have attempted to strike a balance between giving physicians the freedom to use their best clinical judgment and preventing drug manufacturers from inappropriately influencing prescribing practice” (https://tinyurl.com/yaop3m75).

Written prescriptions do not have a place to write the indication, and this has not traditionally been required. Physicians argue that it violates patients’ privacy.


Engineering the “New Normal”

Former CMS Administrator Donald Berwick, M.D., of the Institute for Healthcare Improvement, outlines the “choices” to be made in a post-COVID-19 world (JAMA 6/2/20).

“Is this the time for equity, when the evidence of global interconnectedness and the vulnerabilities of marginalized people will catalyze at last the fair and compassionate redistribution of wealth, security, and opportunity from the few and fortunate to the rest? This virus awaits an answer. So will the next one,” he writes.

Perhaps the new normal will “embrace trusted authority as foundations for reducing harmful, wasteful, and unscientific variation in care.” Will the office visit, for many traditional purposes, become a dinosaur? [One unspoken feature of the virtual visit is that the telehealth platform will likely record everything and enable enforcement of conformity.]

Since people can’t travel, the reduction in carbon emissions has made the planet “a healthier celestial body.” Will policymakers see that we don’t return to normal production and commerce?

Will the new order [central planning, socialism, impoverishment, less mobility] “accomplish more for human health and well-being than any vaccine or miracle drug ever can”?


Mandatory COVID-19 Vaccine Recommended

The Health Law Section of the New York State Bar Association (NYSBA) recommends that COVID-19 vaccination should be mandatory for all New Yorkers except those whose doctors exempt them, “as soon as a safe and viable vaccine becomes available,” citing Jacobson v. Massachusetts, the 1905 U.S. Supreme Court case that upheld the authority of states to enforce compulsory vaccination laws. “The current pandemic shows us how unsafe we all are when we face a virulent contagious disease without a safe and effective vaccine, widely administered,” said attorney Hermes Fernandez, (https://tinyurl.com/y83dfqxv).

NYSBA also proposes mandatory ethical [rationing] guidelines for all providers in case of shortages (tinyurl.com/yb4gejez).

The goal of the Warp Speed vaccine effort is to vaccinate 300 million Americans by January. Tests in hamsters and monkeys will help winnow down leading candidates. “If something’s really bad, we’ll get rid of it,” a program official said. Leading technologies, delivering code for the virus’s spike protein via mRNA or an adenovirus, have yet to lead to an approved vaccine (Science 5/15/20).


Tip of the Month: Prescriptions do not have to be filled by pharmacies in your state. If local pharmacies refuse to fill your prescriptions for hydroxychloroquine, then recommend use of online pharmacies located elsewhere in the United States. They are also less likely to file a false complaint against you with your state medical board, which some jealous or politically motivated local pharmacists have done against physicians. Not all states require their pharmacies to receive a diagnosis on a prescription for hydroxychloroquine, and Texas recently dropped its requirement when physicians can cite a privacy concern.


Medicaid Is a Loan

At the time that states were considering the Medicaid  expansion option in the Affordable Care Act (ACA or ObamaCare), AAPS  warned about the Estate Recovery Program that Bill Clinton signed into law as part of the 1993 Omnibus Deficit Reduction Act (AAPS News, April 2013). Buried in the fine print in the enrollment form, p 20 of MassHealth’s 34-p form, is the notification that Medicaid may collect repayment from the deceased’s estate for funds Medicaid paid for nursing home care. States vary in their enforcement and in the exemptions they allow. Some expand the recovery efforts to other medical expenses, such as every doctor visit, prescription, or procedure that Medicaid paid for. This can be an extreme hardship for financially strapped families who were expecting to receive an inheritance (Atlantic, October 2019, https://tinyurl.com/y3sh68sb). People who lose their insurance because of the COVID-19 shutdown and are thinking of resorting to Medicaid need to be aware of this.


England Presumes Consent for  Organ Donation

A new English law grants the government authority to take organs from those certified as dead unless they specifically registered that they do not want their organs to be used (tinyurl.com/yc9by8wn). While the UK does not have a law on brain death, the Code of Practice of the Academy of Royal Medical Colleges explicitly endorses the view that irreversible apneic unconsciousness should be recognized as death. In contrast to the U.S. position, the Code does not insist that brain death is the same as biological death. It states that while “the body may continue to show signs of biological activity…these have no moral relevance to the declaration of death.”

 The tests used today to diagnose brain death are virtually the same as proposed in 1968. The evidence base is severely limited.  In particular, studies suggest that the bedside tests used to diagnose unconsciousness in the vegetative state may be wrong as much as 40% of the time. In addition, the safety of the apnea test has been questioned (JAMA 6/2/20, tinyurl.com/yb9v954r).


Automatic DNR for COVID-19?

