Research Methodology in the Medical and Biological Sciences

510 Pages·2007·3.187 MB·English

by  Petter Laake, Haakon Breien Benestad, Petter Laake, Haakon Breien Benestad, Bjorn Reino Olsen Professor MD PhD Bjørn Reino Olsen is Hersey Professor of Cell Biology at Harvard Medical School and Professor of Developmental Biology Harvard School of Dental Medicine. Since 2005 he also serves as Dean of Research at Harvard School of Dental Medicine. He has lectured worldwide and mentored and trained a large number of students and postdoctoral fellows. He is a member of and has held leadership positions in several professional organizations has served on several Editorial Boards and is currently Editor-in-Chief of BioMed Central's Journal of Negative Results in Biomedicine.

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RESEARCH METHODOLOGY IN THE MEDICAL AND
BIOLOGICAL SCIENCES
http://avaxhome.ws/blogs/ChrisRedfield
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RESEARCH METHODOLOGY IN
THE MEDICAL AND BIOLOGICAL
SCIENCES
Edited by
Petter Laake
Haakon Breien Benestad
and
Bjørn Reino Olsen
AMSTERDAM • BOSTON (cid:129) HEIDELBERG (cid:129) LONDON (cid:129) NEW YORK (cid:129) OXFORD
PARIS (cid:129) SAN DIEGO (cid:129) SAN FRANCISCO (cid:129) SINGAPORE (cid:129) SYDNEY (cid:129) TOKYO
Academic Press is an imprint of Elsevier
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First published as Forskningsmetode i medisin og biofagby Gyldendal Norsk Forlag 2004
English translation by M.Michael Brady copyright © Gyldendal Norsk Forlag 2007
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CONTENTS
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
List of abbreviations and symbols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxiii
CHAPTER 1 PHILOSOPHY OF SCIENCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Bjørn Hofmann,Søren Holm and Jens-Gustav Iversen
1.1 Philosophy of the natural sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Philosophy of the social sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
CHAPTER 2 ETHICSAND SCIENTIFIC CONDUCT . . . . . . . . . . . . . . . . . . . . . . 33
Søren Holm
2.1 A brief introduction to ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.2 Scientific conduct and misconduct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.3 Misconduct and why it occurs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
2.4 Fabrication and other forms of misconduct affecting the truth claims
of scientific findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.5 Authorship issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2.6 Salami,imalas and duplicate publication . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.7 The investigation and punishment of scientific misconduct . . . . . . . . . . 47
Appendix 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
CHAPTER 3 ETHICS IN HUMANANDANIMAL STUDIES . . . . . . . . . . . . . . . . . . 53
Søren Holm and Bjørn Reino Olsen
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.2 Basic principles of human research ethics . . . . . . . . . . . . . . . . . . . . . . . . 54
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3.3 International regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3.4 The ethics of animal research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Appendix 1 World Medical Association Declaration of Helsinki Ethical
Principles for Medical Research Involving Human Subjects . . . . . . . . . . . . . 74
Appendix 2 Oviedo Convention (Council of Europe,European
Treaty Series 164) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Appendix 3 Oviedo Convention –Additional Protocol Concerning
Biomedical Research,Chapter I–IX (Council of Europe,European
Treaty Series 195) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
CHAPTER 4 RESEARCH METHODOLOGY:STRATEGIES,PLANNINGANDANALYSIS 93
Haakon Breien Benestad and Petter Laake
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
4.2 Your scientific problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
4.3 More on scientific problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.4 Literature,methods and techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.5 Research conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
4.6 Data types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
4.7 Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.8 Repeatability,reproducibility and reliability . . . . . . . . . . . . . . . . . . . . . . 109
4.9 Validity,effect measure and choice of statistical test . . . . . . . . . . . . . . 112
4.10 Experimental protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
4.11 Experimental routine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
CHAPTER 5 LITERATURE SEARCHAND PERSONAL REFERENCE DATABASES . . . . 125
Anne-Marie B.Haraldstad and Ellen Christophersen
5.1 Information literacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
5.2 Systematic literature search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
5.3 How to formulate a query:PICO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
5.4 Search technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
5.5 Methodology filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
5.6 Quality:critical appraisal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
5.7 Impact factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
5.8 Principal bibliographic databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
5.9 Staying up to date . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
5.10 Medical and scientific internet search engines . . . . . . . . . . . . . . . . . . . 154
5.11 Personal reference databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
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CHAPTER 6 METHODS IN MOLECULAR BIOLOGY . . . . . . . . . . . . . . . . . . . . . 161
Sigbjørn Fossum and Erik Dissen
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
6.2 Recombinant DNA technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
6.3 DNA and RNA:isolation,identification,synthesis and analysis . . . . . . . 168
6.4 Practical applications of DNA/RNA technology . . . . . . . . . . . . . . . . . . . 174
6.5 Protein analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
