We first congratulate the authors on an important contribution to the literature of clinical trials in oncology. The authors, including two editors and 52 contributors, are from international communities of both academia and pharmaceutical industry. This highly anticipated book focuses on clinical trials in oncology, ranging from early, middle, and late phase trials to advanced topics such as precision medicine and immunotherapy. This textbook is expected to be extremely useful for statisticians and investigators who have been doing clinical trials for years, and for future clinical researchers and statisticians who are eager to learn about the design, conduct, analysis, and interpretation of clinical trials in oncology.
We strongly recommend this textbook for four reasons. First, it covers multiple stages of clinical trials in oncology, from early, middle, to late development. Second, it examines various designs of clinical trials, including traditional study designs, flexible designs, and SMART (Sequential Multiple Assignment Randomized Trials) designs. Third, it gives insights into unique aspects of clinical trials in oncology compared with other therapeutic areas, such as time-to-event endpoints and censoring. Fourth, it consists of different types of materials that are suitable to different groups of readers, with some materials for readers who like to have an aerial view of the practical considerations and the other materials for readers who like to have deep understanding to motivate their theoretical research. In the following, we explain these four reasons in detail.
The book covers Phases I-III of clinical trials. After the first chapter, which is entitled “Introduction to Clinical Trials”, the book is divided into four coherent sections. Section I is entitled “Early to Middle Development” and it has five chapters. This section focuses on key considerations of the early to middle development that the clinicians need to consider for Phase I and Phase II clinical trials. Section II is entitled “Late Phase Clinical Trials” and it has six chapters. This section focuses on key considerations of the late stage development that the clinicians need to consider for Phase III clinical trials. Section III is entitled “Personalized Medicine” and it has seven chapters. This section is devoted to cutting-edge topics in personalized medicine, which can be considered as biomarker-driven Phase II/III clinical trials. Section 4 is entitled “Advanced Topics” and it has eight chapters. This section is dedicated to advanced topics in the analysis phase of clinical trials. However, the book doesn’t cover Phase IV of clinical trials. Phase IV trials, also known as post-marketing surveillance trials, include the safety surveillance and ongoing technical support of a drug after it receives market authorization from regulatory authorities. The safety surveillance is designed to detect any adverse effects over a much larger patient population and longer time period.
The book examines various designs. In Section 1, both traditional and innovative study designs for Phase I and Phase II clinical trials are discussed. For Phase I clinical trials, Chapter 3 describes various designs for different types of treatments, (1) cytotoxic agents, (2) molecularly targeted agents, and (3) immunotherapies. For Phase II clinical trials, Chapter 4 overviews traditional designs, Chapter 5 discusses immunotherapy trials, and Chapter 6 introduces adaptive designs. In Section 2, both traditional and innovative study designs for Phase III are discussed. Chapter 7 and Chapter 8 describe traditional superiority trials and non-inferiority trials. Chapter 9 discusses multi-arm, multi-stage (MAMS) trials and Chapter 10 discusses cluster randomized trials. In Section 3, the innovative SMART designs are discussed with motivation of dynamic treatment regimens. Since we feel it is so important, we cite an excerpt from the book: “Adaptive designs are defined by the adaptation of the trial operational characteristics during the study based on the collected data. In contrast, a SMART is designed with fixed operational characteristics that remain unmodified throughout the study”.
The book gives insights on unique aspects of oncology trials. There are many books on clinical trials in general, but this is a book on clinical trials in oncology. In every chapter, the authors start with features of general clinical trials, and then move on to unique features of oncology clinical trials. Here we only give two examples. In the first chapter of Section 1, Chapter 2 entitled “Selection of Endpoints”, the authors start with key definitions and endpoints selection, then move on to unique features of oncology endpoints, which are categorized into patient-centered endpoints and tumor-centered endpoints. In the first chapter of Section 2, Chapter 7 entitled “Sample Size Calculations for Phase III Trials in Oncology”, the authors give an introduction of sample size calculation in general clinical trials, then move on to sample size calculation when the outcome variable is time-to-event, an important feature of most of oncology trials.
The book is targeted at a very broad audience. Sections 1–3 are targeted at an audience who are interested in key considerations in the development, design, and conduct of oncology clinical trials. The authors provide a lot of real-examples and case studies, along with simulations and implementing codes. Section 4 is targeted at an audience who are interested in advanced topics related to the analysis of oncology clinical trials. The advanced topics covered in Section 4 are (1) surrogate endpoints, (2) completing risks, (4) cure models, (5) interval censoring, (6) treatment changes, (7) adverse events, (8) quality of life outcomes, and (9) missing data. However, causal inference is not covered as an advanced topic. Causal inference is important in single-arm clinical trials with external controls and Phase IV clinical trials, where it is crucial to control confounding bias because randomization and blinding are not implemented.
To summarize, because of the above four reasons, we strongly recommend this book to clinical researchers and statisticians who are interested in the development, design, conduct and analysis of oncology clinical trials. This book is well-balanced between practical considerations and statistical theories involved in oncology clinical trials. We believe that this book will help advance the design and analysis of oncology clinical trials with the ultimate goal to improve the care of oncology patients and their quality of life.