流病性與偏倚預(yù)防

1Bias&Validity

inEpidemiologicalResearch

流行病學研究中的偏倚與真實性陳裕明教授醫(yī)學統(tǒng)計與流行病學系Tel:873306052MaincontentsMeasurementError測量誤差RandomerrorSystemicerror(Bias)Bias偏倚：sources,commonbias,andcontrolmethods來源、常見偏倚、控制方法Selectionbias選擇偏倚Informationbias信息偏倚Confoundingbias混雜偏倚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

隨機誤差減弱關(guān)聯(lián)強度Physiologicalvariables********r=0.98r=0.6512Randomerror隨機誤差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.)

在設(shè)計、實施、分析、結(jié)果解釋、發(fā)表或評閱過程中，能夠?qū)е陆Y(jié)論系統(tǒng)地偏離真實值的任何趨勢17Question?Canyoucontrolorreducebiasbyincreasingsamplesize?18Errorsinepidemiologicalstudies誤差隨機誤差系統(tǒng)誤差（偏倚）樣本量19Classificationofbias分類Selectionbias

選擇偏倚–differentialaccesstothestudypopulationInformationbias

信息偏倚–inaccuracyinmeasurementorclassificationConfoundingbias

混雜偏倚–unfaircomparison20SELECTIONBIAS-definitionSELECTIONBIAS選擇偏倚:

Errorsintheprocessofidentifyingthestudypopulation,whichcausesthestudysampledoesnotrepresentthetargetpopulation.在確定研究人群時出現(xiàn)的系統(tǒng)誤差，使得研究樣本不能代表總體21SamplingandrepresentativenessSampleTargetPopulationSamplingPopulationTargetPopulationSamplingPopulationSample22SourcesofSelection

bias

選擇性偏倚的來源1.Samplingbias抽樣偏倚--thedegreetowhichthemeasuredsubjectsarenotrepresentativeofthepopulation,isdueto:

ConvenienceSample方便樣本Violatedrandomsamplingscheme偏離隨機抽樣方案HaphazardSample偶然樣本23SourcesofSelection

bias

選擇性偏倚的來源2.Participationbias參加者偏倚–duetoparticipantsSelf-selection(volunteerism)

自我選擇偏倚Healthy(ordiseased)peoplemayseekoutparticipationinthestudyNon-response,refusal無應(yīng)答偏倚Response,orlackofit,dependsonexposureHealthyworkereffect

健康工人效應(yīng)Differentiallosstofollow-up

選擇性失訪Biasduetodifferencesincompletenessoffollow-upbetweencomparisongroups24SourcesofSelection

bias

選擇性偏倚的來源3.Ascertainmentbias確認偏倚--systematicerrorduetoadifferenceincharacteristicsbetweenwhochoosetoparticipateinastudyandwhosewhodonot.

Prevalence-incidencebias

現(xiàn)患與新發(fā)病例偏差Prevalentcaseislikelytobemild,andsurvivelongerReferralbias

轉(zhuǎn)診偏倚Sickerpatientsarereferredtomajorhealthcenters25SourcesofSelection

bias

選擇性偏倚的來源3.Ascertainmentbias確認偏倚Diagnosticbias診斷偏倚DiagnosisofeassociatedwithexposureAdmissionratebias(Berkson’sbias)入院偏差Hospitalizationratesdifferforbydiseaseandpresence/absenceoftheexposureofinterestLeadtimebias領(lǐng)先時間偏倚26Sampling

bias抽樣偏倚Howrepresentativearehospitalisedtraumapatientsofthepopulationwhichgaverisetothecases?OR=627Sampling

bias抽樣偏倚OR=6OR=3628Diagnostic

bias診斷偏倚OralContraceptiveuse

breakthroughbleeding

increasedchanceofdetectinguterinecancerDiagnosticapproachrelatedtoknowingexposurestatus

Overestimationof“a”

overestimationofOR29Non-responsebias無應(yīng)答偏倚Controlschosenamongwomenattheirhomes:13000homescontacted

1060controlsUnderestimationof“b”

overerestimationofORControlsmainlyhousewiveswithlowerchanceofhavingtestthanwomengainfullyemployedPapersmearHadtestDidn’thavetest30Healthyworkereffect

健康工人效應(yīng)31Healthyworkereffect32Admissionbias

HCV與肝癌的meta分析結(jié)果病例-對照來源研究數(shù)目OR(95%CI)醫(yī)院—醫(yī)院87.80(5.04—12.06)醫(yī)院—社區(qū)76.70(3.28—13.68)社區(qū)—社區(qū)93.34(2.44—4.56)（吳江南

等.中華肝臟病雜志

2007）33Losstofollow-upbias

失訪偏倚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嚴謹可行的隨機抽樣方案Cleardefinitionofstudypopulation

清楚定義研究人群Explicitcase/control,

expose/non-exposedefinitions 明確病例/對照,暴露/非暴露的定義Casesandcontrolsfromsamepopulation 病例和對照來自同一人群38MethodstoreduceselectionbiasSelectionofcasesandcontrolswithoutknowingexposurestatus(case-controlstudy)選擇病例對照不要知道暴露狀態(tài)Selectionofexposedandnon-exposedwithoutknowingdiseasestatus(retrospectivecohort)選擇暴露與非暴露人群不要知道結(jié)局Striveforhighparticipationrate(incentive)盡量提高參與率39Information

bias

信息偏倚40Information

biasSystematicerrorinthemeasurementofinformationonexposureore

在測量暴露或結(jié)局時發(fā)生的系統(tǒng)誤差Differencesinaccuracyofexposuredatabetweencasesandcontrolsofedatabetweendifferentexposuregroups41SourcesofInformationbias

