An Introduction to Statistics in Early Phase Trials

All new medicines and devices undergo early phase trials to assess, interpret and better understand their efficacy, tolerability and safety. An Introduction to Statistics in Early Phase Trials describes the practical design and analysis of these important early phase clinical trials and provides the crucial statistical basis for their interpretation. It clearly and concisely provides an overview of the most common types of trials undertaken in early phase clinical research and explains the different methodologies used. The impact of statistical technologies on clinical development and the statistical and methodological basis for making clinical and investment decisions are also explained. Conveys key ideas in a concise manner understandable by non-statisticians Explains how to optimise designs in a constrained or fixed resource setting Discusses decision making criteria at the end of Phase II trials Highlights practical day-to-day issues and reporting of early phase trials An Introduction to Statistics in Early Phase Trials is an essential guide for all researchers working in early phase clinical trial development, from clinical pharmacologists and pharmacokineticists through to clinical investigators and medical statisticians. It is also a valuable reference for teachers and students of pharmaceutical medicine learning about the design and analysis of clinical trials.

All new medicines and devices undergo early phase trials to assessinterpret and better understand their efficacy, tolerability andsafety. An Introduction to Statistics in Early Phase Trialsdescribes the practical design and analysis of these importantearly phase clinical trials and provides the crucial statisticalbasis for their interpretation. It clearly and concisely providesan overview of the most common types of trials undertaken in earlyphase clinical research and explains the different methodologiesused. The impact of statistical technologies on clinicaldevelopment and the statistical and methodological basis for makingclinical and investment decisions are also explained.* Conveys key ideas in a concise manner understandable bynon-statisticians* Explains how to optimise designs in a constrained or fixedresource setting* Discusses decision making criteria at the end of Phase IItrials* Highlights practical day-to-day issues and reporting of earlyphase trialsAn Introduction to Statistics in Early Phase Trials is anessential guide for all researchers working in early phase clinicaltrial development, from clinical pharmacologists andpharmacokineticists through to clinical investigators and medicalstatisticians. It is also a valuable reference for teachers andstudents of pharmaceutical medicine learning about the design andanalysis of clinical trials.

Chapter 1 Early phase trials 1Chapter 2 Introduction to pharmacokinetics 13Chapter 3 Sample size calculations for clinical trials 37Chapter 4 Crossover trial basics 55Chapter 5 Multi-period crossover trials 71Chapter 6 First time into man 87Chapter 7 Bayesian and frequentist methods 113Chapter 8 First-time-into-new-population studies 125Chapter 9 Bioequivalence studies 139Chapter 10 Other Phase I trials 169Chapter 11 Phase II trials: general issues 187Chapter 12 Dose-response studies 197Chapter 13 Phase II trials with toxic therapies 211Chapter 14 Interpreting and applying early phase trial results 223Chapter 15 Go/No-Go criteria 231Appendix 245References 251Index 257