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ISBN: 978-90-8559-069-9 © Bettina E. Hansen, the Netherlands, 2010 All rights reserved. No parts of this thesis may be reproduced or transmitted in any form or by any means, without prior permission of the author. Layout and print: Optima Grafi sche Communicatie Cover: Katrine Amalie van Overhagen Financial support for printing this thesis was kindly given by the department of Gastroenterology and Hepatotlogy, Erasmus MC University Medical Center Rotterdam, Novartis Pharma B.V., Roche Nederland B.V., Schering Plough Nederland and Zambon Nederland B.V.
Statistical Models of Treatment Effects in Chronic Hepatitis B and C Statistische modellen van behandelingseffecten in chronische hepatitis B en C Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnifi cus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 19 november 2010 om 9:30 uur door Bettina Elisabeth Hansen geboren te Gentofte, Denemarken
Page 1: Statistical Models of Treatment Eff
Page 6 and 7: PROMOTIECOMMISSIE Promotor: Prof.dr
Page 9 and 10: CONTENTS Chapter 1. Introduction 11
Page 13: Cha pter 1 Introduction
Page 16 and 17: Chapter 1 14 Epidemiology Worldwide
Page 18 and 19: Chapter 1 16 Prediction models with
Page 20 and 21: Chapter 1 18 standard method fails
Page 22 and 23: Chapter 1 20 The extended non-linea
Page 24 and 25: Chapter 1 22 References 1. Blumberg
Page 27: Cha pter 2 Prediction of response t
Page 30 and 31: Chapter 2.1 28 ABSTRACT The aim of
Page 32 and 33: Chapter 2.1 30 been hepatitis B sur
Page 34 and 35: Chapter 2.1 32 HBV DNA decline The
Page 36 and 37: Chapter 2.1 34 Figure 2 continued.
Page 38 and 39: Chapter 2.1 36 Figure 4. Estimated
Page 40 and 41: Chapter 2.1 38 DNA was observed in
Page 42: Chapter 2.1 40 15. Kao JH. Role of
Page 46 and 47: Chapter 2.2 44 ABSTRACT Background:
Page 48 and 49: Chapter 2.2 46 low baseline HBV DNA
Page 50 and 51: Chapter 2.2 48 patient subgroups wa
Page 52 and 53: Chapter 2.2 50 p=0.002). Previous I
Page 54 and 55:
Chapter 2.2 52 Application of the m
Page 56 and 57:
Chapter 2.2 54 PEG-IFN, the proport
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Chapter 2.2 56 References 1. Lavanc
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Chapter 2.2 58 26. Bonino F, Lau GK
Page 63 and 64:
Chap ter 2.3 Prediction of the resp
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INTRODUCTION Dynamic prediction of
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Statistical analysis Dynamic predic
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Dynamic prediction of response to P
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References Dynamic prediction of re
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Cha pter 2.4 Dynamic prediction of
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INTRODUCTION Dynamic prediction of
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For the indirect approach we rewrit
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logit pi,j = logit Pr(Ri =1|visit =
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Dynamic prediction of response usin
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Table 1. Results of different stopp
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Chapter 2.5 106 ABSTRACT Peginterfe
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Chapter 2.5 108 and placebo daily.
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Chapter 2.5 110 for patients with a
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Chapter 2.5 112 Mean HBV DNA declin
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Chapter 2.5 114 peginterferon and n
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Chapter 2.5 116 hepatocellular carc
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Chapter 2.5 118 13. Werle-Lapostoll
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Chapter 2.5 120 Greece - G Germanid
Page 127 and 128:
Chap ter 3.1 Long-term clinical out
Page 129 and 130:
INTRODUCTION Glycyrrhizin for IFN-n
Page 131 and 132:
Statistics Glycyrrhizin for IFN-non
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Glycyrrhizin for IFN-non responders
Page 135 and 136:
Table 2. Time dependent Cox regress
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Cha pter 3.2 Discriminant analysis
Page 145 and 146:
Introduction Discriminant analysis
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Discriminant analysis using a MLMM
Page 149 and 150:
Estimation Discriminant analysis us
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where wi,k(y i, θ) = (k =1,...,K).
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Appendix Discriminant analysis usin
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Cha pter 4 Statistical models of ea
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Chapter 4.1 176 ABSTRACT Nucleoside
Page 180 and 181:
Chapter 4.1 178 at day 1 at t =0 an
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Chapter 4.1 180 Table 1. Baseline c
Page 184 and 185:
Chapter 4.1 182 Figure 1.
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Chapter 4.1 184 Figure 1. Viral dec
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Chapter 4.1 186 suppression in seru
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Chapter 4.1 188 13. Seifer M, Hamat
Page 193 and 194:
Cha pter 4.2 Viral dynamics during
Page 195 and 196:
INTRODUCTION Viral dynamics during
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Viral dynamics during tenofovir the
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log HBV DNA (copies/mL) 10.0 9.0 8.
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Chap ter 4.3 Modelling of early vir
Page 213 and 214:
INTRODUCTION HBV viral kinetics dur
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HBV viral kinetics during PEG-IFN 2
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SUMMARY AND CONCLUSION Summary and
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Summary and conclusion 233 The mode
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Summary and conclusion 235 The infe
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Summary and conclusion 237 Early st
Page 243 and 244:
SAMENVATTING EN CONCLUSIE Samenvatt
Page 245 and 246:
Samenvatting en conclusie 243 Er we
Page 247 and 248:
Samenvatting en conclusie 245 Data
Page 249 and 250:
Samenvatting en conclusie 247 Behan
Page 253:
Dan kwoord
Page 256 and 257:
Dankwoord 254 Lieve Marion en Margr
Page 259 and 260:
BIBLI OGRAPHY Bibliography 257 1. K
Page 261 and 262:
Bibliography 259 Interferon-ribavir
Page 263 and 264:
Bibliography 261 Long term clinical
Page 265 and 266:
Bibliography 263 Flares in chronic
Page 267 and 268:
Bibliography 265 Genetic characteri
Page 269:
Bibliography 267 106. Reijnders JG,
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