Understanding Evidence-Based Rheumatology: A Guide to Interpreting Criteria, Drugs, Trials, Registries, and Ethics

285 Pages·2014·4.91 MB·English

by  Hasan Yazici, Yusuf Yazici, Emmanuel Lesaffre (eds.)

Hasan Yazici
Yusuf Yazici
Emmanuel Lesaff re Editors
Understanding Evidence-
Based Rheumatology
A Guide to
Interpreting Criteria,
Drugs, Trials,
Registries, and Ethics
123
Understanding Evidence-Based Rheumatology

Hasan Yazici (cid:129) Yusuf Yazici (cid:129) Emmanuel Lesaffre
Editors
Understanding Evidence-
Based Rheumatology
A Guide to Interpreting Criteria, Drugs,
Trials, Registries, and Ethics
Editors
Hasan Yazici , MD Yusuf Yazici , MD
Istanbul University New York University School of Medicine
Beyazit, Istanbul NYU Hospital for Joint Diseases
Turkey New York , NY , USA
Emmanuel Lesaffre , PhD
Department of Biostatistics, Erasmus MC
Rotterdam , The Netherlands
L-Biostat, KU Leuven, Leuven, Belgium
ISBN 978-3-319-08373-5 ISBN 978-3-319-08374-2 (eBook)
DOI 10.1007/978-3-319-08374-2
Springer Cham Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014948050
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Pref ace
What Should the Reader Expect from This Book?
The background for this book is a series of almost-parallel conferences on clinical
research methodology organized by the senior and junior Yazici, in either Bodrum or
Istanbul by the senior and in New York by Yusuf Yazici. However, it was Emmanuel
Lesaffre, our third coeditor and several times a speaker in these conferences, who
came up with the idea of this book. These annual conferences have been held since
2006 as a single-day or weekend courses. The audiences have been, we like to think,
purposefully small with around 40–50 people, to encourage interactive discussion.
The full texts of the majority of the presentations for the New York courses are
available on PubMed as manuscripts derived from the lectures, free to download at
the web page of B ulletin of the Hospital for Joint Diseases ( www.nyuhjdbulletin.org ) .
It should therefore not come as a surprise to the reader that most of the contributors
to this book have been speakers at these conferences.
We acknowledge that an excellent text and source book on similar topics as in this
book has been available, namely, E vidence-Based Rheumatology by Peter Tugwell,
also a speaker in our methodology conferences, since 2004. However, we reasoned
that there still was an unmet need for our book for several reasons. A decade has
passed since the publication of the volume by Tugwell et al. Ten years is a long
period, and we believed that many things in rheumatology have signifi cantly changed
in quantity, direction, and quality. Furthermore, E vidence-Based Rheumatology has
been almost an offi cial guidebook of the Cochrane Foundation and its extension, the
OMERACT (Outcome Measures in Rheumatology) group. Finally, a continuous and
critical appraisal of the evidence for what we do or should do is to us the very
essence of evidence-based medicine. With our book, we attempt to stand up to this
challenge, both recommended and perceived.
W e begin with an account of the birth of evidence-based medicine or, perhaps
more correctly, “new evidence-based medicine,” as we like to call it. Being particular
about evidence in medical practice has surely been around ever since Enlightenment.
On the other ha nd, it surely needed a boost toward the end of the last century with the
v
vi Preface
tremendous increase in our understanding of, and the remedies to, many diseases.
We argue that there were several important considerations for the emergence of
evidence-based medicine. First, the biomedical model, most successful in explaining
and managing acute illness, was surely not that successful in chronic diseases.
Rather, a biopsychosocial model was more promising. The new evidence-based
medicine was needed both to guide the practicing physician away from explaining
the entirety of the multisystem disease of unknown etiology by the biomedical model
and to check the science in the biopsychosocial model. The unnecessary medical
services, especially in the light of ever-rising costs of medical care, were another
main reas on behind the new evidence-based medicine.
