背景:2021年初,英国卫生和社会护理部呼吁研究同时施用COVID-19和流感疫苗的安全性和免疫原性。这些疫苗的共同施用将促进摄取并减少所需的医疗保健访问次数。ComFluCOV试验旨在及时提供必要的证据,以告知2021年秋季(9月至11月)的疫苗接种政策。本文介绍了用于帮助在6个月内成功提供试验结果的统计方法。
方法:ComFluCOV是一项由布里斯托尔试验中心管理的平行组多中心随机对照试验。两名研究统计人员,在高级统计师的支持下,一起完成所有统计任务。开发了工具来帮助预筛选过程。每天制作临床数据和电子日记的自动数据监测报告,并由试验小组审查,并向站点提供反馈。平行独立进行分析,并比较所有结局的推导和结果.
结果:在不到一个月的时间内完成了设置,在8周内招募了679名参与者。每天共有537份[至少]报告概述招聘,遵守协议,和数据质量,在16周的时间内,共制作了695份参与者电子日记报告,以确定任何遗漏的日记条目和不良事件.2021年5月向卫生和社会护理部报告了对验证数据的初步主要结果分析。在最终参与者随访6周后锁定数据库,并在3周后完成最终分析。在获得结果后14天内提交了一份印刷前出版物。结果是在首次讨论该试验6个月后报告的。
结论:在ComFluCOV中实施的统计方法有助于在时间范围内完成研究。在时间紧迫的新临床领域工作具有挑战性。由两名统计学家共同研究提供了一个质量保证过程,使分析能够有效完成,并确保数据得到正确解释。开发的过程可以应用于其他研究,以最大限度地提高质量,降低错误的风险,和整体提供增强的验证方法。
背景:ISRCTN14391248,于2021年3月30日注册。
BACKGROUND: In early 2021, the Department of Health and Social Care in the UK called for research on the safety and immunogenicity of concomitant administration of COVID-19 and influenza vaccines. Co-administration of these vaccines would facilitate uptake and reduce the number of healthcare visits required. The ComFluCOV trial was designed to deliver the necessary evidence in time to inform the autumn (September-November) 2021 vaccination policy. This paper presents the statistical methodology applied to help successfully deliver the trial results in 6 months.
METHODS: ComFluCOV was a parallel-group multicentre randomised controlled trial managed by the Bristol Trials Centre. Two study statisticians, supported by a senior statistician, worked together on all statistical tasks. Tools were developed to aid the pre-screening process. Automated data monitoring reports of clinic data and electronic diaries were produced daily and reviewed by the trial team and feedback provided to sites. Analyses were performed independently in parallel, and derivations and results of all outcomes were compared.
RESULTS: Set-up was achieved in less than a month, and 679 participants were recruited over 8 weeks. A total of 537 [at least] daily reports outlining recruitment, protocol adherence, and data quality, and 695 daily reports of participant electronic diaries identifying any missed diary entries and adverse events were produced over a period of 16 weeks. A preliminary primary outcome analysis of validated data was reported to the Department of Health and Social Care in May 2021. The database was locked 6 weeks after the final participant follow-up and final analyses completed 3 weeks later. A pre-print publication was submitted within 14 days of the results being made available. The results were reported 6 months after first discussions about the trial.
CONCLUSIONS: The statistical methodologies implemented in ComFluCOV helped to deliver the study in the timescale set. Working in a new clinical area to tight timescales was challenging. Having two statisticians working together on the study provided a quality assurance process that enabled analyses to be completed efficiently and ensured data were interpreted correctly. Processes developed could be applied to other studies to maximise quality, reduce the risk of errors, and overall provide enhanced validation methods.
BACKGROUND: ISRCTN14391248, registered on 30 March 2021.