Evolution of Heterogeneity (I2) Estimates and Their 95% Confidence Intervals in Large Meta-Analyses 英文参考文献.docVIP

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Evolution of Heterogeneity (I2) Estimates and Their 95% Confidence Intervals in Large Meta-Analyses 英文参考文献.doc

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Evolution of Heterogeneity (I2) Estimates and Their 95% Confidence Intervals in Large Meta-Analyses 英文参考文献

EvolutionofHeterogeneity(I2)EstimatesandTheir95% ConfidenceIntervalsinLargeMeta-Analyses KristianThorlund1,2*,GeorginaImberger2,BradleyC.Johnston1,3,MichaelWalsh1,4,TahanyAwad2, LehanaThabane1,5,ChristianGluud2,P.J.Devereaux1,6,J?rnWetterslev2 1DepartmentofClinicalEpidemiologyandBiostatistics,McMasterUniversity,Hamilton,Ontario,Canada,2CopenhagenTrialUnit,Department3344,CentreforClinical InterventionResearch, Rigshospitalet,CopenhagenUniversityHospital,Copenhagen, Denmark,3DepartmentofAnaesthesiaandPainMedicine,TheHospitalforSick Children,Toronto,Ontario,Canada,4DivisionofNephrology,DepartmentofMedicine,McMasterUniversity,Hamilton,Ontario,Canada,5BiostatisticsUnit,FatherSean O’Sullivan Research Centre, St Joseph’s Healthcare –Hamilton, Hamilton, Ontario, Canada, 6Public Health Research Institute, McMaster University, Hamilton, Ontario, Canada Abstract Background:Assessmentofheterogeneityisessentialinsystematicreviewsandmeta-analysesofclinicaltrials.Themost commonlyusedheterogeneitymeasure,I2,providesanestimateoftheproportionofvariabilityinameta-analysisthatis explainedby differencesbetweentheincluded trialsrather thanby samplingerror.Recent studieshaveraised concerns aboutthereliabilityofI2estimates,duetotheirdependenceontheprecisionofincludedtrialsandtime-dependentbiases. Authorshavealsoadvocateduseof95%confidenceintervals(CIs)toexpresstheuncertaintyassociatedwithI2estimates. However, no previous studies have explored how many trials and events are required to ensure stable and reliable I2 estimates,orhow95%CIsperformasevidenceaccumulates. Methodology/PrincipalFindings:ToassessthestabilityandreliabilityofI2estimatesandtheir95%CIs,inrelationtothe cumulativenumberoftrialsandeventsinmeta-analysis,welookedat16largeCochranemeta-analyses-eachincludinga sufficientnumberoftrialsandeventstoreliablyestimateI2-andmonitoredtheI2estimatesandtheir95%CIsforeachyear ofpublication.In10ofthe16meta-analyses,theI2estimatesfluctuatedmorethan40%overtime.Themediannumberof eventsan