Outcomes in Clinical Trials

208 Pages·2013·5.954 MB·English

by  Martin Kolb, Claus F. Vogelmeier

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EUROPEAN RESPIRATORY monograph l
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The traditional end-points for clinical studies of lung
diseases were based on functional parameters. Their value
as surrogate markers for disease activity and progression
has been increasingly questioned by scientists, carers,
regulatory agencies and funding bodies. Novel tools and
methods with regard to biomarkers and patient-reported
outcomes have made these parameters emerge from their
status as interesting secondary end-points and become
potential primary outcomes for clinical trials. Nevertheless, Outcomes in
their relevance and validity still needs to be proven. This issue
of the European Respiratory Monograph describes the current
status regarding end-points in all relevant areas of pulmonary Clinical Trials
medicine.
Edited by Martin Kolb
and Claus F. Vogelmeier
EUROPEAN
RESPIRATORY
R 62
E Print ISSN 1025-448x
Online ISSN 2075-6674 EUROPEAN RESPIRATORY

Print ISBN 978-1-84984-044-6
S
Online ISBN 978-1-84984-045-3
P
Number 62 December 2013
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European Respiratory Monograph 62, December 2013
Outcomes in
Clinical Trials
Published by European Respiratory Edited by
Society ©2013
December 2013 Martin Kolb and Claus F. Vogelmeier
Print ISBN: 978-1-84984-044-6
Online ISBN: 978-1-84984-045-3
Print ISSN: 1025-448x
Online ISSN: 2075-6674
Printed by Page Bros Ltd, Norwich, UK
Managing Editors: Rachel White and
Catherine Pumphrey
European Respiratory Society Editor in Chief
442 Glossop Road, Sheffi eld, Tobias Welte
S10 2PX, UK
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E-mail: [email protected]
All material is copyright to European
Respiratory Society. It may not be
reproduced in any way including
electronic means without the express
permission of the company.
Statements in the volume refl ect the
views of the authors, and not necessarily
those of the European Respiratory
Society, editors or publishers.
Th is book is one in a series of European Respiratory Monographs. Each
individual issue provides a comprehensive overview of one specifi c clini-
cal area of respiratory health, communicating information about the
most advanced techniques and systems required for its investigation.
It provides factual and useful scientifi c detail, drawing on specifi c case
studies and looking into the diagnosis and management of individual
patients. Previously published titles in this series are listed at the back of
this Monograph.

Contents
Number 62 December 2013
Preface v
Guest Editors vii

Introduction ix

Outcomes in clinical trials: specific disease areas
1. Chronic obstructive pulmonary disease 1
Emiel F.M. Wouters
2. Asthma 19
Julia Koopmans and Christian Taube
3. Idiopathic pulmonary fibrosis 37
Toby M. Maher
4. Cystic fibrosis 54
Reshma Amin and Felix Ratjen
5. Pulmonary arterial hypertension 70
Gabor Kovacs and Horst Olschewski
6. The intensive care unit 85
Donald M. Arnold and Deborah J. Cook
Outcomes in clinical trials: specific outcomes
7. Biomarkers 90
Jonas Schupp and Antje Prasse
8. Health status measurement 96
Paul W. Jones
9. Electronic patient-reported outcomes 105
Sonya Ludmilla Eremenco
10. Physical activity 117
Henrik Watz
11. Lung function 127
Denis E. O’Donnell, Pierantonio Laveneziana and J. Alberto Neder
12. Imaging 146
David G. Parr
13. Exercise tests 170
Th ierry Troosters
14. Omics 179
Daniel J. Kass and Naft ali Kaminski
CME credit application form 189
C O P E COMMITTEE ON PUBLICATION ETHICS
This journal is a member of and subscribes to
the principles of the Committee on Publication
Ethics.
Preface
The Guest Editors describe, in their introduction to this European
Respiratory Monograph (ERM), a number of reasons why fewer and
fewer new drugs receive regulatory approval, although the funds invested by
the pharmaceutical industry for drug development are higher than ever
before. Two main reasons are mentioned.
First,thephaseIIandIIIstudies,whichareessentialforfinalapprovalbythe
regulatoryauthorities,areextremelyexpensiveandthereisnoguaranteethat
the development costs can be recouped after marketing authorisation.
Outcomeparametersofearlyclinicaltrialsthatdemonstrateahighreliability
for predicting results in phase III studies are important. However, the
classical outcome parameters, such as lung function measurement and
symptom scores, have failed in this regard.
Secondly, drug development has stalled because targets for development are
lacking. New trial outcome parameters can contribute to new target
identification for therapy: targets that had not been thought of when using
the classic method of drug development.
IwanttocongratulatetheGuestEditors,MartinKolbandClausF.Vogelmeier,
forsettingupthisextraordinaryissueoftheERM.Foratopiclikethis,mostof
the authors did not have a template, and the collation of the data involved
substantial work and was sophisticated. Due to time constraints, it was not
possible to cover the entire field of pulmonary medicine, and there are
additionalareasofclinicaltrialoutcomesthatmighthavebeenincludedinthis
issue if preparation time hadbeen available.
Nevertheless, this issue of the ERM should be of interest for a wide
readership, including basic researchers and clinicians in the field of
pneumology and also people working in the pharmaceutical industry or in
regulatory authorities dealing with drug approval. I am convinced that they
will find this Monograph useful for further consideration of clinical trials.
EurRespirMonogr2013;62:v.CopyrightERS2013.DOI:10.1183/1025448x.10011513.PrintISBN:978-1-84984-044-6.
OnlineISBN:978-1-84984-045-3.PrintISSN:1025-448x.OnlineISSN:2075-6674.
v

