St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
Trials. 2022 Sep 2;23(1):735. doi: 10.1186/s13063-022-06640-y.
The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches.
On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures.
Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol.
We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management.
NCT03471247. Registered on March 20, 2018.
由于重症监护病房（ICU）优先考虑患者护理和 COVID 特定研究，COVID-19 大流行在全球范围内中断了非 COVID 关键护理试验。国际随机对照试验 CYCLE（Critical Care Cycling to Improve Lower Extremity Strength）于 2020 年 3 月在所有站点被迫停止招募，这立即带来了挑战。我们应用 CONSERVE（CONSORT 和 SPIRIT 扩展用于 RCTs 修订的减轻情况）声明作为报告大流行对 CYCLE 影响的框架，并描述我们的缓解方法。
2020 年 3 月 23 日，CYCLE 方法中心向所有站点发送了一封标准化电子邮件，以确定仍在住院的患者数量和需要进行即将到来的 90 天终点评估的患者数量。我们通过记录提供住院随机干预（循环或常规物理疗法）和收集主要结局（ICU 出院后 3 天的身体功能）和 90 天结局的尝试来评估方案的一致性。我们建议站点优先考虑研究的主要结局数据。我们征求了与试验程序相关的大流行障碍的反馈意见。
我们的主要方法中心缓解策略包括确定有违反方案风险的患者，及早并频繁地与站点沟通，制定专注于方案高危点的标准化内部工具，以监测患者进展、数据录入和验证，并提供指导以远程进行一些研究活动。对于研究站点，我们的策略包括确定机构大流行研究政策如何适用于 CYCLE，与方法中心沟通继续研究任何部分的能力，并制定应急计划以确保按计划交付方案。在 15 个活跃站点（12 个加拿大，2 个美国，1 个澳大利亚）中，5 名患者仍在 ICU 接受研究干预，6 名患者需要主要结局，17 名患者需要 90 天评估。通过这些缓解策略，我们按照方案尝试了 100%的 ICU 干预、83%的主要结局和 100%的 90 天评估。
我们使用了几种敏感的策略，最大限度地减少了数据缺失，保留了所有入组的患者。尽管 CONSERVE 建议仅报告因减轻情况而产生的主要修改，但我们建议它还为报告缓解策略提供了一个有用的框架，目的是提高研究透明度和试验管理。
NCT03471247。于 2018 年 3 月 20 日注册。
