流行病学队列研究

队列研究CohortStudy,队列研究Cohortstudy,IncidencestudiesLongitudinalstudiesFollow-upstudiesProspectivestudies,发病率研究纵向研究随访研究前瞻性研究,OutlineExampleDesignandimplementMeasuresofRiskDatasortandanalysisBiasandControlAdvantage，disadvantage,概述实例研究设计与实施资料的整理与分析偏倚及控制优缺点,队列研究Cohortstudy,队列研究简史定义与目的原理与类型,HistoryofcohortstudyDefinitionandPurposePrincipleandTypes,历史History,起源OriginsGraunt(17thcentury)usedcross-sectionalmortalitydatatoreconstructlifehistoryusinglife-tablemethodsGraunt(17世纪)用横断面死亡资料，用寿命表方法构建生命史Farr(19thcentury)advancedtheuseoflife-tablemethodsaanindicatorofpopulationhealthFarr（19世纪）将寿命表方法发展为人群健康的指标Insuranceindustrystudy18701899保险业研究18701899,Tuberculosis(20thcentury)结核（20世纪）WHFrostperformedthefirstretrospectivecohortstudyinacohortof132homeswithtuberculosisWHFrost在有结核的132个家庭的队列开展第一个回顾性队列研究Usedperson-yearstoestimateattackrates用人年来估计罹患率,历史History,WHFrostinitiatedprospectivecohortstudyoftuberculosisinWilliamsoncounty,TennesseeWHFrost在德州启动有关结核的前瞻性队列研究,历史History,Framinghamstudyofcardiovasculardisease,1948Japaneseatomicbombsurvivors,1946Britishphysicianstudy,1950sColoradoPlateauuraniumminers,1950s,Aniline-dyeoccupationalcohort,1954Asbestosexposureandlungcancermortality1965,Retrospectivecohortstudies,Prospectivecohortstudies,NursesHealthstudy,1976topresentBritishphysicianstudyMulti-centerAIDSCohortStudyMACS,19841999,CurrentStudies,Anepidemiologicdesigninwhichtheincidenceofadisease(orcondition)iscomparedamongexposedandunexposedindividuals是比较暴露与非暴力人群发病率的一种流行病学设计,定义Whatthecohortstudy,CohortStudy,Beginwithdisease-freepatientsClassifypatientsasexposed/unexposedRecordoutcomesinbothgroupsCompareoutcomesusingrelativerisk,从没有疾病人群开始将研究对象分为暴露与非暴露组记录两组结局用相对危险度比较结果,CohortStudy,KeyPoint:Presenceorabsenceofriskfactorisdeterminedbeforeoutcomeoccurs.,Whatisacohort?队列,Cohort-Latinwordforoneofthe10divisionsofaRomanlegionAgroupofindividualssharingsameexperiencefollowedupforaspecifiedperiodoftimeExamplesbirthcohortoccupationalcohortchemicalplantworkers,队列拉丁语原意是指古罗马军团中的一个分队一组人群有共同经历随访一特定时间例如出生队列职业队列,暴露指接触过某种物质、具备某种特征或处于某种状态。危险因素泛指能引起某特定不良结局,或使其发生的概率增加的因子，包括个人行为、生活方式、环境和遗传等多方面的因素。,ExposurecontactsomematerialofbeinginsomestatusRiskfactorisavariableassociatedwithanincreasedriskofdiseaseorinfection.Includingbehavior,lifestyle,environmentalandgeneticfactorandsoon.,目的Purpose,Describeincidenceofoutcomesovertime,naturalhistoryofdiseaseDeterminecausalrelationshipsbetweenthoseoutcomesandexposures(riskorprognostic)factors.,描述随着时间变化结果的发生率，疾病自然史确定结果与暴露（危险或预后）因素间的因果关系,目的Purpose,DetermineaprognosisEvaluatenewtherapiesanddiagnosticsEvaluatescreeningprocedures,确定预后评价新的治疗与诊断方法评价筛检过程,FraminghamstudyofcardiovasculardiseaseIndividuals3062yearsoldincommunityatriskfordiseaseFramingham,MA,1948topresent,Examplesofcohortstudy,GoaltoelucidatethenaturalhistoryofHIV/AIDS5000gaymen,volunteers5citiesinUS1984ExtensiveevaluationsQuestionnairePhysicalexaminationLaboratorytesting,Multi-CenteredAIDSCohortStudy,Source:partiallyadaptedfromWHO,1993,R1,R0,A1,A0,IncidencerateamongexposedIR1=A1(no.exposedcases)/R1(totalperson-timeexposed)IncidencerateamongunexposedIR0=A0(no.unexposedcases)/R0(totalperson-timeunexposed)Incidencerateratio(exposedvs.unexposed)=IR1/IR0=(A1/A0)/(R1/R0),PrincipleofaCohortStudy,Characteristics特点,ObservationalCategorybyexposureNeedcontrolProspective,观察性研究根据暴露分组需要对照前瞻性,类型Types,BasedonrecruittimeofstudysubjectProspectivestudyv.s.RetrospectiveStudyBasedonthetypeofcohortFixedcohortv.s.Dynamiccohort,依据研究对象召集的时间前瞻性研究VS回顾性依据队列的类型固定队列VS动态队列,类型Types,Combinedwithcase-controlstudyNestedcase-controlstudycase-cohortstudy,与病例对照研究结合巢式病例对照研究病例队列研究,Prospectivecohortstudy,time,Exposure,Studystarts,Diseaseoccurrence,依据研究对象召集的时间分类,Prospectivecohortstudy,IdentifycohortinthepresentDetermineexposurestatusorpossibleexplanatory/prognosticfactorsInthepresentorinthefuture,现在确定队列确定暴露状态或可能暴露/预后因素在现在或将来,依据研究对象召集的时间分类,Follow-uptoidentifyoutcomeQuestioncanbeincidenceorriskofoutcomeQuestioncanbewhatfactorsassociatedwithoutcomeAscertainmentofoutcomedoneinfuture,随访确定结局可以是发病率或结局的风险可以是什么因素与结局有关确认将来发生的结局,依据研究对象召集的时间分类,Prospectivecohortstudy,ProspectiveCohortExample,Question:Arenon-steroidalanti-inflammatorydrugsariskfactorforGIbleeds?,问题:非甾体固醇抗炎药是否为胃肠道出血的危险因素?,Example,Identifycohort:newdiagnosesofrheumatoidarthritisfromOctober17,2002toOctober17,2003Determineexposurestatus:identifypatientsprescribedNSAIDsandthosewhoarenot,确定队列:2002.10-2003.10诊断的类风湿关节炎患者确定暴露状态:确定开与未开NSAIDs药物处方的病人,Determineoutcomes:follow-upallpatientsfor1yearidentifyhowmanyGIbleedsthereareineachsub-cohortorexposuregroup,确定结局:随访所有的病人1年确定在暴露及非暴露组出现多少胃肠道出血的病人,Example,ProspectiveCohortStudies,Advantagetimesequencestrengthensinferenceaboutcausemoreaccuratemeasurementofriskfactors(donotneedtoreconstructpastexposures)morecompletemeasurementofconfounding,优点因果推断的时间顺序强危险因素测量跟准确(不需要够姜过去的暴露)更准确的测量混杂因素,Disadvantage:expensiveandtimeconsuming(inceptionandfollow-up)largenumbersrequiredtostudyrareoutcomesdifficulttostudychronicdiseaseswithlonglatency,缺点:昂贵,费时间(启动及随访)研究罕见结局是需大样本难与研究慢性潜伏期长的疾病,ProspectiveCohortStudies,前瞻性队列研究应用条件,明确地检验假设所研究疾病的发生率较高,一般不低于5明确规定暴露因素和结局变量可靠的测量手段足够的观察人群和暴露情况能完成随访的人群足够的人、财、物力,Retrospectivecohortstudy,time,Exposure,Studystarts,Diseaseoccurrence,Historical(Retrospective)CohortStudy,IdentifycohortinthepastE.g.,throughrecordsoradministrativedatabasesDetermineexposureorprognosticfactorsinthepastAgain,recordsordatabasesIdentifyoutcomeOutcomecanbeidentifiedinpastorpresentOutcomemustbeafterprevioustwosteps,HistoricalCohortExample,Question:Arenon-steroidalanti-inflammatorydrugsariskfactorforGIbleeds?,问题:非甾体固醇抗炎药是否为胃肠道出血的危险因素?,HistoricalCohortExample,Identifycohorte.g.,peoplediagnosedwithrheumatoidarthritisbetweenJanuaryandDecember1992Determineexposurestatus.WhichofthesepatientswereprescribedNSAIDs?Determineoutcome.Didpatientdevelopkidneydiseaseduringthefiveyearsafterinceptionintocohort?