Department of Clinical Research, Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, University of Southern Denmark, Odense, Denmark.
Open Patient Data Exploratory Network (OPEN), Odense University Hospital, Odense, Denmark.
PLoS One. 2021 Nov 29;16(11):e0260544. doi: 10.1371/journal.pone.0260544. eCollection 2021.
Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir showed promising results in early randomised trials but subsequently a large publicly funded trial has shown less favourable results and the evidence is interpreted differently in clinical guidelines. Systematic reviews of remdesivir have been published, but none have systematically searched for unpublished data, including regulatory documents, and assessed the risk of bias due to missing evidence.
We will conduct a systematic review of randomised trials comparing remdesivir to placebo or standard of care in any setting. We will include trials regardless of the severity of disease and we will include trials examining remdesivir for indications other than Covid-19 for harms analyses. We will search websites of regulatory agencies, trial registries, bibliographic databases, preprint servers and contact trial sponsors to obtain all available data, including unpublished clinical data, for all eligible trials. Our primary outcomes will be all-cause mortality and serious adverse events. Our secondary outcomes will be length of hospital stay, time to death, severe disease, and adverse events. We will assess the risk of bias using the Cochranes Risk of Bias 2 tool and the risk of bias due to missing evidence (e.g. publication bias, selective reporting bias) using the ROB-ME tool. Where appropriate we will synthesise study results by conducting random-effects meta-analysis. We will present our findings in a Summary of Findings table and rate the certainty of the evidence using the GRADE approach.
By conducting a comprehensive systematic review including unpublished data (where available), we expect to be able to provide valuable information for patients and clinicians about the benefits and harms of remdesivir for the treatment of Covid-19. This will help to ensure optimal treatment for individual patients and optimal utilisation of health care resources.
CRD42021255915.
需要有效的新冠病毒治疗药物来降低个体的发病率和死亡率，并减轻医疗系统的压力。瑞德西韦在早期的随机试验中显示出了有希望的结果，但随后一项大型公共资助的试验显示出了不太有利的结果，并且临床指南对证据的解释也不同。已经发表了瑞德西韦的系统评价，但没有一个系统地搜索未发表的数据，包括监管文件，并评估由于证据缺失而导致的偏倚风险。
我们将对比较瑞德西韦与安慰剂或标准治疗的随机试验进行系统评价，无论疾病严重程度如何，我们都将纳入试验，并且将纳入检查瑞德西韦治疗除新冠病毒以外适应症的试验进行危害分析。我们将搜索监管机构、试验注册处、文献数据库、预印本服务器的网站，并联系试验赞助商，以获得所有合格试验的所有可用数据，包括未发表的临床数据。我们的主要结局将是全因死亡率和严重不良事件。我们的次要结局将是住院时间、死亡时间、严重疾病和不良事件。我们将使用 Cochrane 偏倚风险 2 工具评估偏倚风险，并使用 ROB-ME 工具评估由于证据缺失（如发表偏倚、选择性报告偏倚）而导致的偏倚风险。在适当的情况下，我们将通过进行随机效应荟萃分析来综合研究结果。我们将在结果总结表中呈现我们的发现，并使用 GRADE 方法评估证据的确定性。
通过进行一项包括未发表数据（如有）的全面系统评价，我们预计能够为患者和临床医生提供关于瑞德西韦治疗新冠病毒的益处和危害的有价值的信息。这将有助于确保为个体患者提供最佳治疗和最佳利用医疗保健资源。
CRD42021255915。
