循证医学与系统评价 - 诊断学课件

循证医学

与系统评价

四川大学华西口腔医院院史宗道循证医学与系统评价-诊断学循证医学的概念循证医学是指在疾病的诊治过程中，将个人的临床经验与现有的最好临床科学证据结合起来进行综合考虑，为病员作出最佳诊治决策。个人的临床经验是指临床医师通过临床实践获得的精湛学识和敏锐的判断能力；现有的最好证据是指从临床相关的研究、基础医学研究、特别是以病人为中心的临床研究中产生的科学结论。循证医学与系统评价-诊断学有必要学习循证医学吗？

层出不穷的临床科学证据，只要为临床医务工作者所熟知和应用，才能对疾病的诊治产生重大影响

临床实践的质量与熟知最新的知识和信息密切相关，随着随机对照试验的增多，我们面临的问题不再是缺乏新的科学证据，而是已有许多最好证据可能被应用于临床第一线。形势迫使临床医生必须不断学习并更新知识。

循证医学与系统评价-诊断学有必要学习

循证医学吗？循证医学与系统评价-诊断学尽管临床实践每天都需要新的信息，却常常难以及时获得据估计临床一线医师每半天会碰到大约16次因疾病诊治问题需要查寻相应信息,但常因三方面的原因而难以及时获得最新信息：没有时间查寻；教科书知识过时；手边杂志的种类数量有限，难以查到急需的必要信息。阅读杂志是获取最新信息的首要途径，但全世界每年约有200万篇有关生物医学的文章发表在4万种医学杂志上，一个繁忙的临床医师有可能随时在信息的海洋中找寻自己所需要的最可靠的临床研究证据吗？循证医学与系统评价-诊断学繁忙的医生读书时间非常有限据估计一个内科医师需要每天不间断地阅读19篇本专业的杂志文章，才能基本上掌握本专业的新证据和新进展。过去在一周内英国内科临床医师阅读医学文献时间的调查，发现其阅读时间中位数不超过90分钟，高年资住院医师以上的各级医师中，有15％～40％在过去一周内未阅读过任何医学文献。这说明繁忙的医生读书的时间非常有限。循证医学与系统评价-诊断学现有的知识和

临床技能将逐渐过时传统的医学教育方式使人们掌握最新知识的水平与从医学院毕业的年限之间呈显著负相关关系。如果不注意获取临床医学研究的新证据，我们的临床技能将逐渐减退，从而影响医疗质量。循证医学与系统评价-诊断学随时更新知识自学以问题为基础的循证医学课程，掌握实践循证医学的技巧和方法；查寻和应用他人进行循证医学研究的结果，一是选择研究方法科学、结论准确且有临床实用价值的文章，以结构摘要形式的二次出版，并附有专家评述。这类文章只占所有临床医学文献的2％，循证医学与系统评价-诊断学系统评价

systematicreviewanditsappraisal循证医学与系统评价-诊断学系统评价

systematicreview它是针对同一临床问题查寻收集所有随机对照试验结果，进行评价和分析总结而成，为疾病防治提供高质量的证据。这使忙碌的临床医务工作者能在短时间内查到科学、可靠的证据信息循证医学与系统评价-诊断学Whyaresystematicreviewsimportant?

Systematicreviewsofrandomisedcontrolledtrialsareconsideredthebestlevelofevidenceforansweringquestionsabouttheeffectivenessofhealthcareinterventions.Inadditiontothereductioninbias,oneofthemanyadvantagesofsystematicreviewsisthattheyenableustoreducetheever-increasingtorrentofbothpublishedandunpublishedresearchliteratureintomanageableportions

循证医学与系统评价-诊断学

Advantageof

meta-analysisPoolingofdatafromindividualstudiesleadstoanincreaseinsamplesize,andanincreaseinpowerwhichisparticularlyimportantwhenthesizeofeffectissmallorthereisarelativelyloweventrate.Theincreaseinsamplesizenotonlymeansanincreaseinpower,butalsoanincreaseintheprecisionintheestimateofeffect循证医学与系统评价-诊断学Wheretofindsystematicreviews?ThebestsolutionistosearchtheCochraneLibrary,whichcontainstwodatabasesdedicatedtohelpingyoulocatethesystematicreviewyouneed.TheCochraneDatabaseofSystematicReviews(CDSR)includesfulltextsystematicreviewsthathavebeencompletedtotheexactingstandardsoftheCochraneCollaboration,andprotocolsofreviewsthatareunderway.TheDatabaseofAbstractsofReviewsofEffectiveness(DARE)isacompilationofabstractsofsystematicreviewsthatarepublishedinpaperjournals,alongwithhelpfulcommentaryontheirquality.循证医学与系统评价-诊断学Criticallyappraisingsystematicreviews

