Simulation of various randomization strategies for a clinical trial in sickle cell disease.
Simulation of various randomization strategies for a clinical trial in sickle cell disease.
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DOI：
10.1080/10245332.2015.1101966
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Glassberg J
中科院分区：
文献类型：
--
作者：
Meurer WJ;Connor JT;Glassberg J
使用数值模拟评估镰状细胞病（SCD）临床试验的各种随机化策略。IMPROVE试验 * 是一项随机、对照、吸入莫米松治疗无哮喘的SCD患者的可行性研究。目标样本量为45例患者，目标之一是限制两个重要协变量的不平衡：1）羟基脲的使用和2）急诊室的历史利用率。我们使用数值模拟（10，000次试验）比较了三种患者分配方法（简单随机化，区组随机化，偏倚硬币自适应随机化）。主要结局指标是模拟试验的比例，两个协变量在数值上存在明显差异：羟基脲的使用（二元）和急诊科的利用（三级有序）。总的来说，只有1.6%的模拟试验有任何协变量比较，对于简单随机化，各组之间的p<0.3，对于区组和自适应随机化，这一比例为0%。在总样本量为45例患者的试验中，区组随机化策略实现了最大的平衡，因为受试者被确定性地分配到平衡协变量的治疗组。自适应策略在没有确定性治疗分配的情况下取得了类似的结果，即使试验仅包括45例患者。适应性临床试验设计有可能减轻一些阻碍SCD试验的挑战。在小型探索性试验中，即使重要协变量的非统计学显著差异也会威胁到可解释性和外部效度。与区组随机化类似，自适应随机化提供了优势，包括更好的分配隐藏和研究者预测下一次分配的能力较低。
To use numerical simulation to evaluate various randomization strategies for a clinical trial in Sickle Cell Disease (SCD). The IMPROVE trial* is a randomized, controlled, feasibility study of inhaled mometasone for individuals with SCD who do not have asthma. The target sample size is 45 patients and one goal is to limit imbalance with respect to two important covariates 1) hydroxyurea use and 2) historical emergency department utilization. We compared three methods of patient allocation (simple randomization, block randomization, biased-coin adaptive randomization) using numerical simulation (10,000 trials). The primary outcome measure was the proportion of simulated trials with numerically apparent differences in the two covariates: hydroxyurea use (binary) and emergency department utilization (three level ordinal). Overall, only 1.6% of simulated trials had any covariate comparison with p<0.3 across groups for simple randomization, and 0% for both the block and adaptive randomization. In trials where the total sample size was 45 patients, the block randomization strategy achieved the greatest balance because participants were deterministically assigned to the treatment arm that balanced covariates. The adaptive strategy achieved similar results without deterministic treatment assignments even when trials included only 45 patients. Adaptive clinical trial designs have potential to mitigate some of the challenges that have hampered SCD trials. In small exploratory trials, even non-statistically significant differences in important covariates can threaten interpretability and external validity. Adaptive randomization performed similarly to block randomization offers advantages including better allocation concealment and less ability for investigators to predict the next assignment.
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影响因子：
20.3
作者：
Ballas, Samir K.;Gupta, Kalpna;Adams-Graves, Patricia
通讯作者：
Adams-Graves, Patricia
影响因子：
4.4
作者：
Glassberg, Jeffrey A.;Wang, Jason;DeBaun, Michael R.
通讯作者：
DeBaun, Michael R.
影响因子：
2
作者：
SIGNORINI, DF;LEUNG, O;CALLAGHAN, T
通讯作者：
CALLAGHAN, T
影响因子：
6.5
作者：
Glassberg, Jeffrey A.;Chow, Annie;Richardson, Lynne D.
通讯作者：
Richardson, Lynne D.
影响因子：
6.5
作者：
Wang, Winfred;Brugnara, Carlo;Kesler, Karen
通讯作者：
Kesler, Karen