ETHICAL AND SCIENTIFIC FEATURES OF CUTOFF-BASED DESIGNS OF CLINICAL-TRIALS - A SIMULATION STUDY
ETHICAL AND SCIENTIFIC FEATURES OF CUTOFF-BASED DESIGNS OF CLINICAL-TRIALS - A SIMULATION STUDY
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DOI：
10.1177/0272989x9501500409
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发表时间：
1995-10-01
影响因子：
3.6
通讯作者：
TROCHIM, WMK
中科院分区：
文献类型：
--
作者：
CAPPELLERI, JC;TROCHIM, WMK
基于临界值的临床试验设计旨在平衡伦理和科学问题，当认为将所有患者随机分配至研究治疗是不道德或不可行的时。在基于临界值的随机化设计中，根据定量基线指标，病情最轻的患者被分配到对照治疗组，根据相同指标，病情最重的患者被分配到试验治疗组，根据指标，病情中度的患者被随机分配。进行模拟以检查具有不同数量的基于截止值的分配和随机化的设计的统计效率和潜在偏倚。所有设计变异均产生了主要治疗效应和线性相互作用效应的无偏估计值。虽然随机化往往会导致更高的效率（或更低的治疗效果标准误），但二元治疗变量和基线分配变量之间的相关性完全决定了设计的效率。
Cutoff-based clinical trial designs are geared towards balancing ethical and scientific concerns when it is deemed unethical or infeasible to randomize all patients to study treatments. In a cutoff-based design with randomization, patients who are the least sick based on a quantitative baseline indicator are assigned the control treatment, patients who are the most sick based on the same indicator are assigned to test treatment, and patients who are moderately sick based on the indicator are randomly assigned. Simulations were conducted to examine statistical efficiency and potential bias for designs with varying amounts of cutoff-based assignment and randomization. All design variations yielded unbiased estimates of a main treatment effect and a linear interaction effect. While randomization tends to lead to greater efficiency (or lower standard errors of treatment effect), the correlation between the binary treatment variable and baseline assignment variable completely determines the efficiency of a design.