A clinical trial design using the concept of proportional time using the generalized gamma ratio distribution.
A clinical trial design using the concept of proportional time using the generalized gamma ratio distribution.
复制标题
使用一般伽马比分布的比例时间概念的临床试验设计。
DOI：
10.1002/sim.7421
复制
发表时间：
2017-11-20
影响因子：
2
通讯作者：
Mayo MS
中科院分区：
文献类型：
--
作者：
Phadnis MA;Wetmore JB;Mayo MS
在具有至事件发生时间终点的临床试验中，传统的样本量和把握度计算方法基于对数秩检验（及其变化）、考克斯比例风险（PH）假设或2个指数分布均值的比较。其中，基于PH假设的样本量计算可能是最常见的，并允许调整一个或多个协变量的影响。然而，在设计试验时，存在PH假设可能不合适的情况。此外，当已知对照组的生存曲线快速下降时，例如从先前进行的观察性研究中，基于PH假设的设计可能仅为治疗组带来轻微的统计学改善，既无临床意义也无实际意义。对于这种情况下，提出了一种临床试验设计，重点是改善患者寿命，基于比例时间的概念，使用广义伽马比分布。进行模拟，以评估的比例时间方法的性能，并确定的情况下，这样的设计将是有益的相比，标准设计使用PH假设，分段指数风险假设，和特定情况下的治愈率模型。一个实际的例子，其中出血性中风患者被随机分配到2组之一，在一个假定的临床试验证明了这种方法的有效性，大大减少了研究招募所需的患者人数。
Traditional methods of sample size and power calculations in clinical trials with a time-to-event end point are based on the logrank test (and its variations), Cox proportional hazards (PH) assumption, or comparison of means of 2 exponential distributions. Of these, sample size calculation based on PH assumption is likely the most common and allows adjusting for the effect of one or more covariates. However, when designing a trial, there are situations when the assumption of PH may not be appropriate. Additionally, when it is known that there is a rapid decline in the survival curve for a control group, such as from previously conducted observational studies, a design based on the PH assumption may confer only a minor statistical improvement for the treatment group that is neither clinically nor practically meaningful. For such scenarios, a clinical trial design that focuses on improvement in patient longevity is proposed, based on the concept of proportional time using the generalized gamma ratio distribution. Simulations are conducted to evaluate the performance of the proportional time method and to identify the situations in which such a design will be beneficial as compared to the standard design using a PH assumption, piecewise exponential hazards assumption, and specific cases of a cure rate model. A practical example in which hemorrhagic stroke patients are randomized to 1 of 2 arms in a putative clinical trial demonstrates the usefulness of this approach by drastically reducing the number of patients needed for study enrollment.
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DOI：
10.1056/nejmoa1609783
发表时间：
2017-03-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kantarjian H;Stein A;Gökbuget N;Fielding AK;Schuh AC;Ribera JM;Wei A;Dombret H;Foà R;Bassan R;Arslan Ö;Sanz MA;Bergeron J;Demirkan F;Lech-Maranda E;Rambaldi A;Thomas X;Horst HA;Brüggemann M;Klapper W;Wood BL;Fleishman A;Nagorsen D;Holland C;Zimmerman Z;Topp MS
通讯作者：
Topp MS
影响因子：
13.6
作者：
Wetmore, James B.;Ellerbeck, Edward F.;Shireman, Theresa I.
通讯作者：
Shireman, Theresa I.
影响因子：
2
作者：
Lakatos, E
通讯作者：
Lakatos, E
在限制的生存分析中，平均生存时间曲线。
影响因子：
1.9
作者：
Zhao L;Claggett B;Tian L;Uno H;Pfeffer MA;Solomon SD;Trippa L;Wei LJ
通讯作者：
Wei LJ
影响因子：
2
作者：
WEI, LJ
通讯作者：
WEI, LJ