Guest Editors
MartinKolbisaGerman–CanadianphysicianwhoobtainedhisMD
at the Julius-Maximilian University Medical School in Wu¨rzburg,
Germany. He received extensive training in clinical and anatomical
pathology in Nu¨rnberg, Germany, before he enrolled in general
internal medicine and intensive care. He specialised in respiratory
medicineandwasboard-certifiedforthisdisciplineandforinternal
medicine in 2002, then received his PhD equivalent the following
year. Currently, Martin Kolb is Associate Professor of Medicine at
McMasterUniversity,Hamilton,ON,Canada,aswellasDirectorof
Martin Kolb the Division of Respirology and Research Director of the Firestone
Institute for Respiratory Health, also in Hamilton. He looks after
severalhundredpatientswithinterstitiallungdiseaseinhisspecialty
clinic andalso practisesingeneral respirology.Heisonthemedical
staffatStJoseph’sHealthcareHamilton,forrespirologyandgeneral
internal medicine.
In addition, Martin Kolb is Deputy Editor for Respirology, the
official journal of the Asian Pacific Society of Respirology and
Academic Editor for PLoS One. He is on the Editorial Boards of the
American Journal of Respiratory and Critical Care Medicine, the
European Respiratory Journal (ERJ) and the European Respiratory
Review. Martin Kolb is on the Executive Committee for the
Respiratory Cell and Molecular Biology Assembly of the American
Thoracic Society (ATS) and Chair of the Lung Injury and Repair
Group of the European Respiratory Society (ERS).
MartinKolb’smajorresearchareaisfocusedonmechanismsoflung
injury, repair and fibrosis, particularly in idiopathic pulmonary
fibrosis. He has a strong interest in growth factor biology,
extracellular matrix and mesenchymal cell progenitors. In his lab
heusesavarietyofanimalmodelstostudydiseasemechanismsand
alsotheefficacyofnoveldrugsinthepreclinicalsetting.Inaddition,
heleadsactivitiesinbiomarkerdevelopmentforlungfibrosisandhe
participates as Principal Investigator and Steering Committee
member in numerous clinical trials on interstitial lung disease.
Martin Kolb has over 80 peer-reviewed publications and has
received funding from the Canadian Institutes of Health Research
(CIHR),theNationalInstitutesofHealth,theCanadianFoundation
for Innovation, the Ontario Thoracic Society and others. He has
received career awards from the Parker B. Francis Families
Foundation, the Dept of Medicine at McMaster University and
the New Investigator Award from the CIHR.
EurRespirMonogr2013;62:vii–viii.
CopyrightERS2013.
DOI:10.1183/1025448x.10011313
PrintISBN:978-1-84984-044-6
OnlineISBN:978-1-84984-045-3
PrintISSN:1025-448x
OnlineISSN:2075-6674
i
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Claus F. Vogelmeier is Professor of Medicine and Head of the Dept
for Pulmonary Medicine at the Philipps University of Marburg,
Germany. After qualifying in medicine from the University of
Munich, Claus Vogelmeier started his professional career at the
hospital of the University of Munich. He is board-certified in
internal medicine, pulmonary medicine, cardiology and allergology.
Claus Vogelmeier spent two years as a postdoctoral fellow at the
PulmonaryBranchoftheNationalHeart,LungandBloodInstitute,
Institutes of Health, in Bethesda, MD, USA. He was nominated
Claus F. Vogelmeier ProfessorofMedicineatthePhilippsUniversityofMarburgin2001.
Claus Vogelmeier is an active member of several respiratory
societies, including the ATS and the ERS. From 2002 until 2008
he was Section Editor of the ERJ. From 2009 until 2011 he was
PresidentoftheGermanRespiratorySociety.In2009healsobecame
Chairman of the German Asthma and Chronic Obstructive
Pulmonary Disease Network. Since 2010, he has been a member
of the Science and the Writing Committees of the Global Initiative
for Chronic Obstructive Lung Disease (GOLD).
Claus Vogelmeier has a long-standing scientific and clinical interest
in obstructive lung diseases, with topics ranging from pathogenetic
aspects to novel diagnostic methods and clinical studies.
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