Remdesivir and mortality reduction in COVID-19 patients: a systematized subgroup analysis of clinical trials

• Main Authors: Emilio Jesús Alegre-del Rey, Manuel David Gil-Sierra, Catalina Alarcón de la Lastra-Romero, Marina Sánchez-Hidalgo
• Format: Article
• Language: English
• Published: Grupo Aula Médica 2021-01-01
• Series: Farmacia Hospitalaria
• Subjects: remdesivir; covid-19 drug treatment; data interpretation; statistical; treatment outcome; drug evaluation; mortality; assessment; outcomes
• Online Access: http://www.aulamedica.es/fh/pdf/11591.pdf
• ISSN: 1130-6343; 2171-8695

<p><strong>Objective:</strong> Remdesivir has not shown survival benefit for patients with severe COVID-19. However, subgroup analysis of ACTT-1 Study Group showed an apparent reduction in mortality for patients who required non?high-flow oxygen. Presentation of SOLIDARITY study results were associated by a meta-analysis combining mortality results by subsets rom randomized clinical trials. The aim is a methodological assessment of reliability and clinical applicability about findings by subgroups on the effect of remdesivir on mortality in patients with COVID- 19.</p><p><strong>Method:</strong> A validated tool was used to evaluate the findings of subgroup analyses in randomized clinical trials, including meta- analysis atached to SOLIDARITY study. It is structured in preliminary questions to reject subset analyses without relevant minimum conditions, and a specific checklist. The latter considers certain criteria: statistical association, which encompassed p of interaction, prespecification of subgroups, sample size, number of factors analyzed, and overall study result; biological plausibility of observed differences; and consistency between results of similar studies. A score was assigned to each criterion and the tool related global summation to a recommendation on the applicability of subset results in clinical decision making.</p><p><strong>Results:</strong> Preliminary questions had positive answers, so checklist was applied. Statistical association obtained “null” assessment (–3 points), including a “doubtful” p of interaction (p = 0.0650) among subgroups and mortality reached no statistical significance for global population. These findings reduced the reliability of subset analysis. Biological plausibility was considered “probable” (+3 points) because antiviral could have a greater effect before the inflammatory process and clinical worsening. Consistency between results of similar studies was evaluated as “possible” (+2 points) analysis for compatibility of ACTT-1 and SOLIDARITY study results. The recommendation about application of subset analysis results according to the risk of patients was “null”.</p><p><strong>Conclusions:</strong> This structured interpretation of subgroup analysis suggested too much uncertainty in hypothesis about remdesivir could reduce mortality in patients with severe COVID-19 who required non-high- flow oxygen. It was probably a random finding. Therefore, a randomized clinical trial about effect of remdesivir in mortality in patients with COVID?19 and non-high-flow oxygen is essential.</p><p> </p>