. 2017 Jan;7(1).
doi: 10.3390/jpm7010001.

Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review

Miranta Antoniou 1 Ruwanthi Kolamunnage-Dona 2 Andrea L Jorgensen 3 
  • PMID: 28125057
  •     116 References
  •     8 citations


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.

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.

Biomarkers and surrogate endpoints: preferred definitions and conceptual framework.
Biomarkers Definitions Working Group..
Clin Pharmacol Ther, 2001 Mar 10; 69(3). PMID: 11240971
Highly Cited. Review.
Issues in clinical trial design for tumor marker studies.
Daniel Sargent, Carmen Allegra.
Semin Oncol, 2002 Jun 14; 29(3). PMID: 12063675
Sample size calculations for randomized controlled trials.
Janet Wittes.
Epidemiol Rev, 2002 Jul 18; 24(1). PMID: 12119854
The clinician as investigator: participating in clinical trials in the practice setting: Appendix 1: fundamentals of study design.
Ellis W Lader, Christopher P Cannon, +12 authors, American Heart Association.
Circulation, 2004 Jun 03; 109(21). PMID: 15173052
Evaluating the efficiency of targeted designs for randomized clinical trials.
Richard Simon, Aboubakar Maitournam.
Clin Cancer Res, 2004 Oct 27; 10(20). PMID: 15501951
On the efficiency of targeted clinical trials.
A Maitournam, R Simon.
Stat Med, 2004 Nov 20; 24(3). PMID: 15551403
Clinical trial designs for predictive marker validation in cancer treatment trials.
Daniel J Sargent, Barbara A Conley, Carmen Allegra, Laurence Collette.
J Clin Oncol, 2005 Mar 19; 23(9). PMID: 15774793
Highly Cited. Review.
Clinical trial designs for prospective validation of biomarkers.
Sumithra J Mandrekar, Axel Grothey, Matthew P Goetz, Daniel J Sargent.
Am J Pharmacogenomics, 2005 Oct 04; 5(5). PMID: 16196501
Use of genomic signatures in therapeutics development in oncology and other diseases.
R Simon, S-J Wang.
Pharmacogenomics J, 2006 Jan 18; 6(3). PMID: 16415922
Clinical trials design and treatment tailoring: general principles applied to breast cancer research.
P Therasse, S Carbonnelle, J Bogaerts.
Crit Rev Oncol Hematol, 2006 Jan 25; 59(2). PMID: 16431124
Designing clinical trials for kidney cancer based on newly developed prognostic and predictive tools.
Daniel Cho, David McDermott, Michael Atkins.
Curr Urol Rep, 2006 Feb 17; 7(1). PMID: 16480663
Medical outcome after immediate computed tomography or admission for observation in patients with mild head injury: randomised controlled trial.
Jean-Luc af Geijerstam, Sven Oredsson, Mona Britton, OCTOPUS Study Investigators.
BMJ, 2006 Aug 10; 333(7566). PMID: 16895944    Free PMC article.
TAILORx: trial assigning individualized options for treatment (Rx).
Joseph A Sparano.
Clin Breast Cancer, 2006 Nov 10; 7(4). PMID: 17092406
A method for testing a prespecified subgroup in clinical trials.
Yang Song, George Y H Chi.
Stat Med, 2007 Feb 03; 26(19). PMID: 17266164
Biomarker-adaptive threshold design: a procedure for evaluating treatment with possible biomarker-defined subset effect.
Wenyu Jiang, Boris Freidlin, Richard Simon.
J Natl Cancer Inst, 2007 Jun 29; 99(13). PMID: 17596577
Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer.
Manuel Cobo, Dolores Isla, +17 authors, Rafael Rosell.
J Clin Oncol, 2007 Jul 03; 25(19). PMID: 17602080
Highly Cited.
Approaches to evaluation of treatment effect in randomized clinical trials with genomic subset.
Sue-Jane Wang, Robert T O'Neill, H M James Hung.
