Systematic benefit-risk assessment for the use of chloroquine or hydroxychloroquine as a treatment for COVID-19: Establishing a dynamic framework for rapid decision-making

ObjectivesGiven the current pandemic, there is an urgent need to identify effective, safe treatments for COVID-19 (coronavirus disease). A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing monitoring of the benefit-risk balance for chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 treatment. MethodsThe overall benefit-risk of the use of chloroquine or hydroxychloroquine as a treatment for COVID-19 compared to standard of care, placebo or other treatments was assessed using the Benefit-Risk Action Team (BRAT) framework. We searched PubMed and Google Scholar to identify literature reporting clinical outcomes in patients taking chloroquine or hydroxychloroquine for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. ResultsSeveral potential key benefits and risks were identified for use of hydroxychloroquine or chloroquine in COVID-19 treatment. Currently available results did not show an improvement in mortality risk; Cox proportional hazard ratio (HR) for death between patients who received HCQ alone vs. neither hydroxychloroquine or azithromycin was 1.08 (95% CI 0.63-1.85). A further study compared the incidence of intubation or death (composite outcome) in a time to event analysis between patients who received HCQ vs. those patients who did not (adjusted Cox proportional HR 1.00 (95% CI 0.76-1.32)). Risk of cardiac arrest, abnormal electrocardiogram (ECG) and QT prolongation was greater among patients taking HCQ (with or without azithromycin) compared to standard of care in the same study. ConclusionsOverall, based on the available data there does not appear to be a favourable benefit-risk profile for chloroquine or hydroxychloroquine compared to standard of care in treatment of severe COVID-19. As further data from clinical trials and real world use on these benefits and risks becomes available, this can be incorporated into the framework for an ongoing benefit-risk assessment.