(follow-uplasteduntilDecember1997),Historical(Retrospective)CohortStudies,Advantage:cohorteasiertoassemble(inceptionperiodinpast)baselinemeasurementsalreadyavailablefollow-upperiodalreadytakenplacelesscostlyandtime-consuming,优点:队列易召集(在过去起始)基线测量已经可以利用已经随访耗费少,省时间,Disadvantage:nocontroloverthequalityofpastmeasurementsincompletedatasetscontrolforconfoundingmaybeincomplete,缺点无法控制过去暴露的质量资料不全混杂因素控制不全,Historical(Retrospective)CohortStudies,MixedCohortExample,Question:Arenon-steroidalanti-inflammatorydrugsariskfactorforGIbleeds?Identifycohort(patientswhowerediagnosedwithrheumatoidarthritisbetweenOctober2000andSeptember2001)WhichofthesepatientsareprescribedNSAIDs?HowmanyofthesepatientswillexperienceGIbleedsduringnextfiveyears?,FixedCohort,Start,End,CohortStudyDesignTypes,FixedCohortAgroupofindividualsrecruitedandenrolledatauniformpointinthenaturalhistoryofadiseaseorbysomedefiningeventCohortdoesnottakeonnewmembersafteritisassembledExamplesPatientsadmittedtotheERwithacuteMISurvivorsofHiroshimabombingsChildrenborntoHIV-infectedmothers,Types,DynamiccohortAgroupofindividualsrecruitedandenrolledthroughamechanismthatallowsforinandoutmigrationofpeopleDefinedbycharacteristicotherthandisease,e.g.,geographiclocation,administrativeunitDynamicpopulationExamplesFraminghamStudyKaiserPermanente,DynamicCohort,Start,End,二硫化碳长期低剂量的暴露与冠心病的关系,第二节实例研究,二硫化碳（CS2）,神经系统毒物，抑制酶的活性，影响脂蛋白代谢，造成心血管疾病长期接触低浓度CS2可引起慢性中毒和动脉粥样硬化短时间接触高浓度的CS2蒸气可急性中毒,研究因素长期低剂量的CS2暴露定义在有CS2暴露但不至引起急性中毒的车间工作5年,20世纪60年代芬兰职业卫生研究所Hernberg和Tolonen教授做的前瞻性队列研究,二、确定研究结局,心肌梗死血压变化心电图的改变心绞痛发作,三、确定研究现场和人群,暴露组19421967年某粘纤厂25至64岁，343名男性工人有5年以上CS2暴露史对照组年龄3岁出生地区相同工种的体力消耗相当在同一城市的造纸厂随机选择的343名男性工人,四、资料收集,查阅档案记录用药情况、既往车间CS2的浓度等询问姓名、性别、年龄、工种及工作年限、吸烟、业余时间的体力活动情况实验室检查血糖、血脂、血清胆固醇水平、血压、心电图、心脏大小、体重及车间CS2浓度的动态变化,五、资料分析,表4-1暴露组和对照组的心肌梗死发生率及RR,CS2暴露组发生心肌梗死的RR为3.57，两组致死性心肌梗死发生率和总的心肌梗死发生率差异有显著性,CS2在不同临床类型冠心病的发生中作用程度不同,表4-2CS2与不同临床类型冠心病的RR和AR比较,六、结论,长期低剂量与冠心病发病和死亡存在因果关系CS2所致的冠心病，以致死性心肌梗死为主措施芬兰当局已于1972年把CS2的车间最高容许浓度从20ppm降至10ppm,IdentifyexposuresIdefineoutcomesIdentifystudyfieldandpopulationSamplesizeDatacollectioanandFollow-upbothgroupsQualitycontrol,确定研究因素确定研究结局确定研究现场与研究人群确定样本量资料的收集与随访质量控制,第三节设计和实施Designandimplement,IdentifyExposure确定研究因素,MainexposureBasedondescriptivestudyandcase-controlstudyFactormayeffectoutcomeconfounder,demographycharacteristic,主要暴露因素在描述性研究和病例对照研究的基础上确定可能影响结局的因素混杂因素人口学特征等,MeasuringExposure,Content-Natureoftheexposure;biologicmechanismsQualityContinuous-e.g.,serumcholesterolPeriodic-e.g.,cigarettes,sexualcontactsSingular-e.g.,nuclearexposureQuantityContinuousandperiodicexposuresmustbequantifiedDose-responserelationship,MeasuringExposure,MeasurementsInterviewMedicalexamBloodtestsorotherspecimens,Biomarkers,OtherlaboratorytestsRecords,medicalrecordsSamplestorageEnvironmentsurveillancedata,MeasuringExposure,MeasuringexposureisoneofthefundamentalactivitiesofacohortstudyExposuremeasurementmustbecomparableforallmembersofthecohortCarefullydefinedinadvanceofstudySpecificattentionshouldbegiventotheaccuracyandprecisionofproposedmeasurementsPilotstudiesoftenneeded,OutcomeDefinition,Expectedresultsoffollow-upPrimaryoutcome-themaineventthatwillberelatedtotheexposureFailure-timeoutcomesDeathDiseaseoccurrenceRepeatedmeasures,OutcomeDefinition,Secondaryoutcomes-othereventsthatareofinterestandmaycorroboratethefindingsofthemainoutcomeUsingexistedinternationalstandard,ExamplesofOutcomesorDiseases,LungCancerHeartDiseaseMotorvehicleinjuryHIVinfectionDiabetesDiphtheria,DefineConfounding,DefineconfoundinginthestudyControlconfoundingindesigndatacollectiondataanalysis,StudyPopulation,DefinePopulationatRiskusinginclusioncriteriaIndividualswithoutcomeofinterestattimeofscreeningandenrollmentarenoteligibleforstudy,Selectionofexposedpopulation,Thegeneralpopulation(i.e.,theoutcomeofinteresthasahighincidencerate)Specialexposuregroups(e.g.,smokers,X-rayworkersSpecialoccupationalexposuregroup(uraniumminersorasbestosworkers.Cooperation,goodrecord,regu.Exam,easyfollow-up),Selectionofexposedpopulation,Specialresourcegroups(e.g.,alumni,physicians,nurses,insured)Geographicallyorfacility-definedgroups(e.g.,ThreeMileIsland,hospitalswithspecializedmaternitycare),SelectionofNonexposedgroup,GeneralpopulationAccordingtotheexposurestatusgroupcanbedividedintosubgroups(exposure+andexposure-),SpecificcomparisongroupExample:foreffectofradiationifradiologistscohortgroupcomparisongroupmaybeinternalizes.Textileworkersforasbestosworkers,SelectionofNonexposedgroup,StudyPopulationsExamples,FraminghamstudyofcardiovasculardiseaseIndividuals3062yearsoldincommunityatriskfordiseaseFramingham,MA,1948topresent,FraminghamStudyCohortAssembly,StudyPopulationsMACS,Multi-CenteredAIDSCohortStudyGoaltoelucidatethenaturalhistoryofHIV/AIDS5000gaymen,volunteers5citiesinUS19841999ExtensiveevaluationsQuestionnairePhysicalexaminationLaboratorytestingRepository,SampleSize,IncidenceingeneralpopulationIncidenceinexposedpopulationSignificantlevelPower(1-)EstimatedofRR,Follow-up,PurposeoffollowingupTracksubjectsinbothexposedandnon-exposedgroupDefineoutcomeeventsFurthercollectdatainexposuresandconfounding,Follow-up,Completenessandnon-participation90%ruleofthumbAllsubjectsmusthaveanequallikelihoodfordetectingtheoutcomeDiseaseascertainmentmustbecomparablebetweentheexposedandunexposedsubjectsNumberofvisitsReasonsforadditionalevaluations,Follow-upmechanismsActivePassive,Follow-up,Follow-up,PassiveSurveillanceHospitalsDiseaseRegistriesClinicsorphysicianofficesSurveillancesystems,e.g.,NationalDeathIndex,CDCreportableconditions,ActivesurveillanceSystematicevaluationsforoutcomeofinterestRegulartimeintervalsInallstudysubjectsRegardlessofactiveorpassivesurveillance,thepersonsevaluatingsubjectsmustbeblindedtoexposurestatus,Follow-up,Followup,WhentostartfollowNeedtohavetimeaftertheexposureforthediseasetodevelop.Theinductionperiod+incubation,Followupperiod,HowlongtofollowupIndividualsfollowuptooutcome(disease,death,syndrome)CohortsfollowupexpectedresultsFollowupintervaldependontheincidence,latency.,THEISSUEOFFOLLOW-UP,Somecohort(retrospectiveorprospective)studiesextendoverlongperiodsoftime.Difficulttotrackindividualsandevents.,Ifalargeproportionofparticipantsarelosttofollow-upthevalidityofthestudymaybequestionfollow-upbiasIflosstofollow-upisdifferentialbetweencohortgroups,and/orforreasonsrelatedtoboththeexposureandoutcome,thevalidityofthestudymaybeinquestion.,THEISSUEOFFOLLOW-UP,调查员选择调查员培训制定调查员手册监督,ChoseofinvestigatorTrainingofinvestigatorFormulationbrochureforinvestigatorMonitor,质量控制QualityInsurance,第三节设计与实施,BasicmodelfordatasortingPersontimecalculateRatecalculateEffectestimation,第四节资料的整理和分析Datasortingandanalysis,资料的基本整理模式人时的计算率的计算效应估计,一、资料的基本整理模式Basicmodelofdatasorting,暴露组发病率=a/n1Incidenceofexposedgroup非暴露组发病率=c/n0Incidenceofnon-exposed,表4-3队列研究资料归纳整理表Datasorttableforcohortstudy,二、人时的计算Calculateforperson-time,精确法近似法寿命表法,ExactmethodApproximationmethodLifeexpectancymethod,三、率的计算calculateofrate,累积发病率发病密度标化死亡比标化比例死亡比,CumulativeincidenceIncidencedensityStandardizedmortalityratio,SMRStandardizedproportionalmortalityratio,SPMR,变化范围0-1range:0-1适用条件样本大suitablefor:largesample人口稳定stablepopulation整齐的资料evendata报告时必须注明时间长短Notethetimeperiodwhenreport,累积发病率(cumulativeincidence,CI),CI=,观察期内发病（或死亡）Numberofnewcase(ordeath),观察开始时的人口数Numberofpersonsenteringobservation,发病密度(incidencedensity),变化范围0-range:0-适用条件观察时间长Suitablefor:longobservation人口不稳定Unstablepopulation存在失访withlostfollowup资料不很整齐datanoteven,ID=,观察期内发病（或死亡）人数Numberofnew(death)cases,观察人时Observedpersontime,标化死亡比(standardizedmortalityratio,SMR),变化范围0-range：0-适用条件结局事件的发生率低suitablefor：lowincidenceofoutcome不宜直接计算率时notsuitablecalculateratedirectly,SMR=,研究人群观察期内发病（或死亡）人数Numberofnew(death)casesinstudiedpopulation,标准人口预期发病（或死亡）人数Numberofexpected(death)casesinstandardpopulation,全人口某病的发病（死亡）率观察人口数Newcases(death)ofadiseaseintotalpopulationXNumberofobservedpersons,预期发病（死亡）数的计算：Expectedcases(death):,SMR的意义被研究人群发生（死于）某病的危险性是标准人群的多少倍Thetimesofriskofadisease(ordeath)instudypopulationoverstandardpopulationSMR=1研究人群某病发病（死亡）危险=标准人群IftheSMRisquotedasaratioandisequalto1.0,thenthismeansthenumberofobserveddeathsequalsthatofexpectedcases.,SMR1研究人群某病发病（死亡）危险标准人群，是标准人群的SMR倍Ifhigherthan1.0,thenthereisahighernumberofdeathsthanisexpected,istheSMRtimesofstandardpopulationSMR1研究人群某病发病（死亡）危险标准人群,标化比例死亡比（standardizedproportionalmortalityratio,SPMR）,变化范围0适用条件不能得到历年人口资料仅有死亡人数、原因、日期和年龄,SPMR=,ActuallydeathNo.,ExpecteddeathNo.,Range0Suitablefor:noyearlypopulationdata,onlythereisdeathNo.,cause,dateandageofdeath,预期死亡数计算（ExpecteddeathNo）：,率的显著性检验significancetestofrate,U检验Utest直接概率法Probablenumbermethod二项分布检验Binomialdistribution泊松分布检验Poissondistribution2检验2test计分检验scoretest,四、效应的估计TheEstimationofEffect,RelativeRisk(RR)AttributableRisk(AR)ARPercent(AR%)PopulationAR(PAR)PARPercent(PAR%)Doseresponserelationship,相对危险度归因危险度归因危险度百分比人群归因危险度人群归因危险度百分比剂量反应关系,相对危险度（RelativeRiskRR）,意义implicationE发病或死亡的危险是的多少倍thetimesoftheprobabilityofthediseaseordeathoccurringintheexposedgroupversusanon-exposedgroup.RR值暴露的效应暴露与结局关联强度RReffectofexposedtheassociationbetweenexposureandoutcome,暴露组率Rateinexposed,非暴露组率Rateinnonexposed,意义implication吸烟者因肺癌死亡的危险是非吸烟者的10.7倍Smokerswouldbe10.7timesaslikelyasnon-smokerstodieoflungcancer吸烟者因心血管疾病死亡的危险是非吸烟者的1.7Smokerswouldbe1.7timesaslikelyasnon-smokerstodevelopcardiovasculardisease,Cardiovasculardisease,170.32,1.7,表4-4吸烟者与非吸烟者死于不同疾病的RRRRofdeathfromdifferentdiseasesinsmokerandnonsmoker,Lungcancer,Disease,296.75,50.12,Smoker,4.69,Non-smoker,10.7,RR,（1/10万人年）,表4-5RR与关联强度RRandstrengthenofassociation,很强verystrengthen,10,0.1,强Strengthen,3.09.9,0.10.3,中Middle,1.52.9,0.40.6,弱Weak,1.21.4,0.70.8,无Noassociation,1.01.1,0.91.0,关联强度,RR,strengthenofassociation,RR的95%CI,RR95%CI,反自然对数即为RR95%CITheanti-logarithmoflnisRR95%CI,Woolf法,ln,ln,归因危险度(AttributableRisk,AR),意义implicationE与人群比较，所增加的疾病发生数量TheincreasedNo.ofdiseasescomparinganexposedpopulationandanunexposedpopulationAR值暴露因素消除后所减少的疾病数量Eliminatingtheexposure,thereducedNo.ofdiseases,c,a,意义RR吸烟对肺癌的病因学意义较大AR戒烟对心血管疾病的预防作用较大即公共卫生意义较大,表4-6RR与AR的区别ThedifferencebetweenRRandAR,Cardiovasculardisease,Lungcancer,Disease,1.7,10.7,RR,126.43,170.32,296.75,45.43,4.69,50.12,AR,Non-smoker,Smoker,（1/10万人年）,ImplicationRRsmokinghaslargeretiologysignificanceofonlungcancerARstopsmokinghashigherpreventablesignificanceoncardiovasculardiseases,i.e.thepublichealthsignificance,归因危险度百分比AR%（病因分值EtiologicfractionEF）,意义implication:暴露人群中的发病或死亡归因于暴露的部分占全部发病或死亡的百分比Theproportionofthecasesthattheexposurehadplayedacausalroleinitsdevelopment.,RR,人群归因危险度(populationattributablerisk,PAR),意义暴露人群与一般人群比较，所增加的疾病发生率的大小TheincreaseddiseaseintheexposedcomparingwithgeneralpopulationPAR值暴露因素消除后所减少的疾病数量PARthereductioninincidenceaftereliminatetheexposure,PAR=ItI0,It：总人群率rateintotalpopulationIo：非暴露组率rateinNon-exposedpopulation,人群归因危险度百分比PAR%,意义implicationPAR占总人群全部发病（或死亡）的百分比TheproportionofPARincasesor(death)intotalpopulation,或,Pe：总人群的暴露比例proportionofexposedintotalpopulation,剂量反应关系Doseresponserelationship,分析方法列出不同暴露水平下的发病率以最低暴露水平组为对照，计算各暴露水平的RR和危险度差(RD)必要时，应对率的变化作率的趋势性检验,AnalysismethodListtheincidenceofdifferentexposedlevelsCalculatetheRRandARofdifferentexposedlevelsusingthelowestasreferenceCarriedouttendencytestifnecessary,结果,血清胆固醇水平患冠心病的RR说明存在剂量效应关系,选择偏倚失访偏倚信息偏倚混杂偏倚,第五节偏倚及其控制Biasandcontrol,Selectionbiasfollowupbiasinformationbiasconfoundingbias,一、选择偏倚selectionbias,Subjectsaredifferentwithgeneralpopulationortargetedtotalpopulationinsomeimportantaspect,whichresultintheoutcomeofresearchbias.,研究人群在一些重要因素方面与一般人群或待研究的总体人群存在差异，而导致研究结果的偏倚。,产生原因Causes,选择对象的方法不当最初选定参加研究的对象中有人拒绝参加历史性队列研究中部分档案丢失或记录不全志愿者队列研究开始时未能发现早期病人等,UnsuitableSelectionmethodforsubjectTheselectedsubjectedrefusetoparticipateFilelostoruncompletedrecordinhistoricalcohortstudyVolunteercohortUnidentifiedearlypatientincohort,控制Control,预防为主抽样方法正确，严格按规定标准选择对象,PreventionfirstCorrectsamplingmethodSelectsubjectedstrictlybasedcriteria,二、失访偏倚losttofollow-up,Thebiasduetomigration,ordiedofnon-out