An Introduction to Epidemiology for Health Professionals PDF
Preview An Introduction to Epidemiology for Health Professionals
Springer Series on Epidemiology and Health SeriesEditors WolfgangAhrens IrisPigeot Forfurthervolumes: http://www.springer.com/series/7251 · · · Jørn Olsen Kaare Christensen Jeff Murray Anders Ekbom An Introduction to Epidemiology for Health Professionals 123 JørnOlsen KaareChristensen SchoolofPublicHealth InstituteofPublicHealth UniversityofCalifornia,LosAngeles UniversityofSouthernDenmark LosAngelesCA90095-1772 Sdr.Boulevard23A Box951772 5000OdenseC USA Denmark [email protected] [email protected] JeffMurray,MD AndersEkbom DepartmentofPediatrics DepartmentofMedicine, 2182MedLabs KarolinskaInstitute SE-17176Stockholm UniversityofIowa Sweden IowaCity,IA52245 [email protected] USA [email protected] ISSN1869-7933 e-ISSN1869-7941 ISBN978-1-4419-1496-5 e-ISBN978-1-4419-1497-2 DOI10.1007/978-1-4419-1497-2 SpringerNewYorkDordrechtHeidelbergLondon LibraryofCongressControlNumber:2010922282 ©SpringerScience+BusinessMedia,LLC2010 Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewritten permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY10013,USA),exceptforbriefexcerptsinconnectionwithreviewsorscholarlyanalysis.Usein connectionwithanyformofinformationstorageandretrieval,electronicadaptation,computersoftware, orbysimilarordissimilarmethodologynowknownorhereafterdevelopedisforbidden. 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Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Therearemanygoodepidemiologytextbooksonthemarket,butmostoftheseare addressedtostudentsofpublichealthorpeoplewhodoclinicalresearchwithepi- demiologicmethods.Thereisaneedforashortintroductiononhowepidemiologic methodsareusedinpublichealth,geneticandclinicalepidemiology,becausehealth professionalsneedtoknowbasicepidemiologicmethodscoveringetiologicaswell asprognosticfactorsofdiseases.Theyneedtoknowmoreaboutmethodologythan introductorytextsonpublichealthhavetooffer. In some health faculties, epidemiology is not even part of the teaching curricu- lum. We believe this to be a serious mistake. Medical students are students of all aspectsofdiseasesandhealth.Withoutknowingsomethingaboutepidemiologythe clinicians and other health professionals cannot read a growing part of the scien- tific literature in any reasonably critical way and cannot navigate in the world of “evidence-based medicine and evidence-based prevention.” Without skills in epi- demiologicmethodologytheyareinthehandsofexpertsthatmaynotonlyhavean interestinhealth. Some health professionals may believe that only common sense is needed to conduct epidemiological studies, but the scientific literature and the public debate on health issues indicate that common sense is often in short supply and may not thrivewithoutsomeformaltraining. Epidemiologic methods play a key role in identifying environmental, social, and genetic determinants of diseases. Clinical epidemiology addresses the tran- sition from disease to health or toward mortality or social or medical handicaps. Publichealthepidemiologyaddressesthetransitionfrombeinghealthytobeingnot healthy.Descriptiveepidemiologyprovidesthediseasepatternthatisneededtolook athealthinabroadperspectiveandtosettheprioritiesright.Epidemiologyisabasic scienceofmedicinewhichaddresseskeyquestionssuchas“Whobecomesill?”and “What are important prognostic factors?” Answers to such questions provide the basisforbetterpreventionandtreatmentofdiseases. Many people contributed to the writing of this book: medical students in Denmark, students of epidemiology at the IEA EEPE summer course in Florence, Italy, and students of public health in Los Angeles. Without technical assistance v vi Preface fromGitteNielsen,JenadeShelley,NinaHoheandPamMasangkaythebookwould neverhavematerialized. LosAngeles,California JørnOlsen Odense,Denmark KaareChristensen IowaCity,Iowa JeffMurray Stockholm,Sweden AndersEkbom Contents PartI DescriptiveEpidemiology 1 MeasuresofDiseaseOccurrence . . . . . . . . . . . . . . . . . . . 3 IncidenceandPrevalence . . . . . . . . . . . . . . . . . . . . . . . . 4 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 RatesandDynamicPopulations . . . . . . . . . . . . . . . . . . . . . 7 CalculatingObservationTime . . . . . . . . . . . . . . . . . . . . . . 