The Lancet is one of the world’s oldest and best-known medical journals. According to its “manifesto,” it “sets extremely high standards. We select only the best research papers for their quality of work and the progression they bring.… We recognize that a great research paper is not enough and that it requires development, mobilization and exposure. So we promise to set agendas, create context, inform leaders, start debates, and advocate for the idea that research can and will make a difference.”
Pursuant to that mission statement, on May 22, 2020, the Lancet published a study by Dr. Mandeep R. Mehra of the Harvard Medical School and Dr. Sapan S. Desai of Surgisphere Corporation that concluded that the malaria drugs hydroxychloroquine (HCQ) and chloroquine (CQ) did not improve the condition of COVID-19 patients and may have harmed some of them. The study was purportedly based on the medical records of 15,000 patients who received either HCQ or CQ and 81,000 who did not.
This study set off an orgy of celebration by the progressive media. Under the headline “Malaria Drug Taken by Trump Is Tied to Increased Risk of Heart Problems and Death in New Study,” the New York Times advised its readers that, according to the researchers, the “drugs did not help coronavirus patients, and should not be used outside clinical trials.” The front page of the Philadelphia Inquirer featured an article by the Washington Post headlined “Antimalarial drug touted by Trump linked to increased risk of death in coronavirus patients, study says.”
And so on.
To anyone who has been paying attention to the excellent patient outcomes and findings by well-qualified treating physicians that have overwhelmingly demonstrated the efficacy of using HCQ to successfully and safely treat COVID-19, the Lancet article makes no sense. The researchers’ conclusions are squarely at odds with the reports by physicians across America and around the world of their positive patient outcomes as well as HCQ’s well-established safety profile. Similarly, they contradict patient studies by researchers affiliated with the Stanford University Medical School and clinical trials in France under the auspices of the world-renowned medical researcher, Dr. Didier Raoult.
On April 9, 2020, Dr. Raoult’s team published its abstract of a “cohort study” of 1,061 patients which found that early treatment of COVID-19 with HCQ and azithromycin yielded a “good clinical outcome and virological cure … in 973 patients within 10 days (91.7%).” The abstract also indicated that “no cardiac toxicity” was noted and concluded the following:
The HCQ-AZ combination, when started immediately after diagnosis, is a safe and efficient treatment for COVID-19, with a mortality rate of 0.5%, in elderly patients. It avoids worsening and clears virus persistence and contagiosity in most cases.
On May 27, 2020, Raoult’s team published “Early Diagnosis and Management of COVID-19 Patients: A Real-Life Cohort Study of 3,737 Patients, Marseille, France.” That study also found that early use of the HCQ and azithromycin combination produced overwhelmingly positive patient outcomes. The researchers concluded the following:
Treatment with HCQ-AZ was associated with a decreased risk of transfer to the ICU or death (HR 0.19 0.12-0.29), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.37 0.26-0.51) and shorter duration of viral shedding (time to negative PCR: HR 1.27 1.16-1.39). QTc prolongation [cardiac arrythmia] (>60 ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 3 cases. No cases of torsade de pointe [abnormal heart rhythm] or sudden death were observed…. Early diagnosis, early isolation and early treatment with at least 3 days of HCQ-AZ result in a significantly better clinical outcome and contagiosity in patients with COVID-19 than other treatments. (Emphasis added.)
Similarly, on May 27, 2020, the American Journal of Epidemiology published “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis,” by Dr. Harvey A. Risch of the Yale School of Public Health. Here, in relevant part, is the abstract:
Hydroxychloroquine+azithromycin has been widely misrepresented in both clinical reports and public media, and outpatient trials results are not expected until September. Early outpatient illness is very different than later hospitalized florid disease and the treatments differ. Evidence about use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease. Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. 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, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe. (Emphasis added.)
Nevertheless, despite all of the above, after publishing the contrary study by Drs. Mehra and Desai, the Lancet successfully lobbied the World Health Organization to suspend all clinical trials of HCQ. And, for added measure, France has banned its use.
