We begin our look at the ongoing hydroxychloroquine (HCQ) saga with a July 10 piece from the often anti-Trump Washington Post titled, “Touting criticized study, White House presses FDA to authorize hydroxychloroquine — again.” White House trade advisor Peter Navarro is leading an effort to get the FDA to “reverse course” and grant a second EUA for the drug. He denounced “media-induced hydroxy hysteria,” and is informed by the recent Henry Ford Health System findings. But, “Scientists have widely criticized the new study…as flawed.” Navarro points out that our Strategic National Stockpile has 60 million doses of HCQ which cannot be used without another EUA. Trump sees the Detroit study as a vindication of his position, and anonymous sources report that he wants the drug “sent to hospitals across the country….” If future studies are positive, “there is blood on the media’s hands” for unfair reporting.
According to the Post, FDA’s March EUA was based on, “scant evidence.” The Ford study looked at 2,400 hospitalized patients, and found a 50% lower death rate in the HCQ group and “no safety problems.” Critics point out that the study was observational and not a randomized trial. And three other major studies have found no benefit. Also, more of the Ford HCQ group got a steroid–a possible confounding factor. The authors made statistical adjustments for this issue, “but other scientists said the methodology wasn’t clear and that it is very hard to correct studies in that way.” And while doctors can still prescribe the drug for COVID-19 “off label,” FDA’s warning and EUA withdrawal, “effectively killed demand.” Peter McCullough, internist at Baylor University Medical Center, agrees with the White House: “This is the public health crisis of the century, and doctors should not have barriers.”
The Lancet Used Bad Data to Show Harm from HCQ
Moving on, back on June 4 Stat News published an important article about HCQ safety. They note that The Lancet “retracted an influential study that raised alarms about the safety of the experimental Covid-19 treatments chloroquine and hydroxychloroquine amid scrutiny of the data underlying the paper.” An hour later, “the New England Journal of Medicine retracted a separate study, focused on blood pressure medications in Covid-19, that relied on data from the same company.” The Lancet authors Mandeep Mehra of Brigham and Women’s Hospital, Frank Ruschitzka of University Hospital Zurich, and Amit Patel of University of Utah said, “We can no longer vouch for the veracity of the primary data sources.” Also, earlier that week, “researchers reported the results of the first gold-standard clinical trial of hydroxychloroquine in COVID-19, concluding that it did not prevent infections any better than placebo.”
Experts raised concerns “after noticing inconsistencies in the data,” and asked the firm which “compiled and analyzed the data, Surgisphere, to explain how it sourced its data.” Some of the authors asked for an audit, and said “that Surgisphere was not cooperating with the independent reviewers and would not provide the data.” They concluded that they “were not able to conduct an independent and private peer review,” and then sought to withdraw the study. The NEJM research also relied on Surgisphere data, and those researchers wrote, “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”
Are Overdosing and “Big Data” the Problems? Website Offers Key Leads, but Delves into Conspiracy
While the source, Age of Autism, appears biased against mainstream science, their article, “WHO ‘Solidarity’ and UK ‘Recovery’ Clinical Trials of Hydroxychloroquine using Potentially Fatal Doses,” offers interesting leads in the HCQ story. The story is by Dr. Meryl Nass, known for advocating against the anthrax vaccine. He points out that India’s ICMR had warned WHO that the Solidarity doses “were 4 times higher than the doses being used in India.” The Recovery doses added up to 2.4 grams HCQ in 24 hours and 9.2 grams over 10 days. The Canadian portion of the Solidarity trial used similar doses.
Brazil trialed both “a high HCQ dose and a low HCQ dose,” and the high dose arm was terminated early for excess deaths. This arm used 600 mg HCQ twice daily for a ten-day cumulative dose of 12 grams. “The low dose trial continues in Brazil.” Normally, HCQ dosing for lupus or Rheumatoid arthritis tops out at 400 mg per day. For acute malaria, 2,000 mg may be given over a three-day period. According to Goldfrank’s Toxicologic Emergencies, all experts agree that “chloroquine has a small toxic to therapeutic margin.”
Back in 1979, WHO consultant H. Weniger examined HCQ toxicity. He found that a single dose of 1.5-2 grams of HCQ base “may be fatal.” The Recovery trial dosed at 1.86 grams HCQ base (equal to 2,400 mg HCQ) in the first 24 hours, over the potentially fatal dose. “The Canadian and Norwegian 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.)” Age of Autism argues that there was no medical justification for the high dosages, and “Excessive dosing makes it impossible to assess therapeutic benefit, if any, of HCQ.”
The article also cites “Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative meta-analysis between the Big data and the real world,” from Science Direct. This later article finds “major differences in treatment and outcomes patients receive when placed in ‘big data’ studies vs. receiving individualized care for Covid-19.” The article posits that “Big data are lacking basic treatment definitions and are linked to conflict of interest.” In other words, folks in a trial may not get as good care as patients not in a trial. Age of Autism closes its article in a conspiratorial manner that costs it some credibility: “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.” Of course, this is reckless to make such an allegation.
TrialSite News is concerned about the politicization of our public health decisions, and we will continue to provide HCQ news as it develops.