Can front-line physicians unilaterally withhold cardiopulmonary resuscitation (CPR)? AMA’s medical ethics experts say it may be ethically justifiable to override the patient’s or the surrogate’s wishes at times such as the COVID-19 pandemic for reasons beyond the probable lack of benefit to the patient. Protecting the ICU from being maxed out and protecting workers from infection  are two possible justifications (https://tinyurl.com/yaf8m36x).


Correspondence

Who Wrote the Guidelines? NIH guidelines for treating COVID-19 do not recommend using HCQ. Note that despite all the insistence on having randomized controlled trials (RCT) so that “science” can guide treatment decisions, the recommendations are based entirely on expert opinion. Panel members include CDC, Dept. of Defense, FDA, and others. At least 10 of the others receive support from Gilead Sciences (https://tinyurl.com/yckgx88w)—the maker of remdesivir.

 Lawrence R. Huntoon, M.D., Ph.D., Lake View, NY


Small Business in N.C. The N.C. Chamber of Commerce says that 50% of small businesses in the state will go out of business permanently. The draconian measures devised by state and local officials pick winners and losers—the ultimate form of discrimination. Some are allowed to remain in business and to work. Others are not. Like in the Twilight Zone episode “The Obsolete Man,” Gov. Roy Cooper is the man at the elevated podium at the head of a long table deciding to liquidate “non-essential” businesses.

 Joseph Guarino, M.D, Reidsville, NC


Fauci’s Cytokine Storm. Severe cases of COVID-19 are at least partially caused by the cytokine storm—the immune system overreaction that destroys vital tissue. Cytokine storm is a metaphor for the lockdown/spacing/school-shuttering overreaction orders and diktats advised by Anthony Fauci that were based on scaremonger modeling. The economic havoc created by the unprecedented quarantines made the treatment more harmful than the target disease. In Europe, best-selling newspaper Das Bild said the lockdowns were a “huge mistake.” University of Hanover Professor Stefan Homburg said: “The damage is increasing every day; the bans must be lifted immediately.”

John Dale Dunn, M.D., J.D., Brownwood, TX


The Long March. When I was 11 and a fifth grader in a suburban New York elementary school, our teacher had us writing essays about what a great liberator Fidel Castro was. To the best of my former-child recall, less than 2 years later Castro publicly proclaimed, “I am a Marxist-Leninist and will be until the day I die.”

Stuart Faxon, Tucson, AZ


Corona Communism. How quickly Americans succumbed to loss of liberty—and property, as all but “essential” businesses (based partly on their crony capitalist size) were destroyed. Where will defectors from globalism go now (tinyurl.com/y95lr64o)?

Ileana Johnson, Ed.D., ileanawrites.blogspot.com


Addio, Italy! The virus will probably be the last nail in the coffin of the economy of my ancestral home. The nails started being hammered at the time of unification at the end of the 19th century, with a series of bad governments almost from the start. Before the virus, about a third of the Italian economy was off the books, due to the high value-added tax (VAT) and mistrust in government, but the 3.7 million people working in the shadow economy are now excluded from the state’s welfare safety net. I wonder how many Americans work in the shadow economy.

Craig Cantoni, Tucson, AZ


Debt Status. A new real-time debt clock with country comparisons is now active at Commodity.com/debt-clock. Compare with USGovernmentSpending.com.

Joel Foster


Operation Warp Speed. It has always taken years to make a vaccine, especially for a virus that just emerged from bats. A little research reveals the following: Moncep Slaoui, just appointed to lead the coronavirus vaccine project, is an investor and on the Board of Moderna, which has just been approved to start a Phase 2 trial. It had already started a clinical Phase 1 trial on Mar 16, which means that by then they had already done animal testing to get all the approvals needed for a human trial. Although Dr. Fauci keeps reminding us that we still don’t know much about the SARS-CoV-2 because it didn’t exist until a few months ago, he and the National Institute of Allergy and Infectious Disease (NIAID) approved that trial. According to Moderna’s webpage, the first clinical batch, which was funded by the Coalition for Epidemic Preparedness (CEPI), was completed on Feb 7 and was shipped to NIH on Feb 24, only 42 days from sequence selection. The first participant in the NIAID-led Phase 1 study of mRNA-1273 was dosed on Mar 16. When did anybody think that we needed to start a vaccine for a virus that as of Feb 7 was barely even out of China? How long had someone been working on it? 

On Jan 17, just two days after the first deaths were even reported in China, Dr. Richard Hatchett, the CEO of CEPI, apparently clairvoyant, was already thinking of ways to get out a vaccine. CEPI and the WHO were fortunate that the Chinese CDC had already discovered and shared the detailed genomic data of this new virus. Hatchett said the genome data is essential to fast-track work on a vaccine using cutting-edge technology platforms that can be adapted to fight specific diseases.  

Could there be hidden agendas and powerful interests?

Tim Ryan, M.D., Cartersville, GA