Manuel David Gil-Sierra, Pharmacy Department, Hospital Universitario Puerto Real. Carretera. N-IV Km. 665, 11510 Puerto Real, Cadiz, Spain.
Rev Esp Quimioter. 2022 Jun;35(3):249-259. doi: 10.37201/req/154.2021. Epub 2022 Mar 17.
A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19.
A search in Pubmed® database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability.
A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution.
We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.
瑞德西韦早期治疗严重 2019 年冠状病毒病（COVID-19）可能有益。该药物的疗效存在争议，可能会对医疗保健系统的效率产生重大影响。本研究旨在根据 COVID-19 症状发作时开始瑞德西韦治疗的时间，对亚组分析进行方法学解释。
在 Pubmed®数据库中进行检索。选择了针对瑞德西韦早期和晚期使用的亚组分析的随机对照试验（RCT）。使用两种方法评估所有终点。第一种方法考虑了统计学交互作用、预先指定、生物学合理性和结果一致性。第二种方法是一种经过验证的工具，具有初步问题以排除没有相关最小条件的亚组分析，并附有应用建议的检查表。
共发现 54 个结果，选择了 5 项 RCT。根据第一种方法，仅在严重 COVID-19患者和症状<7 天的患者中，瑞德西韦治疗<7 天的患者的临床改善时间和第 15 天的临床状态评分更好时，发现了一致的异质性。关于第二种方法，这些关于瑞德西韦早期使用的结果可能需要谨慎应用于临床实践。
我们进行了系统搜索，并应用了一种既定的方法来解释瑞德西韦早期使用的亚组分析。严重 COVID-19 患者的研究结果表明，瑞德西韦治疗<7 天的患者的症状改善时间和第 15 天的临床状态评分更好，因此早期使用瑞德西韦可能会带来更大的益处。未来的研究可以使用 7 天的症状截止值来评估瑞德西韦。
