Pharmacy Department, Hospital Universitario Puerto Real, Puerto Real. Spain..
Pharmacy department, Hospital Doctor José Molina Orosa, Lanzarote. Spain. Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla. Spain..
Farm Hosp. 2021 Jan 13;45(1):28-31. doi: 10.7399/fh.11591.
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.
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.
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".
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.
瑞德西韦并未显示对重症 COVID-19 患者的生存获益。然而，ACTT-1 研究组的亚组分析显示，对于需要非高流量吸氧的患者，死亡率明显降低。SOLIDARITY 研究结果的呈现与通过随机临床试验的亚组对死亡率结果进行的荟萃分析相关。目的是通过评估亚组分析对瑞德西韦治疗 COVID-19 患者死亡率影响的发现的可靠性和临床适用性来进行方法学评估。
使用经过验证的工具评估随机临床试验中的亚组分析发现，包括 SOLIDARITY 研究的荟萃分析。它由初步问题组成，用于拒绝没有相关最低条件的亚组分析，并附有一份特定的清单。后者考虑了某些标准：统计学关联，包括交互作用的 p 值、亚组的预设、样本量、分析的因素数量以及整体研究结果；观察到的差异的生物学合理性；以及类似研究结果之间的一致性。为每个标准分配一个分数，该工具将相关的总体总和与在临床决策中应用亚组结果的建议联系起来。
初步问题的答案为肯定，因此应用了清单。统计学关联获得“无”评估（-3 分），包括亚组之间的“可疑”交互作用的 p 值（p=0.0650），并且全球人群的死亡率没有达到统计学意义。这些发现降低了亚组分析的可靠性。生物学合理性被认为是“可能的”（+3 分），因为抗病毒药物在炎症过程和临床恶化之前可能会产生更大的效果。类似研究结果之间的一致性被评估为“可能的”（+2 分），这是因为 ACTT-1 和 SOLIDARITY 研究结果的分析是兼容的。根据患者风险应用亚组分析结果的建议为“无”。
对亚组分析的这种结构化解释表明，关于瑞德西韦可能降低需要非高流量吸氧的重症 COVID-19 患者死亡率的假设存在太多不确定性。这可能是一个随机发现。因此，关于瑞德西韦对 COVID-19 患者和非高流量吸氧患者死亡率影响的随机临床试验是必要的。
