循证医学原理

文章来源自本坛文献阅读分坛的骨科询证医学阅读专题/bbs/topic/17024687?tpg=1&age=0&ticket=ST-1725698-gcTd9VLrCaMiJQhGcaRraI3KuixKqQtzHwv-20个人能力、水平都十分有限，初次尝试翻译全文，其中肯定存在错误和不足之处，恳请各位前辈同行不吝指点，非常感谢您！！PrinciplesofEvidence-BasedMedicine循证医学原理SukhmeetS.Panesar,BSc(Hons),MBBSa,MarcJ.Philippon,MDb,MohitBhandari,MD,MSc,FRCSCc,*KEYWORDS:Evidence-basedmedicineOrthopedicsStatisticsEvidencesynthesis关键词：循证医学，骨科，统计学，证据分析Theoriginsofwhatiscurrentlyknownasevidence-basedmedicine(EBM)goasfarbackastheseventeenthcentury,whenitwasobservedthatpatientswhoreceivedbleedingaspartoftheirtreatmentofcholerahadamuchhighermortalityratethanthosewhowerenottreatedinthesamemanner.1IthasonlybeenrecentlythatEBMhasseenanexponentialincreaseinitsadoption,andindeedthedevelopmentofEBMhasbeenheraldedasoneofthetopmedicalmilestonesoverthelast160years.2Althoughdefinitionsvary,EBMintegratesclinicalexpertise,patients'valuesandpreferences,andthebestavailableevidencefromthemedicalliterature.3Inotherwords,assuggestedbySackettandcolleagues,4''Evidencebasedmedicineistheconscientious,explicit,andjudicioususeofcurrentbestevidenceinmakingdecisionsaboutthecareofindividualpatients."循证医学的起源最早可以回溯到17实际，当时人们观察到那些接受了放血方法治疗霍乱的患者的死亡率远远高于未接受放血治疗的患者。1直到最近循证医学的使用才开始指数型增长，而且它的发展被认为是过去160年以来医学的最高里程碑之一。2尽管定义多样，循证医学使得医师临床经验、患者的需求以及文献中可获得的最好的证据相结合起来。换而言之，就像Sackett及其同事所说的：''循证医学是在做出决策时，尽责、明确、审慎的使用当前最好的临床证据"。Historically,surgicaldecisionshavelargelybeenbasedonpersonalexperienceandrecommendationsfromsurgicalauthorities.Incontrasttointernalmedicine,trialsofsurgicaltechniquesandtechnologieshaveuniquechallengesandhave,therefore,beenslowtopermeatethesurgicalliterature.Inaddition,regulatorybodieshaveimposedlessstringentcontrolsonthevalidationofthesetechnologies.Assuch,mostsurgicalpracticeisbasedonlowerlevelsofevidence.5Theproportionofsystematicreviewsandrandomizedcontrolledtrials(RCTs)inleadingsurgicaljournalsstandsat5%.6从历史上来说，外科医师的决策大部分基于其个人经验和外科权威的建议。与内科不同，外科手术技术与科技的尝试具有独特的挑战性，因此在外科文献中出现较晚。另外，监管部门对这些技术的批准也比较宽松。如此一来，大部分的外科实践都是基于低水平的证据。在主要的外科杂志中，系统性回顾与随机对照试验的比例为5%。Regardlessoftheoverallnumberoftrialsinsurgery,itisextremelydifficultforpracticingsurgeonstokeepabreastofcriticalevidence,giventhelargenumberofsurgicalarticlespublishedmonthly.Haynesstipulatesthatdoctorsneedtoreadapproximately20articlesadaytokeepuptodateintheirfield.7不论总体手术实验的数量如何，由于每个月都有大量的外科文章发表，对于实践中的外科医师来说很难掌握决定性证据。Haynes认为外科医师要跟上领域内的前沿的话，每天需要读20篇文早。Surgeryisanexponentiallygrowingspecialtywith234millionoperationsperformedgloballyinayear.8Ofthese,64millionareperformedintheUnitedStates,andhealthcareaccountsforone-sixthoftheeconomy.9Furthermore,Internet-savvypatientswhowantthebestindiagnosticsandtherapiesdemandevidence-basedpractice.Theonusisonsurgeonstoprovidehigh-qualityevidenceandinstitutebestpractices.