Review
. 2016 Feb;43().
doi: 10.1016/j.ctrv.2015.12.008.

Clinical trial designs incorporating predictive biomarkers

Lindsay A Renfro 1 Himel Mallick 2 Ming-Wen An 3 Daniel J Sargent 4 Sumithra J Mandrekar 4 
Affiliations
  • PMID: 26827695
  •     79 References
  •     19 citations

Abstract

Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer "targeted" drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research.

Keywords: Adaptive trial design; Bayesian adaptive design; Biomarker-based design; Clinical trial design; Enrichment designs; Targeted therapies.

Issues in clinical trial design for tumor marker studies.
Daniel Sargent, Carmen Allegra.
Semin Oncol, 2002 Jun 14; 29(3). PMID: 12063675
Hierarchical Bayesian approaches to phase II trials in diseases with multiple subtypes.
Peter F Thall, J Kyle Wathen, +3 authors, Robert S Benjamin.
Stat Med, 2003 Feb 15; 22(5). PMID: 12587104
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
Adaptive signature design: an adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patients.
Boris Freidlin, Richard Simon.
Clin Cancer Res, 2005 Nov 10; 11(21). PMID: 16278411
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
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
Cetuximab for the treatment of colorectal cancer.
Derek J Jonker, Chris J O'Callaghan, +12 authors, Malcolm J Moore.
N Engl J Med, 2007 Nov 16; 357(20). PMID: 18003960
Highly Cited.
Disease control rate at 8 weeks predicts clinical benefit in advanced non-small-cell lung cancer: results from Southwest Oncology Group randomized trials.
Primo N Lara, Mary W Redman, +5 authors, Southwest Oncology Group.
J Clin Oncol, 2008 Jan 19; 26(3). PMID: 18202421
Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.
Rafael G Amado, Michael Wolf, +9 authors, David D Chang.
J Clin Oncol, 2008 Mar 05; 26(10). PMID: 18316791
Highly Cited.
Bayesian adaptive design for targeted therapy development in lung cancer--a step toward personalized medicine.
Xian Zhou, Suyu Liu, +2 authors, J Jack Lee.
Clin Trials, 2008 Jun 19; 5(3). PMID: 18559407    Free PMC article.
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.
Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial.
Edward S Kim, Vera Hirsh, +15 authors, Jean-Yves Douillard.
Lancet, 2008 Nov 26; 372(9652). PMID: 19027483
Highly Cited.
Confirmatory adaptive designs with Bayesian decision tools for a targeted therapy in oncology.
Werner Brannath, Emmanuel Zuber, +4 authors, Amy Racine-Poon.
Stat Med, 2009 Mar 07; 28(10). PMID: 19266565
Using short-term response information to facilitate adaptive randomization for survival clinical trials.
Xuelin Huang, Jing Ning, +3 authors, Donald A Berry.
Stat Med, 2009 Mar 28; 28(12). PMID: 19326367    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.
I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy.
A D Barker, C C Sigman, +3 authors, L J Esserman.
Clin Pharmacol Ther, 2009 May 15; 86(1). PMID: 19440188
Highly Cited.
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.
The cross-validated adaptive signature design.
Boris Freidlin, Wenyu Jiang, Richard Simon.
Clin Cancer Res, 2010 Jan 14; 16(2). PMID: 20068112
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.
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.
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.
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
Makoto Maemondo, Akira Inoue, +21 authors, North-East Japan Study Group.
N Engl J Med, 2010 Jun 25; 362(25). PMID: 20573926
Highly Cited.
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial.
Yung-Jue Bang, Eric Van Cutsem, +14 authors, ToGA Trial Investigators.
Lancet, 2010 Aug 24; 376(9742). PMID: 20728210
Highly Cited.
Adaptive clinical trials: the promise and the caution.
Donald A Berry.
J Clin Oncol, 2010 Dec 22; 29(6). PMID: 21172875
Outcome--adaptive randomization: is it useful?
Edward L Korn, Boris Freidlin.
J Clin Oncol, 2010 Dec 22; 29(6). PMID: 21172882    Free PMC article.
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
Review.
