Departments of Neurology and Rehabilitation Medicine (R.J.S., D.J.R., Y.N.A., P.K., J.P.B., M.L.F., D.W., S.F., B.M.K.), University of Cincinnati College of Medicine, OH.
Emergency Medicine (H.S.), University of Cincinnati College of Medicine, OH.
Stroke. 2023 Apr;54(4):1009-1014. doi: 10.1161/STROKEAHA.122.041650. Epub 2023 Feb 28.
Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed.
In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan.
After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0-2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to <6), the number predicted to be eligible for the trial increased to 4%. At the time of trial conclusion, 57% of the enrolled patients qualified only by the modified criteria, and the trial was stopped at an interim analysis that demonstrated efficacy. We estimated that the Wilcoxon rank-sum value for the unadjusted predicted enrollment would not have crossed the threshold for efficacy and the trial not stopped.
Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.
临床试验的入组和完成具有挑战性，近一半的试验未完成或未按时完成。2014 年，美国国立卫生研究院卒中网与 GCNKSS（辛辛那提/北肯塔基州卒中研究）的卒中流行病学家合作，开始对拟议的临床试验进行正式的试验可行性评估。在此，我们描述了使用流行病学数据进行前瞻性可行性分析的过程，该过程可用于提高入组率并增加试验完成的可能性。
2014 年，DEFUSE 3（缺血性卒中血管内治疗后影像学评估 3）试验人员、美国国立卫生研究院卒中网和 GCNKSS 的卒中流行病学家合作，评估了 DEFUSE 3 研究的初始纳入/排除标准。讨论了试验标准，并进行了评估，以评估可能符合该研究条件的卒中人群的比例。DAWN（卒中后 6-24 小时血栓切除术与缺损和梗死之间不匹配）的发表使 DEFUSE 3 试验提前停止，使用 Wilcoxon 秩和检验统计分析，根据 DEFUSE 3 统计分析计划，分析如果未进行拟议的更改，试验是否会提前停止。
在初步的流行病学分析后，GCNKSS 人群中 2.4%的急性卒中患者预计符合该研究条件。与主要研究者讨论后，修改了 4 个关键排除标准（年龄上限提高到 90 岁，基线改良 Rankin 量表拓宽到 0-2，上次良好的时间延长到 16 小时，降低 NIHSS 评分下限至<6），预测符合试验条件的人数增加到 4%。在试验结束时，只有 57%的入组患者符合修改后的标准，并且在中期分析中显示出疗效的情况下停止了试验。我们估计，未经调整的预测入组人数的 Wilcoxon 秩和值不会超过疗效的阈值，试验也不会停止。
在协作和迭代过程中，使用基于人群的资源客观评估试验的纳入/排除标准，包括流行病学家，可以提高招募效果，并增加成功完成试验的可能性。
