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Research in
MEDICAL AND
BIOLOGICAL SCIENCES
Research in
MEDICAL AND
BIOLOGICAL SCIENCES
From Planning and Preparation
to Grant Application and Publication

Edited by

Petter Laake
University of Oslo, Oslo, Norway

Haakon Breien Benestad

University of Oslo, Oslo, Norway

Bjorn Reino Olsen

Harvard University, Cambridge, USA

AMSTERDAM • BOSTON • HEIDELBERG • LONDON

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ISBN: 978-0-12-799943-2
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LIST OF CONTRIBUTORS

Mahmood Amiry-Moghaddam
Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo,
Blindern, Oslo, Norway
Haakon Breien Benestad
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo,
Blindern, Oslo, Norway
Heidi Kiil Blomhoff
Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo,
Blindern, Oslo, Norway
Ellen Christophersen
University of Oslo Library, Medical Library, Blindern, Oslo, Norway
Morten Wang Fagerland
Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo
University Hospital, Oslo, Norway
Anne-Marie B. Haraldstad
University of Oslo Library, Medical Library, Blindern, Oslo, Norway
Bjørn Hofmann
Section for Health, Technology and Society, University College of Gjøvik, Gjøvik,
Norway and Centre for Medical Ethics, Institute of Health and Society, University of
Oslo, Blindern, Oslo, Norway
Søren Holm
Centre for Social Ethics and Policy, School of Law, The University of Manchester,
England, Centre for Medical Ethics, Institute of Health and Society, University of Oslo,
Blindern, Oslo, Norway and Department of Health Science and Technology, Aalborg
University, Denmark
Petter Laake
Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of
Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway
Anne-Lise Middelthon
Department of Community Medicine, Institute of Health and Society, University of Oslo,
Blindern, Oslo, Norway
Kåre Moen
Department of Community Medicine, Institute of Health and Society, University of Oslo,
Blindern, Oslo, Norway
Bjorn Reino Olsen
Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, USA

xiii
xiv List of Contributors

Ole Petter Ottersen

Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo,
Blindern, Oslo, Norway
Eva Skovlund
School of Pharmacy, University of Oslo, Blindern, Oslo, Norway
Dag S. Thelle
Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of
Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway
Kjell Magne Tveit
Department of Oncology, Oslo University Hospital, Nydalen, Oslo, Norway
Preface

The famous physician William Osler once said, while instructing a

student during an autopsy, “it is always best to do a thing wrongly the
first time.” Indeed, in the fledging stages of our scientific careers we are
likely to make not just one but many mistakes. Although one can learn
from one’s mistakes, we believe that some can be prevented by appropri-
ate instruction and reading. Nobel Prize winner Max Perutz allegedly
complained that in his opinion “many young scientists work too much,
and read and think too little.” If this was the case 50 years ago, it is proba-
bly a larger problem today. The pace of graduate studies has accelerated,
and it is often difficult for students to find the time to read even the most
relevant scientific articles, not to mention entire books that have been
written on the various themes that we present in this book. We are not
aware of any other textbook that includes most of the subjects dealt with
in this volume. Our wish in creating this book is to make academic life
easier for graduate students.
The history of this book began several decades ago, when the three of
us started to arrange courses to help PhD students avoid some of the pitfalls
that we ourselves experienced, and to teach them some basic rules, lege
artis, for doing research. At the turn of this century, a national program was
adopted in Norway that applied to all students enrolled in doctoral pro-
grams at Medical Schools. It included a compulsory course that covered a
broad range of topics and that came to comprise the basis of a textbook,
which was first published in Norwegian by Gyldendal Akademisk, and
later in English by Elsevier, as a revised and expanded version of the
Norwegian edition (Research Methodology in the Medical and Biological
Sciences, 2007). Some chapters of the present book resemble those of the
former book, but all chapters have been thoroughly revised. The following
chapters are either completely new or have been written by new authors:
“Ethics and scientific conduct,” “Basic medical science,” “Translational
medical research,” “Qualitative research,” and “Evidence-based practice.”
There are several reasons for the broad range of topics covered in this
book. Master’s and PhD programs should train students for competence
in research as well as other professional pursuits that require scientific
insight, including the basics of the research process. Students entering
these graduate programs typically come from a variety of undergraduate

xv
xvi Preface

programs, including studies in medicine, natural sciences, social sciences,

or nursing. During their undergraduate studies they gain only narrow
scientific capabilities, which can lead to difficulties communicating and
working with colleagues who belong to other fields even after they have
finished their graduate work. This is contrary to the goals established by
the European Qualifications Framework (EQF) as to what a student at
these levels should know, understand, and be able to do. It is therefore
important that graduate studies include schooling in general scientific
research, regardless of the specific discipline pursued.
This book is intended for students with varied professional back-
grounds. Multidisciplinary communication and research cooperation is
increasingly important, as the “learning outcomes” of the EQF imply.
Scientists in any one scientific community should be familiar with and
should respect the traditions of other scientific communities. This book
outlines a possible curriculum for Master’s and PhD students in the medi-
cal and biological fields. We believe that everyone in these fields should
know a little about all the subjects covered in this book, in addition to
the deeper knowledge of topics related to their own disciplines.

