. 2005 Mar;23(9).
doi: 10.1200/JCO.2005.01.112.

Clinical trial designs for predictive marker validation in cancer treatment trials

Daniel J Sargent 1 Barbara A Conley  Carmen Allegra  Laurence Collette  
  • PMID: 15774793
  •     136 citations


Current staging and risk-stratification methods in oncology, while helpful, fail to adequately predict malignancy aggressiveness and/or response to specific treatment. Increased knowledge of cancer biology is generating promising marker candidates for more accurate diagnosis, prognosis assessment, and therapeutic targeting. To apply these exciting results to maximize patient benefit, a disciplined application of well-designed clinical trials for assessing the utility of markers should be used. In this article, we first review the major issues to consider when designing a clinical trial assessing the usefulness of a predictive marker. We then present two classes of clinical trial designs: the Marker by Treatment Interaction Design and the Marker-Based Strategy Design. In the first design, we assume that the marker splits the population into groups in which the efficacy of a particular treatment will differ. This design can be viewed as a classical randomized clinical trial with upfront stratification for the marker. In the second design, after the marker status is known, each patient is randomly assigned either to have therapy determined by their marker status or to receive therapy independent of marker status. The predictive value of the marker is assessed by comparing the outcome of all patients in the marker-based arm to that of all of the patients in the non-marker-based arm. We present detailed sample size calculations for a specific clinical scenario. We discuss the advantages and disadvantages of the two trial designs and their appropriateness to specific clinical situations to assist investigators seeking to design rigorous, marker-based clinical trials.

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
Genetic and epigenetic biomarkers in cancer : improving diagnosis, risk assessment, and disease stratification.
Mukesh Verma, Daniela Seminara, +3 authors, Virginia Hartmuller.
Mol Diagn Ther, 2006 May 02; 10(1). PMID: 16646573
Progress in the development of prognostic and predictive markers for gastrointestinal malignancies.
Crystal S Denlinger, Steven J Cohen.
Curr Treat Options Oncol, 2008 Jan 15; 8(5). PMID: 18193357
Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy.
R Soong, N Shah, +9 authors, B Iacopetta.
Ann Oncol, 2008 Feb 05; 19(5). PMID: 18245778    Free PMC article.
Systematic review of statistical methods used in molecular marker studies in cancer.
Andrew J Vickers, Kwang Jang, +2 authors, Michael W Kattan.
Cancer, 2008 Mar 06; 112(8). PMID: 18320601    Free PMC article.
Systematic Review.
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.
Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.
Lori J Goldstein, Robert Gray, +12 authors, Joseph A Sparano.
J Clin Oncol, 2008 Aug 06; 26(25). PMID: 18678838    Free PMC article.
Highly Cited.
Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design.
Margaret S Pepe, Ziding Feng, +2 authors, John D Potter.
J Natl Cancer Inst, 2008 Oct 09; 100(20). PMID: 18840817    Free PMC article.
Highly Cited.
Lost in translation: problems and pitfalls in translating laboratory observations to clinical utility.
Richard Simon.
Eur J Cancer, 2008 Nov 04; 44(18). PMID: 18977655    Free PMC article.
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.
Asparagine synthetase: a new potential biomarker in ovarian cancer.
Philip L Lorenzi, John N Weinstein.
Drug News Perspect, 2009 Feb 12; 22(1). PMID: 19209300    Free PMC article.
Adjuvant Therapy for Stage II and III Colon Cancer: Consensus Report of the International Society of Gastrointestinal Oncology.
John L Marshall, Daniel G Haller, +4 authors, Richard M Goldberg.
Gastrointest Cancer Res, 2007 Jul 01; 1(4). PMID: 19262703    Free PMC article.
Genomic classifiers in colon cancer - clinical utility.
Daniel Sargent.
Gastrointest Cancer Res, 2009 Apr 04; 2(4 Suppl). PMID: 19343147    Free PMC article.
Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis, and beyond.
R D Riley, W Sauerbrei, D G Altman.
Br J Cancer, 2009 Apr 16; 100(8). PMID: 19367280    Free PMC article.
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.
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.
Analysis of DNA microarray expression data.
