The study included records of 96,032 COVID-19 patients from 671 hospitals in 6 continents who were hospitalized between 12/20/2019 and 4/14/2020. Those receiving the antimalarials were divided into 4 groups: hydroxychloroquine with a macrolide, hydroxychloroquine alone, chloroquine with a macrolide, or chloroquine alone, and a control group of more than 80,000 patients receiving neither of the 4 treatments.
14,888 patients in the treatment groups were found to suffer higher mortality when compared to the control group. “We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19,” the researchers wrote.
These findings resulted in W.H.O temporarily suspending the trial of hydroxychloroquine on COVID-19 patients, the UK regulatory body MHRA requesting a temporary pause of recruitment into all hydroxychloroquine trials, and France changing its national recommendations of using the drug for treatment in the outbreak as well as halting all trials.
Since then over 100 scientists and medical professionals have been raising questions and concerns about the integrity of the data analyzed in the study which subsequently led to the creation of an open letter addressed to the authors of the study and the editor of The Lancet listing 10 major concerns about the study.
These concerns included the fact that there was “no ethics review” and an “unusually small reported variances in baseline variables, interventions and outcomes,” as well as there being “no mention of the countries or hospitals that contributed to the data source and no acknowledgments to their contributions.” Along with the concerns there was also a request made for the authors to supply additional information on the contributing centers, which was denied according to the open letter.
Another concern was that the average daily doses of hydroxychloroquine exceeded the FDA recommendations and that the data which was reportedly from Australian patients did not seem to match data from the Australian government.
“Too many cases for just five hospitals, more in hospital deaths than had occurred in the entire country during the study period,” they wrote, noting that Surgisphere, a healthcare data analytics company, has since stated this was an error of classification of one hospital from Asia. “This indicates the need for further error checking throughout the database,” they wrote. The scientists also said the authors “have not adhered to standard practices in the machine learning and statistics community. They have not released their code or data.”
“Data from Africa indicate that nearly 25% of all COVID-19 cases and 40% of all deaths in the continent occurred in Surgisphere-associated hospitals which had sophisticated electronic patient data recording, and patient monitoring able to detect and record ‘nonsustained [at least 6 secs] or sustained ventricular tachycardia or ventricular fibrillation.’ Both the numbers of cases and deaths, and the detailed data collection, seem unlikely.”
“We discovered that a hospital that joined the Surgisphere registry on April 1, 2020 (in between our quarterly audit periods) self-designated as belonging to the Australasia continental designation. In reviewing the data from each of the hospitals in the registry, we noted that this hospital should have more appropriately been assigned to the Asian continental designation,” Surgisphere said in a statement. Sapan Desai is the president and chief executive officer of Surgisphere, and Desai is listed as one of the 4 authors.
“This hospital was properly reclassified in our database. The findings of the paper are unaffected by this update,” the company said. The recent correction in The Lancet also mentions the same hospital:
“The appendix has also been corrected. An incorrect appendix table S3 was included, originally derived from a propensity score matched and weighted table developed during a preliminary analysis. The unadjusted raw summary data are now included,” adding that there “have been no changes to the findings of the paper,” and that the corrections have been made to the online version and will also be made to the printed version.
In response to the correction made on May 29, 2020, James Watson who led the drafting of the open letter and is with the University of Oxford’s Centre for Tropical Medicine and Global Health in a recent interview says that the authors of the study have failed to address the other 9 points of concern that the open letter specifically made note of.
