Statistical Methods for Survival Trial Design


Book Description

Statistical Methods for Survival Trial Design: With Applications to Cancer Clinical Trials Using R provides a thorough presentation of the principles of designing and monitoring cancer clinical trials in which time-to-event is the primary endpoint. Traditional cancer trial designs with time-to-event endpoints are often limited to the exponential model or proportional hazards model. In practice, however, those model assumptions may not be satisfied for long-term survival trials. This book is the first to cover comprehensively the many newly developed methodologies for survival trial design, including trial design under the Weibull survival models; extensions of the sample size calculations under the proportional hazard models; and trial design under mixture cure models, complex survival models, Cox regression models, and competing-risk models. A general sequential procedure based on the sequential conditional probability ratio test is also implemented for survival trial monitoring. All methodologies are presented with sufficient detail for interested researchers or graduate students.




Introduction to Statistical Methods for Clinical Trials


Book Description

Clinical trials have become essential research tools for evaluating the benefits and risks of new interventions for the treatment and prevention of diseases, from cardiovascular disease to cancer to AIDS. Based on the authors’ collective experiences in this field, Introduction to Statistical Methods for Clinical Trials presents various statistical topics relevant to the design, monitoring, and analysis of a clinical trial. After reviewing the history, ethics, protocol, and regulatory issues of clinical trials, the book provides guidelines for formulating primary and secondary questions and translating clinical questions into statistical ones. It examines designs used in clinical trials, presents methods for determining sample size, and introduces constrained randomization procedures. The authors also discuss how various types of data must be collected to answer key questions in a trial. In addition, they explore common analysis methods, describe statistical methods that determine what an emerging trend represents, and present issues that arise in the analysis of data. The book concludes with suggestions for reporting trial results that are consistent with universal guidelines recommended by medical journals. Developed from a course taught at the University of Wisconsin for the past 25 years, this textbook provides a solid understanding of the statistical approaches used in the design, conduct, and analysis of clinical trials.




Clinical Trial Biostatistics and Biopharmaceutical Applications


Book Description

Since 1945, "The Annual Deming Conference on Applied Statistics" has been an important event in the statistics profession. In Clinical Trial Biostatistics and Biopharmaceutical Applications, prominent speakers from past Deming conferences present novel biostatistical methodologies in clinical trials as well as up-to-date biostatistical applications from the pharmaceutical industry. Divided into five sections, the book begins with emerging issues in clinical trial design and analysis, including the roles of modeling and simulation, the pros and cons of randomization procedures, the design of Phase II dose-ranging trials, thorough QT/QTc clinical trials, and assay sensitivity and the constancy assumption in noninferiority trials. The second section examines adaptive designs in drug development, discusses the consequences of group-sequential and adaptive designs, and illustrates group sequential design in R. The third section focuses on oncology clinical trials, covering competing risks, escalation with overdose control (EWOC) dose finding, and interval-censored time-to-event data. In the fourth section, the book describes multiple test problems with applications to adaptive designs, graphical approaches to multiple testing, the estimation of simultaneous confidence intervals for multiple comparisons, and weighted parametric multiple testing methods. The final section discusses the statistical analysis of biomarkers from omics technologies, biomarker strategies applicable to clinical development, and the statistical evaluation of surrogate endpoints. This book clarifies important issues when designing and analyzing clinical trials, including several misunderstood and unresolved challenges. It will help readers choose the right method for their biostatistical application. Each chapter is self-contained with references.




Statistical Methods for Survival Data Analysis


Book Description

Praise for the Third Edition “. . . an easy-to read introduction to survival analysis which covers the major concepts and techniques of the subject.” —Statistics in Medical Research Updated and expanded to reflect the latest developments, Statistical Methods for Survival Data Analysis, Fourth Edition continues to deliver a comprehensive introduction to the most commonly-used methods for analyzing survival data. Authored by a uniquely well-qualified author team, the Fourth Edition is a critically acclaimed guide to statistical methods with applications in clinical trials, epidemiology, areas of business, and the social sciences. The book features many real-world examples to illustrate applications within these various fields, although special consideration is given to the study of survival data in biomedical sciences. Emphasizing the latest research and providing the most up-to-date information regarding software applications in the field, Statistical Methods for Survival Data Analysis, Fourth Edition also includes: Marginal and random effect models for analyzing correlated censored or uncensored data Multiple types of two-sample and K-sample comparison analysis Updated treatment of parametric methods for regression model fitting with a new focus on accelerated failure time models Expanded coverage of the Cox proportional hazards model Exercises at the end of each chapter to deepen knowledge of the presented material Statistical Methods for Survival Data Analysis is an ideal text for upper-undergraduate and graduate-level courses on survival data analysis. The book is also an excellent resource for biomedical investigators, statisticians, and epidemiologists, as well as researchers in every field in which the analysis of survival data plays a role.




Small Clinical Trials


Book Description

Clinical trials are used to elucidate the most appropriate preventive, diagnostic, or treatment options for individuals with a given medical condition. Perhaps the most essential feature of a clinical trial is that it aims to use results based on a limited sample of research participants to see if the intervention is safe and effective or if it is comparable to a comparison treatment. Sample size is a crucial component of any clinical trial. A trial with a small number of research participants is more prone to variability and carries a considerable risk of failing to demonstrate the effectiveness of a given intervention when one really is present. This may occur in phase I (safety and pharmacologic profiles), II (pilot efficacy evaluation), and III (extensive assessment of safety and efficacy) trials. Although phase I and II studies may have smaller sample sizes, they usually have adequate statistical power, which is the committee's definition of a "large" trial. Sometimes a trial with eight participants may have adequate statistical power, statistical power being the probability of rejecting the null hypothesis when the hypothesis is false. Small Clinical Trials assesses the current methodologies and the appropriate situations for the conduct of clinical trials with small sample sizes. This report assesses the published literature on various strategies such as (1) meta-analysis to combine disparate information from several studies including Bayesian techniques as in the confidence profile method and (2) other alternatives such as assessing therapeutic results in a single treated population (e.g., astronauts) by sequentially measuring whether the intervention is falling above or below a preestablished probability outcome range and meeting predesigned specifications as opposed to incremental improvement.