1.Whatarethereview’sobjectives?Tofocusonwell-definedquestions,statingthepopulations,intervention/controlgroups,andoutcomestobeincluded.2.Howcomprehensivewasthesearchstrategy?Tosearchforalltheliteraturerelevanttothequestion.Publishedandunpublishedliteratureshouldbesought,anyrestrictionsregardinglanguageofpublicationshouldbestatedandjustified,asshouldthetimeperiodcoveredbythesearch.Ideallyasystematicreviewneedstobeuptodate,incorporatingalltherecentliterature.循证医学与系统评价-诊断学AppraisalofSW3.Whatweretheinclusion/exclusioncriteria?Thecriteriaforselectingorrejectingstudiesshouldbeclearlystatedandappropriate.Theprocess*bywhicharticlesareassessedforrelevanceshouldalsoberecorded.4.Howwasthevalidityoftheprimarystudiesassessed?Theprocess*bywhichvalidityassessmentwasundertakenandthecriteriausedtoassessthequalityoftheprimarystudiesshouldbeclear.Itshouldalsobeapparenthowtheresultsofthevalidityassessmentareusedwithinthereview’sdatasynthesis.循证医学与系统评价-诊断学AppraisalofSW5.Howweredataextractedfromtheprimarystudies?Theprocess*bywhichdatawasextractedfromtheprimarystudiesshouldbetransparent.6.Arethecharacteristicsoftheincludedstudiesclearlydisplayed?Atableillustratingthestudycharacteristicsofeachincludedprimarystudyshouldbepresented.循证医学与系统评价-诊断学AppraisalofSW7.Doesthereviewexaminedifferences/similaritiesbetweentheincludedstudiesandtheirresults?Heterogeneitybetweenstudiesshouldbeexploredandthereasonsforanyvariationsdiscussed.Heterogeneitycanbeexploredstatistically,graphicallyorthroughanarrative.8.Wasthesynthesisofthedatacarriedoutappropriately?Wasdatapooledqualitativelyorstatistically?Ifstatisticalpooling(meta-analysis)wasused,wasitusedappropriately?9.Weretheresultsinterpretedappropriately?Anyconclusions,implicationsforresearchorpracticeshouldfollowonlogicallyfromtheresults.循证医学与系统评价-诊断学HowtoproduceaSystematicReview?循证医学与系统评价-诊断学Howisasystematicreviewconducted?

Firststep:tospecifyatightquestion.population(grouptowhomtheinterventionwillapply),intervention(thetherapy,treatmentorpreventivepolicytobecarriedout),comparison(whatwilltheinterventionbecomparedagainst–itcouldbeacommonalternativeintervention,aplaceboornointervention)andoutcomes(whatdowewishtomeasureattheend,whatisimportanttousandtoconsumers?).

循证医学与系统评价-诊断学AclearprotocolDescribingthebackgroundtothework,hypothesistobetestedandmethodologytobeusedAllowingpeer(andoftenconsumer)reviewofthequestiontobeasked,andmethodstobeused,sothatthesecanbeimproved.Italsolimitsvagueinclusioncriteriathatmaypreferentiallyallowinstudieswith‘good’results,anddatadredgingwherelotsofanalysesaretriedout,butonlythosewithsignificantresultsreported.循证医学与系统评价-诊断学ClearinclusionandexclusioncriteriaBesidesthepopulation,intervention,comparisonandoutcomesthatshouldberepresentedintheinclusionandexclusioncriteria,itisimportanttospecifythetypeofstudiesthatwilloffertheleastbiasedevidenceforthereview--RCTIdeallytheprocessofdecidingoninclusionofstudiesisperformedindependentlybyatleasttwopeople,onaformspecificallydesignedforthereview,sometimesblindedtoauthorsandresults.循证医学与系统评价-诊断学

Transparentinclusivesearchstrategy

Toincludeallthepublishedandpreferablyalsounpublisheddatathatexist.Ideallyseveraltypesofsearchingareadopted,sothatifonestrategymissesarelevantstudyitmaybepickedupthroughanothersearchingmethod.Searchstrategiesgenerallyincludeseveralofthefollowing:structuredsearchesofseveralelectronicdatabases(includingtheCochraneLibrary)CheckingthroughthereferencelistsofincludedstudiesandrelevantreviewsLetterstorelevantpharmaceuticalcompaniesandexpertsinthefieldaskingaboutunpublishedorongoingworkHandsearchingofrelevantjournalsorconferenceabstracts,Translationofforeignlanguagearticles.循证医学与系统评价-诊断学Qualityassessmentoftheincludedstudies

