Design & Analysis of Clinical Trials for Economic Evaluation & Reimbursement: An Applied Approach Using SAS & STATA PDF

Preface

Economic evaluation is a firmly established discipline in the field of health research and policymaking. It has also become an increasingly essential component of clinical trial design to show that new treatments (healthcare technologies) offer value to the payers in various healthcare systems.

Several books already exist which address theoretical or practical aspects of cost-effectiveness analysis. What makes this book different from others is its insight into how health economic evaluation is applied in a clinical trial context in both academic and pharmaceutical/commercial settings. This book is not just about performing cost-effectiveness analyses, but it also emphasises the strategic importance of economic evaluation and offers guidance and advice on the complex factors at play before, during and after an economic evaluation has been performed. In addition, this book bridges the gap between applications of economic evaluation in industry (mainly pharmaceutical) and what students may learn in university courses.

An additional feature of this work is the availability of software, such as SAS and STATA code, for performing, in some cases, daunting computations. In addition, Windows-based software (SCET-VA^® version 1.0) for sample size and value of information analysis, which is a menu-driven package avoiding the need for complex programming, is available free of charge. Therefore, this book will be a valuable source of knowledge for students who might pursue a career in this field or simply wish to know more about applying economic evaluation techniques.

Design & Analysis of Clinical Trials for Economic Evaluation & Reimbursement: An Applied Approach Using SAS & STATA is structured to cover many of the topics in economic evaluation that students, clinicians, health economists, epidemiologists, statisticians and other healthcare researchers will come across when designing a clinical trial for cost-effectiveness. No knowledge of economic evaluation, statistics or SAS is required to understand the key concepts in each chapter of the book, and the reader may ignore the SAS/STATA code and read interpretations of the output (the interpretations would be the same with any software).

This book can be used as either a self-study book, a textbook or a reference book.

The format of the book is as follows. Chapter 1 offers the reader who is unfamiliar with economic evaluation the economic background and context. Important economic concepts such as opportunity costs, discounting and the marketing authorisation landscape are reviewed. The clinical hypotheses are discussed in the context of economic hypotheses. The chapter discusses practical examples of strategic thinking necessary when developing a new treatment for market authorisation.

Chapter 2 introduces the incremental cost-effectiveness ratio, the costeffectiveness plane and the different types of economic evaluation undertaken using the incremental net monetary benefit approach, and distinguishes between statistical and economic models. Chapter 3 elaborates on the detailed aspects of clinical trial design for cost-effectiveness, covering issues such as choice of comparator, timing of assessments, clinical report form design, treatment pathways and heterogeneity. The chapter contains a case study from a lung cancer trial.

Chapters 4 and 5 contain material on the analysis of resource use (costs) and quality of life, respectively. Chapter 4 discusses some of the more recent statistical issues and approaches to modelling cost data, distinguishing carefully between modelling health resource data and costs data. Chapter 5 covers the different measures of quality of life used in economic evaluations, such as EQ-5D, quality-adjusted life years, disability-adjusted life years and quality of time spent without symptoms of disease and toxicity. A section also includes more recent research into evaluating the sensitivity of generic measures to detect treatment effects. Mapping functions are also covered: methods applied in practice to estimate health utilities but not often covered in standard texts.

Chapters 6 and 7 detail the approaches to economic modelling and sensitivity analysis. Chapter 6 elaborates on decision trees and Markov and patient-level simulation approaches as well as discussing strategies for checking the Markov model – an area rarely discussed in standard texts but almost always required in industry applications. Chapter 7 provides details on approaches to simulating univariate and multivariate data for probabilistic sensitivity analysis. The complexities of multivariate simulation for probabilistic sensitivity analysis are, again, rarely discussed in most books on health economic evaluation.

Chapter 8 provides extensive details on sample size and power in a Bayesian and frequentist context. A demonstration of the freely available software for sample sizes and value of information methods using SCET-VA v1.0^® discusses how to enter inputs to obtain the sample size required for a given probability of cost-effectiveness.

Chapter 9, although seemingly the odd one out, is still nevertheless relevant, since in most industry applications of cost-effectiveness and economic evaluation, evidence synthesis is often required. Indirect comparisons are sometimes needed to compare treatments that were not compared in the same trial, and some reimbursement agencies do request these. For this reason, this chapter was included, as it complements the methods applied in economic evaluation, particularly for market authorisation.

Chapter 10 is dedicated to examples of economic evaluation specific to cancer trials. Key design aspects of Phase III cancer trials, issues such as extrapolation of survival times after a study follow-up has been completed, treatment switching after disease progression and the relationship between transition probabilities and hazard ratios, as well as other practical considerations when designing and analysing cancer trials for economic evaluation, are discussed. Again, this is an area which is needed, but many standard texts do not distinguish between the peculiarities of economic evaluation in cancer trials and other therapeutic areas. Chapter 11 finally summarises the details and challenges of the reimbursement market in practice and further areas of research in the area.

I candidly admit that my objectives have been set high when structuring this book. Economic evaluation covers several disciplines, and addressing all of these has been challenging. I hope that the material in this book is suitable for a range of researchers of varying abilities, so that some will find the entire book useful, whereas for others some chapters will be useful. As a student textbook, it can be complemented by additional reading materials suggested in the bibliography to provide a book whereby students can be more prepared for the world of industry.

I acknowledge the anonymous reviewers of this book and the early discussions with various researchers at University College London, which have helped to improve the text. I am also grateful to the Cancer Research UK (CRUK) and Cancer Trials Centre, who respected my desire to see this project to completion while running multiple clinical trials. Finally, I thank Drs Suhailah Khan, Yohanis and Hanzalah for putting up with my countless hours on this book.

Iftekhar Khan

University College London

https://www.researchgate.net/profile/Iftekhar_Khan5