Departments of Medicine and Neurology, Melbourne Brain Centre, The Royal Melbourne Hospital (N.Y., B.C.V.C., L.C.), University of Melbourne, Parkville, Australia.
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia (N.Y.).
Stroke. 2021 Nov;52(11):3739-3747. doi: 10.1161/STROKEAHA.121.036537. Epub 2021 Sep 30.
The coronavirus disease 2019 (COVID-19) pandemic has presented unique challenges to stroke care and research internationally. In particular, clinical trials in stroke are vulnerable to the impacts of the pandemic at multiple stages, including design, recruitment, intervention, follow-up, and interpretation of outcomes. A carefully considered approach is required to ensure the appropriate conduct of stroke trials during the pandemic and to maintain patient and participant safety. This has been recently addressed by the International Council for Harmonisation which, in November 2019, released an addendum to the Statistical Principles for Clinical Trials guidelines entitled Estimands and Sensitivity Analysis in Clinical Trials. In this article, we present the International Council for Harmonisation estimand framework for the design and conduct of clinical trials, with a specific focus on its application to stroke clinical trials. This framework aims to align the clinical and scientific objectives of a trial with its design and end points. It also encourages the prospective consideration of potential postrandomization intercurrent events which may occur during a trial and either impact the ability to measure an end point or its interpretation. We describe the different categories of such events and the proposed strategies for dealing with them, specifically focusing on the COVID-19 pandemic as a source of intercurrent events. We also describe potential practical impacts posed by the COVID-19 pandemic on trials, health systems, study groups, and participants, all of which should be carefully reviewed by investigators to ensure an adequate practical and statistical strategy is in place to protect trial integrity. We provide examples of the implementation of the estimand framework within hypothetical stroke trials in intracerebral hemorrhage and stroke recovery. While the focus of this article is on COVID-19 impacts, the strategies and principles proposed are well suited for other potential events or issues, which may impact clinical trials in the field of stroke.
2019 年冠状病毒病（COVID-19）大流行给国际卒中护理和研究带来了独特的挑战。特别是，卒中临床试验在设计、招募、干预、随访和结果解释等多个阶段都容易受到大流行的影响。需要采取谨慎考虑的方法来确保在大流行期间适当进行卒中试验，并确保患者和参与者的安全。国际协调委员会最近针对这一问题发布了一份公告，该委员会于 2019 年 11 月发布了《临床试验统计原则》指南的增编，题为《临床试验中的估计目标和敏感性分析》。在本文中，我们介绍了国际协调委员会用于设计和进行临床试验的估计目标框架，特别关注其在卒中临床试验中的应用。该框架旨在使试验的临床和科学目标与其设计和终点保持一致。它还鼓励前瞻性考虑试验期间可能发生的潜在随机后并发事件，这些事件可能会影响终点的测量能力或其解释。我们描述了此类事件的不同类别以及处理这些事件的建议策略，特别是将 COVID-19 大流行作为并发事件的来源进行了重点描述。我们还描述了 COVID-19 大流行对试验、卫生系统、研究组和参与者带来的潜在实际影响，调查人员应仔细审查这些影响，以确保制定了适当的实际和统计策略来保护试验的完整性。我们提供了在脑出血和卒中康复的假设性卒中试验中实施估计目标框架的示例。虽然本文的重点是 COVID-19 的影响，但提出的策略和原则也非常适合其他可能影响卒中领域临床试验的事件或问题。