T he chapter titled “E vidence-based medicine in rheumatology: how does it differ
from other diseases? ” also reminds us that the birth of rheumatology, as a separate
subspecialty of internal medicine, is contemporary with the new evidence-based
medicine. The idea and the scientifi c methodology of evidence-based medicine
were surely most welcome in that “the multisystem disease of unknown etiology”
has been and is the main preoccupation of our still relatively young discipline.
A fter all this rationalizing and theorizing, the chapter titled “A review of statisti-
cal approaches for the analysis of data in rheumatology ” abruptly and intentionally
brings us to the reality of numbers. With specifi c instructions to stay away from the
integral sign, something that still makes most clinicians uncomfortable, the author
makes a serious attempt to explain to the reader the arithmetic, both what is and
what ought to be, behind evidence-based rheumatology. We like to think t hat the
data-driven approach the author utilizes will help to explain the common, descrip-
tive statistical approaches currently in use. His main focus is on the intuitive ideas
behind the methods rather than on their technical aspects. Practical guidelines are
also present throughout this chapter. Finally, the reader is also introduced to
Bayesian methods that are becoming more and more popular.
T he third chapter begins by emphasizing the importance of disease criteria in
rheumatology since many of the rheumatologic diseases are, yet, constructs. In addi-
tion, the authors propose that our current separation of criteria as diagnostic or clas-
sifi cation, although having an aura of practical or scientifi c sophistication, is ill
founded. They underline that the cerebral exercise behind the two is the same. The
thought barriers to this unhelpful bi-labeling are discussed while proposals for pre-
paring more useful diagnostic/classifi cation criteria are provided.
The chapter titled “ B iomarkers, genetic association, and genomic studies ” on
biomarkers, including those of the genetic kind, is an assiduous account of our
tribulations, accomplishments, hopes, and not uncommon wishful thinking around
how to improve our laboratory capabilities to diagnose and monitor rheumatologic
diseases. We like to think that this chapter, by using rheumatoid arthritis (RA) as a
case example, shows how demanding, be it biochemical or genetic, it is to come up
with a sensitive, specifi c, or more importantly a clinically useful disease marker.
T he ensuing chapter “O utcome measures in rheumatoid arthritis ” is on outcome
measures in RA. While what happens to the patient at the end of what the physicians
do or fail to do is the primary concern of medicine, it is rather surprising that we
have not made a sincere effort to this end until recently. We used to think that we
Preface vii
physicians, with our laboratory tests and imaging gadgetry, always knew better than
the patients themselves how they fared. Well, we now know this is not the case, and
this chapter is all about how this recent realization relates particularly to RA.
The chapter titled “ Issues in setting up a study and data collection ” is a handy
manual on both how to go about a research project and, while doing or interpreting
that, avoid a biomedical bestiary of biases.
The following two chapters are detailed accounts of the randomized clinical trial
(RCT), most certainly the fl agship of evidence-based medicine, especially the new
evidence-based medicine ever since the groundbreaking MRC s treptomycin tuber-
culosis trial of 1948. Over 65 years have passed since the fi rst-ever scientifi c appli-
cation of this very important research tool. As expected, there are many fi ner points
and caveats concerning the many forms of RCT now available dealing with the study
design, its analysis, and most importantly the fi t of the one with the other. The
Bayesian RCT, which is more popular in our age of haste, is also introduced.
T he following chapter by Ted Pincus is a healthy and critical discussion of per-
haps the undue importance we give to the RCT as our golden measure of evidence.
He gives in-depth examples to document his concern. One cannot help thinking that
perhaps it is not only the undue importance the researcher, the practitioner, and the
health authorities gave to this tool but rather its more recent abuse that justifi es
many of Ted Pincus’ concerns.
Whatever their causes, issues with the RCTs have recently led the medical com-
munity to put increasing faith in observational studies. One reason for this turn is
our current ability to electronically collect and interpret vast amounts of data in a
very short time. An additional reason for the recent popularity of observational data
might be the contemporary interest in the inductive scientifi c approach.
Keeping up with our general and hopefully useful critical approach, Marie
Hudson and Samy Suissa give us an expert overview of the many pitfalls in obser-
vational studies, especially in those studies that stem from data based on large
patient repositories, such as administrative databases. A clear account of how to best
recognize and avoid them is provided with special emphasis on data collection
time–related biases in which the authors are leading experts.
