病因和因果推断课件

病因和病因推断CauseofDiseaseandCausalInference流行病学教研室

Departmentofepidemiology，HarbinMedicalUniversity主要内容(outline)

病因的概念

（conceptsofcausation）

因果关联的推断（inferenceofcausalassociation）

病因推断的标准

(criteriaofcausalinference)第一节病因的概念

conceptsofcausation

鬼神、上帝、天意金木水火土人活的传染物迷信阶段朴素唯物主义生物学病因的萌芽病原物环境宿主三角模式生理社会物化机体轮状模式病因网模型一、疾病病因概念的发展（Developmentofcausationinhistory

）

病因模型（causalmodel）三角模型（epdemiologicaltriad）疾病因素轮状模型（wheelmodel）病因网络模型(webofcausation)宿主环境病因健康（health）宿主环境病因疾病（disease）失衡三角模型（epidemiologicaltriad）环境病因宿主AgentEnvironmentalHost病因Agent环境Environmental宿主Host三角模型（epidemiologicaltriad）病因Agent环境Environmental宿主Host三角模型（epidemiologicaltriad）病因Agent环境Environmental宿主Host三角模型（epidemiologicaltriad）病因Agent环境Environmental宿主Host三角模型（epidemiologicaltriad）生物环境社会环境遗传内核理化环境宿主健康Health理化环境生物环境社会环境宿主遗传内核失衡疾病Disease轮状模型（wheelmodel）生物环境社会环境理化环境先天性代谢异常Inbornerrorofmetabolism

宿主遗传内核健康Health病因网络模型（webofcausation）MorbidityandMortality(Stroke,MI)BiologicalRiskFactors

(Hypertension,BloodLipids,Homocysteine)GeneticRiskFactors(FamilyHistory)BehavioralRiskFactors(Cigarette,Diet,Exercise)EnvironmentalFactors(SocioeconomicStatus,WorkEnvironment)病因网络模型（webofcausation）BEINGSModel

PreventablecausesofdiseaseBiologicfactorsandBehavioralfactorsEnvironmentalfactorsImmunologicfactorsNutritionalfactorsGeneticfactorsServices,Socialfactors,andSpiritualfactorsAcausalrelationshipwouldberecognizedtoexistwheneverevidenceindicatesthatthefactorsformpartofthecomplexofcircumstancesthat

increasestheprobabilityoftheoccurrenceofdisease

andthatadiminutionofoneormoreofthesefactorsdecreasesthefrequencyofthatdisease.----Lilienfeld(1980)二、病因的定义（definitionofcausation）

LilienfeldAM.（1920-1984）约翰.霍普金斯大学流行病学教授

LilienfeldAM.（1920-1984）约翰.霍普金斯大学流行病学教授那些能使人群发病概率升高的因素，就可认为是疾病的病因；当其中某个或多个因素不存在时，人群的疾病频率就会下降。二、病因的定义（definitionofcausation）第二节因果关联的推断

inferenceofcausalassociation一、因果推断的一般过程

Commonprocessofcausalinference建立病因假设

hypothesisdevelopment

病因假设的检验和验证

testandcertificationofhypothesis密尔氏准则Mill’scanons建立病因假设（hypothesisdevelopment

）Ifeventsorriskfactorsarecommontoavarietyofdifferentcircumstancesandtheeventsorriskfactorshavebeenpositivelyassociatedwithadisease,thentheprobabilityofthatfactorbeingthecauseisextremelyhigh.求同法（agreementcanon）钩端螺旋体病流行，共同点---下水劳动Thefrequencyofadiseaseoccurrenceisextremelydifferentunderdifferentsituationsorconditions.Ifariskfactororeventcanbeidentifiedinoneconditionandnotinasecond,itmaybethatfactor,ortheabsenceofit,thatmaybethecauseofthedisease.差异法（differentcanon）察布查尔病Thefrequencyorstrengthofaneventorriskfactorvarieswiththefrequencyofthediseaseorcondition.Increasednumbersofchildrennotimmunizedagainstmeaslescausestheincidencerateformeaslestogoup.共变法（concomitantvariationscanon）吸烟与肺癌；氟龋齿、斑釉齿Subductfromanyphenomenonsuchpartasisknownbypreviousinductionstobetheeffectofcertainantecedents,andtheresidueofthephenomenonistheremainingantecedents.剩余法（residuescanon）乙肝病毒＋黄曲霉毒素－肝癌（藻类毒素）

病例对照研究（case-controlstudy）队列研究（cohortstudy）病因假设的检验和验证（testandcertificationofhypothesis）二、病因推断中暴露因素与疾病关联的解释Associationbetweenexposureanddiseaseincausalinference统计学关联（statisticsassociation）虚假关联（spuriousassociation）

间接关联（indirectassociation）

InterpretingAssociations-CausalandNon-CausalCausalNon-Causal(duetoconfounding)CharacteristicUnderStudyCharacteristicUnderStudyDiseaseFactorXDiseaseInterpretingAssociations-CausalandNon-CausalCausalNon-Causal(duetoconfounding)CoffeeConsumptionCoffeeConsumptionPancreaticCancerSmokingPancreaticCancerSpuriousAssociationRealAssociationRealAssociation暴露与疾病exposureanddisease有无统计学关联?statisticalassociation有无偏倚?bias有时间先后否?temporalsequence统计关联到因果关联

FromEpidemiologicalAssociationtoCausation

关联的强度

关联的重复性

关联的时间顺序病因与疾病分布一致终止效应剂量反映关系关联的特异性关联的生物学合理性第三节病因推断标准criteriaofcausalinferencestrengthconsistencytemporalitycoherence

reversibilitydose-responserelationshipspecificitybiologicplausibility因果推断标准(1)--关联的强度关联强度越大，为因果的可能性越大

Astrongassociationbetweenpossiblecauseandeffect,ismorelikelytobecausalthanaweakassociation.

关联强度的测定

measurementofstrengthRR,ORcriteriaofcausalinference1--strength因果推断标准(1)--关联的强度criteriaofcausalinference1--strength不同人群、不同地区、不同时间、不同类型的研究少数或个别研究不同甚或相反的结果并不能简单地反驳因果假设多数得到一致结果的研究可能遭遇共同的偏倚研究间不同的结果可能是因为某些因素的修正作用因果推断标准(2)－关联的重复性criteriaofcausalinference2--consistency因果推断标准(3)－时间顺序前因后果：唯一必须满足的标准实验性研究队列研究采用新病例的病例对照研究生态趋势研究横断面研究>>时间暴露结局criteriaofcausalinference3--temporaliryThecausemustprecedetheeffect.因果推断标准(4)－病因与疾病分布一致criteriaofcausalinference4--coherence饮食脂肪摄入与乳腺癌发病Correlationbetweendietaryfatintakeandbreastcancerbycountry因果推断标准(5)－终止效应这是强有力的反证病因关系的一种方法。例如戒烟与肺癌的关系研究中，我们发现戒烟后，人群肺癌死亡率下降。criteriaofcausalinference5--reversibilityWhenremovalofapossiblecauseresultsinreductionofdiseaserisk,thelikelihoodoftheassociationbeingcausalisstrengthenedForexample,smokerswhogiveupsmokinghavealowerriskoflungcancerthanthosewhocontinuetosmoke.因果推断标准(6)－剂量反映关系Adose-responserelationshipoccurswhenchangesinthelevelofapossiblecauseareassociatedwithchangesinthemagnitudeoftheeffect.criteriaofcausalinference6—dose-responserelationship如果观察到随着某因素暴露剂量的增加．人群发生某病