Pharm Stat, 2007 Aug 11; 6(3). PMID: 17688238
A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician's choice in patients with recurrent platinum-resistant ovarian cancer.
Ian A Cree, Christian M Kurbacher, +3 authors, TCA Ovarian Cancer Trial Group.
Anticancer Drugs, 2007 Aug 21; 18(9). PMID: 17704660
A Bayesian predictive two-stage design for phase II clinical trials.
Valeria Sambucini.
Stat Med, 2007 Sep 01; 27(8). PMID: 17763528
Biomarker as a classifier in pharmacogenomics clinical trials: a tribute to 30th anniversary of PSI.
Sue-Jane Wang.
Pharm Stat, 2007 Oct 25; 6(4). PMID: 17957727
Development of the 21-gene assay and its application in clinical practice and clinical trials.
Joseph A Sparano, Soonmyung Paik.
J Clin Oncol, 2008 Feb 09; 26(5). PMID: 18258979
Highly Cited. Review.
Advances and challenges in the use of biomarkers in clinical trials.
Bruce Chabner.
Clin Adv Hematol Oncol, 2008 Mar 07; 6(1). PMID: 18322440
Randomized phase III clinical trial designs for targeted agents.
Antje Hoering, Mike Leblanc, John J Crowley.
Clin Cancer Res, 2008 Jul 17; 14(14). PMID: 18628448    Free PMC article.
Statistical issues in translational cancer research.
Stephen L George.
Clin Cancer Res, 2008 Oct 03; 14(19). PMID: 18829473
The use of genomics in clinical trial design.
Richard Simon.
Clin Cancer Res, 2008 Oct 03; 14(19). PMID: 18829477
Various randomized designs can be used to evaluate medical tests.
Jeroen G Lijmer, Patrick M M Bossuyt.
J Clin Epidemiol, 2008 Oct 24; 62(4). PMID: 18945590
A flexible strategy for testing subgroups and overall population.
Mohamed Alosh, Mohammad F Huque.
Stat Med, 2008 Nov 06; 28(1). PMID: 18985704
Statistical methods for targeted clinical trials under enrichment design.
Jen-Pei Liu, Jr-Rung Lin.
J Formos Med Assoc, 2009 Mar 31; 107(12 Suppl). PMID: 19129044
Analysis of randomized controlled clinical trials.
Robert N Foley.
Methods Mol Biol, 2009 Jan 24; 473. PMID: 19160734
Biomarkers and surrogates in clinical studies.
Claudio Rigatto, Brendan J Barrett.
Methods Mol Biol, 2009 Jan 24; 473. PMID: 19160736
Development and Validation of Biomarker Classifiers for Treatment Selection.
Richard Simon.
J Stat Plan Inference, 2009 Feb 05; 138(2). PMID: 19190712    Free PMC article.
Adaptive patient enrichment designs in therapeutic trials.
Sue-Jane Wang, H M James Hung, Robert T O'Neill.
Biom J, 2009 Apr 10; 51(2). PMID: 19358222
Clinical trial designs for predictive biomarker validation: one size does not fit all.
Sumithra J Mandrekar, Daniel J Sargent.
J Biopharm Stat, 2009 Apr 23; 19(3). PMID: 19384694    Free PMC article.
Targeting targeted agents: open issues for clinical trial design.
Emilio Bria, Massimo Di Maio, +4 authors, Michele Milella.
J Exp Clin Cancer Res, 2009 May 26; 28. PMID: 19463172    Free PMC article.
Molecular biomarkers to individualise treatment: assessing the evidence.
Chee K Lee, Sarah J Lord, Alan S Coates, R John Simes.
Med J Aust, 2009 Jun 03; 190(11). PMID: 19485842
Clinical trial designs for predictive biomarker validation: theoretical considerations and practical challenges.
Sumithra J Mandrekar, Daniel J Sargent.
J Clin Oncol, 2009 Jul 15; 27(24). PMID: 19597023    Free PMC article.
Highly Cited.
