流病性与偏倚预防

1Bias&Validity

inEpidemiologicalResearch

流行病学研究中的偏倚与真实性陈裕明教授医学统计与流行病学系Tel:873306052MaincontentsMeasurementError测量误差RandomerrorSystemicerror(Bias)Bias偏倚：sources,commonbias,andcontrolmethods来源、常见偏倚、控制方法Selectionbias选择偏倚Informationbias信息偏倚Confoundingbias混杂偏倚3ShouldIbelievetheresults?CoffeeDiabetesRR=0.7(95%CI,0.65-0.84)Chance?Confounding?Bias?Trueassociation

Causal Non-causal4MeasurementErrorRandomerror:leadstounreliablemeasurementSystematicerror:leadstobiasedmeasurement56ReliabilityandValidityReliableBiased

(NotValid)NotReliableBiased

(NotValid)NotReliableValidReliableValidRandomerror–measurementnotreliableSystematicerror–measurementbiased(notvalid)7Measurementerror:

ImplicationsforepidemiologicstudiesMeasurementerrorintheexposureortheeRANDOMERROR–Biastowardthenull(e.g.,RR=1)Systematicerror–biasineitherdirectionMeasurementerrorinaconfounderRandomerror–dilutesabilitytoadjustSystematicerror–confoundedestimateofeffect8Measurementerror:

ImplicationsforepidemiologicstudiesRANDOMERROR

Biastowardthenull(e.g.,RR=1)Systematicerror

biasineitherdirection9RandomerrorErrorduetochance“thatpartofourexperiencethatwecannotpredict”Usuallymosteasilyconceptualizedassamplingvariability10Draw1,000randomsamplesfrompopulationwith50%women11Attenuationoftherelations

随机误差减弱关联强度Physiologicalvariables********r=0.98r=0.6512Randomerror随机误差Errorduetochance“thatpartofourexperiencethatwecannotpredict”Usuallymosteasilyconceptualizedassamplingvariability13Randomerrorcanbeproblematic,but...Influencecanbecontrolledby…–increasingsamplesize

–changingdesign

–improvinginstrumentation14Howdowequantifyrandomerrorinatestorastudy?Foratestofexposures,es,confoundersCoefficientofvariation,CVRepeatmeasures,CV=SD/meanForatestofassociation,incidence,prevalenceHypothesistesting,p-value,95%CI15Bias16Definition

of

biasBias:anytrendinthedesign,conduct,analysis,interpretation,publicationorreviewofdatathatcanleadtoconclusionswhicharesystematicallydifferentfromthetruth.(DictionaryofEpidemiology,3rded.)

在设计、实施、分析、结果解释、发表或评阅过程中，能够导致结论系统地偏离真实值的任何趋势17Question?Canyoucontrolorreducebiasbyincreasingsamplesize?18Errorsinepidemiologicalstudies误差随机误差系统误差（偏倚）样本量19Classificationofbias分类Selectionbias

选择偏倚–differentialaccesstothestudypopulationInformationbias

信息偏倚–inaccuracyinmeasurementorclassificationConfoundingbias

混杂偏倚–unfaircomparison20SELECTIONBIAS-definitionSELECTIONBIAS选择偏倚:

Errorsintheprocessofidentifyingthestudypopulation,whichcausesthestudysampledoesnotrepresentthetargetpopulation.在确定研究人群时出现的系统误差，使得研究样本不能代表总体21SamplingandrepresentativenessSampleTargetPopulationSamplingPopulationTargetPopulationSamplingPopulationSample22SourcesofSelection

bias

选择性偏倚的来源1.Samplingbias抽样偏倚--thedegreetowhichthemeasuredsubjectsarenotrepresentativeofthepopulation,isdueto:

ConvenienceSample方便样本Violatedrandomsamplingscheme偏离随机抽样方案HaphazardSample偶然样本23SourcesofSelection

bias

选择性偏倚的来源2.Participationbias参加者偏倚–duetoparticipantsSelf-selection(volunteerism)

自我选择偏倚Healthy(ordiseased)peoplemayseekoutparticipationinthestudyNon-response,refusal无应答偏倚Response,orlackofit,dependsonexposureHealthyworkereffect

健康工人效应Differentiallosstofollow-up

选择性失访Biasduetodifferencesincompletenessoffollow-upbetweencomparisongroups24SourcesofSelection

bias

选择性偏倚的来源3.Ascertainmentbias确认偏倚--systematicerrorduetoadifferenceincharacteristicsbetweenwhochoosetoparticipateinastudyandwhosewhodonot.

