Comparative effectiveness of neutralising monoclonal antibodies in high risk COVID-19 patients: a Bayesian network meta-analysis.

The purpose of this work was to review and synthesise the evidence on the comparative effectiveness of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality, healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment effects for individual nMABs (compared with placebo and one another) were estimated. Pooled effects for the nMAB class compared with placebo were estimated. Relative effects were combined with baseline natural history models to predict the expected risk reductions per 1000 patients treated. Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab) were identified. All four therapies were associated with a statistically significant reduction in hospitalisation (70-80% reduction in relative risk; absolute reduction of 35-40 hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo. Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efficacy. In conclusion, nMABs are effective at reducing hospitalisation among infected individuals at high-risk of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates; the effect on these latter outcomes is more uncertain. Widespread vaccination and the emergence of nMAB-resistant variants make the generalisability of these results to current patient populations difficult.

Understanding the Challenges and Uncertainties of Seroprevalence Studies for SARS-CoV-2.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers, and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

Coronavirus Disease 2019: Considerations for Health Technology Assessment From the National Centre for Pharmacoeconomics Review Group.

It is expected that the coronavirus disease 2019 (COVID-19) pandemic will leave large deficits in the budgets of many jurisdictions. Funding for other treatments, in particular new treatments, may become more constrained than previously expected. Therefore, a robust health technology assessment (HTA) system is vital. Many clinical trials carried out during the pandemic may have been temporarily halted, while others may have had to change their protocols. Even trials that continue as normal may experience external changes as other aspects of the healthcare service may not be available to the patients in the trial, or the patients themselves may contract COVID-19. Consequently, many limitations are likely to arise in the provision of robust HTAs, which could have profound consequences on the availability of new treatments. Therefore, the National Centre for Pharmacoeconomics Review Group wishes to discuss these issues and make recommendations for applicants submitting to HTA agencies, in ample time for these HTAs to be prepared and assessed. We discuss how the pandemic may affect the estimation of the treatment effect, costs, life-years, utilities, discontinuation rates, and methods of evidence synthesis and extrapolation. In particular, we note that trials conducted during the pandemic will be subject to a higher degree of uncertainty than before. It is vital that applicants clearly identify any parameters that may be affected by the pandemic. These parameters will require considerably more scenario and sensitivity analyses to account for this increase in uncertainty.