HTA257 MOVe-OUT: A Trial of Two Halves – the Impact of Heterogeneity on Cost-Effectiveness Outcomes for COVID-19

In the phase 3 MOVe-OUT trial, non-hospitalised, unvaccinated adults with COVID-19 (at risk for severe illness) were randomised to molnupiravir or placebo. Our objective is to investigate the short-term costs and outcomes associated with molnupiravir (versus standard of care (SoC), defined as ‘no systematic treatment’) from the Irish-payer perspective. An acute-phase (one-month) decision tree was programmed in R. On entering the model, all patients are at risk of hospitalisation; a proportion are admitted to intensive care units (ICU). Treatment effectiveness was informed by the MOVe-OUT trial, with external data and clinical opinion used to estimate ICU admission risk. Irish direct-medical costs were included. Summary statistics of cost per hospitalisation, ICU admission, and death avoided were calculated; no explicit payer-threshold was considered. One-way sensitivity and probabilistic analyses were performed. Using the final analysis of MOVe-OUT, it was estimated that treating 1,000 patients with molnupiravir would prevent approximately 30 hospitalisations, 17 ICU admissions, and 11 deaths, at an incremental cost of approximately €147,229 versus SoC, over the one-month horizon (incremental costs €4,977, €8,800 and €12,841 per hospitalisation, ICU admission and death prevented respectively). Among patients recruited during the latter part of MOVe-OUT, no benefit associated with molnupiravir was observed, at an incremental cost of €772,842 per 1,000 patients. The outcomes of ICU admission and death were particularly uncertain due to small event numbers and the additional assumptions required. This study demonstrates that the clinical evidence provided by the MOVe-OUT trial may be unsuitable to inform comparative and cost effectiveness due to considerable unexplained heterogeneity of treatment effects observed at different time-points. Generalisability of the study results to clinical practice is thus limited, and is likely further compromised given differences in circulating variants and healthcare systems. Additional evidence on the efficacy of molnupiravir is needed to reliably evaluate cost-effectiveness over a lifetime horizon.