SELECTION DESIGNS FOR PILOT-STUDIES BASED ON SURVIVAL
SELECTION DESIGNS FOR PILOT-STUDIES BASED ON SURVIVAL
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DOI：
10.2307/2532552
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发表时间：
1993-06-01
期刊：
影响因子：
1.9
通讯作者：
CROWLEY, J
中科院分区：
文献类型：
--
作者：
LIU, PY;DAHLBERG, S;CROWLEY, J
在癌症临床试验中，新方案通常在晚期患者中进行抗肿瘤活性测试。然后，在一项随机研究中，将有希望的治疗方法与标准治疗方法进行比较，有时对早期疾病患者进行治疗。当有多种有希望的方案时，由于样本量和研究时间的限制，可能不可能将所有方案与对照组进行比较。我们提出了一种设计，在随机比较之前，使用Cox回归模型根据生存率选择最佳治疗方案。样本量的渐近正确选择概率。对于威布尔生存分布，我们提出了90个我们认为有实际意义的参数范围。仿真验证了正确选择概率的渐近逼近是令人满意的。仿真还表明，该程序对比例风险假设具有相当的鲁棒性。与Schaid、Wieand和Therneau （1990, Biometrika 77,507 -513）推荐的两阶段筛选设计相比，我们的设计具有自然拟合癌症试验进展的优势，其中选择和比较阶段是在不同的患者群体中进行的。当感兴趣的总体保持不变时，我们的设计可以在平均上更加保守，但提供了基于在选择阶段获得的经验进行比较试验的机会。
In cancer clinical trials new regimens are typically tested for antitumor activities in patients with advanced disease. The promising ones are then compared to the standard treatment in a randomized study, sometimes performed on patients with earlier-stage disease. When there are multiple promising regimens, it may not be possible to compare all of them to the control group because of the prohibitive sample size and study length requirements. We propose a design that uses the Cox regression model to select a best treatment based on survival before the randomized comparison. Sample sizes for an asymptotically correct selection probability of .90 are presented for Weibull survival distributions with parameters in a range we consider to be of practical interest. Simulations verify that the asymptotic approximations to the correct selection probabilities are quite satisfactory. Simulations also indicate that the procedure is reasonably robust to the proportional hazards assumption. In contrast to the two-stage screening design recommended by Schaid, Wieand, and Therneau (1990, Biometrika 77, 507-513), our design has the advantage of fitting naturally to a progression of cancer trials where the selection and comparison phases are carried out on different populations of patients. When the population of interest stays the same, our design can be more conservative on the average but offers the opportunity to base the comparative trial on the experience gained during the selection phase.