So, how was it that the the Lancet article wound up contradicting the findings of HCQ’s many advocates? Was it because the study pertained to the treatment of hospitalized patients whose COVID-19 had progressed to the point where HCQ would no longer be effective? In other words, to paraphrase Dr. Risch’s abstract in the American Journal of Epidemiology, was the Mehra–Desai study based on “irrelevant evidence” about the use of HCQ to treat “inpatients” whose COVID-19 had reached the point where it was “very different” from the “early outpatient” phase of the disease?
Well, it turns out that the answers to those questions can’t be found in the study. As a matter of fact, the data on which the study is purportedly based are being seriously questioned by the scientific community.
On May 28, 2020, dozens of eminent “clinicians, medical researchers, statisticians and ethicists from [universities and medical centers] across the world” addressed an open letter to the study’s authors and the editor of the Lancet in which they raised “both methodological and data integrity concerns.” Here are some of the highlights:
- The study’s authors did not indicate the “severity” of the disease being treated. Was it early on in the COVID-19 progression or late in the process? Similarly, they did not indicate the dosages of HCQ or CQ used.
- The authors have not adhered to “standard practices in the machine learning and statistics community. They have not released their code or data. There is no data/code sharing and availability statement in the paper.”
- There was no mention of the countries or hospitals from which the data were purportedly obtained, and the authors have denied requests for that information.
- The numbers of cases and deaths as well as the detailed data collection from Surgisphere-associated hospitals in Africa “seem unlikely.”
- Reported ratios of HCQ to CQ are “implausible.”
The open letter then states that “it is imperative” that “Surgisphere provides details on data provenance” and that there be “independent validation” and “additional analyses” by “at least one other independent and respected institution” to “assess the validity of the [study’s] conclusions.”
And it concluded with this: “In the interests of transparency, we also ask The Lancet to make openly available the peer review comments that led to this manuscript to be [sic] accepted for publication.”
There’s much more, but you get the idea. The letter writers smell a rat. As does Dr. Didier Raoult who, on May 29, 2020, tweeted (as translated) the following:
We are wondering about the existence of the company Surgisphere, in charge of collecting Lancet data. To our knowledge, many denials but not a single testimony, neither from a partner hospital, nor from a doctor who provided data on the study.
On the same date, FranceSoir published its investigative report on Surgisphere with the stinging subhead (as translated), “LancetGate: is Surgisphere the company which provided the study data serious?”
Noting that (as translated) “several companies with the same name were successively registered in various [American] states, then liquidated or suspended,” the article observed that, “for a study the size of that of The Lancet (96,000 participants), this company, which claims to be specialized in big data and artificial intelligence, to date does not really provide factual support of its existence or ability to do so.” Instead, citing information from LinkedIn, the article states that “the company reports 5 people working there, 4 of whom arrived either in March or April 2020. We did Google searches on each of them without much success (very few mentions or publications) and the profile of [Surgisphere employee] Stacy Prigmore caught our attention because we cannot find any information on him [sic].… The company’s website gives the impression of only existing or having activity since March 2020 and nothing between 2013 and 2020.”
In addition, many other scientists and researchers have raised their concerns about the impact of this evolving scandal. According to the New York Times, some have posted their concerns online using hashtags like #Lancetgate and #whats_with_hcq_lancet_paper, even as Agence France-Presse has quoted Professor Gilbert Deray of Pitie-Salpetriere University Hospital stating, “If the Lancet article is a fraud, it will shatter trust in scientists in a lasting way. I await with concern the results of the investigation.”
Meanwhile, Dr. Raoult isn’t waiting for the investigative results. He bluntly summed up the Lancet study as “crap” and declared that “We’ve had 4,000 patients [in his studies], so, don’t believe I will change because there are people making of big data a sort of completely delirious fantasy.” He added that he does not trust research involving “big data” that “takes data we don’t know the quality of, that mixes everything, mixes treatments we don’t know what dose has been given.” In short, despite the ban in France on HCQ, he will continue to treat COVID-19 patients with HCQ and azithromycin since they are “the most fitted treatments given the current state of science and knowledge.”
Subsequently, Dr. Raoult posted this tweet:
Winston Churchill: “Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning”… Of the war against chloroquine.
We can only hope he’s right.
George Parry is a former federal and state prosecutor. He blogs at knowledgeisgood.net and may be reached by email at kignet1@gmail.com.
