Imperial College London
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ProfessorVictoriaCornelius

Faculty of Medicine, School of Public Health

Professor in Medical Statistics and Trials Methodology
 
 
 
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Contact

 

+44 (0)20 7594 1218v.cornelius

 
 
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Assistant

 

Mrs Ranjit Rayat +44 (0)20 7594 3445

 
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Location

 

111Stadium HouseWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wheeler:2019:10.1186/s12874-018-0638-z,
author = {Wheeler, GM and Mander, AP and Bedding, A and Brock, K and Cornelius, V and Grieve, AP and Jaki, T and Love, SB and Odondi, L and Weir, CJ and Yap, C and Bond, SJ},
doi = {10.1186/s12874-018-0638-z},
journal = {BMC Medical Research Methodology},
title = {How to design a dose-finding study using the continual reassessment method},
url = {http://dx.doi.org/10.1186/s12874-018-0638-z},
volume = {19},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IntroductionThe 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.MethodsTo 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.ResultsAn 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.ConclusionsThe framework and resources we provide are aimed at clinicians
AU  - Wheeler,GM
AU  - Mander,AP
AU  - Bedding,A
AU  - Brock,K
AU  - Cornelius,V
AU  - Grieve,AP
AU  - Jaki,T
AU  - Love,SB
AU  - Odondi,L
AU  - Weir,CJ
AU  - Yap,C
AU  - Bond,SJ
DO  - 10.1186/s12874-018-0638-z
PY  - 2019///
SN  - 1471-2288
TI  - How to design a dose-finding study using the continual reassessment method
T2  - BMC Medical Research Methodology
UR  - http://dx.doi.org/10.1186/s12874-018-0638-z
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000456161100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/67241
VL  - 19
ER  -
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