4th Edition
Handbook of Statistics in Clinical Oncology
Since the third edition of this handbook, significant advances have transformed the field of oncology. Most cancer types now offer multiple treatment options, with immunotherapies and targeted therapies becoming the standard of care. Master protocols, which allow the addition of new treatment arms without requiring new protocols, have gained popularity—not only to expedite the approval process for new therapies but also to ensure that patients receive the most beneficial treatments tailored to their individual needs. This revised edition features contributions from leading cancer trial statisticians, providing expert insights into modern oncology trial design and methodology. The handbook is structured into five key parts:
- Part 1: Cancer prevention and screening trial designs, including risk prediction models and prevention trials
- Part 2: Early-phase trial designs, covering dose-finding studies, selection designs, and multi-strata trials
- Part 3: Late-stage trial designs, including approaches for IO therapies, cure-rate models, targeted agents, and considerations for pediatric oncology trials
- Part 4: Trial conduct and operations, addressing best practices for Data Monitoring Committees (DMCs), SWOG/CRAB calculators, pragmatic trials, and clinical trial innovation
- Part 5: Beyond primary endpoints, exploring surrogate endpoints, microbiome research, patient-reported outcomes (PROs), and tree-based partitioning methods
This updated edition provides a comprehensive resource for researchers, clinicians, and statisticians involved in the evolving landscape of oncology clinical trials.
SECTION 1 Cancer Prevention & Screening
Chapter 1 Cancer Screening Trials
by Ruth Etzioni and Noel S Weiss
Chapter 2 Cancer Risk Prediction Models
by Oksana Chernova, Ruth M. Pfeiffer, and Donna P. Ankerst
Chapter 3 Incorporating External Registry Data Into Cohort-based Cancer Risk Prediction Tools
by Oksana Chernova, Ruth M. Pfeiffer, and Donna P. Ankerst
SECTION 2 Trial Design | Early-Phase Trials
Chapter 4 Phase I – Overview and Recent Trial Designs
by Motomi Mori
Chapter 5 Statistical and Machine Learning Methods for Phase I Dose-Finding
by Keiichiro Seno, Masataka Igeta, Kota Matsui, Takashi Daimon, and Shigeyuki Matsui
Chapter 6 Seamless Phase I/II Trial Design for Assessing Toxicity and Efficacy for Targeted Agents
by by Antje Hoering, Michael LeBlanc, and John Crowley
Chapter 7 Designs Using Time to Event Endpoints / Single Arm versus Randomized Phase II Designs
by Cathy Tangen and John Crowley
Chapter 8 Phase II Selection Designs
by James Moon, Michael LeBlanc, Michael Wu, P. Y. Liu, and Sarah Samorodnitsky
Chapter 9 Phase II Trials with Multiple Strata
by Michael LeBlanc, Cathryn Rankin, and John Crowley
SECTION 3 Trial Design | Late-Phase Trials
Chapter 10 Cure Rate Survival Models
by Subodh Selukar and Megan Othus
Chapter 11 Phase III Trials for Targeted Agents
by Antje Hoering, Michael LeBlanc, and John Crowley
Chapter 12 Phase II and III Clinical Trial Designs for Precision Medicine
by Shigeyuki Matsui and Masataka Igeta
Chapter 13 SMARTs in Oncology
by Sarah Medley and Kelley M. Kidwell
Chapter 14 Statistical Considerations in the Design and Analysis of Cancer Trials with Immune-Oncology Therapies
by Susan Halabi
Chapter 15 Alpha Splitting
by Steve Snapinn
Chapter 16 Early Stopping of Clinical Trials Evaluating Targeted Therapies
by Mary W. Redman and Megan Othus
Chapter 17 Noninferiority Trials
by Ken Kopecky and Stephanie Green
Chapter 18 Considerations for Pediatric Oncology Trials
by Lindsay Renfro and Todd Alonzo
SECTION 4 Trial Conduct
Chapter 19 An Overview of Master Protocols
by Megan Othus and Michael LeBlanc
Chapter 20 On Use of Covariates in Randomization and Analysis of Clinical Trials
by Garnet Anderson, Michael LeBlanc, PY Liu, and John Crowley
Chapter 21 Pragmatic Clinical Trials in Clinical Oncology: A Statistical Perspective
by Aasthaa Bansal and Scott Ramsey
Chapter 22 Dynamic Treatment Regimens and Sequential Multiple Assignment Randomized Trial in Cancer Research
by Yingqi Zhao
Chapter 23 Outcome-Adaptive Randomization
by Ed Korn and Boris Freidlin
Chapter 24 Current Suggested Practices and Issues for Data and Safety Monitoring Committees in Cancer Clinical Trials
by Catherine M. Tangen and John Crowley
Chapter 25 Improving Data Collection: EHR-to-EDC Assisted Data Transfer
by Keith Goodman and Chris Cook
Chapter 26 Barriers and Disparities in Access to Cancer Clinical Trials – Causes and Implications
by Joseph M. Unger
Chapter 27 SWOG Statistical Calculators for Design and Analysis of Clinical Trials
by Adam Rosenthal, Rachael Sexton, Katie Snapinn, Emily Goren, Antje Hoering, John Crowley, and Michael Leblanc
Chapter 28 Streamlining Data Collection and Trial Conduct
by Mandrekar and Shauna Hillman
SECTION 5 Beyond the Primary Endpoint
Chapter 29 Use of Circulating Tumor DNA in Oncology – ctMoniTR
by Emily Goren, Katie Nishimura, Adam Rosenthal, Megan Eisele, Nevine Zariffa, Mark Stewart, Hillary S. Andrews, Antje Hoering, and Jeff Allen
Chapter 30 Statistical Analysis of -Omics Data
by Amarise Little, Wodan Ling, Anna M. Plantinga, Sarah Samorodnitsky, Michael C. Wu, and Ni Zhao
Chapter 31 Principles of Design and Analysis for Patient-Reported Outcomes
by Joseph M. Unger and Riha Vaidya
Chapter 32 X Intermediate and Surrogate Endpoints in Phase III Randomized
by Edward L. Korn and Boris Freidlin
Chapter 33 Prognostic Groups via Interpretable Function Approximation: Tree-based and Extreme Regression Models
by Michael LeBlanc, Antje Hoering Caleb McKinney, and John Crowley
Biography
Antje Hoering is the President and CEO of Cancer Research And Biostatistics (CRAB) and leads a team of approximately eighty talented and dedicated oncology research professionals, all united in our mission to help conquer cancer. She also serves as the lead statistician of the SWOG Myeloma Committee and holds affiliate appointments at the University of Washington Biostatistics department and the Fred Hutch Cancer Center.
Megan Othus is a Professor of Biostatistics at the Fred Hutchinson Cancer. She serves as the lead statistician of the SWOG Leukemia and Rare Cancer Committees. Her research interests focus on the design and endpoints in oncology clinical trials.
John Crowley received his master’s and doctorate degrees (in 1970 and 1973, respectively) in Biomathematics from the University of Washington, and was the Director of the SWOG Statistical Center from 1984 to 2012. In 1997 Dr. Crowley founded Cancer Research And Biostatistics (CRAB), was the President and CEO of CRAB until 2014, and currently serves as the Chief of Strategic Alliances. Dr. Crowley's research interests focus on the design and analysis of cancer clinical and translation trials.