Population enrichment designs: case study of a large multinational trial.
Cyrus R Mehta, Ping Gao.
J Biopharm Stat, 2011 Apr 26; 21(4). PMID: 21516572
Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31.
Edith A Perez, Edward H Romond, +7 authors, Norman Wolmark.
J Clin Oncol, 2011 Jul 20; 29(25). PMID: 21768458    Free PMC article.
Highly Cited.
Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study.
Caicun Zhou, Yi-Long Wu, +21 authors, Changxuan You.
Lancet Oncol, 2011 Jul 26; 12(8). PMID: 21783417
Highly Cited.
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.
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
Reports from the 2010 Clinical and Translational Cancer Research Think Tank meeting: design strategies for personalized therapy trials.
Donald A Berry, Roy S Herbst, Eric H Rubin.
Clin Cancer Res, 2012 Feb 03; 18(3). PMID: 22298897    Free PMC article.
An adaptive seamless phase II/III design for oncology trials with subpopulation selection using correlated survival endpoints.
Martin Jenkins, Andrew Stone, Christopher Jennison.
Pharm Stat, 2012 Feb 14; 10(4). PMID: 22328327
Clinical trial designs for testing biomarker-based personalized therapies.
Tze Leung Lai, Philip W Lavori, Mei-Chiung I Shih, Branimir I Sikic.
Clin Trials, 2012 Mar 09; 9(2). PMID: 22397801    Free PMC article.
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
Review.
The BATTLE trial: personalizing therapy for lung cancer.
Edward S Kim, Roy S Herbst, +21 authors, Waun K Hong.
Cancer Discov, 2012 May 16; 1(1). PMID: 22586319    Free PMC article.
Highly Cited.
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.
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.
A conditional error function approach for subgroup selection in adaptive clinical trials.
T Friede, N Parsons, N Stallard.
Stat Med, 2012 Aug 07; 31(30). PMID: 22865774
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.
Review.
Selecting breast cancer patients for chemotherapy: the opening of the UK OPTIMA trial.
J Bartlett, P Canney, +19 authors, R Stein.
Clin Oncol (R Coll Radiol), 2012 Dec 27; 25(2). PMID: 23267818
Review.
Adaptive enrichment designs for clinical trials.
Noah Simon, Richard Simon.
Biostatistics, 2013 Mar 26; 14(4). PMID: 23525452    Free PMC article.
An adaptive clinical trials procedure for a sensitive subgroup examined in the multiple sclerosis context.
Corinne A Riddell, Yinshan Zhao, John Petkau.
Stat Methods Med Res, 2013 Apr 18; 25(4). PMID: 23592713
Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials.
Scott M Berry, Kristine R Broglio, Susan Groshen, Donald A Berry.
Clin Trials, 2013 Aug 29; 10(5). PMID: 23983156    Free PMC article.
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.
Sample size and threshold estimation for clinical trials with predictive biomarkers.
Howard M Mackey, Thomas Bengtsson.
Contemp Clin Trials, 2013 Sep 26; 36(2). PMID: 24064355
Adaptive enrichment with subpopulation selection at interim: methodologies, applications and design considerations.
Sue-Jane Wang, H M James Hung.
Contemp Clin Trials, 2013 Oct 01; 36(2). PMID: 24076485
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.
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.
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
Review.
A two-stage patient enrichment adaptive design in phase II oncology trials.
James X Song.
Contemp Clin Trials, 2013 Dec 18; 37(1). PMID: 24342820
A regulatory perspective on essential considerations in design and analysis of subgroups when correctly classified.
Sue-Jane Wang, H M James Hung.
J Biopharm Stat, 2014 Jan 08; 24(1). PMID: 24392976
Review.
Adaptive designs for confirmatory clinical trials with subgroup selection.
Nigel Stallard, Thomas Hamborg, Nicholas Parsons, Tim Friede.
J Biopharm Stat, 2014 Jan 08; 24(1). PMID: 24392984
Review.
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.
Randomised proof-of-concept phase II trial comparing targeted therapy based on tumour molecular profiling vs conventional therapy in patients with refractory cancer: results of the feasibility part of the SHIVA trial.
