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 1 st , 2019 until July 8 th , 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. Article Summary Strengths and limitations of this study provides a living systematic benefit risk assessment based on currently available data for the use of convalescent plasma in patients with severe COVID-19 disease establishes 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 uses a transparent framework (BRAT framework) which can be applied to other potential treatment options in this disease context insufficient data available at the current time from comparative studies to form a benefit risk conclusion