Richard Simon.
Best Pract Res Clin Haematol, 2009 Aug 25; 22(2). PMID: 19698933    Free PMC article.
Topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy.
Ioannis Kostopoulos, Vasilios Karavasilis, +7 authors, George Fountzilas.
BMC Cancer, 2009 Sep 25; 9. PMID: 19775480    Free PMC article.
Use of archived specimens in evaluation of prognostic and predictive biomarkers.
Richard M Simon, Soonmyung Paik, Daniel F Hayes.
J Natl Cancer Inst, 2009 Oct 10; 101(21). PMID: 19815849    Free PMC article.
Highly Cited.
A perspective on challenges and issues in biomarker development and drug and biomarker codevelopment.
Sheila E Taube, Gary M Clark, +3 authors, Steven I Gutman.
J Natl Cancer Inst, 2009 Oct 27; 101(21). PMID: 19855077    Free PMC article.
Heterotransplant mouse model cohorts of human malignancies: A novel platform for Systematic Preclinical Efficacy Evaluation of Drugs (SPEED).
Ashutosh K Pathak, Manisha Bhutani, Pierre Saintigny, Li Mao.
Am J Transl Res, 2009 Dec 08; 1(1). PMID: 19966934    Free PMC article.
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.
Oncologist's/haematologist's view on the roles of pathologists for molecular targeted cancer therapy.
Ulrich Keller, Nikolas von Bubnoff, Christian Peschel, Justus Duyster.
J Cell Mol Med, 2010 Feb 18; 14(4). PMID: 20158573    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
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.
Future of personalized medicine in oncology: a systems biology approach.
Ana Maria Gonzalez-Angulo, Bryan T J Hennessy, Gordon B Mills.
J Clin Oncol, 2010 Apr 22; 28(16). PMID: 20406928    Free PMC article.
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.
Prospective alpha allocation in the Clarification of Optimal Anticoagulation through Genetics (COAG) trial.
Jungnam Joo, Nancy L Geller, +3 authors, Jonas H Ellenberg.
Clin Trials, 2010 Aug 10; 7(5). PMID: 20693186    Free PMC article.
Akt inhibitors in clinical development for the treatment of cancer.
Sumanta Kumar Pal, Karen Reckamp, Hua Yu, Robert A Figlin.
Expert Opin Investig Drugs, 2010 Sep 18; 19(11). PMID: 20846000    Free PMC article.
Highly Cited. Review.
Proteomics as a guiding tool for more effective personalized therapy.
J-M Lee, E C Kohn.
Ann Oncol, 2010 Oct 15; 21 Suppl 7. PMID: 20943616    Free PMC article.
Designing a randomized clinical trial to evaluate personalized medicine: a new approach based on risk prediction.
Stuart G Baker, Daniel J Sargent.
J Natl Cancer Inst, 2010 Nov 04; 102(23). PMID: 21044964    Free PMC article.
Breaking through a plateau in renal cell carcinoma therapeutics: development and incorporation of biomarkers.
Sumanta Kumar Pal, Marcin Kortylewski, Hua Yu, Robert A Figlin.
Mol Cancer Ther, 2010 Nov 17; 9(12). PMID: 21078774    Free PMC article.
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.
An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients.
M A Vollebergh, E H Lips, +15 authors, S C Linn.
Ann Oncol, 2010 Dec 08; 22(7). PMID: 21135055    Free PMC article.
Genetic cardiovascular risk prediction: will we get there?
George Thanassoulis, Ramachandran S Vasan.
Circulation, 2010 Dec 15; 122(22). PMID: 21147729    Free PMC article.
Contribution of biomarkers to personalized medicine.
Daniel F Hayes.
Breast Cancer Res, 2011 Jan 05; 12 Suppl 4. PMID: 21172087    Free PMC article.
Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group.
H H Yoon, P Catalano, +10 authors, K M Murphy.
Cancer Chemother Pharmacol, 2011 Feb 03; 68(4). PMID: 21286719    Free PMC article.
Assessing the role of circulating, genetic, and imaging biomarkers in cardiovascular risk prediction.
Thomas J Wang.
Circulation, 2011 Feb 09; 123(5). PMID: 21300963    Free PMC article.
