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dc.contributor.authorWheeler, GMen_US
dc.contributor.authorMander, APen_US
dc.contributor.authorBedding, Aen_US
dc.contributor.authorBrock, Ken_US
dc.contributor.authorCornelius, Ven_US
dc.contributor.authorGrieve, APen_US
dc.contributor.authorJaki, Ten_US
dc.contributor.authorLove, SBen_US
dc.contributor.authorOdondi, Len_US
dc.contributor.authorWeir, CJen_US
dc.contributor.authorYap, Cen_US
dc.contributor.authorBond, SJen_US
dc.identifier.citationBMC Med Res Methodol, 2019, 19 (1), pp. 18 - ?en_US
dc.description.abstractINTRODUCTION: The continual reassessment method (CRM) is a model-based design for phase I trials, which aims to find the maximum tolerated dose (MTD) of a new therapy. The CRM has been shown to be more accurate in targeting the MTD than traditional rule-based approaches such as the 3 + 3 design, which is used in most phase I trials. Furthermore, the CRM has been shown to assign more trial participants at or close to the MTD than the 3 + 3 design. However, the CRM's uptake in clinical research has been incredibly slow, putting trial participants, drug development and patients at risk. Barriers to increasing the use of the CRM have been identified, most notably a lack of knowledge amongst clinicians and statisticians on how to apply new designs in practice. No recent tutorial, guidelines, or recommendations for clinicians on conducting dose-finding studies using the CRM are available. Furthermore, practical resources to support clinicians considering the CRM for their trials are scarce. METHODS: To help overcome these barriers, we present a structured framework for designing a dose-finding study using the CRM. We give recommendations for key design parameters and advise on conducting pre-trial simulation work to tailor the design to a specific trial. We provide practical tools to support clinicians and statisticians, including software recommendations, and template text and tables that can be edited and inserted into a trial protocol. We also give guidance on how to conduct and report dose-finding studies using the CRM. RESULTS: An initial set of design recommendations are provided to kick-start the design process. To complement these and the additional resources, we describe two published dose-finding trials that used the CRM. We discuss their designs, how they were conducted and analysed, and compare them to what would have happened under a 3 + 3 design. CONCLUSIONS: The framework and resources we provide are aimed at clinicians and statisticians new to the CRM design. Provision of key resources in this contemporary guidance paper will hopefully improve the uptake of the CRM in phase I dose-finding trials.en_US
dc.format.extent18 - ?en_US
dc.subjectAdaptive designsen_US
dc.subjectContinual reassessment methoden_US
dc.subjectDose escalationen_US
dc.subjectMaximum tolerated doseen_US
dc.subjectPhase I trialsen_US
dc.titleHow to design a dose-finding study using the continual reassessment method.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBMC Med Res Methodolen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.publication-statusPublished onlineen_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorYap, Christinaen_US

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