Controlled multi-arm platform design using predictive probability

Statistical Methods in Medical Research
Brian P HobbsJ Jack Lee

Abstract

The process of screening agents one-at-a-time under the current clinical trials system suffers from several deficiencies that could be addressed in order to extend financial and patient resources. In this article, we introduce a statistical framework for designing and conducting randomized multi-arm screening platforms with binary endpoints using Bayesian modeling. In essence, the proposed platform design consolidates inter-study control arms, enables investigators to assign more new patients to novel therapies, and accommodates mid-trial modifications to the study arms that allow both dropping poorly performing agents as well as incorporating new candidate agents. When compared to sequentially conducted randomized two-arm trials, screening platform designs have the potential to yield considerable reductions in cost, alleviate the bottleneck between phase I and II, eliminate bias stemming from inter-trial heterogeneity, and control for multiplicity over a sequence of a priori planned studies. When screening five experimental agents, our results suggest that platform designs have the potential to reduce the mean total sample size by as much as 40% and boost the mean overall response rate by as much as 15%. We explain how to desi...Continue Reading

References

Mar 1, 1989·Controlled Clinical Trials·R Simon
Aug 10, 1999·Controlled Clinical Trials·P Y LiuM Desai
Dec 24, 2002·Biometrics·Lurdes Y T InoueDonald A Berry
Jul 5, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J Jack Lee, Lei Feng
Jan 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Primo N LaraUNKNOWN Southwest Oncology Group
Apr 1, 2008·Clinical Trials : Journal of the Society for Clinical Trials·J Jack Lee, Diane D Liu
Jul 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Boris FreidlinAlison Martin
Aug 30, 2008·Statistics in Medicine·J Kyle Wathen, Peter F Thall
Jan 20, 2009·Statistics in Medicine·Peter K KimaniJane L Hutton
Jun 29, 2010·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sumithra J Mandrekar, Daniel J Sargent
Nov 5, 2011·Statistics in Medicine·Nigel Stallard
May 16, 2012·Cancer Discovery·Edward S KimWaun K Hong
Jun 1, 2012·The New England Journal of Medicine·Tatiana M Prowell, Richard Pazdur
Jul 25, 2012·Statistics in Medicine·James M S Wason, Thomas Jaki
Mar 27, 2013·Statistics in Medicine·James M S WasonNigel Stallard
Jun 7, 2013·Clinical Pharmacology and Therapeutics·J A DiMasiA Malins
Mar 1, 2012·Journal of the Royal Statistical Society. Series C, Applied Statistics·Guosheng YinJ Jack Lee
Jan 15, 2014·Statistics in Medicine·James M S Wason, Lorenzo Trippa
Apr 17, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Cheng-Yi WangKuen-Feng Chen
Jul 30, 2014·Lancet·Mahesh K B ParmarMatthew R Sydes
Feb 14, 2015·Clinical Pharmacology and Therapeutics·C E SteuerD R Gandara

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Citations

May 23, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Steffen VentzLorenzo Trippa
Jul 25, 2018·Statistical Methods in Medical Research·Meilin Huang, Brian P Hobbs
Feb 15, 2019·Journal of Biopharmaceutical Statistics·Zhenning YuCaitlyn Meinzer
Aug 28, 2019·Clinical Trials : Journal of the Society for Clinical Trials·Rebecca S Slack TidwellJ Jack Lee
Apr 3, 2020·Journal for Immunotherapy of Cancer·Luca MazzarellaGiuseppe Curigliano
Sep 7, 2017·Journal of Biopharmaceutical Statistics·Lindsay A Renfro, Sumithra J Mandrekar
Sep 30, 2020·Journal of Biopharmaceutical Statistics·Xiaofei BaiDacheng Liu
May 23, 2019·Statistics in Medicine·Kim May LeeNigel Stallard
Sep 15, 2020·JCO Precision Oncology·Ying YuanSusan G Hilsenbeck
Dec 19, 2018·Journal of the National Cancer Institute·Brian P HobbsGary L Rosner
Jul 25, 2019·Contemporary Clinical Trials Communications·Ellie G SidenEdward J Mills
Jul 6, 2020·Clinical Therapeutics·Elias Laurin MeyerFranz König
Mar 28, 2021·Statistics in Medicine·Daniel KangJun Yin
Jun 8, 2021·Journal of Clinical Child and Adolescent Psychology : the Official Journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53·Michael C Mullarkey, Jessica L Schleider
Aug 28, 2021·International Journal of Environmental Research and Public Health·Valeria Sambucini

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