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A dose finding design for seizure reduction in neonates

机译:用于减少新生儿癫痫发作的剂量寻找设计

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摘要

Clinical trials in vulnerable populations are extremely difficult to conduct. A sequential phase Ⅰ-Ⅱ trial aimed at finding the appropriate dose of levetiracetam for treating neonatal seizures was planned with a maximum sample size of 50 newborns. Three primary outcomes are considered: efficacy and two types of toxicity that occur at the same time but are measured at different time points. In the case of failure, physicians could add a second agent as a rescue medication.The primary outcomes were modelled via a logistic model for efficacy and a weighted likelihood with pseudo-outcomes for the two toxicities taking into account the dependences under Bayesian inference. Simulations were conducted to assess the design properties.
机译:在脆弱人群中进行临床试验非常困难。计划进行一项Ⅰ-Ⅱ期连续试验,旨在寻找合适剂量的左乙拉西坦治疗新生儿癫痫发作,最大样本量为50个新生儿。考虑了三个主要结局:功效和两种毒性同时发生,但在不同时间点进行测量。在失败的情况下,医生可以添加第二种药物作为急救药物。主要结果通过logistic模型进行建模,以功效和加权可能性与两种毒性的假性结果(考虑到贝叶斯推断的依赖性)进行建模。进行了仿真以评估设计属性。

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  • 来源
    《Journal of the royal statistical society》 |2019年第2期|427-444|共18页
  • 作者单位

    Institut National de la Sante et de la Recherche Medicate, Universite Paris Descartes and Universite Paris-Sorbonne, France;

    University of Texas MD Anderson Cancer Center, Houston, USA;

    Institut National de la Sante et de la Recherche Medicate, Hopital Robert-Debre and Universite Paris Diderot, France;

    Institut National de la Sante et de la Recherche Medicate, Universite Rennes-1 and Universite Paris Diderot, France;

    Centre Hospitallers Regionaux et Universitaire de Tours, France;

    Universitaetsmedizin Goettingen, Germany;

    Federal Institute for Drugs and Medical Devices, Bonn, Germany;

    University of Warwick, Coventry, UK;

    Institut National de la Sante et de la Recherche Medicale, Universite Paris Descartes and Universite Paris-Sorbonne, France;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Efficacy; Newborns; Phase Ⅰ-Ⅱ; Time to event; Toxicity constraints;

    机译:功效;新生儿Ⅰ-Ⅱ期;活动时间;毒性约束;

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