9 Prevalence,Incidence,Duration . . . . . . . . . . . . . . . . . . . . . 10 MortalityandLifeExpectancy . . . . . . . . . . . . . . . . . . . . . 11 LifeExpectancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2 EstimatesofAssociations . . . . . . . . . . . . . . . . . . . . . . . 15 3 AgeStandardization . . . . . . . . . . . . . . . . . . . . . . . . . . 19 4 CausesofDiseases . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 5 DescriptiveEpidemiologyinPublicHealth . . . . . . . . . . . . . . 29 GraphicalModelsofCausalLinks . . . . . . . . . . . . . . . . . . . 33 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 6 DescriptiveEpidemiologyinGeneticEpidemiology . . . . . . . . . 37 OccurrenceDatainGeneticEpidemiology . . . . . . . . . . . . . . . 37 ClusteringofTraitsandDiseasesinFamilies . . . . . . . . . . . . . . 38 TheOccurrenceofGeneticDiseases . . . . . . . . . . . . . . . . . . 40 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 7 DescriptiveEpidemiologyinClinicalEpidemiology . . . . . . . . . 43 SuddenInfantDeathSyndrome(SIDS) . . . . . . . . . . . . . . . . . 44 CytologicalScreeningforCervixCancer . . . . . . . . . . . . . . . . 45 ChangesinTreatmentofJuvenileDiabetes . . . . . . . . . . . . . . . 46 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 vii viii Contents PartII AnalyticalEpidemiology 8 DesignOptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 CommonDesignsUsedtoEstimateAssociations . . . . . . . . . . . . 51 EcologicalStudy . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Case–ControlStudy . . . . . . . . . . . . . . . . . . . . . . . . . . 54 CohortStudy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 ExperimentalStudy . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 9 Follow-UpStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 TheNon-experimentalFollow-Up(Cohort)Study . . . . . . . . . . . 59 StudyingRiskasaFunctionofBMI . . . . . . . . . . . . . . . . . . 60 LongitudinalExposureData . . . . . . . . . . . . . . . . . . . . . . . 62 DifferentTypesofCohortorFollow-UpStudies . . . . . . . . . . . . 63 10 Case–ControlStudies. . . . . . . . . . . . . . . . . . . . . . . . . . 67 Case–CohortSampling . . . . . . . . . . . . . . . . . . . . . . . . . 69 DensitySamplingofControls . . . . . . . . . . . . . . . . . . . . . . 69 Case–Non-caseStudy . . . . . . . . . . . . . . . . . . . . . . . . . . 71 PatientControls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 SecondaryIdentificationoftheSourcePopulation . . . . . . . . . . . 74 Case–ControlStudiesUsingPrevalentCases . . . . . . . . . . . . . . 74 WhentoDoaCase–ControlStudy? . . . . . . . . . . . . . . . . . . . 77 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 11 TheCross-SectionalStudy . . . . . . . . . . . . . . . . . . . . . . . 79 12 TheRandomizedControlledTrial(RCT) . . . . . . . . . . . . . . 81 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 13 AnalyticalEpidemiologyinPublicHealth . . . . . . . . . . . . . . 85 TheCase-CrossoverStudy . . . . . . . . . . . . . . . . . . . . . . . . 86 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 14 AnalyticalEpidemiologyinGeneticEpidemiology . . . . . . . . . 89 DisentanglingtheBasisforClusteringinFamilies . . . . . . . . . . . 89 AdoptionStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 TwinStudies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Half-SibStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 InterpretationofHeritability . . . . . . . . . . . . . . . . . . . . . . . 91 Exposure–DiseaseAssociationsThroughStudiesofRelatives . . . . . 91 Gene–EnvironmentInteraction . . . . . . . . . . . . . . . . . . . . . 92 Cross-SectionalStudiesofGeneticPolymorphisms. . . . . . . . . . . 93 IncorporationofGeneticVariablesinEpidemiologicStudies. . . . . . 93 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Contents ix 15 AnalyticalEpidemiologyinClinicalEpidemiology . . . . . . . . . 95 CommonDesignsUsedtoEstimateAssociations . . . . . . . . . . . . 95 Case-ReportsandCross-SectionalStudies . . . . . . . . . . . . . . . 95 Case–ControlStudies . . . . . . . . . . . . . . . . . . . . . . . . . . 96 CohortStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 RandomizedClinicalTrials(RCTs) . . . . . . . . . . . . . . . . . . . 