全球每年以两亿三千四百万台手术量呈指数型增长，这当中美国有六千四百万，医保占其中六分之一。将来全球的希望得到最好诊治的患者都需要循证医学实践。医师们的责任是提供高质量的证据以及开始最好的实践。EVIDENCE-BASEDORTHOPEDICS骨科循证医学Currentestimatessuggestthatlessthan5%oftheorthopedicliteraturerepresentsrandomizedtrials,althoughthishasbeensteadilyincreasing.10However,eventhequalityofreportinginRCTsishighlyvariable.Completereportingofallocationconcealment,detailsofblindinginfollow-up,andsurgicalexpertiseintrialreportshavebeenuncommon.11目前骨科文献中有5%是随机研究，这仍在持续增长中，但是随机对照试验研究的质量参差不起。关于分配隐藏及其后的盲测的细节，还有外科专家的详细的报道仍然不常有。Althoughmanyorthopedicjournals(eg,JournalofBoneandJointSurgery,ClinicalOrthopaedicsandRelatedResearch,ActaOrthopaedica,JournalofOrthopaedicTrauma,andOrthopedicClinicsofNorthAmerica)haveadoptedevidence-basedapproachestoreportingclinicalresearch,thereremainconsiderableopportunitiestoimproveprocesses.Providingadditionalevidence-basedresourcesandeducationforreadersisakeyfirststep.尽管许多骨科杂志采用循证医学的方式来报道临床研究，仍然存在有待改进的地方，对读者的循证医学信息及相关教育是首要步骤。GRADINGOFEVIDENCE证据等级TheOxfordCenterforEvidenceBasedMedicinehascomeupwithadetailedhierarchyofevidence,asillustratedinFig.1.12ThehighestformofevidenceremainsasystematicreviewofhomogeneousRCTs.AfurtherstepingradingofevidenceisGRADE(GradesofRecommendation,Assessment,Development,andEvaluation).GRADEallowsforacomprehensive,explicit,andtransparentmethodologyforgradingthequalityofevidenceandstrengthofrecommendationsaboutthemanagementofpatients.13牛津循证医学中心进行了详细的证据分级，见表1。对同一类型的随机对照试验的系统性回顾时最高级的证据形式。更进一步的证据的分级是GRADE（对推荐、评估、发展和评价的分级）。GRADE可以采用综合的明确的透明的方法学对治疗患者的证据的质量以及推荐的力度分级。Surgeonsmaybelievethattheyareatriskoflosingtheirautonomywiththeproliferationofevidence-basedguidelines.Intoday'sapproachtousinginformation,surgeonshavetoconsiderachangefromatraditionalparadigmof''thisishowwehavealwaysdoneit"towardtheapplicationofcurrentbestevidencepracticesbasedonreliableandvalidinformationsources.AttheheartofEBMliestheamalgamationofindividualclinicalexpertise,patientpreferences,andbestavailableevidence.14外科医生们担心随着循证指导的深化，他们的自主权利可能会丧失。如今利用信息的途径中，外科医师们必须改变原来''我们一直这么做”的做法，而应该采用源于真实可靠的信息资源最好的实践证据。循证医学的核心就在于将医师个人临床经验与患者需求、最好的可获得的证据融合在一起。