Measuring the performance of markers for guiding treatment decisions.
Holly Janes, Margaret S Pepe, Patrick M Bossuyt, William E Barlow.
Ann Intern Med, 2011 Feb 16; 154(4). PMID: 21320940    Free PMC article.
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
Translational application of epigenetic alterations: ovarian cancer as a model.
Marie E Maradeo, Paul Cairns.
FEBS Lett, 2011 Mar 16; 585(13). PMID: 21402071    Free PMC article.
Future directions of mammalian target of rapamycin (mTOR) inhibitor therapy in renal cell carcinoma.
Sumanta Kumar Pal, Robert A Figlin.
Target Oncol, 2011 Apr 13; 6(1). PMID: 21484496    Free PMC article.
Proteomics and biomarkers in clinical trials for drug development.
Jung-min Lee, Jasmine J Han, Gary Altwerger, Elise C Kohn.
J Proteomics, 2011 May 17; 74(12). PMID: 21570499    Free PMC article.
Somatic variation and cancer: therapies lost in the mix.
Andrew V Biankin, Thomas J Hudson.
Hum Genet, 2011 Jun 07; 130(1). PMID: 21643984
Antiangiogenic therapy for patients with recurrent and newly diagnosed malignant gliomas.
Katsuyuki Shirai, Michael R Siedow, Arnab Chakravarti.
J Oncol, 2011 Aug 02; 2012. PMID: 21804824    Free PMC article.
Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers.
Marieke A Vollebergh, Jos Jonkers, Sabine C Linn.
Cell Mol Life Sci, 2011 Sep 17; 69(2). PMID: 21922196
Recent progress and clinical importance on pharmacogenetics in cancer therapy.
Thomas I Peng Soh, Wei Peng Yong, Federico Innocenti.
Clin Chem Lab Med, 2011 Sep 29; 49(10). PMID: 21950596    Free PMC article.
Clinical trials in the era of personalized oncology.
Michael L Maitland, Richard L Schilsky.
CA Cancer J Clin, 2011 Oct 29; 61(6). PMID: 22034206    Free PMC article.
Assessing treatment-selection markers using a potential outcomes framework.
Ying Huang, Peter B Gilbert, Holly Janes.
Biometrics, 2012 Feb 04; 68(3). PMID: 22299708    Free PMC article.
Cancer biomarkers.
N Lynn Henry, Daniel F Hayes.
Mol Oncol, 2012 Feb 24; 6(2). PMID: 22356776    Free PMC article.
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.
Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819.
Mary W Redman, John J Crowley, +2 authors, David R Gandara.
Clin Cancer Res, 2012 May 18; 18(15). PMID: 22592956    Free PMC article.
Algorithm for codevelopment of new drug-predictive biomarker combinations: accounting for inter- and intrapatient tumor heterogeneity.
David R Gandara, Tianhong Li, +6 authors, Mary W Redman.
Clin Lung Cancer, 2012 Jun 09; 13(5). PMID: 22677432    Free PMC article.
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.
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.
Personalized therapy for urothelial cancer: review of the clinical evidence.
Elizabeth A Guancial, Dipanjan Chowdhury, Jonathan E Rosenberg.
Clin Investig (Lond), 2011 Apr 01; 1(4). PMID: 22754656    Free PMC article.
Biomarker-based targeting of the androgen-androgen receptor axis in advanced prostate cancer.
Manish Kohli, Rui Qin, Rafael Jimenez, Scott M Dehm.
Adv Urol, 2012 Sep 08; 2012. PMID: 22956944    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.
Low ERK phosphorylation in cancer-associated fibroblasts is associated with tamoxifen resistance in pre-menopausal breast cancer.
Susann Busch, Lisa Rydén, +2 authors, Göran Landberg.
PLoS One, 2012 Oct 03; 7(9). PMID: 23029174    Free PMC article.
Efficiency of study designs in diagnostic randomized clinical trials.
Bo Lu, Constantine Gatsonis.
Stat Med, 2012 Oct 17; 32(9). PMID: 23071073    Free PMC article.
Publication of tumor marker research results: the necessity for complete and transparent reporting.
