严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)大流行期间中断的临床试验的统计方法:综述。
Statistical methods for clinical trials interrupted by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic: A review.
机构信息
Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
Department of Medical Statistics, University Medical Center Göttingen, Germany.
出版信息
Stat Methods Med Res. 2024 Nov;33(11-12):2131-2143. doi: 10.1177/09622802241288350. Epub 2024 Oct 30.
Cancellation or delay of non-essential medical interventions, limitation of face-to-face assessments or outpatient attendance due to lockdown restrictions, illness or fear of hospital or healthcare centre visits, and halting of research to allow diversion of healthcare resources to focus on the pandemic led to the interruption of many clinical trials during the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic. Appropriate analysis approaches are now required for these interrupted trials. In trials with long follow-up and longitudinal outcomes, data may be available on early outcomes for many patients for whom final, primary outcome data were not observed. A natural question is then how these early data can best be used in the trial analysis. Although recommendations are available from regulators, funders, and methodologists, there is a lack of a review of recent work addressing this problem. This article reports a review of recent methods that can be used in the setting of the analysis of interrupted clinical trials with longitudinal outcomes with monotone missingness. A search for methodological papers published during the period 2020-2023 identified 43 relevant publications. We categorised these articles under the four broad themes of missing value imputation, modelling and covariate adjustment, simulation and estimands. Although motivated by the interruption due to SARS-CoV-2 and the resulting disease, the papers reviewed and methods discussed are also relevant to clinical trials interrupted for other reasons, with follow-up discontinued.
由于封锁限制、疾病或担心医院或医疗中心就诊、取消或延迟非必要的医疗干预、限制面对面评估或门诊就诊,以及停止研究以便将医疗资源转移到关注大流行,导致许多临床试验在严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)大流行期间中断。现在需要为这些中断的试验采用适当的分析方法。在随访时间长和纵向结局的试验中,对于许多未观察到最终主要结局数据的患者,可能已经有早期结局数据。那么,这些早期数据如何才能在试验分析中得到最佳利用呢?尽管监管机构、资助者和方法学家都有建议,但缺乏对解决这个问题的最新工作的综述。本文报告了对最近在具有单调缺失的纵向结局的中断临床试验分析中可以使用的方法的综述。在 2020-2023 年期间,我们对发表的方法学论文进行了搜索,确定了 43 篇相关文献。我们将这些文章分为缺失值插补、建模和协变量调整、模拟和估计量四个主题。虽然这些文章是受 SARS-CoV-2 中断以及由此产生的疾病的启发,但所审查的文章和讨论的方法也与其他原因导致随访中断的临床试验相关。