Point and interval estimation in two-stage adaptive designs with time to event data and biomarker-driven subpopulation selection.
Point and interval estimation in two-stage adaptive designs with time to event data and biomarker-driven subpopulation selection.
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DOI：
10.1002/sim.8557
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发表时间：
2020-08-30
影响因子：
2
通讯作者：
Stallard N
中科院分区：
文献类型：
--
作者：
Kimani PK;Todd S;Renfro LA;Glimm E;Khan JN;Kairalla JA;Stallard N
在个性化医疗中，通常需要确定是否所有患者或仅其中的一部分患者受益于治疗。我们考虑两阶段自适应设计中的估计，即在第1阶段从全部人群中招募患者。在第2阶段，患者招募仅限于根据第1阶段数据从实验性治疗中获益的人群。现有的估计值，调整使用第1阶段数据选择部分人群，从第2阶段患者招募，以及第2阶段后的验证性分析，不考虑事件患者结局的时间。在这项工作中，对于事件数据的时间，我们推导出一个新的渐近无偏估计的对数风险比和一个新的区间估计具有良好的覆盖概率和概率的上限低于真实值。估计量适用于基于单个或多个生物标志物的几种选择规则，这些生物标志物可以是分类的或连续的。
In personalized medicine, it is often desired to determine if all patients or only a subset of them benefit from a treatment. We consider estimation in two-stage adaptive designs that in stage 1 recruit patients from the full population. In stage 2, patient recruitment is restricted to the part of the population, which, based on stage 1 data, benefits from the experimental treatment. Existing estimators, which adjust for using stage 1 data for selecting the part of the population from which stage 2 patients are recruited, as well as for the confirmatory analysis after stage 2, do not consider time to event patient outcomes. In this work, for time to event data, we have derived a new asymptotically unbiased estimator for the log hazard ratio and a new interval estimator with good coverage probabilities and probabilities that the upper bounds are below the true values. The estimators are appropriate for several selection rules that are based on a single or multiple biomarkers, which can be categorical or continuous.
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影响因子：
2
作者：
Kimani PK;Todd S;Renfro LA;Stallard N
通讯作者：
Stallard N
影响因子：
2
作者：
Kimani, Peter K.;Todd, Susan;Stallard, Nigel
通讯作者：
Stallard, Nigel
影响因子：
2.7
作者：
MARCUS, R;PERITZ, E;GABRIEL, KR
通讯作者：
GABRIEL, KR
影响因子：
11.5
作者：
Grothey, Axel;Strosberg, Jonathan R.;Diaz, Luis Alberto, Jr.
通讯作者：
Diaz, Luis Alberto, Jr.
影响因子：
1.7
作者：
Kimani, Peter K.;Todd, Susan;Stallard, Nigel
通讯作者：
Stallard, Nigel