Implementing the EffTox dose-finding design in the Matchpoint trial.
Implementing the EffTox dose-finding design in the Matchpoint trial.
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DOI：
10.1186/s12874-017-0381-x
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发表时间：
2017-07-20
影响因子：
4
通讯作者：
Yap C
中科院分区：
文献类型：
--
作者：
Brock K;Billingham L;Copland M;Siddique S;Sirovica M;Yap C
Matchpoint试验旨在确定泊那替尼与常规化疗（包括氟达拉滨、阿糖胞苷和伊达比啶）联合治疗急变期慢性粒细胞白血病患者的最佳剂量。剂量应是可耐受的和有效的。本文介绍了我们在Matchpoint试验中实施EffTox的经验。EffTox是一种贝叶斯自适应剂量探索试验设计，共同审查二元疗效和毒性结果。我们描述了一个简洁描述I/II期剂量探索试验结果的命名法。我们使用剂量转换途径，在未来队列中为每个可行的结果集计算剂量。我们介绍了剂量矛盾的现象，EffTox可以在观察到相同的结果后推荐不同的剂量。我们还描述了我们的经验与结果的模糊性，其中一些主要结果的分类评价是暂时延迟。我们得到了一个EffTox参数化，该参数化被模拟为在一系列场景中表现良好。在出现剂量矛盾的情况下，我们遵循剂量转换途径。这种技术有助于规划，也有助于我们克服短期结果的模糊性。EffTox是一种高效而强大的设计，但并非没有挑战。联合I/II期临床试验设计在未来几年可能会变得越来越重要，因为我们进一步研究非细胞毒性治疗并简化药物审批程序。我们希望我们所面临的问题和我们使用的解决方案的描述将有助于其他人实施这种剂量探索临床试验设计。2013年12月30日，将Matchpoint添加至欧洲临床试验数据库（https：//www.clinicaltrialsregister.eu/ctr-search/trial/2012-005629-65/GB）。
The Matchpoint trial aims to identify the optimal dose of ponatinib to give with conventional chemotherapy consisting of fludarabine, cytarabine and idarubicin to chronic myeloid leukaemia patients in blastic transformation phase. The dose should be both tolerable and efficacious. This paper describes our experience implementing EffTox in the Matchpoint trial. EffTox is a Bayesian adaptive dose-finding trial design that jointly scrutinises binary efficacy and toxicity outcomes. We describe a nomenclature for succinctly describing outcomes in phase I/II dose-finding trials. We use dose-transition pathways, where doses are calculated for each feasible set of outcomes in future cohorts. We introduce the phenomenon of dose ambivalence, where EffTox can recommend different doses after observing the same outcomes. We also describe our experiences with outcome ambiguity, where the categorical evaluation of some primary outcomes is temporarily delayed. We arrived at an EffTox parameterisation that is simulated to perform well over a range of scenarios. In scenarios where dose ambivalence manifested, we were guided by the dose-transition pathways. This technique facilitates planning, and also helped us overcome short-term outcome ambiguity. EffTox is an efficient and powerful design, but not without its challenges. Joint phase I/II clinical trial designs will likely become increasingly important in coming years as we further investigate non-cytotoxic treatments and streamline the drug approval process. We hope this account of the problems we faced and the solutions we used will help others implement this dose-finding clinical trial design. Matchpoint was added to the European Clinical Trials Database (https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005629-65/GB) on 2013-12-30.
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影响因子：
3.8
作者：
Briasoulis E;Aravantinos G;Kouvatseas G;Pappas P;Biziota E;Sainis I;Makatsoris T;Varthalitis I;Xanthakis I;Vassias A;Klouvas G;Boukovinas I;Fountzilas G;Syrigos KN;Kalofonos H;Samantas E
通讯作者：
Samantas E
影响因子：
6.2
作者：
Saglio G;Hochhaus A;Goh YT;Masszi T;Pasquini R;Maloisel F;Erben P;Cortes J;Paquette R;Bradley-Garelik MB;Zhu C;Dombret H
通讯作者：
Dombret H
DOI：
10.1093/jnci/djp079
发表时间：
2009-05-20
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Le Tourneau C;Lee JJ;Siu LL
通讯作者：
Siu LL
影响因子：
5.7
作者：
Thall, Peter F.
通讯作者：
Thall, Peter F.
影响因子：
2.7
作者：
Thall, Peter F.;Herrick, Richard C.;Norris, J. Clift
通讯作者：
Norris, J. Clift