醫(yī)學(xué)研究設(shè)計(jì)簡(jiǎn)介課件

醫(yī)學(xué)研究設(shè)計(jì)簡(jiǎn)介2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter2科學(xué)的思考方式演譯法歸納法猜測(cè)與否證-KarlPopper我們雖然無(wú)法證明某個(gè)假說(shuō)為真,卻可以經(jīng)由不斷地否證,除去錯(cuò)誤的假說(shuō),如此留下來(lái)的假說(shuō)比較可能趨近為真。2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter3提出假說(shuō)推論出小前提研究設(shè)計(jì)並進(jìn)行測(cè)量估計(jì)或檢定分析結(jié)果得到研究摘要演繹歸納流行病學(xué)方法論,p11。第三版。王榮德著2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter4吸煙導(dǎo)致肺癌臺(tái)灣的男子吸煙者比不吸煙者易得肺癌研究設(shè)計(jì)測(cè)量的臺(tái)灣男子中，吸煙者與不吸煙者的肺癌死亡率吸煙者之肺癌死亡率為不吸煙者之10倍演繹歸納流行病學(xué)方法論,p11。第三版。王榮德著2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter5因果關(guān)係的判定標(biāo)準(zhǔn)必要條件—時(shí)序性次要條件—一致性不能用機(jī)會(huì)解釋沒有其他干擾因素合理性參考條件—相關(guān)強(qiáng)度、相關(guān)的特定程度、劑量效應(yīng)關(guān)係、生物學(xué)上的贊同性2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter6ConfoundingeffectexposureoutcomeConfoundingfactorassociationassociationMarkElwood.CriticalAppraisalofEpidemiologicalStudiesandClinicalTrails.2ndEdition.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter7TheassociationbetweenO.C.useandMI-overestimationOralcontraceptiveuseMyocardialinfarctionsmoking+O.C.userssmokemoreheavilythannonusers+Smokers,irrespectiveofO.C.use,haveahigherinfarctionthannon-smokersMarkElwood.CriticalAppraisalofEpidemiologicalStudiesandClinicalTrails.2ndEdition.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter8TheassociationbetweenO.C.useandMI-underestimationOralcontraceptiveuseMyocardialinfarctionobesity—O.C.usersarelessobesethannon-users+ObesityincreasestheriskofmyocardialinfarctionMarkElwood.CriticalAppraisalofEpidemiologicalStudiesandClinicalTrails.2ndEdition.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter9常見的研究設(shè)計(jì)法觀察性研究法Caseseriesstudy世代研究法(cohortstudy)病例對(duì)照研究(casecontrolstudy)斷代研究法(cross-sectionalstudy)試驗(yàn)性研究法社區(qū)試驗(yàn)法臨床試驗(yàn)法2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter10CohortstudyRecruitedsamplesexposedgr.Non-exposedgr.diseasedgr.Non-diseasedgr.Now!(concurrentcohortstudy)Now!(retrospectivecohortstudy)2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter11Cohortstudy-advantages適於研究rareexposure可直接觀察exposed和non-exposedgroup的疾病發(fā)生率可觀察多重健康事件事件發(fā)生的時(shí)序性、先後次序Eligibilitycriteria和outcomeassessments可以標(biāo)準(zhǔn)化比RCT的行政作業(yè)簡(jiǎn)單、便宜2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter12CohortStudy-disadvantage前瞻性研究,費(fèi)時(shí)、昂貴不適於研究稀有或潛伏期夠長(zhǎng)的疾病若是retrospectivecohortstudy,需要有過(guò)去exposurestatus的紀(jì)錄Lossoffollowup可能影響效度2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter13RR(RelativeRisk,RateRatio)MIMIO.C.6040100O.C.445610010496200RR=(60/100)/(44/100)=1.36MIMIO.C.aba+bO.C.cdc+da+cb+da+b+c+dRR=(a/(a+b))/(c/(c+d))2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter140<=RR<∞0<=RR<1,protectionfactorRR=1,noeffectRR>1,riskfactorRR(RelativeRisk,RateRatio)2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter15Case-controlstudyRecruitedsamplesexposedgr.Non-exposedgr.diseasedgr.Non-diseasedgr.Now!2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter16SelectionofstudysubjectCases:一或多個(gè)醫(yī)院中就醫(yī)的所有病例整個(gè)社區(qū)或團(tuán)體族群的所有病例Control:整個(gè)社區(qū)醫(yī)院其他病人病人親屬病人的同學(xué)、同事、鄰居2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter17Case-ControlStudy-Advantage較適用於研究稀有或潛伏期長(zhǎng)的疾病較快得到結(jié)果,較便宜保留探討多種致病因子的可能性2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter18Matching-控制干擾因子的一種方法Frequencymatching要有整個(gè)族群的資料Individualmatching找符合條件裡頭最接近病例的人Cases是陸續(xù)收案時(shí)先考慮age,gender,race,避免overmatching2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter19Case-ControlStudy-disadvantageExposurestatus需要靠過(guò)去的紀(jì)錄或回憶bias:recallbias,selectionbias不容易研究多重疾病事件，且疾病事件的時(shí)序性不易建立Controlgroup不好選Confoundingeffect2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter20OR(OddsRatio)MIMISmkaba+bsmkcdc+da+cb+da+b+c+dodds1=a/b