Statistical Methods for Survival Data Analysis


Book Description

Functions of survival time; Examples of survival data analysis; Nonparametric methods of estimating survival functions; Nonparametric methods for comparing survival distributions; Some well-known survival distributions and their applications; Graphical methods for sulvival distribution fitting and goodness-of-fit tests; Analytical estimation procedures for sulvival distributions; Parametric methods for comparing two survival distribution; Identification of prognostic factors related to survival time; Identification of risk factors related to dichotomous data; Planning and design of clinical trials (I); Planning and design of clinicL trials(II).




Statistical Design, Monitoring, and Analysis of Clinical Trials


Book Description

Statistical Design, Monitoring, and Analysis of Clinical Trials, Second Edition concentrates on the biostatistics component of clinical trials. This new edition is updated throughout and includes five new chapters. Developed from the authors’ courses taught to public health and medical students, residents, and fellows during the past 20 years, the text shows how biostatistics in clinical trials is an integration of many fundamental scientific principles and statistical methods. The book begins with ethical and safety principles, core trial design concepts, the principles and methods of sample size and power calculation, and analysis of covariance and stratified analysis. It then focuses on sequential designs and methods for two-stage Phase II cancer trials to Phase III group sequential trials, covering monitoring safety, futility, and efficacy. The authors also discuss the development of sample size reestimation and adaptive group sequential procedures, phase 2/3 seamless design and trials with predictive biomarkers, exploit multiple testing procedures, and explain the concept of estimand, intercurrent events, and different missing data processes, and describe how to analyze incomplete data by proper multiple imputations. This text reflects the academic research, commercial development, and public health aspects of clinical trials. It gives students and practitioners a multidisciplinary understanding of the concepts and techniques involved in designing, monitoring, and analyzing various types of trials. The book’s balanced set of homework assignments and in-class exercises are appropriate for students and researchers in (bio)statistics, epidemiology, medicine, pharmacy, and public health.




Survival Analysis


Book Description

A straightforward and easy-to-follow introduction to the main concepts and techniques of the subject. It is based on numerous courses given by the author to students and researchers in the health sciences and is written with such readers in mind. A "user-friendly" layout includes numerous illustrations and exercises and the book is written in such a way so as to enable readers learn directly without the assistance of a classroom instructor. Throughout, there is an emphasis on presenting each new topic backed by real examples of a survival analysis investigation, followed up with thorough analyses of real data sets. Each chapter concludes with practice exercises to help readers reinforce their understanding of the concepts covered, before going on to a more comprehensive test. Answers to both are included. Readers will enjoy David Kleinbaums style of presentation, making this an excellent introduction for all those coming to the subject for the first time.




Sequential Experimentation in Clinical Trials


Book Description

Sequential Experimentation in Clinical Trials: Design and Analysis is developed from decades of work in research groups, statistical pedagogy, and workshop participation. Different parts of the book can be used for short courses on clinical trials, translational medical research, and sequential experimentation. The authors have successfully used the book to teach innovative clinical trial designs and statistical methods for Statistics Ph.D. students at Stanford University. There are additional online supplements for the book that include chapter-specific exercises and information. Sequential Experimentation in Clinical Trials: Design and Analysis covers the much broader subject of sequential experimentation that includes group sequential and adaptive designs of Phase II and III clinical trials, which have attracted much attention in the past three decades. In particular, the broad scope of design and analysis problems in sequential experimentation clearly requires a wide range of statistical methods and models from nonlinear regression analysis, experimental design, dynamic programming, survival analysis, resampling, and likelihood and Bayesian inference. The background material in these building blocks is summarized in Chapter 2 and Chapter 3 and certain sections in Chapter 6 and Chapter 7. Besides group sequential tests and adaptive designs, the book also introduces sequential change-point detection methods in Chapter 5 in connection with pharmacovigilance and public health surveillance. Together with dynamic programming and approximate dynamic programming in Chapter 3, the book therefore covers all basic topics for a graduate course in sequential analysis designs.




Prognosis Research in Healthcare


Book Description

"What is going to happen to me?" Most patients ask this question during a clinical encounter with a health professional. As well as learning what problem they have (diagnosis) and what needs to be done about it (treatment), patients want to know about their future health and wellbeing (prognosis). Prognosis research can provide answers to this question and satisfy the need for individuals to understand the possible outcomes of their condition, with and without treatment. Central to modern medical practise, the topic of prognosis is the basis of decision making in healthcare and policy development. It translates basic and clinical science into practical care for patients and populations. Prognosis Research in Healthcare: Concepts, Methods and Impact provides a comprehensive overview of the field of prognosis and prognosis research and gives a global perspective on how prognosis research and prognostic information can improve the outcomes of healthcare. It details how to design, carry out, analyse and report prognosis studies, and how prognostic information can be the basis for tailored, personalised healthcare. In particular, the book discusses how information about the characteristics of people, their health, and environment can be used to predict an individual's future health. Prognosis Research in Healthcare: Concepts, Methods and Impact, addresses all types of prognosis research and provides a practical step-by-step guide to undertaking and interpreting prognosis research studies, ideal for medical students, health researchers, healthcare professionals and methodologists, as well as for guideline and policy makers in healthcare wishing to learn more about the field of prognosis.