Thelle - Epidemiology

The book is aimed at students in medical school, as well as public health and other health sciences students at the Bachelor and Master’s level.

Dag S. Thelle has served as professor of preventive medicine at the University of Tromsø, and has chaired professorships in epidemiology at the Nordic School of Public Health, Gothenburg, the University of Oslo, and at the University of Gothenburg.

He was principal investigator of the Tromsø Study, 1974–88, the Oslo Health Study conducted 2000–2001, and the INTERGENE Study conducted in Gothenburg and West Sweden from 2001–2004. He has published more than 200 scientific papers, mainly focused on the epidemiology of cardiovascular and chronic diseases.

EPIDEMIOLOGY

The first twelve chapters concern epidemiologic methods, including discussion of study designs and bias, together with an overview of vital statistics and a discussion on causality. The final eight chapters discuss changes in health more generally (or the epidemiologic transition), prevention, an introduction to genetic epidemiology, infectious disease, reporting observational studies, and assessing new information.

Dag S. Thelle

www.gyldendal.no/akademisk

Epidemiology involves the study of the distribution and determinants of disease and health in a given population, and the subsequent application of this study to improve outcomes. This book introduces major topics in this field, and where applicable, illustrated by tables and figures from Norwegian and Swedish studies.

Dag S. Thelle

EPIDEMIOLOGY A basis for public health and disease prevention

Table of contents Chapter 1 Epidemiology and public health.................................................................. 14 1.1 Clinical medicine and public health .................................................... 14 1.2 Definition of health ............................................................................ 16 1.3 Definitions of public health ................................................................ 16 1.4 Definition of disease........................................................................... 17 1.5 Definitions of epidemiology ................................................................ 22 1.6 The role of epidemiology.................................................................... 22 1.7 Epidemiologic measurements.............................................................. 24 1.8 John Snow and the London cholera epidemic ..................................... 25 1.9 Summary ........................................................................................... 27 1.10 References.......................................................................................... 27

Chapter 2 Measuring disease....................................................................................... 29 2.1 Measures of disease frequency in populations and cohorts .................. 29 2.2 Incidence and rates ............................................................................ 30 2.3 Survival ratio and relative survival ...................................................... 37 2.4 Summary ........................................................................................... 38 2.5 References.......................................................................................... 39

Chapter 3 Vital 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 3.10

statistics and register epidemiology .................................................... 40 The use of vital statistics in epidemiology ........................................... 40 Mortality statistics .............................................................................. 41 Life expectancy and life span .............................................................. 45 Morbidity and mortality registers........................................................ 48 Exposure variables, intermediary factors, treatment effect and disease frequency................................................................................ 50 Global Burden of Disease ................................................................... 52 A brief history of vital statistics .......................................................... 53 Examples of use of register data in epidemiological studies.................. 54 Summary ........................................................................................... 58 References.......................................................................................... 58 7

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Chapter 4 Study 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 4.10 4.11

designs, effect measures, impact and importance............................. 60 Trials or observational studies ............................................................ 60 Case stories ........................................................................................ 63 Effect estimates, risk and implications................................................. 64 Denominators, numerators and time................................................... 64 Effect measures in epidemiological studies .......................................... 66 Calculation of Relative Risk and Odds Ratio ....................................... 67 Attributable fraction ........................................................................... 69 Prevented fractions............................................................................. 71 The importance of differences............................................................. 72 Summary ........................................................................................... 75 References.......................................................................................... 76

Chapter 5 Case-control studies .................................................................................... 78 5.1 Definition of case-control study .......................................................... 78 5.2 Advantages of the case-control study .................................................. 79 5.3 Disadvantages of case-control studies.................................................. 79 5.4 Reversed causality .............................................................................. 80 5.5 Key issues in case-control studies ....................................................... 80 5.6 Analyzing case-control studies ............................................................ 87 5.7 Nested case-control study ................................................................... 92 5.8 Case-crossover studies ........................................................................ 93 5.9 A short history of case-control studies ................................................ 95 5.10 Summary ........................................................................................... 98 5.11 References.......................................................................................... 98

Chapter 6 Cross-sectional studies .............................................................................. 101 6.1 Definition of a cross-sectional study ................................................. 101 6.2 Cross-sectional studies, advantages and disadvantages ....................... 101 6.3 Planning and implementation of cross-sectional studies .................... 103 6.4 The development of questionnaires and standardized instruments ..... 106 6.5 Difficulties when inferring from cross-sectional study results ............. 108 6.6 Summary ......................................................................................... 110 6.7 References........................................................................................ 110 8

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Chapter 7 Cohort studies ........................................................................................... 112 7.1 Definitions of a cohort study ............................................................ 112 7.2 Effect measures in cohort studies (RR and IRR) ................................ 113 7.3 Confidence interval for IRR .............................................................. 115 7.4 Advantages of cohort studies ............................................................ 116 7.5 Disadvantages of cohort studies ........................................................ 116 7.6 Outline of cohort studies .................................................................. 117 7.7 Examples of cohort studies with different aim and design ................. 118 7.8 The pooling of compatible cohort studies in Norway (CONOR)........ 123 7.9 Summary ......................................................................................... 123 7.10 References........................................................................................ 124

Chapter 8 Trials 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9

and experiments .............................................................................. 126 Definition of randomized controlled trial .......................................... 126 Experiments and trials...................................................................... 127 Randomization................................................................................. 130 Trial designs .................................................................................... 131 The crossover trial............................................................................ 135 When to use clinical trials ................................................................ 136 Inconclusive trials - more pain than gain.......................................... 138 Summary ......................................................................................... 140 References........................................................................................ 140

