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1、STATISTICSINMEDICINE,VOL.6,733-744(1987)META-ANALYSISOFCLINICALTRIALSASASCIENTIFICDISCIPLINE.11:REPLICATEVARIABILITYANDCOMPARISONOFSTUDIESTHATAGREEANDDISAGREETHOMASC.CHALMERS,JAYNEBERRIER,HENRYS.SACKS,HOWARDLEVIN,DINAHREITMAN,ANDRAGURAMANNAGALINGAMClinicalTrialsUni
2、t,MountSinaiSchoolofMedicineofCUNY,IGustaveL.LevyPlace,NewYork,NY10029.U.S.A..andDepartmentofHealthPolicyandManagement,HarvardSchoolofPublicHealth.677HuntingtonAvenue,Boston.MA02115,U.S.A.SUMMARYThereplicatevariabilityofmeta-analysesofcontrolledclinicaltrialshasbee
3、nassessedasameasureofscientificprecision.46of91knownmeta-analysispapersweredividedinto20cohortsofstudiesofthesametherapies.Tencohortscontainedmeta-analyseswithdifferentstatisticalconclusions;14containeddifferingclinicalconclusionswithawiderspreadthan.thestatistical
4、lydifferingstudies.Possiblecausesofvariability,suchasdifferenttrialsincluded,differentpoliciesregardingtheinclusionofnon-randomizedandunpublishedtrials,anddifferentstatisticalmethodologies,werenotobviouscausesofdifferingconclusions.Furtherworkinthisareashouldinclud
5、emultivariateanalysesinordertoexplorepossibleinteractionsinthefactorsaccountingforthevariabilityfoundinreplicatemeta-analyses.KEYWORDSMeta-analysisClinicaltrialsReplicatevariabilityRandomizedcontroltrialsINTRODUCTIONIfmeta-analysisistoassumeanimportantplaceinthetra
6、nsmissionofclinicalresearchdatafromoriginatorstootherinvestigatorsandpractitioners,onemustcarryitoutwithasmuchattentiontoscientificrigoraspossible.Itisretrospectiveresearch,andassuchrequiresmeticulousattentiontothepossibilitythatbiasmayinfluencetheresults.Intwoprev
7、iouspaperswehavesurveyedallofthemeta-analysesofcontrolledclinicaltrialswecouldfindintheEnglishlanguage,andhavecomparedtheresultsofmeta-analysesofmultiplesmallstudieswiththoseoflargeco-operativestudies.Wefoundthatthemajorityofpublishedtrialslackedevidenceofeffortsto
8、controlbias,andpresentedinsufficientdetailsofmethodsemployedtoengenderconfidenceintheirresults.'Intwoofthethreesituationsinwhichwecouldcomparelar
