神经保护剂的早期和随后的III期中风研究分析:结果和成功的预测因素。

Jens Minnerup, Heike Wersching, Matthias Schilling, Wolf Rüdiger Schäbitz
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引用次数: 30

摘要

背景:到目前为止,在临床III期试验中还没有令人信服地证明神经保护治疗对缺血性卒中的疗效,而之前的一些早期研究发现神经保护是有益的。我们的目的是确定在III期研究之前进行阳性早期研究的频率,并确定与III期研究正确预测相关的早期研究特征。方法:我们确定了脑卒中神经保护治疗的III期研究和相应的早期研究。提取早期试验的研究特征数据,并使用逻辑回归分析将结果分类为“假阳性”和“真中性”的研究进行比较。结果:确定了46项III期研究和59项相应的早期研究。只有一项III期研究是阳性的,该研究之后是一项更大的阴性研究。22例(37.3%)早期研究被认为是假阳性,37例(62.7%)被认为是真中性。没有任何早期研究特征与III期研究的正确预测显著相关。结论:超过三分之一的神经保护性脑卒中治疗的早期研究是假阳性。早期中风研究的结果和特定的研究设计特征都不能可靠地预测III期试验的成功。需要进一步努力改进早期阶段的可预测性研究,并确定哪些早期研究应推进到第三阶段试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of early phase and subsequent phase III stroke studies of neuroprotectants: outcomes and predictors for success.

Background: Efficacy of neuroprotective treatments for ischemic stroke was not convincingly demonstrated in clinical phase III trials so far, whereas some preceding early phase studies found neuroprotection to be beneficial. We aimed to determine the frequency with which phase III studies are preceded by positive early phase studies, and to identify characteristics of early phase studies that are associated with correct prediction of phase III studies.

Methods: We identified phase III studies and corresponding early phase studies of neuroprotective treatments for stroke. Data on study characteristics of early phase trials were extracted and compared between studies that were classified according to their results as "false positive" and "true neutral" using logistic regression analysis.

Results: Forty-six phase III studies and 59 corresponding early phase studies were identified. Only one phase III study was positive and this study was followed by a larger negative study. Twenty-two (37.3%) early phase studies were considered to be false positive and 37 (62.7%) to be true neutral. None of the early phase study characteristics were significantly associated with correct prediction of phase III studies.

Conclusions: More than one third of early phase studies on neuroprotective stroke treatments are false positive. Neither the results nor specific study design characteristics of early phase stroke studies reliably predict success in phase III trials. Further efforts are needed to improve early phase studies regarding its predictability and to identify those early studies that should be advanced to phase III trials.

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