CHALLENGESOFCONDUCTINGRCTSINSURGERY对手术进行随机对照试验的挑战ProponentsofEBMhavealwaysbeencautiousaboutthegeneralizabilityofresultstoaspecificpopulationorsetting.SeveralproblemsinconductingRCTsinsurgeryhavebeenreported.Theseproblemsincludeagenerallackofknowledge,tendencytorigorouslydefendhistoricallyperformedtechniques,learningcurveissues（seniorityusuallyresultsinbetteroutcomes）,difficultyinblinding,andethicalconsiderations.15Onesolutiontoovercomeknownbiasesinsurgicaltrialsistheexpertise-basedRCT.Inthistypeoftrial,asurgeonwithexpertiseinoneoftheproceduresbeingevaluatedispairedwithasurgeonwithexpertiseintheotherprocedurewhoshouldideallybefromthesameinstitution.Subjectsarerandomizedtotreatmentsandtreatedbyasurgeonwhoisan''expert"intheprocedure.ThisstudyovercomessomeofthechallengesassociatedwithtraditionalorthopedicRCTs,includingthecaveatthatsurgeonswhowishtoparticipateintraditionalRCTsmustbewillingtoperformbothtechniques,andthatalackofexpertiseorbeliefinoneoftheinterventionsunderevaluationmayunderminethevalidityandapplicabilityoftheresults.16Arecentsurveyoforthopedicsurgeonsfoundthatmostwouldconsiderthistypeofstudydesignasitmaydecreasethelikelihoodofproceduralcrossoversandenhancevaliditybecause,unliketheconventionalRCT,thereisalowlikelihoodofdifferentialexpertisebias.17Furthermore,positivestepsarebeingmadewiththeadventoflargermulticentertrialsinorthopedicsurgery.18EBM的支持者们一直关注结果对特定人群或环境的普遍性。有报道提出对手术进行随机对照试验中存在几个问题，这些问题包括循证医学知识不足、倾向于保护老的技术、学习曲线问题（年资高者通常结果较好）、难以盲测以及医学伦理学方面等。消除偏差的一个办法是专业的随机对照试验。在这种试验中，一种治疗程序中专业的外科医师与另一种治疗程序的外科医师相比较，他们最好来自相同的机构。研究对象被一种治疗程序的专业外科医师采用治疗，治疗方案随机。这种研究克服了传统骨科随机对照试验中的一些困难，包括参加传统RCT的医师必须掌握两种技术，缺乏对评价中的一种技术的专业性或者信赖，会使结果丧失有效性和适应性。最近调查发现骨科医师认为这种研究设计可以降低发生程序交叉率并且增强其有效性，因为不像常用的RCT,这种研究专业性偏差较低。此外，随着较大的骨科多中心试验出现，人们采取了积极的步骤。THEVALUEOFOBSERVATIONALSTUDIESWHENNORCTSEXIST无随机对照试验时观察研究的价值Asignificantproportionofthesurgicalliteraturefindsitsformasobservationalstudies.Itmustberememberedthatmuchoftheresearchintothecauseofdiseasesreliesoncohort,case-control,orcross-sectionalstudies.Observationalstudiescangeneratesignificanthypothesesandhavearoleindelineatingtheharmsandbenefitsofinterventions.Toensuretherobustnessofreportingobservationalstudies,theSTROBEstatementwascreated.TheSTROBEguidelinesaimtoassistinvestigatorswhenwritingupanalyticalobservationalstudies,tosupporteditorsandreviewerswhenconsideringsucharticlesforpublication,andtohelpreaderswhencriticallyappraisingpublishedarticles.19相当大比例的外科文献采用的形式是观察性研究。必须记住对疾病病因的研究大多数依赖于人群、病例对照研究或者代表性研究。观察性研究可以形成有意义的假设，而且对勾画出干预因素的利与害有着重要作用。STROBE声明保证了报道的观察性研究的稳健性，它帮助研究者们撰写分析性的观察性研究的文章，使编者与评论者得以考虑它是否可发表，帮助读者严格鉴定已发表的文章。LEARNINGTHE''NEW〃LANGUAGEOFEBM学习EBM的''新"语言EBMpractitionersdonothavetobecomestatisticians;however,theydoneedtounderstandkeyconceptsandterminologytooptimizetheirexperiences.循证医学实践者不需要成为统计学家，但是，他们确实需要理解关键的概念和术语来优化他们的经验。