Response-adaptive decision-theoretic trial design: operating characteristics and ethics.
Response-adaptive decision-theoretic trial design: operating characteristics and ethics.
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DOI：
10.1002/sim.5807
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发表时间：
2013-09-20
影响因子：
2
通讯作者：
Lewis, Roger J.
中科院分区：
文献类型：
--
作者：
Lipsky, Ari M.;Lewis, Roger J.
关键词：
在临床试验中使用自适应随机化来提高统计效率。此外，一些临床医生和研究人员认为，在试验中使用适应性随机化必然会导致对受试者进行更道德的治疗。我们开发了贝叶斯、决策理论和临床试验设计，采用响应自适应随机化，并以估计治疗效果为主要目标，然后将这些设计与在其损失函数中也包括较差受试者结果的成本的设计进行比较。当损失函数不包含不良受试者结果的成本时，响应适应性随机化带来的效率提高伴随着与受试者分配有关的伦理问题。相反，包括不良受试者结果的成本，显示了试验中相互竞争的需求之间更可接受的平衡。随后的一组旨在明确控制I型和II型错误率的平行试验表明，通过修改损失函数实现的大部分改进基本上被否定了。因此，通过使用使用自适应随机化的决策理论、响应自适应设计而获得的效率收益可能仅适用于明确包括在损失函数中的那些目标。没有出现在损失函数中的试验目标，包括伦理目标被忽视，甚至可能受到损害；因此，假设所有适应性试验必然更符合伦理是不合适的。控制第一类和第二类错误率在很大程度上抵消了包括竞争需求的好处，有利于参数估计的目标。
Adaptive randomization is used in clinical trials to increase statistical efficiency. In addition, some clinicians and researchers believe that using adaptive randomization leads necessarily to more ethical treatment of subjects in a trial. We develop Bayesian, decision-theoretic, clinical trial designs with response-adaptive randomization and a primary goal of estimating treatment effect, and then contrast these designs with designs that also include in their loss function a cost for poor subject outcome. When the loss function did not incorporate a cost for poor subject outcome, the gains in efficiency from response-adaptive randomization were accompanied by ethically concerning subject allocations. Conversely, including a cost for poor subject outcome demonstrated a more acceptable balance between the competing needs in the trial. A subsequent, parallel set of trials designed to control explicitly type I and II error rates showed that much of the improvement achieved through modification of the loss function was essentially negated. Therefore, gains in efficiency from the use of a decision-theoretic, response-adaptive design using adaptive randomization may only be assumed to apply to those goals which are explicitly included in the loss function. Trial goals, including ethical ones, which do not appear in the loss function are ignored and may even be compromised; it is thus inappropriate to assume that all adaptive trials are necessarily more ethical. Controlling type I and II error rates largely negates the benefit of including competing needs in favor of the goal of parameter estimation.
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DOI：
10.1177/1740774511406950
发表时间：
2011-08
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Lipsky AM;Greenland S
通讯作者：
Greenland S
影响因子：
3.7
作者：
LEWIS, RJ;BERRY, DA
通讯作者：
BERRY, DA
影响因子：
1.1
作者：
Gallo, Paul;Chuang-Stein, Christy;Pinheiro, Jose
通讯作者：
Pinheiro, Jose
影响因子：
5.7
作者：
Berry, DA
通讯作者：
Berry, DA
影响因子：
2.7
作者：
Cheng, Y;Su, FS;Berry, DA
通讯作者：
Berry, DA