Much ado about nothing? Discrepancy between the available data on the antiviral effect of hydroxychloroquine in March 2020 and its inclusion in COVID-19 clinical trials and outpatient prescriptions

Abstract

Objectives: Many of the 2020 COVID-19 clinical trials included an (hydroxy)chloroquine ((H)CQ) arm. We aimed to juxtapose the state of science before April 2020 regarding the benefits of (H)CQ for viral infections with the number and size of the clinical trials studying (H)CQ and the volume of (H)CQ dispensed in France.

Study design: We identified and analysed published scientific material regarding the antiviral activity of (H)CQ and publicly available data regarding clinical trials and drug dispensation in France.

Methods: We conducted a review of scientific publications available before April 2020 and a systematic analysis of COVID-19 clinical trials featuring (H)CQ registered on clinicaltrials.gov.

Results: Before April 2020, 894 scientific publications mentioning (H)CQ for viruses other than coronaviruses were available, including 35 in vitro studies (reporting an inconstant inhibition of viral replication), 11 preclinical studies (reporting no or disputable positive effects), and 32 clinical trials (reporting no or disputable positive effects). Moreover, 67 publications on (H)CQ and coronavirus infections were available, including 12 in vitro studies (reporting an inconstant inhibition of viral replication), two preclinical studies (reporting contradictory results), and no clinical trials. Meanwhile, 253 therapeutic clinical trials featuring an HCQ arm were registered in 2020, intending to enrol 246,623 patients.

Conclusions: The number and size of (H)CQ clinical trials for COVID-19 launched in 2020 were not supported by the literature published before April 2020.

Keywords: COVID-19; Chloroquine; Clinical trial; Health expenditure; Hydroxychloroquine; Public health; SARS-CoV-2.