Chapter 9 Bias and errors .......................................................................................... 143 9.1 Definitions of errors ......................................................................... 143 9.2 Validity and repeatability.................................................................. 144 9.3 Selection bias ................................................................................... 145 9.4 Information bias............................................................................... 149 9.5 Misclassification ............................................................................... 151 9.6 A floating numerator – a source for biased interpretation ................. 152 9.7 Publication bias................................................................................ 155 9.8 Summary ......................................................................................... 155 9.9 References........................................................................................ 156

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Chapter 10 Confounding and effect modification........................................................ 157 10.1 Definitions of confounding, colliders and effect modification............. 157 10.2 More on confounders and colliders................................................... 159 10.3 Age Standardization, an example of adjusting for confounding variables....................................................................... 167 10.4 Effect modification ........................................................................... 172 10.5 Summary ......................................................................................... 176 10.6 References........................................................................................ 176

Chapter 11 The causal concept ................................................................................... 177 11.1 Postulates for causality ..................................................................... 177 11.2 The hidden associations within homogeneous populations ................ 181 11.3 Definitions of causes of disease......................................................... 183 11.4 Causal inference ............................................................................... 188 11.5 A causal algebra and a new terminology ........................................... 189 11.6 Summary ......................................................................................... 193 11.7 References........................................................................................ 193

Chapter 12 Validity, conditional probability and diagnostic tests ................................ 195 12.1 Diagnostic reasoning ........................................................................ 195 12.2 Tests and their validity ..................................................................... 196 12.3 Predictive power .............................................................................. 202 12.4 Number needed to treat ................................................................... 204 12.5 Summary ......................................................................................... 205 12.6 References........................................................................................ 205

Chapter 13 The epidemiological transition .................................................................. 206 13.1 Constant mortality or dynamic changes ............................................ 206 13.2 Diseases of the twentieth century...................................................... 207 13.3 A century of violent deaths .............................................................. 210 13.4 The expectations of the public and morbidity, future aspects............. 211 13.5 Summary ......................................................................................... 212 13.6 References........................................................................................ 212 10

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Chapter 14 Social status and health ............................................................................ 214 14.1 Differences between groups, but not between individuals? ................. 214 14.2 The poorer, the sicker ...................................................................... 215 14.3 Causes of disease and social inequality.............................................. 217 14.4 It is all about education.................................................................... 220 14.5 Summary ......................................................................................... 221 14.6 References........................................................................................ 221

Chapter 15 Infectious diseases..................................................................................... 223 15.1 Brief introduction to infectious disease epidemiology ........................ 223 15.2 The origin of infectious diseases ....................................................... 224 15.3 Measures of infectious diseases ......................................................... 225 15.4 Short description of three major infectious diseases........................... 230 15.5 Vaccination programs ...................................................................... 235 15.6 Summary ......................................................................................... 236 15.7 References........................................................................................ 236

Chapter 16 Genetic epidemiology ............................................................................... 238 16.1 Genetics in epidemiology, terminology and concepts......................... 238 16.2 Linkage analysis ............................................................................... 239 16.3 Linkage disequilibrium ..................................................................... 240 16.4 The role of genes in an epidemiological context ................................ 241 16.5 The dualism in genetic epidemiology ................................................ 241 16.6 Genetic attributable fraction ............................................................. 242 16.7 Hardy-Weinberg’s equilibrium.......................................................... 243 16.8 Founder effect .................................................................................. 246 16.9 From great expectations to cooleer attitudes...................................... 247 16.10 Genome-wide association study ........................................................ 248 16.11 Epigenetics....................................................................................... 249 16.12 Mendelian randomization................................................................. 249 16.13 Summary ......................................................................................... 252 16.14 References........................................................................................ 253

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Chapter 17 Disease prevention and intervention......................................................... 255 17.1 What to prevent? ............................................................................. 255 17.2 Short summaries of current screening programs................................ 268 17.3 An example of shift in strategy – from screening to vaccination........ 270 17.4 A small increase in risk can offset a small gain ................................. 271 17.5 Causality and unpredictability........................................................... 273 17.6 Summary ......................................................................................... 275 17.7 References........................................................................................ 275

Chapter 18 Reporting observational studies ................................................................ 278 18.1 Unfounded basis for preventive actions............................................. 278 18.2 STROBE .......................................................................................... 279 18.3 STROBE Statement .......................................................................... 280 18.4 Summary ......................................................................................... 283 18.5 References........................................................................................ 283

Chapter 19 Reviews, meta-analyses and evidence based medicine ............................. 285 19.1 From data to scientific knowledge..................................................... 285 19.2 Meta-analyses................................................................................... 286 19.3 Evidence based medicine .................................................................. 287 19.4 Grading of scientific knowledge ........................................................ 291 19.5 Comments and critical remarks ........................................................ 291 19.6 Summary ......................................................................................... 295 19.7 References........................................................................................ 297

Chapter 20 Ethics in epidemiology and trials .............................................................. 298 20.1 Background...................................................................................... 298 20.2 The Nuremberg Code....................................................................... 298 20.3 The Helsinki Declaration on ethics in medical science ...................... 299 20.4 Epidemiology and ethics in science................................................... 299 20.5 References........................................................................................ 300

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Appendix A The ten points of the Nuremberg Code (Government, 1949).................... 301

Appendix B WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects.......................................................... 303

Appendix C Study questions......................................................................................... 311

Glossary Glossary..................................................................................................... 315

Index Index ......................................................................................................... 317

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