Assessmentofstudyvalidity(preferablyindependentlyduplicated)andsomestatementonhowthosebiasesmayaffectoutcomesisessentialinunderstandingthebelievabilityoftheresultsofasystematicreview

SelectionbiasAttritionbias(wheremoreparticipantsdropoutofoneexperimentalarmforsomereason),Performancebias(wherethosereceivingtheinterventionand/orthosecaringforthemareawareoftheexperimentalallocationandmayalterconcurrenttreatmentsaccordingly)Detectionbias(wherethoseassessingoutcomesareawareoftheexperimentalallocationandmaybeopentobiasedoutcomemeasurement).8循证医学与系统评价-诊断学ExtractingdataIdeallytheprocessisindependentlyduplicated,basedonpriordecisions(intheprotocol),comprehensive(onaformdesignedforthereview,andmayinvolvecontactingauthorstofillinanygapsinpublishedreports)Clearlytabulatedtoallowtransparencyandpossiblycorrectionsatalaterdate.循证医学与系统评价-诊断学PoolingofdataNarrativeorstatisticalpoolingormeta-analysis?Narrativeormeta-analyticcomparisonsandsub-groupingsshouldbepre-specifiedintheprotocol(toavoidmultipleanalysesbeingcarriedoutwithonlythe‘statisticallysignificant’onesbeingpublished).循证医学与系统评价-诊断学Whatismeta-analysis?

Topoolextractednumericaldata,weightedsothatlargerstudies,orthosewithlessvariability,contributemoretotheoutcome.ThispoolingprovidesananswerwithgreaterprecisionthateachincludedstudyonitsownThepictorialrepresentationofameta-analysisiscalledaforestplot(seeexample).循证医学与系统评价-诊断学Forestplotofcontinuousdata

循证医学与系统评价-诊断学StatisticalanalysisFixedeffects(whereitisassumedthatthetrueoutcomesofthevariousstudiesarethesame)Randomeffectsmethodologies(wherethetrueoutcomesareassumedtovaryalittlewithdifferingstudyinclusion,dose,durationetc).Wherefixedeffectsmeta-analysisproducesaresultthatisstatisticallyheterogeneousitisusualtoswitchtorandomeffectsmeta-analysis.Statisticalheterogeneityofstudies(largedifferencesintheirresults,suggestingdifferingtrueoutcomes)isideallyexploredthroughsubgroupingormeta-regression.循证医学与系统评价-诊断学HowcanIperformameta-analysis?

Ameta-analysisisaverygoodwayofsummarisingdatafromagroupofstudies.However,thisisonlyusefulwherethesetofstudiesisrepresentativeofthewholebodyofliterature,soshouldgenerallyberestrictedtousewithinsystematicreviews.Meta-analysescanbeperformedbyhandorwithacalculator,butareusuallycompletedwiththehelpofspecialisedcomputersoftware(thatmayalsocreateaforestplot).Therearemanyverygoodtypesofsoftwareavailable,butforthoseembarkingonaCochranereviewthefreeReviewManagersoftware(downloadablefromthemainCochranewebsite)isexcellent,creatingforestplots循证医学与系统评价-诊断学CochraneCollaboration，CochraneLibraryandOralHealthGroup循证医学与系统评价-诊断学BackgroundoftheCochraneCollaboration

In1972,theBritishepidemiologistArchieCochranepublishedaninfluentialbookEffectivenessandEfficiency.RandomReflectionsonHealthServices.

“Itissurelyagreatcriticismofourprofessionthatwehavenotorganisedacriticalsummary,byspecialityorsubspecialty,updatedperiodically,ofallrelevantrandomisedcontrolledtrials”(ArchieCochrane)循证医学与系统评价-诊断学StructureoftheCochraneCollaboration