RelativeRisk,OddsRatios,andNumberNeededtoTreat相对危险度，优势比和需要处理的数字Iftheendpointofastudyisbinaryordichotomous,suchasmortalityornomortality,thentheoddsratio(OR)orrelativeriskorriskratio(RR)canbecalculated.TheORistheprobabilitythataparticulareventwilloccurtotheprobabilitythatitwillnotoccur,andcanbeanynumberbetweenzeroandinfinity.Riskdescribestheprobabilitywithwhichahealthoutcome(usuallyanadverseevent)willoccur.Measuresofrelativeeffectexpresstheoutcomeinonegrouprelativetothatintheother.Fortreatmentsthatincreasethechancesofevents,theORwillbelargerthantheRR,sothetendencywillbetomisinterpretthefindingsintheformofanoverestimationoftreatmenteffect.ORisforcase-controlledstudiesandRRisforcohortstudies.Absolutemeasures,suchastheabsoluteriskreductionorthenumberofpatientsneededtobetreated(NNT)topreventoneevent,aremorehelpfulwhenapplyingresultsinclinicalpractice.TheNNTcanbecalculatedas1/riskdifference(RD).20如果研究得到的是二元结果或者二分变相，比如是死亡率或者未死亡率，那么优势比或者相对危险度就能够计算得出。优势比就是一个特定事件的发生的可能性与不发生的可能性，数值可能是0到无穷大之间的任意值。风险度是一个健康的结果（通常是有害事件）出现的可能性。相对的方法表示了一组的结果与另一组的结果。对于能够增加事件机会的治疗，其优势比大于相对危险度，所以趋势将会误解结果，表现为高估了治疗效果。优势比是用于病例对照研究，相对危险度则用于群体研究。当将结果应用于临床实践时，一些绝对的措施是非常有帮助的，比如绝对风险的降低、为了阻止事件发生的需治疗的患者的数量。需要治疗的NNT可以由风险差的倒数计算得出。LetustaketheexampleshowninTable1,whichisahypotheticaldatasetfromacohortofpatientswhohadcementinsertedafterhemiarthroplastyandwhowerecomparedwithamatchedsampleofpatientswhodidnothaveanycementinsertedduringhemiarthroplasty.以表1举例，这是一个假设的数据组，其中包含部分在半关节置换时置入了骨水泥的患者和没有置入骨水泥的患者。Theabsoluteriskreduction(ARR),whichisthedifferenceinriskbetweenthecontrolgroupandtheinterventiongroup,iscalculatedasARR=[(c/(c+d)-a/(a+b))]x100%=[(12/(12+60))-(3/(3+50))]x100%=11%绝对风险降低ARR是对照组与治疗组之间风险的差异，计算方法如下。Therelativerisk(RR)istheratioofriskintheintervention(Y)totheriskinthecontrolgroup(X)andassuchRR=(a/(a+b))/(c/(c+d))=(3/(3+40))(12/(12+60))=0.35相对风险RR是治疗组风险Y与对照组风险X的比值，计算如下Therelativeriskreduction(RRR)isthepercentagereductioninriskintheinterventioncomparedwiththecontrolgroup,soRRR=1-RR=(1-x/y)x100%=65%相对危险降低是介入组与对照组风险降低的百分比Bias偏误Allresearchstudiesarepronetoadegreeofbias.Biasistheinclusionofanonrandomsystematicerrorinthedesignofastudy.Severalformsofbiasexist,includingpatientselection(selectionandmembershipbias),studyperformance(performanceandinformationbias),patientfollow-up(nonresponderandtransferbias),andoutcomedetermination(detection,recall,acceptability,andinterviewerbias).Frequentbiasesintheorthopedicliteratureincludeselectionbias,whendissimilargroupsarecompared;nonresponderbias,whenthefollow-uprateislow;andinterviewerbias,whentheinvestigatordeterminestheoutcome.21Anotherkeyformofbiasispublicationbias,whichreferstothegreaterlikelihoodofstudieswithpositiveresultsbeingpublished.22Theexclusionofstudiesforbeingsmallinsize,publishingnegativeresultsorotherwisecanbiastheresults.Eventhougharecentstudyfoundnoevidenceofpublicationbiasintheorthopedicsliterature,itisimportantthatorthopedicsurgeonsknowaboutthefindingsofstudieswithanegativeorneutralresult.23所有的研究都会产生偏误，偏误是研究设计中产生的非随机的系统性错误。