Analysis of ordered composite endpoints.
Analysis of ordered composite endpoints.
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DOI：
10.1002/sim.8431
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发表时间：
2020-02-28
影响因子：
2
通讯作者：
Evans, Scott
中科院分区：
文献类型：
--
作者：
Follmann, Dean;Fay, Michael P.;Hamasaki, Toshimitsu;Evans, Scott
复合终点常用于临床试验，但简单的方法（如至首次事件的时间）并不能反映终点之间的任何顺序。然而，一些终点，如死亡率，比其他终点更差。已经提出了各种程序来反映单个终点的严重程度，如成对排序方法、获胜率和结局排序的可取性。然而，当患者有不同的随访时间时，排序可能很困难，并且所提出的方法不会自然地导致回归方法，并且需要专门的软件。本文定义了一个排序得分O操作化的病人等级隐含的分层终点。我们展示了如何差分右删失的后续行动对应于多个区间删失的排序得分，允许标准软件的生存模型被用来计算非参数最大似然估计（NPMLEs）的不同措施。此外，如果假设排序得分是可转换为指数随机变量，半参数回归，这是等效的比例风险模型的多个区间删失。标准软件可用于估算。我们表明，NPMLE可以表现不佳相比，交错进入试验中的简单估计。我们还表明，半参数估计可以比简单的估计更有效，并探讨如何标准的考克斯回归演习可以用来评估模型拟合，允许灵活的概括，并评估治疗的协变量的相互作用。我们使用我们的方法分析了一项短期与长期抗血小板治疗的试验。
Composite endpoints are frequently used in clinical trials, but simple approaches, such as the time to first event, do not reflect any ordering among the endpoints. However, some endpoints, such as mortality, are worse than others. A variety of procedures have been proposed to reflect the severity of the individual endpoints such as pairwise ranking approaches, the win ratio, and the desirability of outcome ranking. When patients have different lengths of follow-up, however, ranking can be difficult and proposed methods do not naturally lead to regression approaches and require specialized software. This paper defines an ordering score O to operationalize the patient ranking implied by hierarchical endpoints. We show how differential right censoring of follow-up corresponds to multiple interval censoring of the ordering score allowing standard software for survival models to be used to calculate the nonparametric maximum likelihood estimators (NPMLEs) of different measures. Additionally, if one assumes that the ordering score is transformable to an exponential random variable, a semiparametric regression is obtained, which is equivalent to the proportional hazards model subject to multiple interval censoring. Standard software can be used for estimation. We show that the NPMLE can be poorly behaved compared to the simple estimators in staggered entry trials. We also show that the semiparametric estimator can be more efficient than simple estimators and explore how standard Cox regression maneuvers can be used to assess model fit, allow for flexible generalizations, and assess interactions of covariates with treatment. We analyze a trial of short versus long-term antiplatelet therapy using our methods.
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影响因子：
2
作者：
FOLLMANN, D;WITTES, J;CUTLER, JA
通讯作者：
CUTLER, JA
影响因子：
2.1
作者：
Bebu, Ionut;Lachin, John M.
通讯作者：
Lachin, John M.
影响因子：
2.7
作者：
PRENTICE, RL
通讯作者：
PRENTICE, RL
影响因子：
--
作者：
MANN, HB;WHITNEY, DR
通讯作者：
WHITNEY, DR
影响因子：
11.3
作者：
Nakamura, Masato;Iijima, Raisuke;Yokoi, Hiroyoshi
通讯作者：
Yokoi, Hiroyoshi