Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies Ja-An Lin 1 and Pei He 2, * 1 Department of Biostatistics, The University of North Carolina at Chapel Hill, 170 Rosenau Hall, Chapel Hill, NC, USA, and 2 Department of Statistics, Stanford University, Stanford, CA, USA *Correspondence address. Department of Statistics, Stanford University, 390 Serra Mall, Stanford, CA 94305, USA. E-mail: he.pei@stanford.edu Accepted 17 March 2015 Abstract Introduction: Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorp- orating the rapid growing basic research into clinical practices. Sources of data: Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. Areas of agreement: The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Areas of controversy: Regulatory agency has restrictions on confirmatory trials ‘using adaptive designs’. No rule of thumb to pick the most appropriate design for biomarker-related trials. Growing points: Statistical issues to solve in new designs. Regulatory acceptance of the ‘newly proposed trial designs’. Areas timely for developing research: Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. Key words: clinical trial, adaptive design, biomarker, personalized medicine Introduction Clinical trials, defined as ‘a prospective studies com- paring the effect and value of intervention(s) against ‘control group’ in human beings, where the control group can either receive placebo or active treatments by Friedman et al. 1 In clinical trial, typically a subject will be randomly assigned to one of the treat- ment groups during the study, to reduce possible British Medical Bulletin, 2015, 114:17–27 doi: 10.1093/bmb/ldv011 Advance Access Publication Date: 28 April 2015 © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Downloaded from https://academic.oup.com/bmb/article-abstract/114/1/17/246161 by guest on 09 June 2020