Emilio Jesús Alegre-Del Rey1, Manuel David Gil-Sierra2, Catalina Alarcón de la Lastra-Romero3, Marina Sánchez-Hidalgo4. 1. Pharmacy Department, Hospital Universitario Puerto Real, Puerto Real. Spain.. mangilsie@yahoo.com. 2. Pharmacy department, Hospital Doctor José Molina Orosa, Lanzarote. Spain. Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla. Spain.. mangilsie@yahoo.com. 3. Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla. Spain.. calarcon@us.es. 4. Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla. Spain.. hidalgosanz@us.es.
Abstract
OBJECTIVE: 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. METHOD: 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. RESULTS: 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". CONCLUSIONS: 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. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
OBJECTIVE: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. METHOD: 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. RESULTS: 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". CONCLUSIONS: 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. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.