Genomic advances and their impact on clinical trial design.
Sumithra J Mandrekar, Daniel J Sargent.
Genome Med, 2009 Jul 30; 1(7). PMID: 19638184    Free PMC article.
Trial design for evaluation of novel targeted therapies.
John Farley, Peter G Rose.
Gynecol Oncol, 2009 Oct 27; 116(2). PMID: 19853899
Methodological aspects of lung cancer clinical trials in the era of targeted agents.
Massimo Di Maio, Ciro Gallo, +4 authors, Francesco Perrone.
Lung Cancer, 2009 Oct 31; 67(2). PMID: 19875193
Genomic markers for decision making: what is preventing us from using markers?
Vicky M Coyle, Patrick G Johnston.
Nat Rev Clin Oncol, 2009 Dec 17; 7(2). PMID: 20010899
Randomized clinical trials with biomarkers: design issues.
Boris Freidlin, Lisa M McShane, Edward L Korn.
J Natl Cancer Inst, 2010 Jan 16; 102(3). PMID: 20075367    Free PMC article.
Highly Cited.
Phase II clinical trials in oncology: are we hitting the target?
Mei-Kim Ang, Say-Beng Tan, Wan-Teck Lim.
Expert Rev Anticancer Ther, 2010 Mar 11; 10(3). PMID: 20214523
Clinical trials for predictive medicine: new challenges and paradigms.
Richard Simon.
Clin Trials, 2010 Mar 27; 7(5). PMID: 20338899    Free PMC article.
Biomarkers and surrogate end points--the challenge of statistical validation.
Marc Buyse, Daniel J Sargent, +2 authors, Aimery de Gramont.
Nat Rev Clin Oncol, 2010 Apr 07; 7(6). PMID: 20368727
Clinical trial designs for evaluating the medical utility of prognostic and predictive biomarkers in oncology.
Richard Simon.
Per Med, 2010 Apr 13; 7(1). PMID: 20383292    Free PMC article.
Predictive biomarker validation in practice: lessons from real trials.
Sumithra J Mandrekar, Daniel J Sargent.
Clin Trials, 2010 Apr 16; 7(5). PMID: 20392785    Free PMC article.
Biostatistic tools in pharmacogenomics--advances, challenges, potential.
Yasunori Sato, Nan M Laird, Teruhiko Yoshida.
Curr Pharm Des, 2010 May 13; 16(20). PMID: 20459388
Biomarkers and the design of clinical trials in cancer.
Graeme A M Fraser, Ralph M Meyer.
Biomark Med, 2007 Oct 01; 1(3). PMID: 20477382
Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study.
Federico Cappuzzo, Tudor Ciuleanu, +11 authors, SATURN investigators.
Lancet Oncol, 2010 May 25; 11(6). PMID: 20493771
Highly Cited.
Bayesian adaptive randomization designs for targeted agent development.
J Jack Lee, Xuemin Gu, Suyu Liu.
Clin Trials, 2010 Jun 24; 7(5). PMID: 20571130    Free PMC article.
A Bayesian adaptive design with biomarkers for targeted therapies.
Jens C Eickhoff, KyungMann Kim, +2 authors, Jason R Gee.
Clin Trials, 2010 Jun 24; 7(5). PMID: 20571131    Free PMC article.
The efficiency of clinical trial designs for predictive biomarker validation.
K Y Young, A Laird, X H Zhou.
Clin Trials, 2010 Jun 24; 7(5). PMID: 20571132
Design, operation, and interpretation of clinical trials.
B L Pihlstrom, M L Barnett.
J Dent Res, 2010 Jun 29; 89(8). PMID: 20581353
Adjusted significance levels for subgroup analyses in clinical trials.
Bart Spiessens, Muriel Debois.
Contemp Clin Trials, 2010 Sep 14; 31(6). PMID: 20832503
Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial.
Benjamin French, Jungnam Joo, +7 authors, COAG (Clarification of Optimal Anticoagulation through Genetics) Investigators.
Trials, 2010 Nov 19; 11. PMID: 21083927    Free PMC article.
Incorporation of biomarker assessment in novel clinical trial designs: personalizing brain tumor treatments.
Evanthia Galanis, Wenting Wu, +4 authors, David A Reardon.
Curr Oncol Rep, 2010 Dec 03; 13(1). PMID: 21125354    Free PMC article.
Biomarker-adaptive clinical trial designs.
Boris Freidlin, Edward L Korn.
Pharmacogenomics, 2010 Dec 15; 11(12). PMID: 21142910
Why, when, and how should pharmacogenetics be applied in clinical studies?: current and future approaches to study designs.
J C Stingl Kirchheiner, J Brockmöller.
Clin Pharmacol Ther, 2011 Jan 07; 89(2). PMID: 21209614
Implementing prognostic and predictive biomarkers in CRC clinical trials.
Sandra Van Schaeybroeck, Wendy L Allen, Richard C Turkington, Patrick G Johnston.
Nat Rev Clin Oncol, 2011 Feb 16; 8(4). PMID: 21321566
Integrating biomarkers in clinical trials.
Marc Buyse, Stefan Michiels, +3 authors, Aimery de Gramont.
Expert Rev Mol Diagn, 2011 Mar 17; 11(2). PMID: 21405968
Genomic markers to tailor treatments: waiting or initiating?
Parvin Tajik, Patrick M Bossuyt.
Hum Genet, 2011 Apr 14; 130(1). PMID: 21487770    Free PMC article.
All-comers versus enrichment design strategy in phase II trials.
Sumithra J Mandrekar, Daniel J Sargent.
J Thorac Oncol, 2011 May 03; 6(4). PMID: 21532916    Free PMC article.
Statistical considerations for the next generation of clinical trials.
Wenting Wu, Qian Shi, Daniel J Sargent.
Semin Oncol, 2011 Aug 04; 38(4). PMID: 21810519
Integrating predictive biomarkers and classifiers into oncology clinical development programmes.
Robert A Beckman, Jason Clark, Cong Chen.
Nat Rev Drug Discov, 2011 Oct 01; 10(10). PMID: 21959287
A capture-recapture analysis demonstrated that randomized controlled trials evaluating the impact of diagnostic tests on patient outcomes are rare.
Lavinia Ferrante di Ruffano, Clare Davenport, +2 authors, Jonathan J Deeks.
J Clin Epidemiol, 2011 Oct 18; 65(3). PMID: 22001307
Adaptive clinical trial designs for simultaneous testing of matched diagnostics and therapeutics.
Howard I Scher, Shelley Fuld Nasso, Eric H Rubin, Richard Simon.
Clin Cancer Res, 2011 Nov 03; 17(21). PMID: 22046024    Free PMC article.
Clinical trial design in the age of molecular profiling.
Alexander Spira, Kirsten H Edmiston.
Methods Mol Biol, 2011 Nov 15; 823. PMID: 22081336
Predictive biomarkers in colorectal cancer: usage, validation, and design in clinical trials.
Qian Shi, Sumithra J Mandrekar, Daniel J Sargent.
Scand J Gastroenterol, 2011 Dec 21; 47(3). PMID: 22181041
A two-stage Bayesian design for co-development of new drugs and companion diagnostics.
Stella Wanjugu Karuri, Richard Simon.
Stat Med, 2012 Jan 13; 31(10). PMID: 22238151
Cancer biomarkers: selecting the right drug for the right patient.
Gary J Kelloff, Caroline C Sigman.
Nat Rev Drug Discov, 2012 Feb 11; 11(3). PMID: 22322254
Highly Cited. Review.
Design of clinical trials for biomarker research in oncology.
Sumithra J Mandrekar, Daniel J Sargent.
Clin Investig (Lond), 2012 Mar 06; 1(12). PMID: 22389760    Free PMC article.
Practical perspectives of personalized healthcare in oncology.
Darren R Hodgson, Robert Wellings, Christopher Harbron.
N Biotechnol, 2012 Mar 20; 29(6). PMID: 22426411
Biomarkers, subgroup evaluation, and clinical trial design.
Stuart G Baker, Barnett S Kramer, Daniel J Sargent, Marco Bonetti.
Discov Med, 2012 Apr 03; 13(70). PMID: 22463794
Sample size estimation in single-arm clinical trials with multiple testing under frequentist and Bayesian approaches.
Boris G Zaslavsky, John Scott.
J Biopharm Stat, 2012 Jun 02; 22(4). PMID: 22651117
Randomized controlled trials on PET: a systematic review of topics, design, and quality.
Fülöp Scheibler, Polina Zumbé, +6 authors, Stefan Lange.
J Nucl Med, 2012 Jun 09; 53(7). PMID: 22677702
Systematic Review.
A 2-stage phase II design with direct assignment option in stage II for initial marker validation.
Ming-Wen An, Sumithra J Mandrekar, Daniel J Sargent.
Clin Cancer Res, 2012 Jun 16; 18(16). PMID: 22700865    Free PMC article.
Clinical trials for predictive medicine.
Richard Simon.
Stat Med, 2012 Jun 21; 31(25). PMID: 22714719
NHLBI clinical trials workshop: an executive summary.
Gang Zheng, Colin O Wu, +3 authors, Nancy L Geller.
Stat Med, 2012 Jun 27; 31(25). PMID: 22733431
Personalized medicine using DNA biomarkers: a review.
Andreas Ziegler, Armin Koch, Katja Krockenberger, Anika Grosshennig.
Hum Genet, 2012 Jul 04; 131(10). PMID: 22752797    Free PMC article.
Incorporating biomarkers into clinical trial designs: points to consider.
Edward Bradley.
Nat Biotechnol, 2012 Jul 12; 30(7). PMID: 22781677
Randomized phase II trial designs with biomarkers.
Boris Freidlin, Lisa M McShane, Mei-Yin C Polley, Edward L Korn.
J Clin Oncol, 2012 Aug 08; 30(26). PMID: 22869885    Free PMC article.
Study designs and statistical analyses for biomarker research.
Masahiko Gosho, Kengo Nagashima, Yasunori Sato.
Sensors (Basel), 2012 Sep 27; 12(7). PMID: 23012528    Free PMC article.
Incorporation of prognostic and predictive factors into glioma clinical trials.
Derek R Johnson, Evanthia Galanis.
Curr Oncol Rep, 2012 Nov 06; 15(1). PMID: 23125011    Free PMC article.
Novel strategies to test biological hypotheses in early drug development for advanced prostate cancer.
Roberta Ferraldeschi, Gerhardt Attard, Johann S de Bono.
Clin Chem, 2012 Dec 04; 59(1). PMID: 23204221
Creative trial design in RA: optimizing patient outcomes.
Maya H Buch, Sue Pavitt, Mahesh Parmar, Paul Emery.
Nat Rev Rheumatol, 2013 Feb 06; 9(3). PMID: 23381561
Omics-based clinical trial designs.
Marc Buyse, Stefan Michiels.
Curr Opin Oncol, 2013 Mar 12; 25(3). PMID: 23475192
Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.
Richard Simon.
Expert Opin Med Diagn, 2008 Jun 01; 2(6). PMID: 23495781
Phase III clinical trials that integrate treatment and biomarker evaluation.
Boris Freidlin, Zhuoxin Sun, Robert Gray, Edward L Korn.
J Clin Oncol, 2013 Apr 10; 31(25). PMID: 23569306    Free PMC article.
Statistical inference on censored data for targeted clinical trials under enrichment design.
Chen-Fang Chen, Jr-Rung Lin, Jen-Pei Liu.
Pharm Stat, 2013 Apr 23; 12(3). PMID: 23606647
Design of oncology clinical trials: a review.
Revathi Ananthakrishnan, Sandeep Menon.