Prevalence-incidencebias

现患与新发病例偏差Prevalentcaseislikelytobemild,andsurvivelongerReferralbias

转诊偏倚Sickerpatientsarereferredtomajorhealthcenters25SourcesofSelection

bias

选择性偏倚的来源3.Ascertainmentbias确认偏倚Diagnosticbias诊断偏倚DiagnosisofeassociatedwithexposureAdmissionratebias(Berkson’sbias)入院偏差Hospitalizationratesdifferforbydiseaseandpresence/absenceoftheexposureofinterestLeadtimebias领先时间偏倚26Sampling

bias抽样偏倚Howrepresentativearehospitalisedtraumapatientsofthepopulationwhichgaverisetothecases?OR=627Sampling

bias抽样偏倚OR=6OR=3628Diagnostic

bias诊断偏倚OralContraceptiveuse

breakthroughbleeding

increasedchanceofdetectinguterinecancerDiagnosticapproachrelatedtoknowingexposurestatus

Overestimationof“a”

overestimationofOR29Non-responsebias无应答偏倚Controlschosenamongwomenattheirhomes:13000homescontacted

1060controlsUnderestimationof“b”

overerestimationofORControlsmainlyhousewiveswithlowerchanceofhavingtestthanwomengainfullyemployedPapersmearHadtestDidn’thavetest30Healthyworkereffect

健康工人效应31Healthyworkereffect32Admissionbias

HCV与肝癌的meta分析结果病例-对照来源研究数目OR(95%CI)医院—医院87.80(5.04—12.06)医院—社区76.70(3.28—13.68)社区—社区93.34(2.44—4.56)（吴江南

等.中华肝脏病杂志

2007）33Losstofollow-upbias

失访偏倚Biasduetodifferencesincompletenessoffollow-upbetweencomparisongroupsExampleStudyofdiseaseriskinmigrantsMigrantsmorelikelytoreturntoplaceoforiginwhenhavingdisease

losttofollow-up

lowerdiseaserateamongexposed(=migrant)34QuickQuizToassesstheassociationofexerciseandCHDinacohortstudySupposethatinfact,theannualincidenceofCHDdeathamongexercisersis5/105andamongnon-exercisersit’s10/105.Subjectswithouttelephonesaremorelikelythanphoneownerstobenon-exercisers.Doesnotincludingtheminthesamplerepresentabias?35QuizAnswerIftheno-phonesubjectsdifferonlyintheirexercisepatterns,thenno,thisisnotabias.Westillhaveexercisersandnon-exercisers,andpresumablywillstillfindthesameincidenceratesineachgroup.But,iftheydifferalsointheirotherrisksforCHDdeath,thenthiswouldbeabias.36Answercontinued...Forinstance,theno-phonenon-exercisersmayhaveothermajorriskfactors,likesmoking,obesity,anddiabetes.Losingthemwouldremovesomeoftheriskseenwithnon-exercising–maybenowwewouldfind5/105fortheexercisersand8/105forthenon-exercisers.Exclusioncausesabiasiftheexcludeddifferinboththeexposureandthee.37MethodstoreduceselectionbiasRigorous,butfeasiblerandomsamplingscheme严谨可行的随机抽样方案Cleardefinitionofstudypopulation

清楚定义研究人群Explicitcase/control,

expose/non-exposedefinitions 明确病例/对照,暴露/非暴露的定义Casesandcontrolsfromsamepopulation 病例和对照来自同一人群38MethodstoreduceselectionbiasSelectionofcasesandcontrolswithoutknowingexposurestatus(case-controlstudy)选择病例对照不要知道暴露状态Selectionofexposedandnon-exposedwithoutknowingdiseasestatus(retrospectivecohort)选择暴露与非暴露人群不要知道结局Striveforhighparticipationrate(incentive)尽量提高参与率39Information

bias

信息偏倚40Information

biasSystematicerrorinthemeasurementofinformationonexposureore

在测量暴露或结局时发生的系统误差Differencesinaccuracyofexposuredatabetweencasesandcontrolsofedatabetweendifferentexposuregroups41SourcesofInformationbias

偏倚的来源Respondent应答者,:inabilitytounderstand,recall,articulate;unwillingnesstodiscloseorsocialdesirabilityDatacollector资料收集者:unclearorambiguousquestions,lackofaneutraldemeanor,insufficientlyconscientious,inaccuratetranscription,fraudInstrument测量工具:inaccurateinstrument42SourcesofinformationbiasDatamanagers资料管理者:inaccuratetranscription,mis-reading,miscoding,programmingerrorsDataanalysts资料分析者:variablecodingandprogrammingerrorsDatainterpreters资料解释者:inadequateappreciationofthecharacteristicsofthemeasureoroftherelationsbeingstudied43MaintypesofinformationbiasReportingbias

报告偏倚Recallbias回忆偏倚Biasedreporting偏倚的报告Observerbias

观察者偏倚Datacollectionbias资料收集偏倚Interviewerbias访问者偏倚Biasedfollow-up

偏性随访detectionbias检测偏倚Measurementbias测量偏倚44DefinitionofcommoninformationBias-1Datacollectionbias资料收集偏倚Biasthatresultsfromabstractingcharts,interviewsorsurrogateinterviewsRecallbias回忆偏倚DiseaseoccurrenceenhancesrecallaboutpotentialexposuresDetectionbias检测偏倚Theexposurepromotedmorecarefulevaluationfortheeofinterest45DefinitionofcommoninformationBias-1Interviewerbias访问者偏倚Systematicdifferenceinsoliciting,recording,interpretinginformation.Reportingbias报告偏倚Exposuremaybeunder-reportedbecauseofattitudes,perceptions,orbeliefs46MothersofchildrenwithmalformationswillrememberpastexposuresbetterthanmotherswithhealthychildrenRecall