Lisa M McShane, Daniel F Hayes.
J Clin Oncol, 2012 Oct 17; 30(34). PMID: 23071235    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.
Moving from correlative science to predictive oncology.
Richard Simon.
EPMA J, 2010 Sep 01; 1(3). PMID: 23199082    Free PMC article.
Tumor prognostic factors and the challenge of developing predictive factors.
Emma B Holliday, Erik P Sulman.
Curr Oncol Rep, 2012 Dec 12; 15(1). PMID: 23224629
Feasibility and safety of sequential research-related tumor core biopsies in clinical trials.
Jung-min Lee, John L Hays, +9 authors, Elise C Kohn.
Cancer, 2013 Jan 03; 119(7). PMID: 23280317    Free PMC article.
A 12-gene set predicts survival benefits from adjuvant chemotherapy in non-small cell lung cancer patients.
Hao Tang, Guanghua Xiao, +10 authors, Yang Xie.
Clin Cancer Res, 2013 Jan 30; 19(6). PMID: 23357979    Free PMC article.
Highly Cited.
Recent development on statistical methods for personalized medicine discovery.
Yingqi Zhao, Donglin Zeng.
Front Med, 2013 Feb 05; 7(1). PMID: 23377890
Enzalutamide for the treatment of prostate cancer.
Sumanta K Pal, Cy A Stein, Oliver Sartor.
Expert Opin Pharmacother, 2013 Feb 28; 14(5). PMID: 23441761    Free PMC article.
Estimating Individualized Treatment Rules Using Outcome Weighted Learning.
Yingqi Zhao, Donglin Zeng, A John Rush, Michael R Kosorok.
J Am Stat Assoc, 2013 May 01; 107(449). PMID: 23630406    Free PMC article.
Highly Cited.
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.
Impact of bioinformatic procedures in the development and translation of high-throughput molecular classifiers in oncology.
Charles Ferté, Andrew D Trister, +8 authors, Stephen H Friend.
Clin Cancer Res, 2013 Jun 20; 19(16). PMID: 23780890    Free PMC article.
A framework for evaluating markers used to select patient treatment.
Holly Janes, Margaret S Pepe, Ying Huang.
Med Decis Making, 2013 Jul 03; 34(2). PMID: 23811760    Free PMC article.
Prospective validation of candidate SNPs of VEGF/VEGFR pathway in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab.
Fotios Loupakis, Chiara Cremolini, +17 authors, Heinz-Josef Lenz.
PLoS One, 2013 Jul 19; 8(7). PMID: 23861747    Free PMC article.
Development of omics-based clinical tests for prognosis and therapy selection: the challenge of achieving statistical robustness and clinical utility.
Lisa M McShane, Mei-Yin C Polley.
Clin Trials, 2013 Sep 04; 10(5). PMID: 24000377    Free PMC article.
Run-in phase III trial design with pharmacodynamics predictive biomarkers.
Fangxin Hong, Richard Simon.
J Natl Cancer Inst, 2013 Oct 08; 105(21). PMID: 24096624    Free PMC article.
Multicenter trials using ¹⁸F-fluorodeoxyglucose (FDG) PET to predict chemotherapy response: effects of differential measurement error and bias on power calculations for unselected and enrichment designs.
Brenda F Kurland, Robert K Doot, +2 authors, Paul E Kinahan.
Clin Trials, 2013 Oct 31; 10(6). PMID: 24169628    Free PMC article.
Criteria for the use of omics-based predictors in clinical trials: explanation and elaboration.
Lisa M McShane, Margaret M Cavenagh, +12 authors, Barbara A Conley.
BMC Med, 2013 Nov 16; 11. PMID: 24228635    Free PMC article.
OMICS-based personalized oncology: if it is worth doing, it is worth doing well!
Daniel F Hayes.
BMC Med, 2013 Nov 16; 11. PMID: 24228698    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.
Clinical implications of using molecular diagnostics for ovarian cancers.
E C Kohn, S Romano, J-M Lee.
Ann Oncol, 2013 Dec 07; 24 Suppl 10. PMID: 24265398    Free PMC article.
Adaptive prediction model in prospective molecular signature-based clinical studies.