Crit Rev Oncol Hematol, 2013 Apr 30; 88(1). PMID: 23623356
A review of phase II trial designs for initial marker validation.
Sumithra J Mandrekar, Ming-Wen An, Daniel J Sargent.
Contemp Clin Trials, 2013 May 15; 36(2). PMID: 23665336    Free PMC article.
Genomic biomarkers for personalized medicine: development and validation in clinical studies.
Shigeyuki Matsui.
Comput Math Methods Med, 2013 May 22; 2013. PMID: 23690882    Free PMC article.
Trial designs for personalizing cancer care: a systematic review and classification.
Parvin Tajik, Aleiko H Zwinderman, Ben W Mol, Patrick M Bossuyt.
Clin Cancer Res, 2013 Jun 22; 19(17). PMID: 23788580
Systematic Review.
Group sequential designs for developing and testing biomarker-guided personalized therapies in comparative effectiveness research.
Tze Leung Lai, Olivia Yueh-Wen Liao, Dong Woo Kim.
Contemp Clin Trials, 2013 Sep 03; 36(2). PMID: 23994669    Free PMC article.
Marker Sequential Test (MaST) design.
Boris Freidlin, Edward L Korn, Robert Gray.
Clin Trials, 2013 Oct 03; 11(1). PMID: 24085774
Statistical and practical considerations for clinical evaluation of predictive biomarkers.
Mei-Yin C Polley, Boris Freidlin, +3 authors, Lisa M McShane.
J Natl Cancer Inst, 2013 Oct 19; 105(22). PMID: 24136891    Free PMC article.
Evaluating many treatments and biomarkers in oncology: a new design.
Richard Kaplan, Timothy Maughan, +4 authors, Mahesh Parmar.
J Clin Oncol, 2013 Nov 20; 31(36). PMID: 24248692    Free PMC article.
Statistical design and evaluation of biomarker studies.
Kevin K Dobbin.
Methods Mol Biol, 2013 Nov 22; 1102. PMID: 24259005
Biomarker enrichment strategies: matching trial design to biomarker credentials.
Boris Freidlin, Edward L Korn.
Nat Rev Clin Oncol, 2013 Nov 28; 11(2). PMID: 24281059
Adaptive clinical trial design.
Shein-Chung Chow.
Annu Rev Med, 2014 Jan 16; 65. PMID: 24422576
Randomized reverse marker strategy design for prospective biomarker validation.
Kevin H Eng.
Stat Med, 2014 Mar 19; 33(18). PMID: 24639051    Free PMC article.
Adaptive designs for clinical trials assessing biomarker-guided treatment strategies.
J Wason, A Marshall, +2 authors, N Stallard.
Br J Cancer, 2014 Mar 29; 110(8). PMID: 24667651    Free PMC article.
Comparison of statistical analysis plans in randomize-all phase III trials with a predictive biomarker.
Shigeyuki Matsui, Yuki Choai, Takahiro Nonaka.
Clin Cancer Res, 2014 Apr 03; 20(11). PMID: 24691019
Biomarker evaluation in randomized trials: addressing different research questions.
Stuart G Baker.
Stat Med, 2014 Sep 10; 33(23). PMID: 25196226    Free PMC article.
Estimation of treatment effects in all-comers randomized clinical trials with a predictive marker.
Yuki Choai, Shigeyuki Matsui.
Biometrics, 2014 Oct 11; 71(1). PMID: 25303178
Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.
Ja-An Lin, Pei He.
Br Med Bull, 2015 Apr 30; 114(1). PMID: 25921239
Methods for identification and confirmation of targeted subgroups in clinical trials: A systematic review.
Thomas Ondra, Alex Dmitrienko, +4 authors, Martin Posch.
J Biopharm Stat, 2015 Sep 18; 26(1). PMID: 26378339    Free PMC article.
Systematic Review.
Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials.
Munyaradzi Dimairo, Jonathan Boote, +2 authors, Susan Todd.