Petter Laake
Bjorn Reino Olsen
Haakon Breien Benestad
CHAPTER 1

Philosophy of Science
Bjørn
1
Hofmann1 and Søren Holm2
Section for Health, Technology and Society, University College of Gjøvik, Gjøvik, Norway and Centre
for Medical Ethics, Institute of Health and Society, University of Oslo, Blindern, Oslo, Norway
2
Centre for Social Ethics and Policy, School of Law, The University of Manchester, England, Centre for
Medical Ethics, Institute of Health and Society, University of Oslo, Blindern, Oslo, Norway and
Department of Health Science and Technology, Aalborg University, Denmark

1.1 INTRODUCTION
The sciences provide different approaches to the study of man. Man can
be scrutinized in terms of molecules, tissues and organs, as a living crea-
ture, and as a social agent and a cultural person. Correspondingly, the
philosophy of science investigates the philosophical assumptions, founda-
tions, and implications of the sciences. It is an enormous field that covers
the formal sciences, such as mathematics, computer sciences, and logic;
the natural sciences; the social sciences; and the methodologies of some
of the humanities, such as history. Discussion in the current chapter is
limited to the natural sciences (Section 1.2) and the social sciences
(Section 1.13), and comprises a brief overview of the philosophical aspects
salient to research in the medical and biological sciences.

1.2 PHILOSOPHY OF THE NATURAL SCIENCES

What does it mean when one says that “smoking is the cause of lung
cancer”? What counts as a scientific explanation? What is science about,
e.g., what is a cell? How does one obtain scientific evidence? How can
one reduce uncertainty? What are the limits of science? These are but a
few of the issues discussed in the philosophy of the natural sciences that
will be presented in this chapter.
The traditional philosophy of science has aimed to put forth logical
analyses of the premises of science; in particular the logical analysis of the
syntax of basic scientific concepts. In the following sections, the principal
traditional issues regarding the rationality, method, evidence, and the
object of science (the world) are discussed. But first the core concepts of
science, knowledge, and truth will be addressed: What is science? What is
scientific knowledge, and what constitutes a scientific fact?

Research in Medical and Biological Sciences © 2015 Elsevier Ltd.

DOI: http://dx.doi.org/10.1016/B978-0-12-799943-2.00001-X All rights reserved. 1
2 Research in Medical and Biological Sciences

1.3 WHAT IS SCIENCE? DIFFERENTIATING SCIENCE

FROM NONSCIENCE
Science is traditionally defined as “the systematic search for knowledge,”
meaning that science has an aim (knowledge) and it is an activity (search)
with certain qualifications (systematic). However, not everyone who car-
ries out a systematic search for knowledge can obtain research funding.
For example, though a religious man may search for knowledge through
highly systematic meditation techniques, it is unlikely that this will be
considered a project in need of research funding. Indeed, much of the
time even well-funded scientists do not perform systematic searches for
knowledge. They struggle with experimental designs, analyze data, pres-
ent research results, argue with other researchers over conflicting results,
and write funding proposals.
Therefore, a more complete definition of science may be: “Scientific
research is the systematic and socially organized (a) search for, (b) acquisi-
tion of, and (c) use or application of knowledge and insight brought forth
by acts and activities involved in (a) and (b).”1 This definition better
reflects what scientists actually do. They search for new knowledge, e.g.,
by investigating the possibility of using biomolecular tests of cell-free fetal
DNA/RNA in the blood of pregnant women to find defects in the fetus
(noninvasive prenatal testing, NIPT). They acquire knowledge by testing,
accepting, or rejecting a hypothesis, e.g., that NIPT is better than com-
bined ultrasound and serum tests for detecting fetuses with trisomy 13,
18, and 21. Finally, scientists apply knowledge when they argue that a
certain study is either appropriate or flawed, and therefore its results either
valid or invalid. Although this definition of science is closer to what
scientists do, it may still be difficult to differentiate those doing science
from those doing nonscience.
Throughout history a series of criteria has been used to demarcate
science from nonscience (sometimes also referred to as pseudoscience), and
thereby also to define science. Francis Bacon (1561 1626) defined science
as a specific method, i.e., performing a systematic analysis of data without
preconception. Data analysis framed by preconception was considered non-
science. However, in reality it can be very difficult to analyze data without
preconception. To illustrate this fact, if you study the figure below
(Figure 1.1), what do you see? A rabbit, a duck, or perhaps both?
When viewed on paper (or on a screen) the figure has black dots on
a white background. So where are the duck and the rabbit? Are they
 Philosophy of Science 3

Figure 1.1 The duck/rabbit.

figments of the imagination? Are they preconceptions? Hence, to say that

science is the systematic analysis of data without preconception is too
restrictive; it would rule out most of what is called science today. Indeed,
all observations and analyses are based on preconceptions.
Another way to differentiate science from nonscience is to say that
preconception is acceptable in the context of discovery but not in the
context of justification, i.e., when the data are tested. The basic idea is
that the pattern of nature is neutral, and will stand out in the end.
However, this does not solve the problem of preconception when the
hypothesis is tested, as testing presupposes observations, and observations
presuppose preconceptions.
A third classical demarcation criterion is that a scientific hypothesis or
theory can be contested with possible observations, i.e., it can be falsified
(or refuted).2 However, theories are seldom really falsified,3 and to falsify
a theory presupposes that the researcher has an idea about what will hap-
pen. As scientists we are seldom ready to give up our theories, and instead
add specifications or modifications.
It has been argued that scientists are preoccupied with puzzle-solving,
i.e., solving puzzles within a given mode of thought (paradigm), when
they should be concentrating on falsification.3 Until the 1960s it was
commonly thought that science progressed in a linear and piecemeal fash-
ion, in which new knowledge added to existing knowledge. However,
Thomas Kuhn (1922 1996) and others argued that science evolved
through anomalies. Hard cases that could not be explained within the
given paradigm challenged existing theories and resulted in a scientific
revolution. A new set of theories established a new paradigm, and scien-
tists turned to puzzle-solving within this new paradigm. The shift from
Newton’s mechanics to Einstein’s theory of (special) relativity is a key
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