Convalescent Plasma in treatment of COVID-19: A review of evidence for a living systematic benefit-risk assessment

ObjectivesWe aimed to review the evidence for a living systematic benefit risk assessment for convalescent plasma use amongst patients with severe COVID-19 disease, based on currently available data. MethodsThe assessment used the Benefit-Risk Action Team (BRAT) framework. Convalescent plasma treatment in severe COVID-19 was compared to standard of care, placebo or other treatments. A literature search was conducted to identify published papers from January 1st, 2019 until July 8th, 2020. A value tree was constructed which included ranked key benefits and risks. ResultsWe screened 396 papers from PubMed and 127 papers from Embase. Four studies were eligible for inclusion as they contained comparative data. Results from a randomised controlled trial revealed a non-statistically significant shortening of time to clinical improvement of 2.15 days (95% CI, -5.28 to 0.99 days) in the intervention group compared with the control group, with a possible signal of increased efficacy amongst a small subset of patients with severe disease (but not life threatening disease), however this study may have been underpowered. Interpretation of findings amongst the three controlled non-randomised studies were limited by small patient numbers, lack of randomisation, and confounding by co-administration of other treatments. Limited data availability at the current time precluded construction of a data summary table and further quantitative analysis. ConclusionsThere was insufficient evidence from controlled studies to complete a data summary table for a systematic benefit-risk assessment of the use of CP for severe COVID-19 disease at the current time, and as such a benefit-risk conclusion could not be made. Whilst uncontrolled case series have suggested positive findings with CP, results from these studies are very difficult to interpret. We provide a framework which can be updated when further data that have an impact on the benefit-risk become available. Article SummaryStrengths and limitations of this study O_LIprovides a living systematic benefit risk assessment based on currently available data for the use of convalescent plasma in patients with severe COVID-19 disease C_LIO_LIestablishes a framework inclusive of ranked key benefits and risks for convalescent plasma in severe COVID-19 disease, into which additional data can be added as this becomes available facilitating re-assessment of the benefit risk profile C_LIO_LIuses a transparent framework (BRAT framework) which can be applied to other potential treatment options in this disease context C_LIO_LIinsufficient data available at the current time from comparative studies to form a benefit risk conclusion C_LI