CochraneCollaborationwasformedinOctober1993.TheCochraneCollaborationaimstohelppeoplemakewell-informeddecisionsabouthealthcarebypreparing,maintaining,andpromotingtheaccessibilityofsystematicreviewsoftheeffectsofhealthcareinterventions.Overthelasttenyearsithasgrownintoaninternationalorganisation,currentlyover6,000peoplecontributingfromover60countries.WhatisremarkableabouttheCochraneCollaborationisthatthemajorityofthesecontributorsundertaketheirCochraneworkintheirowntime.循证医学与系统评价-诊断学TheCochraneLibraryThemainproductoftheCochraneCollaborationisTheCochraneDatabaseofSystematicReviewsthatformspartofTheCochraneLibrary,aquarterlyelectronicpublication.Itcontainsthefulltextofmorethan1350regularlyupdatedsystematicreviewsandmorethan1,000protocolsforreviewsinprogress.Severalhundredreviewsandprotocolsareaddedannually.循证医学与系统评价-诊断学CLpolicyItisCochranepolicythatreviewersrevisittheirreviewandupdateitwithintwoyearsofitbeingpublishedonTheCochraneLibrary.ThereareseveralstagestotheCochranepeerreviewprocess,includingtheassessmentofprotocols,evaluationofthereview’smethodologyandcontentbyeditors,peerreviewersandpotentialendusers/consumers.IthasbeensuggestedthattheexistenceofsuchathoroughrefereeingprocessultimatelyleadstoCochranereviewsbeinglesspronetobiasthansystematicreviewsandmeta-analysispublishedinpaper-basedjournals.

循证医学与系统评价-诊断学CochraneOralHealthGroupResponsibleforpreparingandmaintainingsystematicreviewswithinthescopeoforalhealth.Oralhealthisbroadlyconceivedtoincludetheprevention,treatmentandrehabilitationororal,dentalandcraniofacialdiseasesanddisorders.AlexiaAntczak-BouckomsinitiallysetuptheOHGinNewEngland(USA)in1994.ThegroupmovedtoManchester(UK)in1996andsecuredNationalHealthService(NHS)fundingfortheeditorialbasein1997.TheeditorialbaseissituatedintheManchesterDentalEducationCentre,UniversityDentalHospitalofManchesterundertheCo-ordinatingEditorshipofProfessorWilliamShawandDrHelenWorthington.循证医学与系统评价-诊断学OHG’sSpecialisedRegisterofTrialsItcurrentlyholdsover13,400reportsoforalhealthrelatedtrials(RCTs,CCTs)andrelatedreferencesfromawiderangeofbibliographicalsourcesincludingMEDLINE,EMBASE,CINAHL,CANCERLIT,PSYCLIT,andtheCochraneControlledTrialsRegisterinadditiontoconferenceproceedings.Theregisteriscontinuallygrowingasaresultofon-goingelectronicsearchingandtheOHG’sorganisedprogrammeofhandsearchingtheoralhealthliterature.ThishandsearchingprogrammealsocontributestotheCochraneCollaboration’sworldwidehandsearchingprogrammeco-ordinatedbytheNewEnglandCochaneCentre,USA.ThiscollectionofreferencesfromvarioussourcesmakestheSpecialisedRegisterauniqueandvaluableresourceandthebeststartingpointforanyoneconsideringasystematicreviewwiththeoralhealthfield.循证医学与系统评价-诊断学WaystocontributeTheOralHealthGroupwelcomesallthoseinterestedincontributingtotheworkofthegroup.Thereareseveraloptionsforparticipation,eitherasaleadreviewer,assistingasaco-reviewer,handsearchingajournaltoidentifyRCTs,orbybecomingamemberofthepanelofpeerreviewersorconsumers.Forfurtherdetailsoraninformationpackpleaserefertothegroup’swebsite:Contact:EmmaTavender,Co-ordinator,CochraneOralHealthGroup,MANDEC,UniversityDentalHospitalofManchester,HigherCambridgeStreet,ManchesterM156FH.Tel:+441612757818,Fax:+441612757815,Email:emma.tavende循证医学与系统评价-诊断学如何在临床

应用循证医学？循证医学与系统评价-诊断学提出可问答的临床问题

临床发现如何全面正确地搜集病史和进行体格检查？如何合理地解释临床发现？病因如何通过各项检查找到明确的病因？疾病的病因及危险因素具体患者的疾病病因及危险因素治疗过程与不良事件的因果关系●鉴别诊断根据病因存在的可能性、严重性和可处理性进行排序？如冠心病心肌梗死患者，伴有高血压、血脂升高及糖尿病，在抢救病人时，如何处理这些因素才能迅速取得疗效？循证医学与系统评价-诊断学提出可问答的临床问题(2).诊断试验如何根据诊断试验的精确性、准确性、病人的可接受性、费用和安全性等方面进行选择，如何解释诊断试验结果？预后如何估计疾病的病程和并发症？治疗如何为患者选择利大于弊、成本低效果好的最佳治疗方案？循证医学与系统评价-诊断学提出可问答的临床问题(3)预防如何通过识别和消除危险因素以减少疾病的发生？如何通过筛查以早期诊断疾病？知识的自我更新如何更新知识、提高临床技能、进行更有效的临床实践？是花1小时到图书馆查阅教科书和杂志，还是花30分钟在计算机上查阅最近5－10年的有关文献？循证医学与系统评价-诊断学如何选择急需解决的问题？在临床实践中，每天都会要面临许多问题，一下解决所有问题是不可能的在病人的诊治过程中，哪一个问题最重要？在现在有限的时间内，最有可能回答哪一个问题？最感兴趣的问题是什么？哪一个问题在临床实践中经常遇到？循证医学与系统评价-诊断学

