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

Objectives: We 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. Methods: The 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. Results: We 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. Conclusions: There 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.