醫(yī)學研究設計簡介課件

醫(yī)學研究設計簡介2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter2科學的思考方式演譯法歸納法猜測與否證-KarlPopper我們雖然無法證明某個假說為真,卻可以經(jīng)由不斷地否證,除去錯誤的假說,如此留下來的假說比較可能趨近為真。2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter3提出假說推論出小前提研究設計並進行測量估計或檢定分析結果得到研究摘要演繹歸納流行病學方法論,p11。第三版。王榮德著2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter4吸煙導致肺癌臺灣的男子吸煙者比不吸煙者易得肺癌研究設計測量的臺灣男子中，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方法論,p11。第三版。王榮德著2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter5因果關係的判定標準必要條件—時序性次要條件—一致性不能用機會解釋沒有其他干擾因素合理性參考條件—相關強度、相關的特定程度、劑量效應關係、生物學上的贊同性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常見的研究設計法觀察性研究法Caseseriesstudy世代研究法(cohortstudy)病例對照研究(casecontrolstudy)斷代研究法(cross-sectionalstudy)試驗性研究法社區(qū)試驗法臨床試驗法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)生的時序性、先後次序Eligibilitycriteria和outcomeassessments可以標準化比RCT的行政作業(yè)簡單、便宜2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter12CohortStudy-disadvantage前瞻性研究,費時、昂貴不適於研究稀有或潛伏期夠長的疾病若是retrospectivecohortstudy,需要有過去exposurestatus的紀錄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:一或多個醫(yī)院中就醫(yī)的所有病例整個社區(qū)或團體族群的所有病例Control:整個社區(qū)醫(yī)院其他病人病人親屬病人的同學、同事、鄰居2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter17Case-ControlStudy-Advantage較適用於研究稀有或潛伏期長的疾病較快得到結果,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)收案時先考慮age,gender,race,避免overmatching2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter19Case-ControlStudy-disadvantageExposurestatus需要靠過去的紀錄或回憶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簡單便宜容易推廣到參考族群2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter24Cross-SectionalStudy-disadvantage頂多建立相關(association),無法推論因果關係（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)依照隨機分派當時的名單作資料分析,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序性Randomization的程序可能使統(tǒng)計分析較單純2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter33RCT-disadvantage昂貴、費時注意volunteerbias注意醫(yī)療倫理的問題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（錯分）Cohortstudy診斷標準的效度不足疾病組與非疾病組的分類錯誤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誤2024/10/13DepartmentofMedicalResearch,ChimeiMedicalCenter36MisclassificationDifferentialmisclassification結論的偏差方向難以估計Non-Differentialmisclassification導致低估了「暴露」與「疾病」的相關性(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控制干擾效應的方法研究設計階段:Restriction限制條件Matching配對選樣Randomization隨機分派資料分析階段:Stratification分層分析Multivariatemodel(adjust)多元模型建構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)生率的相關性，隨著抽樣狀態(tài)不同而有不同。抽煙者，服用O.C.的風險是不服用者的7.5倍；不抽煙者，服用O.C.的風險是不服用者的2.5倍X和Y之間的相關性，受到Z的修飾作用；X和Z對於Y的相關性，有交互作用。X和Y是否相關？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年人類首次檢測到乙型肝炎的表面抗原。我國經(jīng)濟和科學技術日益發(fā)展，學術文化領域百家爭鳴，（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)學理論的創(chuàng)新和突破性進展，提供了有利的文化背景。宋代陳無擇著《三因極一病證方論》一書，（45傳染病q566丙肝964jo乙肝28jgsx甲肝gh）提出三因學說；并產(chǎn)生了最具盛名四大學派，劉完素倡導火熱論；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。編輯本段明清時期（df肺25s血液f369血小板t5172紅血球gdf55m白血球fd2）是中醫(yī)學理論綜合匯編、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)學綱目》和王肯堂的《證治準繩》，清代吳謙等編著的《醫(yī)宗金鑒》和陳夢雷主編的《古今圖書集成·醫(yī)部全錄》等。王清任著《醫(yī)林改錯》，注重實證研究，（df高血壓958心臟病983u6糖尿病87fr）糾正了古醫(yī)籍中關于解剖知識的某些錯誤，肯定了“腦主思維”，發(fā)展了瘀血理論。溫病學說的形成和發(fā)展，標志著中醫(yī)理論的創(chuàng)新與突破，吳有性著《溫疫論》，葉天士著《溫熱病篇》，吳鞠通著《溫病條辨》等，在藥物學研究方面，（45傳染病q566丙肝964jo乙肝28jgsx甲肝gh）李時珍著的《本草綱目》，總