Heterogeneity of patients in clinical trials Subgroup analysis and covariate adjustment in cardiovascular and neurosurgical trials Adrián V. Hernández ACKNOWLEDGEMENTS The work presented in this thesis was conducted at the Department of Public Health, Department of Neurosurgery, and the Department of Cardiology of the Erasmus MC- University Medical Centre Rotterdam, Rotterdam, The Netherlands. The studies described in this thesis were supported by the Netherlands Organization for Scientific Research (ZON/MW) project No. 908-02-117, and by the National Institutes of Health, USA (Clinical Trial Design and Analysis in TBI Project, Grant 1 R01 NS- 042691-001A1). The author gratefully acknowledges the collaboration with the Coronary Care Unit, Department of Cardiology, Hospital Universitario Gregorio Marañón, Madrid, Spain (Héctor Bueno), and the Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece (John P. A. Ioannidis). The Department of Public Health of the Erasmus Medical Center, Rotterdam, Centocor B.V. Leiden, and the Nederlandse Hartstichting, Den Haag, The Netherlands, provided financial support for the publication of this thesis. Cover design and layout: Adrián V. Hernández, Madrid, Spain
[email protected] Machu Picchu walls were built with stones of different and unique shapes. It is difficult to find two equal stones. Patients recruited for clinical trials are also unique. Printed by: Optima Grafische Communicatie, Rotterdam, The Netherlands. ISBN: 90-8559-130-9 © Adrián V. Hernández, 2006 No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without permission of the author or, when appropriate, of the scientific journal in which parts of this book have been published.