meta分析资料全集之How to do Meta Analysis

HowtodoMetaAnalysisArindam

BasuAssociateDirector,FogartyInternationalTrainingProgramKolkata,IndiaFebruary,2005arin.basu@phone:919830153666Whatismetaanalysis?Quantitative

approachfor

systematicallycombining

resultsof

previousresearch

toarriveatconclusions

aboutthebodyofresearch.Whatdoesitmean?Quantitative:numbersSystematic:methodicalcombining:puttingtogetherpreviousresearch:what'salreadydoneconclusions:newknowledgeThepopularityofmetaanalysesNumberofMetaAnalysispublicationsaresteadilyincreasingsince1993.Wegraphedthecountsofjournalarticlesincluded“metaanalysis”as“publicationtype”fromPubmed,fromyears1993through2004FourStepsofMetaAnalysisIdentifyyourstudiesDetermineeligibilityofstudiesInclusion:whichonestokeepExclusion:whichonestothrowoutAbstractDatafromthestudiesAnalyzedatainthestudiesstatisticallyIdentifyyourstudiesBemethodical:planfirstListofpopulardatabasestosearchPubmed/MedlineEmbaseCochraneReview/TrialsRegisterOtherstrategiesyoumayadoptHandsearch(gotothelibrary...)Personalreferences,andemailsweb,eg.Google(http://)HowtoSearchforliteratureFormulateyourquestionappropriatelyIfyouaresearchingpubmedUseMedicalSubjectHeadings(MeSH)[1]Lookupwordintextword,abstract,title[2]Combine[1]with[2]usingbooleanlogicSetupproperfiltersForOthers,usetextword,abstractHuh?!,whatisbooleanlogic??BooleanLogic:ANDthisisANDzone,coveringcommonareabetweentwoellipsesBooleanLogicORthisisboolean

OR,coveringthetwoellipsesExample:ResearchIssueLet'ssaywewanttoknowwhetherstreptokinaseisprotectivefordeathfromacutemyocardialinfarction.Howshouldwesetupasearchstrategy?WewillsearchpubmedonlyTheSearch“streptokinase”[textword]OR“acutemyocardialinfarction”[textword]producesALLarticlesthatcontainEITHER

streptokinase

OR

acutemyocardialinfarctionanywhereinthetext–inclusive,manystreptokinase[textword]AND“acutemyocardialinfarction”[textword]willcaptureonlythosesubsetsthathaveBOTH

streptokinase

AND

acutemyocardialinfarctionanywhereinthetext–restrictive,fewNext,weshalllookatthePUBMEDScreen…ChooseyourDATABASEhereRemembertochoosebothPUBMED,andMESHforformulatingsearch.ChoosePUBMEDCENTRALforfreearticles!Keepsome,throwoutothers

CannotincludeallstudiesKeeptheoneswithhighlevelsofevidencegoodqualitycheckwithQUOROMguidelinesUsually,MAdonewithRCTs

Caseseries,andcasereportsdefinitelyoutSelectionproblemsaremajorproblemsreadthearticleIsentMA=MetaAnalysis;RCT=RandomizedControlledTrialPlanofActionARETHESTUDIESELIGIBLEFORMA(STEPI)?DISCARDYESNOENTERINTOASPECIFIEDFORMATABSTRACTTHEDATAHowtoAbstractData:GuidelinesCreateaspreadsheet(Excel,orOpenOfficeCalc)Foreachstudy,createthefollowingcolumns:nameofthestudynameoftheauthor,yearpublished

numberofparticipantswhoreceivedinterventionnumberofparticipantswhowereincontrolarmnumberwhodevelopedoutcomesininterventionnumberwhodevelopedoutcomesincontrolarmLet’sdothattoourstreptokinasemyocardialinfarctionstudy,next…SpreadsheetDataforStreptoStudyWecreatedsevencolumnstrial:trialidentitycodetrialname:nameoftrialyear:yearofthestudypop1:studypopulationdeaths1:deathsinstudypop0:controlpopulationdeaths0:deathsincontrolWegotlike22studiestodoourmetaanalysis,afterallAnalyzeDataStatisticallyCombinedatatoarriveatasummary,3measuresEffectSize(OddsRatio)Variancewith95%ConfidenceIntervalTestofheterogeneityTwoGraphsForestPlotFunnelPlotExaminewhythestudiesareheterogeneous,iftheyareUseStatisticalPackages,severalchoicesLet’sseewhatwegotforstreptokinaseversusdeathsfromAMISummaryEstimatesforStreptoStudyMantelHaenszelOR=0.7795%ConfidenceInterval[0.72,0.83]TestofHeterogeneity:Chi-square(df=21)=31.5P-Value=0.07ThepooledOddsRatioshowsthatthosereceivingstreptokinaseatAMIareabout77%atriskofdeath(23%lesslikelytodie)Thatin95outof100suchmetaanalyses,thepooledOddsRatiowouldliebetween0.72and0.83,indicatingastatisticallysignificantprotectiveeffectThatthesestudieswerenotsignificantlyheterogeneousForestPlotThedottedlinepassesacrossnull,or1.0TheRiskEstimateofeachstudyislineduponeachsideofthedottedline,with95%CIspreadasthelineThediamondinthebelowisthesummaryestimateThetwoendsofthediamondindicate95%CITheycallitaforestplotsothatyoudon’tmissthewoodforthetrees!

ThesizeoftheblacksquareboxindicatesweightofthestudyFunnelPlot:whatandhowtoreadPlotstheeffectsizeagainstthesamplesizeofthestudyTostudyafunnelplot,lookatitsLOWERLEFTcorner,that’swherenegativeornullstudiesarelocatedIfEMPTY,thisindicates“PUBLICATIONBIAS”Notethathere,theplotfitsinafunnel,andthattheleftcornerisnotallthatempty,butwecannotruleoutpublicationbiasIssuesinmetaanalysisChoosingamodelFixedeffectsmodelorrandomeffects?BiasinmetaanalysispoorqualityoftrialspublicationbiasQualitycontrolinmetaanalysisQUOROMguidelinesStatisticalSoftwareformetaanalysisFixedEffectsorRandomEffectsModel?conductifitisreasonabletoassumeunderlyingRxeffectisSAMEforallstudiesPooling:MantelHaenszelORTest:testofheterogeneityIfsignificant,goforrandomeffectsmodelshort95%CIforsummarysmallersummaryestimateOR=0.77[0.72,0.83]Conductiftestofheterogeneityissignificant(showsheterogeneity)AssumethatTRUElogoddsratiocomesfromanormaldistributionMethod:DerSimonianLair’smethod(DSL)ofcalculatingOdds’RatioOR=0.78[0.69,0.88]FixedEffectsModelRandomEffectsModelBiasinMetaanalysisPoorQualityofTrialsToavoidthem,learnmoreatCONSORTstatement[]PublicationBiasstudyshowingbeneficialeffectsofnewtreatmentmorelikelytobepublishedthanoneshowingnoeffectnegativetrialsassumedtocontributeless;nevershowupintheliteraturebaseuseseveralapproachestoavoidthi