Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, WI, USA.
Neurology. 2012 Sep 25;79(13 Suppl 1):S221-33. doi: 10.1212/WNL.0b013e31826992cf.
Randomized, double-blinded, placebo-controlled trials have significant impact on clinical practice. The ultimate goal of a clinical trial of therapy for acute ischemic stroke (AIS) is to compare 2 interventions. Challenges may include interventional therapy standardization, enrollment rate, patient selection, biases, data and safety monitoring, reporting, and financial and logistical support.
Selected randomized and single-arm prospective AIS trial designs. Clinical trial elements and their challenges are reviewed. Innovative designs and proposed recommendations to overcome some of the specific challenges and limitations are discussed.
AIS therapy trials have specific challenges related to ethical issues, enrollment rate, outcome measures, limited time to treatment, efficacy, safety, and limited or variable operator experience with complex technology in a delicate end organ. Proposed suggestions for improving trial design include the following: incorporation of a lead-in phase; careful patient and outcome measure selection; historical, concurrent, or hybrid controls; open data access; and a Bayesian approach. An open data paradigm may facilitate creation of computerized prediction models for future trials (minimizing cost by decreasing sample size or providing futility analyses and directing resources to other trials). Collaborative, consortium, and network infrastructures may allow more effective and efficient study completion. Self-learning, self-correcting trials with intrinsic flexibility to adapt may help future clinical trial design in AIS.
The randomized clinical trial design in AIS endovascular therapy is challenging. Lead-in phases, careful patient selection, use of innovative outcome measures, control groups, and newer clinical trial design may enhance conduct of future trials, their validity, and their results.
随机、双盲、安慰剂对照试验对临床实践有重大影响。急性缺血性脑卒中（AIS）治疗临床试验的最终目标是比较两种干预措施。挑战可能包括介入治疗标准化、入组率、患者选择、偏倚、数据和安全监测、报告以及财务和后勤支持。
选择随机和单臂前瞻性 AIS 试验设计。审查临床试验要素及其挑战。讨论了创新设计和提出的建议，以克服一些特定的挑战和局限性。
AIS 治疗试验具有与伦理问题、入组率、结局指标、治疗时间有限、疗效、安全性以及在精细终末器官中对复杂技术的有限或可变操作人员经验相关的特定挑战。改进试验设计的建议包括以下内容：引入期；仔细选择患者和结局指标；历史、同期或混合对照；开放数据访问；以及贝叶斯方法。开放数据范式可能有助于为未来试验创建计算机预测模型（通过减少样本量或提供无效性分析并将资源引导至其他试验来最小化成本）。协作、联盟和网络基础设施可以使研究更有效和高效地完成。具有内在灵活性的自我学习、自我修正试验可能有助于未来 AIS 临床试验设计。
AIS 血管内治疗的随机临床试验设计具有挑战性。引入期、仔细的患者选择、使用创新的结局指标、对照组以及新的临床试验设计可以提高未来试验的进行、有效性和结果。