偏倚的來源Respondent應(yīng)答者,:inabilitytounderstand,recall,articulate;unwillingnesstodiscloseorsocialdesirabilityDatacollector資料收集者:unclearorambiguousquestions,lackofaneutraldemeanor,insufficientlyconscientious,inaccuratetranscription,fraudInstrument測量工具:inaccurateinstrument42SourcesofinformationbiasDatamanagers資料管理者:inaccuratetranscription,mis-reading,miscoding,programmingerrorsDataanalysts資料分析者:variablecodingandprogrammingerrorsDatainterpreters資料解釋者:inadequateappreciationofthecharacteristicsofthemeasureoroftherelationsbeingstudied43MaintypesofinformationbiasReportingbias

報告偏倚Recallbias回憶偏倚Biasedreporting偏倚的報告Observerbias

觀察者偏倚Datacollectionbias資料收集偏倚Interviewerbias訪問者偏倚Biasedfollow-up

偏性隨訪detectionbias檢測偏倚Measurementbias測量偏倚44DefinitionofcommoninformationBias-1Datacollectionbias資料收集偏倚Biasthatresultsfromabstractingcharts,interviewsorsurrogateinterviewsRecallbias回憶偏倚DiseaseoccurrenceenhancesrecallaboutpotentialexposuresDetectionbias檢測偏倚Theexposurepromotedmorecarefulevaluationfortheeofinterest45DefinitionofcommoninformationBias-1Interviewerbias訪問者偏倚Systematicdifferenceinsoliciting,recording,interpretinginformation.Reportingbias報告偏倚Exposuremaybeunder-reportedbecauseofattitudes,perceptions,orbeliefs46MothersofchildrenwithmalformationswillrememberpastexposuresbetterthanmotherswithhealthychildrenRecall

bias回憶偏倚Casesrememberexposuredifferentlythancontrols

Overestimationof“a”

overestimationofOR47Recall

bias回憶偏倚子女患風濕性關(guān)節(jié)炎與父母患病關(guān)聯(lián)的病例對照研究風濕性關(guān)節(jié)炎風濕性關(guān)節(jié)炎父母風濕性關(guān)節(jié)炎子女病例普通對照OR子女病例同胞對照OR無31111.011201.0一方10745.023172.5雙方61613.9633.6（SchullandCobb,1969）48InvestigatormayprobelisteriosiscasesaboutconsumptionofsoftcheeseInterviewer

bias訪問者偏倚Investigatoraskscasesandcontrolsdifferentlyaboutexposure

Overestimationof“a”

overestimationofOR49Biased

follow-up偏性隨訪UnexposedarelessdiagnosedfordiseasethanexposedExampleCohortstudytoinvestigateriskfactorsformesothelioma

間皮瘤DifficulthistologicaldiagnosisHistologistmorelikelytodiagnosespecimenasmesotheliomaifasbestos(石棉)exposurekown50Impactofinformationbias:

MisclassificationMeasurementerrorleadstoassigningwrongexposureorecategory51Impactofinformationbias:

MisclassificationNon-differential無差異錯誤分類（錯分）ErrorinassessingexposureordiseaseissimilarbetweenstudygroupsMeasureofeffecttendstoward1Differential差異錯分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混雜58ConfoundingConfoundingisadistortioninanassociationbetweenastudyexposureanddiseasebroughtaboutbytheinfluenceofextraneousfactors

混雜是由于外來因素的影響導致的暴露與結(jié)局聯(lián)系的扭曲。Latin:confundere–“tomixtogether”

59ConfoundingConfounders混雜因素:extraneousfactorthatbiasestheassociationweareinterestedinarecalledconfounders.混雜因素：扭曲暴露與結(jié)局之間聯(lián)系的外來因素60Confounding暴露因素混雜因素結(jié)局？混雜因素特征圖（SzkloM&NietoFJ,2007）61混雜因素特征混雜因子必須同疾病有關(guān)聯(lián)（作為病因或病因標志物，但不是疾病的結(jié)果），且該關(guān)聯(lián)獨立于暴露因素；混雜因子必須同暴露有關(guān)聯(lián)；混雜因子既不能是暴露的效應(yīng)，也不能是疾病結(jié)果，尤其不能是暴露與疾病之間的中間變量。6262Example1:Case-control:OC–breastCa;Covariate:SmokingSocialstatusOCUsers

NonusersORDNon-DDNon-DLow2550751501Middle505050501High1204030101Total1951401552101.89ConfoundingoccurredbecausesmokingispositivelyassociatedwithOCandbreastCa63常見混雜因素表現(xiàn)形式年齡分布地區(qū)死亡a？c孕婦年齡產(chǎn)次新生兒畸形？社會經(jīng)濟地位其他飲食、生活方式因素維生素C攝入量結(jié)腸癌？d總體健康狀況性功能死亡？b64Avariablecannotbeaconfounderifitisastepinthecausalchainorpathway.ExampleModeratealcoholconsumption

高脂高熱能飲食肥胖TC

TG

LDLHDL

FG

Insulin

冠心病糖尿病高血壓低體力活動65Question?

Whichvariablesarepotentialconfounders?Howdoyouknowifavariableisaconfounderinyourdataornot?

Usually,riskfactorsfordisease.

Comparecrudeandadjustedmeasuresofassociation.Iftheydifferappreciably,theansweris“yes.”66ControlofconfoundingDesignstrategiesRandomizationRestrictionMatchingAnalysisstrategiesStandardizationStratificationMultivariateanalyses67

PartIII:

Validity68ValidityDefinition:thedegreetowhichameasurementorstudyreachesacorrectconclusion.Types:internalvsexternalvalidity69StudyValidityInternalvalidityThedegreetowhichtheobservedresultsofthestudyaretrue.Inferencesarecorrectregardingthepar