odds2=c/dOddsRatio=odds1/odds2=ad/bcMIMIsmk30200230smk1535036545550595OR=30×350/200×15=3.52024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter21OR(OddsRatio)0<=OR<∞0<=OR<1,protectionfactorOR=1,noeffectOR>1,riskfactor2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter22Cross-sectionalstudyexposedgr.Non-exposedgr.diseasedgr.Non-diseasedgr.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter23Cross-SectionalStudy-Advantage簡(jiǎn)單便宜容易推廣到參考族群2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter24Cross-SectionalStudy-disadvantage頂多建立相關(guān)(association),無(wú)法推論因果關(guān)係（causal-effectrelationship）注意selectivesurvivalbiasConfoundingeffect2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter25ClinicalTrial

RCT(Randomizedcontrolledtrial)ParalleldesignCross-Overdesign2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter26RCT

ParallelDesignRecruitedsamplesTreatmentATreatmentBOutcome1Outcome2Randomization2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter27RCT

Cross-OverDesignRecruitedsamplesTreatmentATreatmentBOutcome1Outcome2TreatmentBTreatmentARandomization2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter28RandomizationControlledBlind-DesignIITorPP?2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter29BlindDesignStudysubjectInvestigatoranalyzerSingleBlindDoubleBlindTripleBlind○○○○○○2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter30Intentiontotreatrandomizationclofibraten=1065placebon=2095compliantn=708compliantn=1813Non-compliantn=882Non-compliantn=357TreatmentacceptedTreatmentallocatedPercentmortality15.024.615.128.2All18.2All19.42024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter31Analysisstrategy:IITorPP？IIT(intention-to-treat)依照隨機(jī)分派當(dāng)時(shí)的名單作資料分析,包括沒有完全服從治療策略以及沒有完成試驗(yàn)者。PP(perprotocol)只納入完全遵從治療分組及治療策略者,作資料分析。又稱作“Ontreatmentanalysis”2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter32RCT-advantageConfounders可能接近平衡分佈可以建立因果時(shí)序性Randomization的程序可能使統(tǒng)計(jì)分析較單純2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter33RCT-disadvantage昂貴、費(fèi)時(shí)注意volunteerbias注意醫(yī)療倫理的問(wèn)題2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter34IEvidenceobtainedfromatleastoneproperlyrandomized,controlledtrialII-1Evidenceobtainedfromwell-designedcontrolledtrialswithoutrandomizationII-2Evidenceobtainedfromwell-designedcohortorcase-controlanalyticstudies,preferablyfrommoretheonecenterorresearchgroup.II-3Evidenceobtainedfrommultipletimeserieswithorwithouttheintervention.Dramaticresultsoftheuncontrolledexperimentscouldalsoberegardedasthistypeofevidence.IIIOpinionsofrespectedauthorities,basedonclinicalexperience;descriptivestudiesandcasereports;orreportsofexpertcommittees.GradesofEvidenceforthePurportedQualityofStudyDesign

(NEnglJMed2000;342:1887-92)2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter35Misclassification（錯(cuò)分）Cohortstudy診斷標(biāo)準(zhǔn)的效度不足疾病組與非疾病組的分類錯(cuò)誤Case-Controlstudy暴露(exposure)的分組的效度不足暴露組與非暴露組的分類錯(cuò)誤2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter36MisclassificationDifferentialmisclassification結(jié)論的偏差方向難以估計(jì)Non-Differentialmisclassification導(dǎo)致低估了「暴露」與「疾病」的相關(guān)性(towardthenull,H0)Ex:RR=2→RR=1.52024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter37ConfoundingeffectexposureoutcomeConfoundingfactorassociationassociationMarkElwood.CriticalAppraisalofEpidemiologicalStudiesandClinicalTrails.2ndEdition.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter38TheassociationbetweenO.C.useandMI-overestimationOralcontraceptiveuseMyocardialinfarctionsmoking+O.C.userssmokemoreheavilythannonusers+Smokers,irrespectiveofO.C.use,haveahigherinfarctionthannon-smokersMarkElwood.CriticalAppraisalofEpidemiologicalStudiesandClinicalTrails.2ndEdition.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter39TheassociationbetweenO.C.useandMI-underestimationOralcontraceptiveuseMyocardialinfarctionobesity—O.C.usersarelessobesethannon-users+ObesityincreasestheriskofmyocardialinfarctionMarkElwood.CriticalAppraisalofEpidemiologicalStudiesandClinicalTrails.2ndEdition.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter40ConfoundingeffectMIMIsmk202040Non-smk2810222850MIMIsmk104050Non-smk89210018132150MIMIO.C.222850O.C.1813215040160200RR=(22/50)/(18/150)=3.67O.C.組抽煙率80％Non-O.C.組抽煙率33.3％CrudeRR2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter41AdjustingconfoundingeffectsmkMIMIO.C202040O.C.104050306090Non-smkMIMIO.C.2810O.C.89210010100110RR=(20/40)/(10/50)=2.5RR=(20/40)/(8/92)=2.5Adjusted-RR2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter42Confoundingeffect2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter43控制干擾效應(yīng)的方法研究設(shè)計(jì)階段:Restriction限制條件Matching配對(duì)選樣Randomization隨機(jī)分派資料分析階段:Stratification分層分析Multivariatemodel(adjust)多元模型建構(gòu)2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter44Interaction(effectmodification)smkMIMIO.C301040O.C.54550355590Non-smkMIMIO.C.2810O.C.89210010100110RR=(30/40)/(5/50)=7.5RR=(2/10)/(8/100)=2.5CigarettesmokingisaneffectmodifierfortheassociationbetweenMIandO.C.use.2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter45交互作用2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter46交互作用(interaction)使用O.C.和MI發(fā)生率的相關(guān)性，隨著抽樣狀態(tài)不同而有不同。抽煙者，服用O.C.的風(fēng)險(xiǎn)是不服用者的7.5倍；不抽煙者，服用O.C.的風(fēng)險(xiǎn)是不服用者的2.5倍X和Y之間的相關(guān)性，受到Z的修飾作用；X和Z對(duì)於Y的相關(guān)性，有交互作用。X和Y是否相關(guān)？不能一言以蔽之，需依Z的不同狀態(tài)，分別討論之。下次議題:線性迴歸分析與相關(guān)分析2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter481、病毒性肝炎：由病毒造成的肝炎按照其病毒系列不同分為甲、乙、丙、丁、戊和庚共六種類型病毒性肝炎。能引起肝臟細(xì)胞腫脹，是世界上流傳廣泛，危害很大的傳染病之一。1908年，才發(fā)現(xiàn)病毒也是肝炎的致病因素之一。1947年，將原來(lái)的傳染性肝炎（infectioushepatitis）稱為甲型肝炎（HepatitisA,HA）；血清性肝炎（serumhepatitis）稱為乙型肝炎（HepatitisB,HB）。1965年人類首次檢測(cè)到乙型肝炎的表面抗原。我國(guó)經(jīng)濟(jì)和科學(xué)技術(shù)日益發(fā)展，學(xué)術(shù)文化領(lǐng)域百家爭(zhēng)鳴，（df高血壓958心臟病983u6糖尿病87fr）特別是思想家的革新精神，為中醫(yī)學(xué)理論的創(chuàng)新和突破性進(jìn)展，提供了有利的文化背景。宋代陳無(wú)擇著《三因極一病證方論》一書，（45傳染病q566丙肝964jo乙肝28jgsx甲肝gh）提出三因?qū)W說(shuō)；并產(chǎn)生了最具盛名四大學(xué)派，劉完素倡導(dǎo)火熱論；張從正力倡“攻邪論”；李杲提出“內(nèi)傷脾胃，百病由生”的理論；朱震亨創(chuàng)造性地闡明了相火的演變規(guī)律。編輯本段明清時(shí)期（df肺25s血液f369血小板t5172紅血球gdf55m白血球fd2）是中醫(yī)學(xué)理論綜合匯編、深化發(fā)展，臨床各科辨證體系豐富、提高階段。如明代樓英的《醫(yī)學(xué)綱目》和王肯堂的《證治準(zhǔn)繩》，清代吳謙等編著的《醫(yī)宗金鑒》和陳夢(mèng)雷主編的《古今圖書集成·醫(yī)部全錄》等。王清任著《醫(yī)林改錯(cuò)》，注重實(shí)證研究，（df高血壓958心臟病983u6糖尿病87fr）糾正了古醫(yī)籍中關(guān)于解剖知識(shí)的某些錯(cuò)誤，肯定了“腦主思維”，發(fā)展了瘀血理論。溫病學(xué)說(shuō)的形成和發(fā)展，標(biāo)志著中醫(yī)理論的創(chuàng)新與突破，吳有性著《溫疫論》，葉天士著《溫?zé)岵∑?，吳鞠通著《溫病條辨》等，在藥物學(xué)研究方面，（45傳染病q566丙肝964jo乙肝28jgsx甲肝gh）李時(shí)珍著的《本草綱目》，總