This monograph offers well-founded training and expertise on the statistical analysis of data from clinical vaccine trials, i.e., immunogenicity and vaccine field efficacy studies. The book's scope is practical rather than theoretical. It opens with two introductory chapters on the immunology of vaccines to provide readers with the necessary background knowledge. It then continues with an in-depth exploration of the statistical methodology. Many real-life examples and SAS codes are presented, making application of the methods straightforward. Topics discussed include maximum likelihood estimation for censored antibody titers, ANCOVA for antibody values, analysis of equivalence and non-inferiority immunogenicity trial data, analysis of data from vaccine field efficacy trials (including data from studies with recurrent infection data), fitting protection curves to data of challenge or field efficacy studies, and the analysis of vaccine safety data.
Statistics in Clinical Vaccine Trials • Jozef Nauta Statistics in Clinical Vaccine Trials 123 Jozef Nauta Solvay Pharmaceuticals Global Statistics C.J. van Houtenlaan 36 1381 CP Weesp Netherlands
[email protected] ISBN 978-3-642-14690-9 e-ISBN 978-3-642-14691-6 DOI 10.1007/978-3-642-14691-6 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2010937985 c Springer-Verlag Berlin Heidelberg 2011 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design: WMXDesign GmbH, Heidelberg Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) To my wife Erna Kimp, and our son Izaak. • Preface This book is intended for statisticians working in clinical vaccine development in the pharmaceutical industry, at universities, at national vaccines institutes, etc. Statisticians already involved in clinical vaccine trials may find some interesting new ideas in it, while colleagues who are new to vaccines will be able to familiarize themselves quickly with the statistical methodology. A good knowledge of statistics is assumed. The reader should be familiar with hypothesis testing, point and confidence interval estimation, likelihood methods, regression, mathematical and statistical notation, etc. A book that would provide the necessary background is: Armitage P., Berry G. and Matthews J.N.S. Statistical Methods in Medical Research, 4th edition, Blackwell Science, New York, 2001. The scope of the book is practical rather than theoretical. Many real-life examples are given, and SAS codes are provided, making application of the methods straightforward. SAS codes are also given for accurate sample size estimation, including codes for the estimation of required sample sizes for equivalence and noninferiority vaccine trials. The first two chapters are introductions to the immunology of vaccines, and they