C Le Tourneau, X Paoletti, +29 authors, M Kamal.
Br J Cancer, 2014 Apr 26; 111(1). PMID: 24762958    Free PMC article.
Biomarker-based Bayesian randomized phase II clinical trial design to identify a sensitive patient subpopulation.
Satoshi Morita, Hideharu Yamamoto, Yasuo Sugitani.
Stat Med, 2014 May 14; 33(23). PMID: 24820639
The use of Bayesian hierarchical models for adaptive randomization in biomarker-driven phase II studies.
William T Barry, Charles M Perou, +2 authors, Joseph G Ibrahim.
J Biopharm Stat, 2014 May 20; 25(1). PMID: 24836519    Free PMC article.
Biomarker driven population enrichment for adaptive oncology trials with time to event endpoints.
Cyrus Mehta, Helmut Schäfer, Hanna Daniel, Sebastian Irle.
Stat Med, 2014 Aug 19; 33(26). PMID: 25130879
Adaptive designs for subpopulation analysis optimizing utility functions.
Alexandra C Graf, Martin Posch, Franz Koenig.
Biom J, 2014 Nov 18; 57(1). PMID: 25399844    Free PMC article.
Drug designs fulfilling the requirements of clinical trials aiming at personalizing medicine.
Sumithra J Mandrekar, Daniel J Sargent.
Chin Clin Oncol, 2014 Nov 22; 3(2). PMID: 25414851    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.
The direct assignment option as a modular design component: an example for the setting of two predefined subgroups.
Ming-Wen An, Xin Lu, Daniel J Sargent, Sumithra J Mandrekar.
Comput Math Methods Med, 2015 Feb 05; 2015. PMID: 25649690    Free PMC article.
ALCHEMIST: Bringing genomic discovery and targeted therapies to early-stage lung cancer.
D E Gerber, G R Oxnard, R Govindan.
Clin Pharmacol Ther, 2015 Feb 14; 97(5). PMID: 25677079    Free PMC article.
Review.
Multistage adaptive biomarker-directed targeted design for randomized clinical trials.
Zhong Gao, Anindya Roy, Ming Tan.
Contemp Clin Trials, 2015 Mar 18; 42. PMID: 25778672
Biomarker based clinical trial design.
Richard Simon.
Chin Clin Oncol, 2015 Apr 07; 3(3). PMID: 25841465
The Brave New World of clinical cancer research: Adaptive biomarker-driven trials integrating clinical practice with clinical research.
Donald A Berry.
Mol Oncol, 2015 Apr 19; 9(5). PMID: 25888066    Free PMC article.
Review.
Optimal decision rules for biomarker-based subgroup selection for a targeted therapy in oncology.
Johannes Krisam, Meinhard Kieser.
Int J Mol Sci, 2015 May 12; 16(5). PMID: 25961947    Free PMC article.
Improving Clinical Trial Efficiency: Thinking outside the Box.
Sumithra J Mandrekar, Suzanne E Dahlberg, Richard Simon.
Am Soc Clin Oncol Educ Book, 2015 May 21;. PMID: 25993165    Free PMC article.
Review.
Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials.
Funda Meric-Bernstam, Lauren Brusco, +16 authors, Gordon B Mills.
J Clin Oncol, 2015 May 28; 33(25). PMID: 26014291    Free PMC article.
Highly Cited.
Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial.
Christophe Le Tourneau, Jean-Pierre Delord, +21 authors, SHIVA investigators.
Lancet Oncol, 2015 Sep 08; 16(13). PMID: 26342236
Highly Cited.
An overview of the design and conduct of the BATTLE trials.
Suyu Liu, J Jack Lee.
Chin Clin Oncol, 2015 Sep 27; 4(3). PMID: 26408300
Review.
Adaptive Clinical Trials: Overview of Early-Phase Designs and Challenges.
Olga Marchenko, Valerii Fedorov, +2 authors, José Pinheiro.
Ther Innov Regul Sci, 2014 Jan 01; 48(1). PMID: 28670507    Free PMC article.
Use of big data in drug development for precision medicine.
Rosa S Kim, Nicolas Goossens, Yujin Hoshida.
