Department of Computer Science and School of Biological Sciences, University of Texas, Austin, TX 78712, USA.
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22387-92. doi: 10.1073/pnas.0912378106. Epub 2009 Dec 14.
As electronic medical records enable increasingly ambitious studies of treatment outcomes, ethical issues previously important only to limited clinical trials become relevant to unlimited whole populations. For randomized clinical trials, adaptive assignment strategies are known to expose substantially fewer patients to avoidable treatment failures than strategies with fixed assignments (e.g., equal sample sizes). An idealized adaptive case--the two-armed Bernoulli bandit problem--can be exactly optimized for a variety of ethically motivated cost functions that embody principles of duty-to-patient, but the solutions have been thought computationally infeasible when the numbers of patients in the study (the "horizon") is large. We report numerical experiments that yield a heuristic approximation that applies even to very large horizons, and we propose a near-optimal strategy that remains valid even when the horizon is unknown or unbounded, thus applicable to comparative effectiveness studies on large populations or to standard-of-care recommendations. For the case in which the economic cost of treatment is a parameter, we give a heuristic, near-optimal strategy for determining the superior treatment (whether more or less costly) while minimizing resources wasted on any inferior, more expensive, treatment. Key features of our heuristics can be generalized to more complicated protocols.
随着电子病历能够进行越来越雄心勃勃的治疗效果研究,以前仅对有限临床试验重要的伦理问题现在与无限的整个人群相关。对于随机临床试验,适应性分配策略被认为比固定分配策略(例如,相等的样本量)能够使更少的患者遭受可避免的治疗失败。理想化的适应性病例 - 双臂伯努利带问题 - 可以针对各种基于道德的成本函数进行精确优化,这些函数体现了对患者的责任原则,但当研究中的患者数量(“视野”)很大时,人们认为解决方案在计算上是不可行的。我们报告了产生启发式近似的数值实验,即使对于非常大的视野也适用,并且我们提出了一种接近最优的策略,即使视野未知或无界也仍然有效,因此适用于大型人群的比较效果研究或标准护理建议。对于治疗经济成本是一个参数的情况,我们给出了一种启发式的、接近最优的策略,用于确定在最小化浪费在任何较差、较昂贵的治疗上的资源的同时,确定更好的治疗方法(无论是更昂贵还是更便宜)。我们启发式的关键特征可以推广到更复杂的方案。