TRAFIC: statistical design and analysis plan for a pragmatic early phase 1/2 Bayesian adaptive dose escalation trial in rheumatoid arthritis.
TRAFIC: statistical design and analysis plan for a pragmatic early phase 1/2 Bayesian adaptive dose escalation trial in rheumatoid arthritis.
复制标题
TRAFIC：类风湿关节炎实用早期 1/2 期贝叶斯自适应剂量递增试验的统计设计和分析计划。
DOI：
10.1186/s13063-021-05384-5
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发表时间：
2021-07-06
期刊：
影响因子：
2.5
通讯作者：
Stocken DD
中科院分区：
文献类型：
--
作者：
Cole M;Yap C;Buckley C;Ng WF;McInnes I;Filer A;Siebert S;Pratt A;Isaacs JD;Stocken DD
基于自适应模型的剂量探索设计已证明比传统的基于规则的设计具有优势，但增加了统计复杂性，但采用速度缓慢，尤其是在癌症试验之外。 TRAFIC 是一项针对类风湿关节炎的多中心早期试验，采用基于模型的设计。贝叶斯自适应剂量探索 I 期试验进入单组、单阶段 II 期试验。第一阶段的模型参数是通过蒙特卡罗模拟选择的，评估临床相关场景下的客观性能指标，并纳入提前终止的停止规则。利用剂量转换途径进一步校准潜在的设计。 TRAFIC 是一项由 MRC 资助的重新用途治疗试验，表明可以在传统研究资助轨道和监管限制范围内，在非癌症人群中设计、资助和实施基于模型的 I 期试验。第一阶段的设计允许借用以前试验的信息，所有积累的数据都用于决策，通过模拟验证操作特性，通过剂量转换途径提高管理和监督团队的理解。滚动二期设计提高了试验实施的效率，包括现场和监测活动以及成本。 TRAFIC 是第一个资助的基于模型的炎症性疾病剂量探索试验，表明小型 I/II 期试验可以为决策和解释提供潜在的统计基础。试验注册：ISRCTN、ISRCTN36667085。 2014年9月26日注册。
Adaptive model-based dose-finding designs have demonstrated advantages over traditional rule-based designs but have increased statistical complexity but uptake has been slow especially outside of cancer trials. TRAFIC is a multi-centre, early phase trial in rheumatoid arthritis incorporating a model-based design. A Bayesian adaptive dose-finding phase I trial rolling into a single-arm, single-stage phase II trial. Model parameters for phase I were chosen via Monte Carlo simulation evaluating objective performance measures under clinically relevant scenarios and incorporated stopping rules for early termination. Potential designs were further calibrated utilising dose transition pathways. TRAFIC is an MRC-funded trial of a re-purposed treatment demonstrating that it is possible to design, fund and implement a model-based phase I trial in a non-cancer population within conventional research funding tracks and regulatory constraints. The phase I design allows borrowing of information from previous trials, all accumulated data to be utilised in decision-making, verification of operating characteristics through simulation, improved understanding for management and oversight teams through dose transition pathways. The rolling phase II design brings efficiencies in trial conduct including site and monitoring activities and cost. TRAFIC is the first funded model-based dose-finding trial in inflammatory disease demonstrating that small phase I/II trials can have an underlying statistical basis for decision-making and interpretation. Trials Registration: ISRCTN, ISRCTN36667085. Registered on September 26, 2014.
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影响因子：
6.4
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