6.6 Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
CHAPTER 7 STRATEGIESAND METHODS OF BASIC MEDICAL RESEARCH . . . . . . 199
Bjørn Reino Olsen and Haakon Breien Benestad
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
7.2 Long-term goals and specific aims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
7.3 Background and significance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
7.4 Experimental strategies and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
7.5 Pilot studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
7.6 Rules for basic medical research projects . . . . . . . . . . . . . . . . . . . . . . . . 209
CHAPTER 8 CLINICAL RESEARCH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Eva Skovlund and Morten H.Vatn
8.1 Controlled clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
8.2 Publication bias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
8.3 Estimating sample size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
8.4 ‘Non-inferiority’ studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
8.5 Generalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
CHAPTER 9 EPIDEMIOLOGY:CONCEPTSAND METHODS . . . . . . . . . . . . . . . . 241
Dag S.Thelle and Petter Laake
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
9.2 Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
9.3 The role of epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
9.4 Population and sample . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
9.5 Measures of disease occurrence,association,risk and implications . . . . 246
9.6 Vital statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
9.7 Study designs of epidemiological studies . . . . . . . . . . . . . . . . . . . . . . . . . 254
9.8 Effect measures in epidemiological studies . . . . . . . . . . . . . . . . . . . . . . . 261
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9.9 Experimental studies and randomized control trials . . . . . . . . . . . . . 268
9.10 Measurement error and sources of error . . . . . . . . . . . . . . . . . . . . . . 268
9.11 Tests and validity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
9.12 Causes of disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
9.13 Association versus causality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
CHAPTER 10 QUALITATIVE RESEARCH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Harald Grimen and Benedicte Ingstad
10.1 Qualitative versus quantitative research . . . . . . . . . . . . . . . . . . . . . . . 281
10.2 Using qualitative research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
10.3 What qualitative research cannot be used for . . . . . . . . . . . . . . . . . . 284
10.4 Samples in qualitative studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
10.5 Reliability and validity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
10.6 Ethical challenges in qualitative research . . . . . . . . . . . . . . . . . . . . . . . 287
10.7 Qualitative data collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
10.8 Triangulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
10.9 Analyses of qualitative data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
10.10 Releasing qualitative data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
CHAPTER 11 STATISTICAL ISSUES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Petter Laake,Thore Egeland and Eva Skovlund
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
11.2 Effect measure,hypothesis testing and confidence interval . . . . . . . . 312
11.3 Bernoulli trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
11.4 Comparing two proportions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
11.5 Measures of association in 2 (cid:3)2 tables . . . . . . . . . . . . . . . . . . . . . . . 323
11.6 Normal distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
11.7 Comparison of means . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
11.8 Non-parametric methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
11.9 Regression analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
CHAPTER 12 EVIDENCE-BASED PRACTICEAND CRITICALAPPRAISAL OF
SYSTEMATIC REVIEWS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Liv Merete Reinar and Peter M.Bradley
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
12.2 Systematic reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
12.3 Critical appraisal of a systematic review:one example . . . . . . . . . . . . 368
12.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
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CHAPTER 13 SCIENTIFIC COMMUNICATION . . . . . . . . . . . . . . . . . . . . . . . . 383
Haakon Breien Benestad
13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
13.2 The scientific paper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
13.3 Posters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
CHAPTER 14 SUCCESSFUL LECTURING . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Heidi Kiil Blomhoff
14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
14.2 Preparing the lecture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
14.3 Lecture content and form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418
14.4 Manuscript . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424
14.5 Delivering a lecture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
CHAPTER 15 GUIDETO GRANTAPPLICATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . 433
Bjørn Reino Olsen,Petter Laake and Ole Petter Ottersen
15.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
15.2 Getting started . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
15.3 The postdoctoral fellow and junior scientist . . . . . . . . . . . . . . . . . . . . 437
15.4 What goes into a successful grant application? . . . . . . . . . . . . . . . . . . . 443
15.5 The investigator-initiated research grant . . . . . . . . . . . . . . . . . . . . . . . . 445
15.6 Multiproject grants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
15.7 International research collaborations . . . . . . . . . . . . . . . . . . . . . . . . . . 451
15.8 The European Union’s seventh Framework Programme . . . . . . . . . . . 454
15.9 Summary and perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
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