实验流行病学研究课件

1,实验流行病学研究ExperimentalEpidemiology,哈尔滨医科大学流行病学教研室Departmentofepidemiology，HarbinMedicalUniversity,2,理论流行病学,流行病学研究方法ResearchMethodofEpidemiology,3,JamesLind(1716-1794)维C缺乏坏血病(1747)VitaminCdeficiency-scurvy,第一节概述Overview,4,EdwardSalk,脊髓灰质炎疫苗(poliomyelitisvaccine)现场试验(1955)美国+加拿大疫苗组(vaccine)安慰奖200,745人，安慰剂组（placebo）201,229人保护率(Protectiverate)：60-90%,ThomasFrancis,Jr,5,一、定义(definition),Patientsorhealthadults)wererandomlydividedintoexperimentgroupandcontrolgroup，interventionwasgiventotheindividualsofexperimentgroup，andtheoutcomesoftwogroupswerefollowedupandcomparedinordertodetermineeffectofintervention.,将研究对象（病人或正常人）随机分配给实验组和对照组，将干预措施给予实验组人群后，随访观察(followup)一段时间并比较两组人群的结局,以便确定干预措施的效果。,6,二、基本原则(basicprinciple),对照的原则control随机的原则randomization盲法的原则blinding重复的原则duplication,7,TheresearchquestioncannotbeansweredbyobservationalstudiesEarlierobservationalstudieshavenotansweredtheresearchquestionExistingknowledgeisnotsufficienttodetermineclinicalorpublichealthpolicyAnexperimentislikelytoprovideanimportantextensionofthisknowledge,Whentochooseanexperimentaldesign?,8,三、基本特征(basiccharacteristic),前瞻前瞻性研究干预施加一种或多种人为干预处理随机研究对象随机分配到比较组对照有平行的或可比的实验组和对照组,ProspectiveInterventionortreatmentRandomallocationParalleledcontrolgroup,9,四、实验流行病学的类型(typesofexperimentalepidemiology),ClinicaltrialFieldtrialorfieldexperimentCommunitytrial.,临床试验现场试验社区试验,10,(一)个体试验(individualtrial),研究对象（未患病者）,实验组（干预组）,对照组,有效,无效,有效,无效,11,（二）社区试验(communitytrial),12,FieldTrialorFieldExperimentEffectofHepatitisBVaccineAgainstHepatitisB,infectionsofhepatitisB,(randomly),13,CommunityTrial(communityinterventiontrial)FluoridationofDrinkingWatertoPreventSaprodontia,(randomly),communities,Prevalenceofsaprodontia,14,（三）临床试验(clinicaltrial),15,ClinicalTrialTherapeuticEfficacyofDrugA,effectsofDrugA,patients,experimentgroup(DrugA),controlgroup(placebo),followup,(randomly),16,PhasesofClinicalTrials(FDA),Phase1:Safety,Clinicalpharmacologyandtoxicology15-30peopleWhatdosageissafe?Howshouldtreatmentbegiven?Howdoestreatmentaffectthebody?Phase2:Efficacy,InitialinvestigationfortreatmenteffectLessthan100peopleDoestreatmentdowhatitissupposedto?Howdoestreatmentaffectthebody?,17,Phase3:Effectiveness,Fullscaleevaluationoftreatment;licensingapprovalFrom100tothousandsofpeopleComparenewtreatmentwithcurrentstandardPhase4:Postmarketingsurveillance,MonitoradversereactionsFromhundredstothousandsofpeopleUsuallytakesplaceafterdrugisapprovedUsedtofurtherevaluatelong-termsafetyandeffectivenessofnewtreatment,18,应该注意的问题Issuesshouldbepaidattentionto,临床依从性cliccalcompliance临床不一致性clinicaldisagreement安慰剂效应placeboeffect向均数回归regressiontothemean,19,现场试验与临床试验比较,注意!,DifferenceBetweenFiledTrialandClinicalTrial,20,现场试验与临床试验比较DifferenceBetweenFiledTrialandClinicalTrial,21,真实验trueexperiment,按所具备设计的基本特征（basicfeatures）,真实验(trueexperiment),对照前瞻干预随机,randomization,prospective,control,intervention,22,类实验quasi-experiment,按所具备设计的基本特征（basicfeatures）,不设对照组（withoutcontrolgroup）自身前后比较与已知干预措施比较设对照组（withcontrolgroup）不能随机分组,23,第二节研究设计与实施DesignandExecution,24,一明确研究目的二研究对象的选择三确定实验现场四样本大小的确定,PurposeObjectExperimentalspotSample,25,四、样本量估计（estimatethequantityofthesamples）,非连续变量Non-continuousvariable连续变量Continuousvariable,26,五、随机化分组（randomization）,简单随机分组SimpleRandomization分层随机分组StratifiedRandomization整群随机分组ClusterRandomization,27,简单随机分组(simpleRandomization),28,SimpleRandomization,29,分层随机分组(stratifiedrandomization),总体,层,层,层,可按年龄、性别、种族、教育水平等分层,在各层内再进行简单随机分组,30,StratificationRandomizationCategorizingsubjectsintosubgroupsbyspecificcharacteristicsEnablesresearcherstolookintoseparatesubgroupstoseewhetherdifferencesexist,31,整群随机分组(clusterrandomization),以家庭、学校、医院、村庄或居民区等为单位随机分组要保证组间可比性,Baseonfamily,hospital,communication,school,parability,32,六、设立对照(control),不能预知的结局Un-predicableoutcome霍桑效应Hawthorneeffect安慰剂效应Placeboeffect潜在的未知因素的影响Unknownfactor,33,六、设立对照(control),方式（means）安慰剂对照（placebocontrol）自身对照（owncontrol）交叉对照（cross-overcontrol）,34,交叉对照对照cross-overcontrol,A疗法,B疗法,第一阶段间歇时间第二阶段,B疗法,A疗法,甲组,乙组,time,PhaseIntervalPhase,35,八、盲法的应用(blindingapplication),单盲（singleblind）研究对象不知分组情况双盲（doubleblind）研究对象、研究者不知分组情况三盲（tripleblind）研究对、研究者、负责资料收集者不知分组情况,开放试验(opentrial),36,37,博君一笑：双盲实验,38,单盲(singleblind),39,双盲(doubleblind),40,三盲(tripleblind),41,三盲研究(tripleblind),42,开放试验(opentrial),不可能实现盲法外科手术（surgery）锻炼锻炼（exercise）饮食（diet）教育（education）,43,第三节资料的收集与分析DataCollectandAnalyze,44,排除exclusion退出withdrawal不合格ineligibility不依从noncompliance失访losstofollow-up,一、偏倚的防止（biasavoiding）,45,二、评价指标选择的基本原则(basicprincipleofevaluatestandardizationselection),客观的定量指标较高的真实性和可靠性易于观察和测量且易于为受试者所接受,objectivevalidityandreliabilityacceptabilityandeasyobserve,46,三、实验效果的主要评价指标(evaluatestandardizationofefficacyofexperiment),47,效果指数Indexofeffectiveness，IE,48,四、研究中的伦理问题(ethicsintheresearch),研究必须具有科研依据公平选择研究对象获得社区的知情同意“延误”的问题“善后”处理,MustbescientificSelectobjectfairlyHavepermissiontoknowthefactDelayproblemTryourbesttodothefinishing-up,49,第四节实验流行病学优缺点AdvantageandLimitation,50,优点（Advantage）,为前瞻性研究，不存在回忆偏倚研究对象是随机抽样，随机分组，均衡性较好，具有较高的可比性，减少了混杂偏倚随访将每个研究对象的反应和结局，实验组和对照组同步比较，检验假设的能力强,Prospectivestudy,norecallbiasMinimizeconfoundingbiasduetorandomizedstudysubject,betterheterogeneityPowerfulabilitytotestthehypothesisduetotheexperimentalgroupandcontrolgroupcomparable,51,条件要求高、难度较大，在实际工作中有时难以做到费时间、费人力、花费高研究对象代表性不够，影响实验结果推论到总体研究人群数量较大，随访时间长，依从性