Expert Rev Precis Med Drug Dev, 2016 Jul 19; 1(3). PMID: 27430024    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.
Review.
Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples.
L A Renfro, D J Sargent.
Ann Oncol, 2017 Feb 09; 28(1). PMID: 28177494    Free PMC article.
Highly Cited. Review.
Bayesian population finding with biomarkers in a randomized clinical trial.
Satoshi Morita, Peter Müller.
Biometrics, 2017 Mar 04; 73(4). PMID: 28257141    Free PMC article.
Testing many treatments within a single protocol over 10 years at MRC Clinical Trials Unit at UCL: Multi-arm, multi-stage platform, umbrella and basket protocols.
Mahesh Kb Parmar, Matthew R Sydes, +11 authors, Patrick J Royston.
Clin Trials, 2017 Aug 24; 14(5). PMID: 28830236    Free PMC article.
Electronic Health Record Phenotypes for Precision Medicine: Perspectives and Caveats From Treatment of Breast Cancer at a Single Institution.
Matthew K Breitenstein, Hongfang Liu, +2 authors, Rui Zhang.
Clin Transl Sci, 2017 Oct 31; 11(1). PMID: 29084368    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.
Accelerating Therapeutic Development through Innovative Trial Design in Colorectal Cancer.
Michael Lam, Jonathan M Loree, +2 authors, Scott Kopetz.
Curr Treat Options Oncol, 2018 Mar 01; 19(2). PMID: 29488033
Review.
Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02).
Xabier García-Albéniz, Vicente Alonso, +17 authors, Joan Maurel.
Oncologist, 2019 Jun 27; 24(11). PMID: 31235483    Free PMC article.
Two-stage enrichment clinical trial design with adjustment for misclassification in predictive biomarkers.
Yong Lin, Weichung J Shih, Shou-En Lu.
Stat Med, 2019 Oct 18; 38(29). PMID: 31621944    Free PMC article.
Biomarker threshold adaptive designs for survival endpoints.
Guoqing Diao, Jun Dong, +3 authors, Joseph G Ibrahim.
J Biopharm Stat, 2018 Feb 14; 28(6). PMID: 29436940    Free PMC article.
The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design.
Munyaradzi Dimairo, Philip Pallmann, +17 authors, ACE Consensus Group.
Trials, 2020 Jun 18; 21(1). PMID: 32546273    Free PMC article.
The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design.
Munyaradzi Dimairo, Philip Pallmann, +17 authors, ACE Consensus Group.
BMJ, 2020 Jun 20; 369. PMID: 32554564    Free PMC article.
Biomarkers in critical care nutrition.
Christian Stoppe, Sebastian Wendt, +4 authors, Arnold S Kristof.
Crit Care, 2020 Aug 14; 24(1). PMID: 32787899    Free PMC article.
Review.
Biomarker-Driven Oncology Clinical Trials: Key Design Elements, Types, Features, and Practical Considerations.
Chen Hu, James J Dignam.
JCO Precis Oncol, 2020 Sep 15; 3. PMID: 32923854    Free PMC article.
Review.
Guidelines for Statistical Reporting in Medical Journals.
Fang-Shu Ou, Jennifer G Le-Rademacher, +2 authors, Sumithra J Mandrekar.
J Thorac Oncol, 2020 Aug 29; 15(11). PMID: 32858236    Free PMC article.
Review.
The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis.
Lei Zhang, Yiyi Liang, +6 authors, Fenglei Yu.
Mol Cancer, 2019 Mar 10; 18(1). PMID: 30849971    Free PMC article.
Review.
Clinical outcomes of breast cancer patients treated in phase I clinical trials at University of Colorado Cancer Center.
Jennifer A Weiss, Andrew Nicklawsky, +9 authors, Jennifer R Diamond.
Cancer Med, 2020 Oct 17; 9(23). PMID: 33063469    Free PMC article.
Innovative trial designs and analyses for vaccine clinical development.
Mengya Liu, Qing Li, +2 authors, Elaine Hoffman.
Contemp Clin Trials, 2020 Nov 24; 100. PMID: 33227451    Free PMC article.