Did HCQ Really Cause 17,000 Deaths? Experts Weigh in on Flawed But Highly Touted Study

From Childrens Health Defense, today. Pleased to see the article used a lot of my original research on HCQ from 2020.

https://childrenshealthdefense.org/defender/hydroxychloroquine-flawed-study-deaths-covid/

I suggest you read this at the link above, because several videos and tweets are cut out of what I reproduced below, including one of Joe Rogan reporting what Bobby Kennedy responded when he asked about this trial.

A new French retrospective study claimed hydroxychloroquine caused nearly 17,000 deaths when used on hospitalized COVID-19 patients. But experts contended the analysis relied on flawed data, ignored evidence showing efficacy with early outpatient treatment, and amounted to a political attack on HCQ pioneer Dr. Didier Raoult.

By John-Michael Dumais

Nearly 17,000 people in the U.S. and five other countries “may have died” early in the pandemic because they used hydroxychloroquine (HCQ) to treat COVID-19, according to a paper published in the February 2024 issue of Biomedicine & Pharmacotherapy.

Major media outlets, including Politico, The Hill and Forbes ran with the headline.

However, physicians and scientists interviewed by The Defender said the study’s authors based their conclusions on flawed data and ignored the large body of evidence showing the efficacy of HCQ for early, outpatient treatment of the virus.

The French study is a retrospective meta-analysis of 44 papers with data on hospitalized patients in the U.S., France, Belgium, Italy, Spain and Turkey from March through July 2020.

The researchers stated that mortality rates varied significantly from across hospitals and regions, and acknowledged they could not account for how these rates were influenced by “age, sex, comorbidities, ICU capacity, improvement in COVID-19 management” and other factors.

For 90% of the total hospitalizations reviewed, the researchers had to guess at the rate of patients exposed to HCQ, offering ranges from a low of 16.3% to a high of 99.1%. In the U.S., which accounted for 73% of the study’s data set, that number ranged from 16.3% to 75.9%, or between 144,750 and 674,020 patients.

They also had to guess how much HCQ or its analog chloroquine (CQ) was administered. Furthermore, they readily admitted, “The effect of HCQ on mortality was the main source of uncertainty for the proposed estimates” and that those estimates could be overstated by a factor of 5 (i.e., only 3,000 may have died) or understated by a factor of 2 (i.e., 30,000 may have died).

The study also said nothing about the impact of other drugs patients may have received, such as remdesivir, or whether patients were put on ventilators prior to dying. These two factors alone — widely practiced in U.S. hospitals during the pandemic — are known to have significantly increased COVID-19 mortality.

Dr. Peter McCullough told The Defender the 44 studies used in the meta-analysis were “heterogeneous” and that “Nonrandomized, retrospective cross-sectional cohorts created from administrative data demonstrated confounding by indication.”

In other words, this type of look-back study could not reliably tell if HCQ had an effect or not as it is unable to control for the various ways the treatment and non-treatment groups differed from the start, nor could it account for the different methods or results used in the studies.

“That means hospitalists desperate to help patients administered HCQ too late in the course and patients were too far gone,” McCullough said. “In this circumstance, it wasn’t the HCQ that caused death — it was COVID-19 illness.”Harvey Risch, M.D., Ph.D., professor emeritus of epidemiology at Yale, told The Defender that such studies must address not just the risks associated with a medication, but the additional risks associated with patients’ pre-existing conditions. He said:

“In the case of hospital use of HCQ, studies must adjust for the various chronic conditions that predispose to HCQ use, such as obesity, diabetes, chronic cardiac diseases, chronic kidney diseases, cancer history, immunocompromise, etc.

“I don’t see that the cohort studies used as data for analysis in this paper have been able to do that, so conclusions about HCQ associations as actually causal are inappropriate and unsupported.

“Virtually every nonrandomized study that I have seen over the last four years shows that patients taking HCQ tend to have worse health and worse chronic conditions. That makes this paper’s assumption that HCQ use is causally associated with increased mortality risk fiction, which makes the study’s conclusions fiction.”

Risch also said, “Hospitalized COVID-19 is a totally different disease than outpatient COVID-19.” He said the French study “is irrelevant for that,” and that his work showing the effectiveness of HCQ is with outpatient use “to prevent hospitalization and mortality.”

Joe Rogan on his Tuesday episode of “The Joe Rogan Experience” shared what Robert F. Kennedy Jr., Children’s Health Defense chairman on leave, told him about the study:

Studies cited for odds ratio used ‘potentially fatal’ HCQ dosages

The researchers derived the 1.11 (11%) odds ratio they used to estimate HCQ-linked mortality from a 2021 meta-analysis of randomized trials.

That meta-analysis drew 63% of its data from the World Health Organization (WHO) Solidarity trial and the Wellcome Trust and Bill & Melinda Gates Foundation-sponsored U.K. Recovery trial, both of which were deeply flawed.

Dr. Meryl Nass reported on the “potentially fatal” dosages of HCQ and CQ used in the Solidarity trial — 2.4 grams during the first 24 hours, and a cumulative dose of 9.2 grams over 10 days. Nass also called out the trial design, which led to HCQ being given too late in the progression of the disease to be of benefit.

After Nass contacted the WHO to report her observations, the trial was paused and several countries withdrew from the trial before it restarted.