偏误有几种类型，包括选择患者（选择与成员偏误）、研究性能（性能与信息偏误）、患者随访（无反应、转让偏误）、结果决策（检测、回忆、可接受性、访问者偏误）。骨科文献中常见的偏误包括选择偏误，当不同的组被比较时；无反应偏误，患者随访率低；访问者偏误，研究者决定其预后。另一种关键的偏误是发表偏误，这是指那些获得阳性结果的文章更加容易被发表，样本量小的、结果为阴性的文章不被发表，也会导致结果的偏误。尽管最近有篇文章认为骨科文献中不存在发表偏误，而骨科医师也必须了解那些结果为阴性或中性的研究。PValuesandConfidenceIntervalsP值与可信区间APvalueistheprobabilitythatresultsasextremeasormoresothanthoseobservedwouldoccurifthenullhypothesiswastrueandtheexperimentswererepeatedoverandover.Confidenceintervalsarearangeof2valueswithinwhichitisprobablethatthetruevalueliesfortheentirepopulationofpatientsfromwhichthestudypatientswereselected.24IthasalreadybeenshownthatPvalues,whensignificant,undulyinfluencetheperceptionsoforthopedicsurgeonsregardingtheimportanceofstudyresults.25Itisworthnotingthatastrictcut-offpointsuchasP<.05isarbitrary,andassuch,thereisatendencytomakebetteruseofconfidenceintervals.Pvaluesgivenoinformationaboutthestrengthoftheassociation,andthePvaluemaybestatisticallysignificantwithouttheresultsbeingclinicallyimportant.Conversely,95%confidenceintervalsrevealthemagnitudeofdifferencesandtheprecisionofmeasurement.21P值是指当零假设为真，实验无限重复下去的情况下，实验结果等于或高于观测结果的可能性。可信区间是指在实验患者所来自的整个人群中，真实值可能存在的范围。P值严重过度的影响了骨科医师对研究结果重要性的理解。值得指出的是，譬如P<0.5这样严格的分界点是随意选择的，因此应更好的利用可信区间。P值提供不了任何信息，它仅仅是统计学上的数据，不存在任何临床意义。相反，95%可信区间揭示了差异的程度与测量的精度。PRACTICINGEBM实践EBMSurgeonslackingproficiencyinEBMmaybemisledbytheorthopedicliterature.Theonusisontheorthopedicsurgeontodeveloparobustmethodtoappraisetheevidence.Thereare5mainstepsinvolvedinthepracticeofEBM.ThisapproachwassuggestedbytheSicilystatementandhavearobustevidencebasesurroundingtheiruse26:不精通循证医学的外科医师也许会被骨科文献引入歧途。他的责任是用可靠的方法评价证据。根据Sicily声明，实践循证医学有五个主要步骤，每一步都有紧紧围绕着证据。AskingaFocusedQuestion提出一个焦点的问题Askingafocusedquestionhelpstotranslateuncertaintyintoananswerablequestion.Toachieveitsgoalthequestionmustincludethefollowingcomponents:Thepatientortheproblembeingaddressed(eg,''inpatientswithfemoralneckfractures.”)Theinterventionorexposurebeingconsidered(eg,''..wouldperformarthroplasty.”)Thecomparisoninterventionorexposure(eg,''...bemoreefficaciousthaninternalfixation.'')Theclinicaloutcomesofinterest(eg,''.andleadtolowermortality,fastermobilization,anddecreasedratesofrevision.'').