Using Epidemiological Data to Inform Clinical Trial Feasibility Assessments: A Case Study.
Using Epidemiological Data to Inform Clinical Trial Feasibility Assessments: A Case Study.
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使用流行病学数据为临床试验可行性评估提供信息：案例研究。
作者：
Stanton,RobertJ;Robinson,DavidJ;Aziz,YasminN;Sucharew,Heidi;Khatri,Pooja;Broderick,JosephP;Janis,LScott;Kemp,Stephanie;Mlynash,Michael;Lansberg,MaartenG;Albers,GregoryW;Saver,JeffreyL;Flaherty,MatthewL;Adeoye,Opeolu;Wo
背景临床试验的入组和完成具有挑战性，所有试验中近一半未完成或未按时完成。 2014 年，美国国立卫生研究院 StrokeNet 与 GCNKSS（大辛辛那提/北肯塔基州中风研究）的中风流行病学家合作，开始提供拟议的临床试验以及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，该数据可用于提高入组率并增加试验完成的可能性。方法2014年，DEFUSE 3（缺血性中风影像评估后的血管内治疗3）试验者、美国国立卫生研究院StrokeNet和来自GCNKSS的中风流行病学家合作评估了DEFUSE 3研究的初始纳入/排除标准。讨论了试验标准并完成了评估，以评估可能符合该研究资格的中风人群的百分比。 DEFUSE 3 试验随着 DAWN（中风后 6 至 24 小时血栓切除术，缺损与梗塞之间不匹配）的发表而提前停止，并使用 Wilcoxon 秩和统计来分析如果不按照 DEFUSE 3 统计分析计划进行拟议的更改，试验是否会停止。结果经过初步流行病学分析，GCNKSS 人群中有 2.4% 的急性中风患者预计有资格参加这项研究。经过与主要研究者讨论并修改 4 项关键排除标准（年龄上限提高至 90 岁，基线修改后的 Rankin 量表扩大至 0-2，自上次井起的时间扩大至 16 小时，并将美国国立卫生研究院卒中量表评分下限降低至 <6），预计符合试验资格的人数增加至 4%。在试验结论时，57% 的入组患者仅符合修改后的标准，试验在中期分析证明疗效时停止。我们估计，未经调整的预测入组的 Wilcoxon 秩和值不会超过疗效阈值，并且试验不会停止。 结论 在包括流行病学家在内的协作和迭代过程中使用基于人群的资源客观评估试验纳入/排除标准可以改善招募情况，并增加试验成功完成的可能性。
BackgroundClinical 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.MethodsIn 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.ResultsAfter 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.ConclusionsObjectively 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.
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