Trials, 2015 Sep 30; 16. PMID: 26416387    Free PMC article.
Clinical trial designs incorporating predictive biomarkers.
Lindsay A Renfro, Himel Mallick, +2 authors, Sumithra J Mandrekar.
Cancer Treat Rev, 2016 Feb 02; 43. PMID: 26827695    Free PMC article.
Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes.
Julien Tanniou, Ingeborg van der Tweel, Steven Teerenstra, Kit C B Roes.
BMC Med Res Methodol, 2016 Feb 20; 16. PMID: 26891992    Free PMC article.
Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.
Miranta Antoniou, Andrea L Jorgensen, Ruwanthi Kolamunnage-Dona.
PLoS One, 2016 Feb 26; 11(2). PMID: 26910238    Free PMC article.
Clinical trials for precision oncology using next-generation sequencing.
Richard Simon, Eric Polley.
Per Med, 2013 Jul 01; 10(5). PMID: 29758837
Sample-size formula for the proportional-hazards regression model.
D A Schoenfeld.
Biometrics, 1983 Jun 01; 39(2). PMID: 6354290
Highly Cited.
Tables of the number of patients required in clinical trials using the logrank test.
L S Freedman.
Stat Med, 1982 Apr 01; 1(2). PMID: 7187087
Highly Cited.
Planning the duration of a comparative clinical trial with loss to follow-up and a period of continued observation.
L V Rubinstein, M H Gail, T J Santner.
J Chronic Dis, 1981 Jan 01; 34(9-10). PMID: 7276137
Multiple significance tests: the Bonferroni method.
J M Bland, D G Altman.
BMJ, 1995 Jan 21; 310(6973). PMID: 7833759    Free PMC article.
Highly Cited.
Promise, Progress, and Pitfalls in the Search for Central Nervous System Biomarkers in Neuroimmunological Diseases: A Role for Cerebrospinal Fluid Immunophenotyping.
Bibiana Bielekova, Michael R Pranzatelli.
Semin Pediatr Neurol, 2017 Nov 07; 24(3). PMID: 29103430    Free PMC article.
Fixed and Adaptive Parallel Subgroup-Specific Design for Survival Outcomes: Power and Sample Size.
Miranta Antoniou, Andrea L Jorgensen, Ruwanthi Kolamunnage-Dona.
J Pers Med, 2017 Dec 07; 7(4). PMID: 29207572    Free PMC article.
Correction: Antoniou, M.; et al. Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review. J. Pers. Med. 2017, 7, 1.
Miranta Antoniou, Ruwanthi Kolamunnage-Dona, Andrea L Jorgensen.
J Pers Med, 2018 May 08; 8(2). PMID: 29735910    Free PMC article.
Evidence to Support Inclusion of Pharmacogenetic Biomarkers in Randomised Controlled Trials.
Danielle Johnson, Dyfrig Hughes, Munir Pirmohamed, Andrea Jorgensen.
J Pers Med, 2019 Sep 05; 9(3). PMID: 31480618    Free PMC article.
Biomarker-guided trials: Challenges in practice.
M Antoniou, R Kolamunnage-Dona, +7 authors, A L Jorgensen.
Contemp Clin Trials Commun, 2019 Dec 04; 16. PMID: 31788574    Free PMC article.
Design of experiments for a confirmatory trial of precision medicine.
Kim May Lee, James Wason.
J Stat Plan Inference, 2019 Apr 23; 199. PMID: 31007363    Free PMC article.
How to Ease the Pain of Taking a Diagnostic Point of Care Test to the Market: A Framework for Evidence Development.
Sara Graziadio, Amanda Winter, +12 authors, A Joy Allen.
Micromachines (Basel), 2020 Mar 14; 11(3). PMID: 32164393    Free PMC article.
Specific requirements for translation of biological research into clinical radiation oncology.
Mechthild Krause, Jan Alsner, +3 authors, Rob Bristow.
Mol Oncol, 2020 Mar 17; 14(7). PMID: 32175659    Free PMC article.