Center for Applied Statistics, Renmin University of China, Beijing, China.
School of Statistics, Renmin University of China, Beijing, China.
Stat Med. 2022 Oct 30;41(24):4903-4923. doi: 10.1002/sim.9543. Epub 2022 Aug 10.
Patients with chronic diseases, such as cancer or epilepsy, are often followed through multiple stages of clinical interventions. Dynamic treatment regimes (DTRs) are sequences of decision rules that assign treatments at each stage based on measured covariates for each patient. A DTR is said to be optimal if the expectation of the desirable clinical benefit reaches a maximum when applied to a population. When there are three or more options for treatments at each decision point and the clinical outcome of interest is a time-to-event variable, estimating an optimal DTR can be complicated. We propose a doubly robust method to estimate optimal DTRs with multicategory treatments and survival outcomes. A novel blip function is defined to measure the difference in expected outcomes among treatments, and a doubly robust weighted least squares algorithm is designed for parameter estimation. Simulations using various weight functions and scenarios support the advantages of the proposed method in estimating optimal DTRs over existing approaches. We further illustrate the practical value of our method by applying it to data from the Standard and New Antiepileptic Drugs study. In this analysis, the proposed method supports the use of the new drug lamotrigine over the standard option carbamazepine. When the actual treatments match the estimated optimal treatments, survival outcomes tend to be better. The newly developed method provides a practical approach for clinicians that is not limited to cases of binary treatment options.
患有慢性疾病（如癌症或癫痫）的患者通常会经历多个临床干预阶段。动态治疗方案（DTR）是一系列决策规则，根据每个患者的测量协变量在每个阶段分配治疗方法。如果将其应用于人群时，理想的临床益处的期望达到最大值，则可以说 DTR 是最优的。当每个决策点有三种或更多种治疗选择，且感兴趣的临床结果是时间事件变量时，估计最优 DTR 可能会很复杂。我们提出了一种用于估计具有多类别治疗和生存结果的最优 DTR 的双重稳健方法。定义了一个新颖的“毛刺函数”来测量治疗之间预期结果的差异，并设计了一种双重稳健加权最小二乘算法来进行参数估计。使用各种权重函数和场景进行的模拟支持了与现有方法相比，该方法在估计最优 DTR 方面的优势。我们通过将其应用于标准和新型抗癫痫药物研究的数据进一步说明了我们方法的实际价值。在这项分析中，该方法支持使用新药拉莫三嗪代替标准选择卡马西平。当实际治疗与估计的最优治疗相匹配时，生存结果往往会更好。新开发的方法为临床医生提供了一种实用的方法，不仅限于二进制治疗方案的情况。
