title: Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.
abstract: Biomarker-guided treatment is a rapidly developing area of medicine, where treatment choice is personalised according to one or more of an individual's biomarker measurements. A number of biomarker-guided trial designs have been proposed in the past decade, including both adaptive and non-adaptive trial designs which test the effectiveness of a biomarker-guided approach to treatment with the aim of improving patient health. A better understanding of them is needed as challenges occur both in terms of trial design and analysis. We have undertaken a comprehensive literature review based on an in-depth search strategy with a view to providing the research community with clarity in definition, methodology and terminology of the various biomarker-guided trial designs (both adaptive and non-adaptive designs) from a total of 211 included papers. In the present paper, we focus on non-adaptive biomarker-guided trial designs for which we have identified five distinct main types mentioned in 100 papers. We have graphically displayed each non-adaptive trial design and provided an in-depth overview of their key characteristics. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. Our comprehensive review provides guidance for those designing biomarker-guided trials.
authors.affiliation: MRC North West Hub for Trials Methodology Research, Liverpool L69 3GL, UK. Miranta.Antoniou@liverpool.ac.uk.|Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK. Miranta.Antoniou@liverpool.ac.uk.
authors.forename: Miranta
authors.initials: M
authors.lastname: Antoniou
authors.affiliation: MRC North West Hub for Trials Methodology Research, Liverpool L69 3GL, UK. Ruwanthi.Kolamunnage-Dona@liverpool.ac.uk.|Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK. Ruwanthi.Kolamunnage-Dona@liverpool.ac.uk.
authors.forename: Ruwanthi
authors.initials: R
authors.lastname: Kolamunnage-Dona
authors.affiliation: MRC North West Hub for Trials Methodology Research, Liverpool L69 3GL, UK. A.L.Jorgensen@liverpool.ac.uk.|Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK. A.L.Jorgensen@liverpool.ac.uk.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Jorgensen
keywords: biomarker-guided trial design; clinical research design; clinical trials methodology; non-adaptive trial designs; personalized medicine; phase II; phase III; predictive biomarker; prognostic biomarker; sample size