2020-08-25 Mehra et al. was worse than fraud.
On August 22, The Lancet published an editorial Trump versus Biden: a fight for the health of a nation, attacking Trump administration and repeating talking points of the Democrat-Socialist party. For example: “The US must move away from a system in which health care is politicised, contentious, and tied to employment, income, and immigration status. In addition, President Trump’s isolationist and anti-scientific adminstration [sic!] has de-prioritised health and health care.” The Lancet is a British journal. This act is an open and in-your-face interference in the American elections.
The British government might re-consider any support it provides to The Lancet. Scientists, regulatory bodies, and the public in both countries should take notice that The Lancet became a political journal, publishing scientific articles matching its politics, and discount them.
On August 21, The Lancet Rheumatology published another anti-HCQ paper, with a surprisingly similar title to the fraudulent Mehra et al., which was published on May 22 and retracted on June 4. This new paper is titled: Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study. While it might not be be an outright fraud, it is incorrect and produced by dubious methods.
A closer look at the study reveals that the title and abstract contradict the article’s data. The data shows the safety of Hydroxychloroquine alone and Hydroxychloroquine + Azithromycin combination, for short term treatment.
To manufacture the anti-HCQ conclusions, the study authors included a dubious dataset from the US Veterans Health Administration (VA). This VA data is was already used in another anti-HCQ fraud Magagnoli et al., discounting the fact that the HCQ treatment was administered only in the most desperate cases, thus the initial conditions of the HCQ groups were much worse than those of the untreated group
The paper also focused on a short term cardiac mortality. Most of the deaths came from the flawed VA dataset. If we exclude it, the mortality rate is very low and not statistically significant. There is one group of ~24,000 patients treated with HCQ+AZM (Azithromycin), and another – with HCQ+AMX (Amoxicillin), for up to 30 days. There were 9 & 6 deaths, respectively. This is 0.05% mortality without a statistically significant difference. Additionally, in long term follow ups, the frequency of adverse effects with AMX is the same, & sometimes higher than with AZM.
Also consider that for a COVID-19 treatment, HCQ+AZM are only used for 5 days, not for “up to 30”.
See this tweet for in-depth analysis of the dubious methods behind this study of databases.
Earlier, The Lancet doubled down on its previous smear of Hydroxychloroquine (Mehra et al.), the main component of an effective COVID-19 treatment. On July 9, the Lancet published
Christian Funck-Brentano, Lee S Nguyen, Joe-Elie Salem
Notice that two of the three authors (Funck-Brentano and Salem) were also authors of the op-ed or comment to Mehra et al., published on the same day, which was also retracted.
This latest article re-uses the debunked Magagnoli et al., Rosenberg et al., and the tragicomic RECOVERY trial. In addition, it relies on an earlier fraudulent paper from the same authors Nguyen et al. (with additional co-authors). Coincidentally, it was published on the same day as Mehra et al.
Nguyen et al. , May 22
Lee S. Nguyen, Charles Dolladille, Milou-Daniel Drici, Charlotte Fenioux, Joachim Alexandre, Jean-Paul Mira, Javid J. Moslehi, Dan M. Roden, Christian Funck-Brentano, and Joe-Elie Salem. AHA Journals.
This is another example of “database studies”. It uses fake methodology, described in gibberish. This is an excerpt from the methods (self-references are omitted):
Association between hydroxychloroquine, azithromycin, and their combination with CV-ADR was assessed using reporting-odds-ratio (ROR) and information component (IC), an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and ADR. The lower end of the IC’s 95% credibility interval is IC025. It is considered significant when above 0.
ROR and IC are BS. The authors made up these quantities. The data is extracted from WHO’s VigiBase, using VigiAccess interface (Vigi– comes from vigilance. Its description can be found in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051262/). VigiBase is similar to FDA’s FAERS, containing mostly unverified reports of adverse effects, possibly linked to the drug. In addition, it contains complaints about the drugs’ effectiveness and even administration procedures.
The number of records in this database has little relation to the drug’s safety. For comparison, on July 13 there were the following number of adverse reports for each of the following drugs:
Paracetamol: 151, 575
These numbers represent unverified reports, not adjudicated cases. For HCQ, the largest group category of concern was “General disorders and administration site conditions” (accounting for 10422 of the reports); the largest subcategory of concern was “Drug ineffective” (accounting for 6182 of the reports).
The authors claim that they have found “76,822 ADR cases associated with hydroxychloroquine alone” – this number is significantly higher than actual non-duplicate records. In less than 500 of these cases, HCQ was associated with cardiovascular adverse reactions. Hydroxychloroquine with Azithromycin were suspected in only 9 (nine) cases.
This paper contains no abstract and no subsections. Its only coherent conclusion, “Hydroxychloroquine was also associated with potentially lethal HF [heart failure] when exposure was prolonged over several months“, is neither relevant for a 5-day treatment needed for COVID-19, nor in agreement with other literature on the subject. Another oddity of this paper is that it has only five references, three of which are self-references (i.e., references to papers including at least one of the same authors). Most papers have dozens of references to the work of many other scientists who have come to the same conclusions.
As expected, the authors have hidden conflicts of interest. Christian Funck-Brentano is a Scientific Advisor to Banook Group (http://www.banookgroup.com/ap/webinar/). The Banook Group (formerly Cardiabase) offers services in the field of cardiac safety (https://www.banookgroup.com/for-all/solutions/cardiac-safety/).
A huge clinical trial RECOVERY, conducted in the Britain, would be comical if it were not so tragic. The clinical researchers confused HCQ with another drug and consequently gave their patients 6x the dose normally recommended (2,400 mg/day instead of 400 mg/day). Even at this exorbitant dosage, the drug was tolerated well.
CQ/HCQ Cardiac Safety
In 2017, WHO investigated suspicions of cardiotoxicity of various anti-malarial drugs. It found CQ and HCQ to be exceptionally safe. Out of hundreds of millions of doses, only 11 deaths were reportedly in association with CQ or HCQ, four of which were clearly shown to be overdoses.
Exposure to chloroquine and hydroxychloroquine was reported in six and five cases of sudden death, respectively. In four of these cases, overdose was listed as the indication. Hydroxychloroquine was used to treat rheumatoid arthritis, systemic lupus erythematosus and small cell lung carcinoma in one case each.
Despite hundreds of millions of doses administered in the treatment of malaria, there have been no reports of sudden unexplained death associated with quinine, chloroquine or amodiaquine, although each drug causes QT/QTc interval prolongation.
Originally published on July 13. Updated on August 25.