A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS
A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS
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DOI：
10.1212/01.wnl.0000201182.60750.66
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发表时间：
2006-03-14
期刊：
影响因子：
9.9
通讯作者：
Thompson, JLP
中科院分区：
文献类型：
--
作者：
Levy, G;Kaufmann, P;Thompson, JLP
背景资料：在任何给定时间将一小部分患者与许多潜在的神经保护剂在ALS中进行测试的可用性相结合，需要有效的II期试验设计。目的：描述大剂量辅酶Q10（CoQ 10）治疗ALS的临床试验（QALS研究）的设计-一项II期、随机、安慰剂对照、双盲、多中心临床试验。方法：研究设计分为两个阶段。第一阶段（剂量选择）使用选择程序而不是正式的假设检验来确定两种剂量的辅酶Q10（1800 mg或2700 mg）中的哪一种是优选的。第二阶段（早期疗效测试）使用非优效性或无效性设计比较CoQ 10与安慰剂的首选剂量。在第一阶段中分配到CoQ 10首选剂量的患者的数据也用于第二阶段。主要结果指标是肌萎缩侧索硬化症功能评定量表-修订版（ALSFRSr）评分从基线至9个月的下降。结果如下：所需的总样本量为185例患者，相比之下，使用传统优效性设计估计需要更大的样本量（总计：852例患者）。作者报告了在第二阶段纳入第一阶段的患者数据所需的偏倚校正。结论：ALS研究设计中高剂量辅酶Q10临床试验的几个特征提高了效率。这些特征可能有益于肌萎缩侧索硬化症和其他领域的II期试验。
Background: The combination of a small pool of patients at any given time with the availability of many potential neuroprotective agents to be tested in ALS requires efficient phase II trial designs. Objective: To describe the design of the Clinical Trial of High Dose Coenzyme Q10 (CoQ10) in ALS (QALS study) - a phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial. Methods: The study design features two stages. The first stage (dose selection) identifies which of two doses of CoQ10 (1800 mg or 2700 mg) is preferred using a selection procedure rather than a formal hypothesis test. The second stage (early efficacy test) compares the preferred dose of CoQ10 against placebo using a non-superiority or futility design. Data from patients assigned to the preferred dose of CoQ10 in the first stage are also used in the second stage. The primary outcome measure is the decline in Amyotrophic Lateral Sclerosis Functional Rating Scale - revised (ALSFRSr) score from baseline to 9 months. Results: The total sample size required is 185 patients, as compared to a much larger sample size estimated to be necessary using a conventional superiority design (total: 852 patients). The authors report a bias correction made necessary by the inclusion of patient data from the first stage in the second stage. Conclusions: Several features of the Clinical Trial of High Dose Coenzyme Q10 in ALS study design promote efficiency. These features may be beneficial in phase II trials in amyotrophic lateral sclerosis and other fields.