提出一个焦点的问题可以使不确定问题成为可以回答的问题，为达成这个目标，这个问题必须包含以下几个部分：患者或问题(如：股骨颈骨折患者)选择的干预或者暴露(如：关节置换术)被比较的干预或者暴露(如：是否比内固定更有效)临床结果(如：低的死亡率、更快功能恢复、低返修率)ThesecomponentscanberememberedbythePICO(patient,population,problem,intervention,comparison,andoutcome)mnemonicasshowninFig.2.24这些内容可以记为PICO(患者、人群、问题、干预、比较、结果)，见表2.24FindingtheEvidence寻找证据Findingtheevidenceinvolvessystematicallyretrievingthebestevidenceavailable.Thereareseveralsourcesofinformationotherthantext-bookswhicharestillfrequentlyusedbyorthopedicsurgeons,andtheinformationisoftenoutofdatebythetimeatextbookhasgonetopress.14Medicaldatabasescanbeausefulsourceofinformation.Studiesareusuallyindexedintosearchablefields(suchasauthor,title,source,orsubject).OnepopulardatabaseisMedline/PubMed.PubMedispartoftheUSNationalLibraryofMedicine(NLM)thatincludesover19millioncitationsfromMEDLINEandotherlifesciencejournalsforbiomedicalarticlesdatingbackto1948.MEDLINEisthelargestcomponentofPubMed.Approximately5200journalspub-lishedintheUnitedStatesandmorethan80othercountrieshavebeenselectedandarecurrentlyindexedforMEDLINE.AdistinctivefeatureofMEDLINEisthattherecordsareindexedwithNLM'scontrolledvocabulary,theMedicalSubjectHeadings.27寻找证据包含对可获得的证据的系统性的回顾。教科书上的信息常常在印刷出版时就已经过时了，除了教科书以外，有几个外科医生常用获得信息的途径。医学数据库是一个有用的信息来源。研究常常根据可搜索的关键词建立索引(作者、标题、来源、主题)。一个流行的数据库是Medline/PubmedoPubmed是美国国家医学图书馆的一部分，包含了自1948年以来的一千九百万篇引文，这些引文来自MEDLINE和其他生命科学杂志。MEDLINE是Pubmed的最大组成部分，，大约5200种美国期刊和超过80个国家加入了MEDLINE，它的主要特征是所有记录都可以通过美国国家医学图书馆的医学科目索引词汇表检索。InadditiontobeingabletonavigatepopulardatabasessuchasMedlineorEmbase,orthopedicsurgeonsshouldfamiliarizethemselveswithothersourcesofinformationsuchasCumulativeIndextoNursingandAlliedHealthLiterature(CINAHL),EducationalResourcesInformationCenter(ERIC),PsycInfo,PublicAffairsInformationService(PAIS)International,BandolierBestBETS,andtheCochranecollaboration,tonamebutafew.为了能够浏览这些数据库比如Medline或者Embase，骨科医师必须熟悉这些资源比如护理联合保健累计索引CINAHL、教育资源信息中心ERIC、心理信息、国际公共事务查询台PAIS、Bandolier、BestBets和Cochrane协作网。CriticalAppraisal严格的评价Criticalappraisalisacrucialstepthatinvolvestestingtheevidenceforvalidity,clinicalrelevance,andapplicabilityofastudy.Mostsurgicalevidencedoesnotcomeintheformofmeta-analysesorindeedRCTs.WhenfacedwiththelatestpapercomparinganimplantXversusimplantYorconservativemanagement,thereadermustconsiderafewquestions.BothobservationalstudiesandRCTshaveasetofquestions,whichhelpinthecriticalappraisalofthearticle,andwhichmustresonateinthemindoftheorthopedicsurgeon.ThesequestionsareshowninTable2.28,29严格评价是一个严禁的步骤，它包括测试研究相关的证据效度、临床相关性和适用性。多数手术证据并不是META分析或者真正的随机对照试验。当面对这些最新的文献来比较XY两种植入物或者保守治疗时，读者必须考虑几个问题。观察性研究和随机对照试验都存在一系列问题，这些可以用来严格评价文章，也是必须引起