Adaptive Methods: Telling "The Rest of the Story"
Adaptive Methods: Telling "The Rest of the Story"
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DOI：
10.1080/10543406.2010.514457
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发表时间：
2010-01-01
影响因子：
1.1
通讯作者：
Fleming, Thomas R.
中科院分区：
文献类型：
--
作者：
Emerson, Scott S.;Fleming, Thomas R.
美国食品药品监督管理局（FDA）关于适应性设计随机临床试验的指南草案对临床试验设计的非盲适应可能带来的困难进行了深入考虑。我们对这些困难进行了深入的讨论，重点关注自适应设计在随机临床试验结果的科学解释中所带来的问题，为监管机构以及希望就治疗选择做出循证决策的患者和护理人员提供帮助。我们考虑了在充分和良好对照研究中使用非盲治疗效果指标进行治疗适应性选择/修改、主要终点适应性选择、最大样本量适应性修改、随机化比例适应性修改和目标人群适应性修改（适应性富集）的影响，然后我们考虑了无缝2-3期设计的特殊主题。我们检查的程度，自适应设计不符合具有更高的效率，更有可能确定真正有效的治疗方法，信息量更大，并提供更大的灵活性的目标。我们完全支持FDA继续要求进行充分和良好对照的确证性研究，并以允许准确和精确估计治疗有效性的方式对整个随机临床试验设计进行前瞻性详细说明。
The Food and Drug Administration (FDA) draft guidance on adaptive design randomized clinical trials provides in-depth consideration of the difficulties that unblinded adaptation of clinical trial design might introduce. We provide extended discussion of these difficulties, with focus on the problems that the adaptive designs pose in the scientific interpretation of randomized clinical trial results, for regulatory authorities as well as for patients and caregivers who wish to make evidence-based decisions regarding the choice of treatment. We consider implications in adequate and well-controlled studies of the use of unblinded measures of treatment effect to make adaptive selection/modification of treatments, adaptive selection of primary endpoints, adaptive modification of maximal sample size, adaptive modification of randomization ratios, and adaptive modification of target populations (adaptive enrichment), and then we consider the special topic of seamless phase 2-3 designs. We examine the extent to which the adaptive designs do not meet the goals of having greater efficiency, being more likely to identify truly effective treatments, being more informative, and providing greater flexibility. We fully support the FDA's continued requirement of adequate and well-controlled confirmatory studies, complete with prospective, detailed specification of the entire randomized clinical trial design in a way that allows accurate and precise estimation of treatment effectiveness.