查寻最好的证据

查寻临床医学证据的渠道

教科书、专著、专业杂志电子出版物CochranelibraryMEDLINE(1966-)EMBASESciesearch(ScienceCitationIndex)中国生物医学文献数据库CBMdisc(1981-)累积期刊索引循证医学与系统评价-诊断学查寻的策略

要系统、全面地查寻与某一临床问题相关的最新信息，检索前确定检索的渠道和资料库，具体检索方法、检索年限和语种等。采用多种渠道查寻，避免遗漏重要信息；图书管理员共同检索提高检索的敏感性和特异性；正确应用检索词先用多个检索词或意义相近的检索词进行检索，然后逐渐缩窄范围。检索词应包括：研究的疾病、采用的干预措施以及研究的设计方案等，检索词应明确、具体。循证医学与系统评价-诊断学

评价临床证据临床证据的评价应包括两方面的内容：◆证据的真实性(validity)

◆临床重要性(importance)●应对病因、诊断、治疗、预后等方面证据评价循证医学与系统评价-诊断学诊断试验:

是否具有真实性、重要性诊断性试验的可行性、准确性和精确性是否具备实施该诊断试验的技术和设备条件？其准确性和精确性如何？成本－效果比如何？在不同的亚组病人中，应用同一诊断性试验，其价值是不同的。在晚期病例中，诊断试验的似然比较高，而在早期轻型病例中则较低。应使用多层次的似然比，减少诊断试验偏差。在应用诊断试验证据时，要考虑上述因素的影响，并估计由此产生的似然比或验后概率的变化是否足以改变诊断的结果和临床的决策。循证医学与系统评价-诊断学诊断试验:

是否具有真实性、重要性(1)能否合理估计具体医疗环境中病人的验前概率在临床实践中应根据病人的症状、体征等重要资料估计所在医疗机构某一疾病的验前概率（患病率）如缺乏此资料，诊治条件、病人特征类似于诊断试验报告中的情况时可应用文献的验前概率；诊断条件、病人特征与文献报道有差别，可以报告的验前概率为基点并根据实际情况在一定的范围内变动，观察验后概率的变化，确定该诊断试验的实用价值。循证医学与系统评价-诊断学诊断试验:

是否具有真实性、重要性(2)验后概率能否影响对病人的诊断和治疗决策“试验阈值”，诊断试验为阴性时患某病的验后概率很低，不必再作进一步的诊断试验。“治疗阈值”，即诊断试验为阳性时患病的验后概率很高，据此可肯定诊断以选择最佳治疗方案。上述两种情况下，可停止诊断试验。当验后概率介于试验阈值与治疗阈值之间时，则要做进一步的检查以肯定或否定待查的疾病。当单个诊断试验不能确定试验－治疗阈值时，可采用联合试验的方法，然后计算总的验后概率以帮助临床决策。循证医学与系统评价-诊断学治疗性研究

是否具有真实、重要性?

疗措施是否适合具体病人

具体患者同文献中的研究对象在性别、年龄、并存症、疾病严重程度、社会因素、生物学及临床特征等方面的差异如何?结合生物学知识和临床专业知识综合判断该治疗研究的外延性。样本大的试验或系统综述的结论对指导具体病人用药更有参考价值。循证医学与系统评价-诊断学治疗性研究

是否具有真实、重要性?(1)治疗措施用于具体病人时效果如何？治疗性试验报告的结果是作用于病人的平均治疗效果，针对单个具体的病人如何考虑其效果？采用测量治疗措施是否有效的指标NNT，即治疗多少例病人才能防止一例发生某种结局。循证医学与系统评价-诊断学治疗性研究

是否具有真实、重要性?(2)确定发生某种结局的绝对易感性即期望事件率(patientexpectedeventrate,PEER)，乘以文献报告的RRR值(相对危险降低率)得到ARR，然后转换为NNT。例如：某一病人的PEER为40％，文献报