Guanghua Xiao, Shuangge Ma, John Minna, Yang Xie.
Clin Cancer Res, 2013 Dec 11; 20(3). PMID: 24323903    Free PMC article.
Stratified medicine in European Medicines Agency licensing: a systematic review of predictive biomarkers.
Kinga Malottki, Mousumi Biswas, +4 authors, Lucinda Billingham.
BMJ Open, 2014 Jan 29; 4(1). PMID: 24468721    Free PMC article.
Systematic Review.
Testing Overall and Subpopulation Treatment Effects with Measurement Errors.
Yanyuan Ma, Guosheng Yin.
Stat Sin, 2014 Feb 07; 23(3). PMID: 24501537    Free PMC article.
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.
Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer.
Gerald W Prager, Kira H Braemswig, +6 authors, Christoph C Zielinski.
Cancer Sci, 2014 May 23; 105(8). PMID: 24850362    Free PMC article.
Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy.
Marieke A Vollebergh, Esther H Lips, +9 authors, Sabine C Linn.
Breast Cancer Res, 2014 Jun 03; 16(3). PMID: 24887359    Free PMC article.
Evaluation of a chemoresponse assay as a predictive marker in the treatment of recurrent ovarian cancer: further analysis of a prospective study.
C Tian, D J Sargent, +4 authors, R L Coleman.
Br J Cancer, 2014 Jul 09; 111(5). PMID: 25003664    Free PMC article.
Decade in review--clinical trials: shifting paradigms in cancer clinical trial design.
Daniel J Sargent, Edward L Korn.
Nat Rev Clin Oncol, 2014 Oct 08; 11(11). PMID: 25286977
A comprehensive review of nongenetic prognostic and predictive factors influencing the heterogeneity of outcomes in advanced non-small-cell lung cancer.
Gebra Cuyún Carter, Amy M Barrett, +3 authors, William J John.
Cancer Manag Res, 2014 Nov 05; 6. PMID: 25364274    Free PMC article.
Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some simple themes.
Stuart G Baker, Barnett S Kramer.
Clin Trials, 2014 Nov 12; 12(4). PMID: 25385934    Free PMC article.
Biomarker validation and testing.
Daniel F Hayes.
Mol Oncol, 2014 Dec 03; 9(5). PMID: 25458054    Free PMC article.
Adaptive randomized phase II design for biomarker threshold selection and independent evaluation.
Lindsay A Renfro, Christina M Coughlin, Axel M Grothey, Daniel J Sargent.
Chin Clin Oncol, 2014 Dec 09; 3(1). PMID: 25485277    Free PMC article.
Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity.
Daniel V T Catenacci.
Mol Oncol, 2015 Jan 06; 9(5). PMID: 25557400    Free PMC article.
Adaptive clinical trial designs in oncology.
Yong Zang, J Jack Lee.
Chin Clin Oncol, 2015 Mar 27; 3(4). PMID: 25811018    Free PMC article.
Designing a study to evaluate the benefit of a biomarker for selecting patient treatment.
Holly Janes, Marshall D Brown, Margaret S Pepe.
Stat Med, 2015 Jun 27; 34(27). PMID: 26112650    Free PMC article.
Evaluating Prognostic Markers Using Relative Utility Curves and Test Tradeoffs.
Stuart G Baker, Barnett S Kramer.
J Clin Oncol, 2015 Jul 01; 33(23). PMID: 26124476    Free PMC article.
Clinical Neuropathology practice guide 5-2015: MGMT methylation pyrosequencing in glioblastoma: unresolved issues and open questions.
Michal Bienkowski, Anna S Berghoff, +4 authors, Matthias Preusser.
Clin Neuropathol, 2015 Aug 22; 34(5). PMID: 26295302    Free PMC article.
Personalized Medicine: Genomics Trials in Oncology.
Daniel F Hayes, Anne F Schott.
Trans Am Clin Climatol Assoc, 2015 Sep 04; 126. PMID: 26330667    Free PMC article.
The role of PET and PET-CT scanning in assessing response to neoadjuvant therapy in esophageal carcinoma.