bias回忆偏倚Casesrememberexposuredifferentlythancontrols

Overestimationof“a”

overestimationofOR47Recall

bias回忆偏倚子女患风湿性关节炎与父母患病关联的病例对照研究风湿性关节炎风湿性关节炎父母风湿性关节炎子女病例普通对照OR子女病例同胞对照OR无31111.011201.0一方10745.023172.5双方61613.9633.6（SchullandCobb,1969）48InvestigatormayprobelisteriosiscasesaboutconsumptionofsoftcheeseInterviewer

bias访问者偏倚Investigatoraskscasesandcontrolsdifferentlyaboutexposure

Overestimationof“a”

overestimationofOR49Biased

follow-up偏性随访UnexposedarelessdiagnosedfordiseasethanexposedExampleCohortstudytoinvestigateriskfactorsformesothelioma

间皮瘤DifficulthistologicaldiagnosisHistologistmorelikelytodiagnosespecimenasmesotheliomaifasbestos(石棉)exposurekown50Impactofinformationbias:

MisclassificationMeasurementerrorleadstoassigningwrongexposureorecategory51Impactofinformationbias:

MisclassificationNon-differential无差异错误分类（错分）ErrorinassessingexposureordiseaseissimilarbetweenstudygroupsMeasureofeffecttendstoward1Differential差异错分Errorinassessingexposure(ordisease)differsindifferentstudygroupsMayincreaseordecreasemeasureofeffect52HypotheticalCase-Controlstudy60404060DEˉEDˉOR=60*60/40*40=2.2510010048325268DEˉEDˉ100100PercentExposureMisclassification:20%20%OR=48*64/36*52=1.96OR

Differentialmisclassification53DifferentialmisclassificationHypotheticalCase-Controlstudy60404060DEˉEDˉOR=60*60/40*40=2.2510010057324368DEˉEDˉ100100PercentExposureMisclassification:5%20%OR=48*64/36*52=2.7454Techniquestoreduceinformationbias(1)StandardizemeasurementinstrumentsAdministerinstrumentsequallytocases/controlsorexposed/unexposedUseobjectiveparametersifpossibleUsemultiplesourcesofinformationQuestionnairesDirectmeasurementsRegistriesCaserecords55Techniquestoreduceinformationbias(2)UsemultiplecontrolsUsere-classifiedsubjectstocheckforbiasUsememoryaidsandvalidateexposuresProvidestandardizedtrainingsessionsandprotocols56Techniquestoreduceinformationbias(3)Blinding:Blindparticipantsastostudygoalsandparticipants’classificationstatusBlindresearchersastosubjects’studystatusTrytoensurethatquestionareclearlyunderstoodthroughcarefulwordingandpretesting57Confounding混杂58ConfoundingConfoundingisadistortioninanassociationbetweenastudyexposureanddiseasebroughtaboutbytheinfluenceofextraneousfactors

混杂是由于外来因素的影响导致的暴露与结局联系的扭曲。Latin:confundere–“tomixtogether”

59ConfoundingConfounders混杂因素:extraneousfactorthatbiasestheassociationweareinterestedinarecalledconfounders.混杂因素：扭曲暴露与结局之间联系的外来因素60Confounding暴露因素混杂因素结局？混杂因素特征图（SzkloM&NietoFJ,2007）61混杂因素特征混杂因子必须同疾病有关联（作为病因或病因标志物，但不是疾病的结果），且该关联独立于暴露因素；混杂因子必须同暴露有关联；混杂因子既不能是暴露的效应，也不能是疾病结果，尤其不能是暴露与疾病之间的中间变量。6262Example1:Case-control:OC–breastCa;Covariate:SmokingSocialstatusOCUsers

NonusersORDNon-DDNon-DLow2550751501Middle505050501High1204030101Total1951401552101.89ConfoundingoccurredbecausesmokingispositivelyassociatedwithOCandbreastCa63常见混杂因素表现形式年龄分布地区死亡a？c孕妇年龄产次新生儿畸形？社会经济地位其他饮食、生活方式因素维生素C摄入量结肠癌？d总体健康状况性功能死亡？b64Avariablecannotbeaconfounderifitisastepinthecausalchainorpathway.ExampleModeratealcoholconsumption

高脂高热能饮食肥胖TC

TG

LDLHDL

FG

Insulin

冠心病糖尿病高血压低体力活动65Question?

Whichvariablesarepotentialconfounders?Howdoyouknowifavariableisaconfounderinyourdataornot?

Usually,riskfactorsfordisease.

Comparecrudeandadjustedmeasuresofassociation.Iftheydifferappreciably,theansweris“yes.”66ControlofconfoundingDesignstrategiesRandomizationRestrictionMatchingAnalysisstrategiesStandardizationStratificationMultivariateanalyses67

PartIII:

Validity68ValidityDefinition:thedegreetowhichameasurementorstudyreachesacorrectconclusion.Types:internalvsexternalvalidity69StudyValidityInternalvalidityThedegreetowhichtheobservedresultsofthestudyaretrue.Inferencesarecorrectregardingthepar