With RCT struggling to maintain its fl agship status in the face of many whips and
arrows, recent years quietly put another mode of research into the pinnacle of evi-
dence in evidence-based medicine. Meta-analysis is the science of reanalyzing the
outcomes of different studies on a same subject by amalgamating individual research
reports. Its most popular approach is to combine the experience from the RCTs. The
Achilles heel of this approach is to put apples and oranges together in such analyses.
We believe the authors of this relatively short chapter “S ystematic reviews and meta-
analyses in rheumatology ” give a very useful account of how not to do this.
Our penultimate chapter is “ E thical issues in study design and reporting . ” Any
talk about ethics has the danger of being either too dry or too juicy. In this chapter,
we have tried to avoid a discourse on the Helsinki declaration or provide particular
examples of physician or industry misconduct which everybody knows and recog-
nizes either from boring texts or daily tabloids. We have attempted to better describe
what is not readily recognized not only by the public but many a time by the medical
viii Preface
professi on itself. This we like to call the cerebral form of ethics, as distinct from the
pudendal form of the tabloids. The cerebral form, we propose, is perhaps more per-
tinent to many things we do not like about the science and practice of medicine
today.
O ur fi nal chapter is “F uture directions . ” It is our sincere hope that the readers of
this book will have formulated their own priorities once they have gone this far in
our book.
We extend our appreciation and many thanks to the other invited speakers in the
New York and Bodrum/Istanbul conferences over the years, who have contributed
immensely to the ideas presented in this book. They include (in alphabetical order)
Nurullah Akkoc, Anca Askanase, Martin Bergman, Maarten Boers, Hermann
Brenner, Isabel Castrejon, David Cella, Jeffrey Curtis, Ayhan Dinc, Haner
Direskeneli, Maxime Dougados, Anders Ekbom, Onder Ergonul, Brian Feldman,
Jeffrey Greenberg, Ahmet Gul, Vedat Hamuryudan, Tom Huizinga, Murat Inanc,
John Ioannidis, Hilal Maradit Kremers, Alfred Mahr, Fredrick Naftolin, Cem
Ozesen, Salih Pay, Alan Silman, Richard Smith, Tuulikki Sokka- Isler, Samy Suissa,
Necdet Sut, Koray Tascilar, Peter Tugwell, and Nathan Vastesaeger.
F inally and surely we also much thank our Springer editors for their expert help
in putting all this together.
Istanbul, Turkey Hasan Yazici, MD
New York, NY, USA Yusuf Yazici, MD
Rotterdam, The Netherlands Emmanuel Lesaffre, Dr. Sc.
Contents
Evidence-Based Medicine in Rheumatology:
How Does It Differ from Other Diseases? .................................................... 1
Theodore Pincus and Hasan Yazici
A Review of Statistical Approaches for the Analysis
of Data in Rheumatology ................................................................................ 13
Emmanuel Lesaffre and Jolanda Luime
Disease Classifi cation/Diagnosis Criteria ...................................................... 65
Hasan Yazici and Yusuf Yazici
Biomarkers, Genetic Association, and Genomic Studies ............................ 79
Mehmet Tevfi k Dorak and Yusuf Yazici
Outcome Measures in Rheumatoid Arthritis ............................................... 127
Yusuf Yazici and Hilal Maradit Kremers
Issues in Setting Up a Study and Data Collection ........................................ 141
Hilal Maradit Kremers and Banu Çakir
The Randomized Controlled Trial: Methodological Perspectives .............. 159
Emmanuel Lesaffre
Limitations of Traditional Randomized Controlled
Clinical Trials in Rheumatology .................................................................... 179
Theodore Pincus
Methodological Issues Relevant to Observational Studies,
Registries, and Administrative Health Databases in Rheumatology ......... 209
Marie Hudson and Samy Suissa
Systematic Reviews and Meta-analyses in Rheumatology .......................... 229
Theo Stijnen and Gulen Hatemi
ix