Milly Schröer-Günther, Fülöp Scheibler, +3 authors, Stefan Lange.
Dtsch Arztebl Int, 2015 Sep 12; 112(33-34). PMID: 26356551    Free PMC article.
Molecular and clinical implementations of ovarian cancer mouse avatar models.
Amira A Zayed, Sumithra J Mandrekar, Paul Haluska.
Chin Clin Oncol, 2015 Sep 27; 4(3). PMID: 26408297    Free PMC article.
Patient-centric trials for therapeutic development in precision oncology.
Andrew V Biankin, Steven Piantadosi, Simon J Hollingsworth.
Nature, 2015 Oct 16; 526(7573). PMID: 26469047
Highly Cited. Review.
Molecular profiling of childhood cancer: Biomarkers and novel therapies.
Federica Saletta, Carol Wadham, +5 authors, Jennifer A Byrne.
BBA Clin, 2014 Jun 01; 1. PMID: 26675306    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.
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.
Lyndsay N Harris, Nofisat Ismaila, +11 authors, American Society of Clinical Oncology.
J Clin Oncol, 2016 Feb 10; 34(10). PMID: 26858339    Free PMC article.
Highly Cited. Review.
Establishing the Quantitative Relationship Between Lanreotide Autogel®, Chromogranin A, and Progression-Free Survival in Patients with Nonfunctioning Gastroenteropancreatic Neuroendocrine Tumors.
Núria Buil-Bruna, Marion Dehez, +2 authors, Iñaki F Trocóniz.
AAPS J, 2016 Feb 26; 18(3). PMID: 26908127    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.
Optimal marker-strategy clinical trial design to detect predictive markers for targeted therapy.
Yong Zang, Suyu Liu, Ying Yuan.
Biostatistics, 2016 Mar 10; 17(3). PMID: 26951724    Free PMC article.
Precision oncology: A new era of cancer clinical trials.
Lindsay A Renfro, Ming-Wen An, Sumithra J Mandrekar.
Cancer Lett, 2016 Mar 19; 387. PMID: 26987624    Free PMC article.
Osteopontin splice variants are differential predictors of breast cancer treatment responses.
Krzysztof Zduniak, Anil Agrawal, +3 authors, Georg F Weber.
BMC Cancer, 2016 Jul 13; 16. PMID: 27400751    Free PMC article.
Subgroup-Based Adaptive (SUBA) Designs for Multi-Arm Biomarker Trials.
Yanxun Xu, Lorenzo Trippa, Peter Müller, Yuan Ji.
Stat Biosci, 2016 Sep 13; 8(1). PMID: 27617041    Free PMC article.
Optimal sequential enrichment designs for phase II clinical trials.
Yong Zang, Ying Yuan.
Stat Med, 2016 Sep 20; 36(1). PMID: 27640874    Free PMC article.
Strategies for power calculations in predictive biomarker studies in survival data.
Dung-Tsa Chen, Po-Yu Huang, +4 authors, Jhanelle E Gray.
Oncotarget, 2016 Sep 24; 7(49). PMID: 27661007    Free PMC article.
Evaluating Biomarkers for Guiding Treatment Decisions.
Patrick M Bossuyt, Tajik Parvin.
EJIFCC, 2015 Jan 01; 26(1). PMID: 27683482    Free PMC article.
A subgroup cluster-based Bayesian adaptive design for precision medicine.
Wentian Guo, Yuan Ji, Daniel V T Catenacci.
Biometrics, 2016 Oct 25; 73(2). PMID: 27775814    Free PMC article.
Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.
Miranta Antoniou, Ruwanthi Kolamunnage-Dona, Andrea L Jorgensen.
J Pers Med, 2017 Jan 27; 7(1). PMID: 28125057    Free PMC article.
Beyond Correlations, Sensitivities, and Specificities: A Roadmap for Demonstrating Utility of Advanced Imaging in Oncology Treatment and Clinical Trial Design.
Erich P Huang, Frank I Lin, Lalitha K Shankar.
Acad Radiol, 2017 May 01; 24(8). PMID: 28456570    Free PMC article.
Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma.
Eun-Jung Lee, Seung-Hyun Yang, +6 authors, Jinsil Seong.
