Dynamic treatment regimes: practical design considerations.
Dynamic treatment regimes: practical design considerations.
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DOI：
10.1191/1740774s04cn002oa
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发表时间：
2004-02-01
期刊：
影响因子：
--
通讯作者：
Dawson, Ree
中科院分区：
文献类型：
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作者：
Lavori, Philip W;Dawson, Ree
背景：慢性病的临床管理需要动态治疗方案（DTR）：根据对过去治疗的反应史选择新治疗的规则。从观察到的治疗和结果轨迹样本中估计和比较 DTR 的效果取决于不可检验的假设，即新治疗的分配独立于未来对治疗的潜在反应，以治疗历史和迄今为止的反应为条件（“顺序可忽略性”）。在纵向观察研究中，必须假设顺序可忽略性，而动态机制的随机化可以保证这一点。方法：使用几个临床例子，我们描述了用于比较 DTR 的最简单的随机实验设计。我们首先考虑初始治疗 A 和第二治疗 B，并讨论如何将从 A 开始并导致（有时）B 的动态治疗方案与固定治疗 A 或 B 进行比较。我们还说明了当有多种选择时在 DTR 中找到最佳治疗顺序的问题。我们描述并对比了将随机化纳入研究中以比较此类方案的两种方法：DTR 之间的基线随机化与决策点的随机化（顺序随机设计）。结论：我们讨论了基线随机和顺序随机设计的估计和推断，并最后讨论了优化和比较动态治疗方案的实验方法和观察方法之间的差异。
BACKGROUND: Clinical management of chronic disease requires a dynamic treatment regime (DTR): rules for choosing the new treatment based on the history of response to past treatments. Estimating and comparing the effects of DTRs from a sample of observed trajectories of treatment and outcome depends on the untestable assumption that new treatments are assigned independently of potential future responses to treatment, conditional on the history of treatments and response to date ("sequential ignorability"). In longitudinal observational studies, sequential ignorability must be assumed, while randomization of dynamic regimes can guarantee it.METHODS: Using several clinical examples, we describe the simplest randomized experimental designs for comparing DTRs. We begin by considering an initial treatment A and a second treatment B, and discuss how a dynamic treatment regime that starts with A and leads (sometimes) to B, might be compared to either fixed treatment A or B. We also illustrate the problem of finding the optimal sequence of treatments in a DTR, when there are several choices. We describe and contrast two ways of incorporating randomization into studies to compare such regimes: baseline randomization among DTRs versus randomization at the decision points (sequentially randomized designs).CONCLUSIONS: We discuss estimation and inference from both baseline randomized and sequentially randomized designs and conclude with a discussion of the differences between the experimental and observational approaches to optimizing and comparing dynamic treatment regimes.