Normally, chronic daily use of HCQ for people experiencing systemic lupus or rheumatoid arthritis is between 200 and 400 milligrams (mg) daily or a maximum of 5 mg/kilogram (kg). Malaria treatments call for 2,000 mg (2 grams) divided over three days for patients over 60 kg. A prophylactic dose for malaria is typically 400 mg once a week for eight weeks.

The U.K. Recovery trial had similar issues related to dosages — more than 4 times the amount typically recommended for any similar medical condition. Nass reported that Twitter users who noticed the dosing problem in the study protocol began reporting on it with the hashtag #RecoveryGate.

During the Recovery trial, 396 of 1,542 people who received HCQ while hospitalized died — about 10% higher than standard care. Researchers reported “no clinical benefit” from the use of HCQ.

“The doses used in these trials are not recommended for therapy of any medical condition,” wrote Nass. “These trials are not, in fact, testing the benefits of HCQ on Covid-19, but rather are testing whether patients survive toxic, non-therapeutic doses.”

HCQ, in use since 1955, is included on WHO’s list of “essential medicines.”

HCQ and COVID

Many doctors began using HCQ early in the pandemic, often in combination with zinc and an antibiotic such as azithromycin (AZM).

“Consented, prospective cohort studies that administered HCQ with AZM early in the hospitalization demonstrated reductions in mortality early in the pandemic,” McCullough said, citing Arshad et al., 2020.

In April 2020, a survey of U.S. doctors found that two-thirds would prescribe CQ or HCQ to “treat or prevent COVID-19 in a family member.”

Among the HCQ pioneers was French physician Didier Raoult, who ran numerous studies showing the effectiveness of the anti-malarial drug against COVID-19.

By early spring 2020, Raoult had treated more than 1,000 patients with an HCQ and AZM protocol, finding a 91% direct success rate and a .47% death rate (for five people ranging from 74-95 years old), with 0% cardiac toxicity, when treatment was started immediately after diagnosis.

A group of French doctors subsequently filed a petition urging the prime minister and minister of health to make HCQ available in all French hospitals.

Dr. Vladimir “Zev” Zelenko (since deceased) used a similar protocol in the U.S., adding zinc, initially treating over 900 cases with a 99.9% success rate.

McCullough told The Defender there are 417 studies with HCQ that “demonstrate a signal of benefit particularly when administered early in the ambulatory phase of illness within an established safety protocol well understood by senior physicians familiar with COVID-19 management.”

A study published October 2023 in New Microbes and New Infections is one of the latest to show the efficacy and safety of in-hospital treatment of COVID-19 infection with low-dose hydroxychloroquine and azithromycin. The researchers concluded, “Patients who did not receive HCQ had a 57% higher risk of mortality. A survival benefit in the treatment group was consistent across all age groups.”

HCQ has been a mainstay in the McCullough Protocol for early ambulatory treatment of COVID-19 since its original publication in The American Journal of Medicine in August 2020.

Despite his early success and some support from colleagues, Raoult, now retired, has ultimately become a lightning rod for the kind of character assassination and censorship that was rampant during the pandemic, with French medical bodies last May calling on authorities to punish him for “unauthorized” trials of HCQ to treat COVID-19.

Given that six of the seven authors of the study are from France, McCullough told The Defender he was “suspicious this is a political attack” against Raoult, whom he called a “pioneer and leader in the development of HCQ as a proven therapeutic in the early ambulatory treatment of SARS-Cov-2 infection.”

The study authors admit this plainly enough in the discussion section:

“It is critical that representatives of public authorities should not, on the basis of their personal conviction, promote the prescription of medicines that have not been formally evaluated, thereby falsely raising hopes as to the existence of a solution to a complex health crisis.”

Politico, offering further support to McCullough’s argument, stated, “Hydroxychloroquine gained prominence partly due to French virologist Didier Raoult who had headed the Méditerranée Infection Foundation hospital, but was later removed amid growing controversy.”

The ultimate goal of the paper may have been to restrict the use of off-label medications. The authors stated their conclusion “argues in favour of tightly regulating access to off-label prescriptions during future pandemics.”

HCQ long known as effective against coronaviruses

In a post published Monday, Nass said Dr. Anthony Fauci not only refused to pay for trials to study HCQ, but canceled two National Institute of Allergy and Infectious Disease (NIAID)-sponsored trials of HCQ in outpatient settings before they could be completed.

The trials were reportedly canceled due to lack of adequate enrollments. After reviewing the consent document for the trial, Nass concluded that enrollments were “discouraged … by making the drug appear to be very dangerous.”

Nass pointed to “proof he [Fauci] knew the drug would work,” highlighting 2014 study published by NIAID reviewing the “repurposing of existing drugs” in treating Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV).

Both HCQ and CQ were found to kill both SARS-1 and MERS viruses in tissue culture.

Nass in 2022 pointed out a 2005 Centers for Disease Control and Prevention study showing CQ to be a potent inhibitor of SARS coronavirus infection and spread.

The paper concluded, “Chloroquine has strong antiviral effects on SARS-COV infection … suggesting both prophylactic and therapeutic advantage.”

“Our governments already knew of options for treating COVID before it appeared,” Nass wrote, “but … did everything they could to stop people from obtaining the chloroquine drugs.”

Dr. Sabine Hazan will host a discussion of the French study on Jan. 12 at 8 p.m. PST.