Cancer Res Treat, 2017 Jul 21; 50(3). PMID: 28724284    Free PMC article.
On Enrichment Strategies for Biomarker Stratified Clinical Trials.
Xiaofei Wang, Jingzhu Zhou, Ting Wang, Stephen L George.
J Biopharm Stat, 2017 Sep 22; 28(2). PMID: 28933670    Free PMC article.
Case-only approach to identifying markers predicting treatment effects on the relative risk scale.
James Y Dai, C Jason Liang, +2 authors, Holly Janes.
Biometrics, 2017 Sep 30; 74(2). PMID: 28960244    Free PMC article.
Chemosensitivity-directed therapy compared to dacarbazine in chemo-naive advanced metastatic melanoma: a multicenter randomized phase-3 DeCOG trial.
Selma Ugurel, Carmen Loquai, +18 authors, Jürgen C Becker.
Oncotarget, 2017 Nov 05; 8(44). PMID: 29100289    Free PMC article.
Relative efficiency of precision medicine designs for clinical trials with predictive biomarkers.
Weichung Joe Shih, Yong Lin.
Stat Med, 2017 Dec 06; 37(5). PMID: 29205435    Free PMC article.
Estimating causal effects of time-dependent exposures on a binary endpoint in a high-dimensional setting.
Vahé Asvatourian, Clélia Coutzac, +3 authors, Emilie Lanoy.
BMC Med Res Methodol, 2018 Jul 05; 18(1). PMID: 29969993    Free PMC article.
Auxiliary variable-enriched biomarker-stratified design.
Ting Wang, Xiaofei Wang, +2 authors, Stephen L George.
Stat Med, 2018 Sep 18; 37(30). PMID: 30221368    Free PMC article.
IHC Color Histograms for Unsupervised Ki67 Proliferation Index Calculation.
Rokshana S Geread, Peter Morreale, +4 authors, April Khademi.
Front Bioeng Biotechnol, 2019 Oct 22; 7. PMID: 31632956    Free PMC article.
Noncoding RNAs and Liquid Biopsy in Lung Cancer: A Literature Review.
Antonia Haranguș, Ioana Berindan-Neagoe, +2 authors, Mărioara Șimon.
Diagnostics (Basel), 2019 Dec 11; 9(4). PMID: 31818027    Free PMC article.
An alternative method to analyse the biomarker-strategy design.
Cornelia Ursula Kunz, Thomas Jaki, Nigel Stallard.
Stat Med, 2018 Sep 28; 37(30). PMID: 30260533    Free PMC article.
Natural agents inhibit colon cancer cell proliferation and alter microbial diversity in mice.
Lulu Farhana, Sarah Sarkar, +5 authors, Adhip P N Majumdar.
PLoS One, 2020 Mar 21; 15(3). PMID: 32196510    Free PMC article.
Designing precision medicine trials to yield a greater population impact.
Ying-Qi Zhao, Michael L LeBlanc.
Biometrics, 2019 Oct 11; 76(2). PMID: 31598964    Free PMC article.
Pharmaceutical Advances and Proteomics Researches.
Ensieh KhalKhal, Mostafa Rezaei-Tavirani, Mohammad Rostamii-Nejad.
Iran J Pharm Res, 2020 Aug 18; 18(Suppl1). PMID: 32802089    Free PMC article.
Phase III Precision Medicine Clinical Trial Designs That Integrate Treatment and Biomarker Evaluation.
Mei-Yin C Polley, Edward L Korn, Boris Freidlin.
JCO Precis Oncol, 2020 Sep 15; 3. PMID: 32923845    Free PMC article.
• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.
Sonja Kappel-Latif, Johannes Zacherl, +23 authors, Pancho trialists and for the Medical University of Vienna p53research group.
Eur Surg, 2018 Dec 19; 50(4). PMID: 30559831    Free PMC article.
ctDNA and Adjuvant Therapy for Colorectal Cancer: Time to Re-Invent Our Treatment Paradigm.
Mahendra Naidoo, Peter Gibbs, Jeanne Tie.
Cancers (Basel), 2021 Jan 23; 13(2). PMID: 33477814    Free PMC article.