98 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 PartIII SourcesofError 16 ConfoundingandBias . . . . . . . . . . . . . . . . . . . . . . . . . 103 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 17 Confounding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 18 InformationBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 19 SelectionBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 20 MakingInferenceandMakingDecisions . . . . . . . . . . . . . . . 123 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 21 SourcesofErrorinPublicHealthEpidemiology. . . . . . . . . . . 129 BerksonBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 MendelianRandomization . . . . . . . . . . . . . . . . . . . . . . . . 132 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 22 SourcesofErrorinGeneticEpidemiology . . . . . . . . . . . . . . 135 MultipleTesting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 PopulationStratification . . . . . . . . . . . . . . . . . . . . . . . . . 136 LaboratoryErrors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 23 SourcesofErrorinClinicalEpidemiology . . . . . . . . . . . . . . 139 ConfoundingbyIndication . . . . . . . . . . . . . . . . . . . . . . . 139 DifferentialMisclassificationofOutcome . . . . . . . . . . . . . . . . 140 DifferentialMisclassificationofExposure . . . . . . . . . . . . . . . 141 SelectionBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 PartIV StatisticsinEpidemiology AdditiveModel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 MultiplicativeModel. . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 24 PValues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 x Contents 25 CalculatingConfidenceIntervals . . . . . . . . . . . . . . . . . . . 155 Erratum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Epilogue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 A Short Introduction to Epidemiology Epidemiology is an old scientific discipline that dates back to the middle of the nineteenth century. It is a discipline that aims at identifying the determinants of diseases and health in populations. It uses a population approach like demogra- phy, perhaps the scientific discipline that most closely resembles epidemiology. Epidemiology is defined by the object of research, “to identity determinants that changetheoccurrenceofhealthphenomenainhumanpopulations.” Epidemiology is often associated with infectious diseases because an epidemic ofadiseaseoriginallyreferredtoanunexpectedriseintheincidenceofinfectious diseases.Epidemiologicmethodswerefirstusedtostudydiseaseslikecholeraand measles. Now all diseases or health events are studied by means of epidemiologic methodsandthesemethodsareconstantlychangingtomeetthesenewneeds.Even theterm“epidemic”isusedtodescribeanunexpectedincreaseinthefrequencyof anydiseasesuchasmyocardialinfarction,obesity,orasthma. Today the discipline is used to study genetic, behavioral, and environmental causes of infectious and non-infectious diseases. The discipline is used to evalu- atetheeffectoftreatmentsorscreeninganditisthekeydisciplineinthemovement thatmayhavebeenoversoldwiththetitle“evidence-basedmedicine.” Publichealthepidemiologyusesthe“healthy”populationtostudythetransition from being healthy to being diseased or ill. Clinical epidemiology uses the popu- lation of patients to study predictors of cure or changes in the disease state. Both disciplinesuseexperimentalandnon-experimentalmethods.Experimentalmethods are,however,oftennotapplicableforethicalreasonsinpublichealthresearchsince wecannotinducepossiblyharmfulexposuresonhealthypeopletoaddressscientific hypotheses. Epidemiologists have often been actors in political conflicts. Poverty, social inequalities, unemployment, and crowding are among the main determinants of health [1], and studying these determinants may bring epidemiologists into con- flict with those who benefit from maintaining an unjust society. To some extent, these internal conflicts gave rise to clinical epidemiology. Many clinicians saw a need for using the methods developed in public health but did not like the idea of beingassociatedwithleft-wingdoctorsfightingtuberculosisinIndiaorpovertyin LosAngeles.Aclinicalepidemiologistcanstudyhowbesttotreatdiseaseswithout takinganinterestinhowthesediseasesemerged. xi
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