reviewedregister.com

GSKPublicpolicypositionsApublicationofGlaxoSmithKlineCommunicationsandGovernmentAffairs1PublicDisclosureofClinicalResearchTheIssueThepharmaceuticalindustrycommunicatestheresultsofitsclinicalresearchbypublishinginscientificjournals;bypresentingresultsatscientificcongresses;and,inlinewithestablishedindustrycommitmentsandevolvinglegalrequirements,bypostinginformationandresultsoninternet-basedpublicregisters.
Thisdisclosureisinadditiontosubmissionofinformationtonationalorregionalregulatoryauthoritiesaspartoftheproductdevelopmentorapprovalprocess.
Despitethis,however,concernshavebeenraisedbysomestakeholdersabout:–whetherstudyresultswhichmaybeviewedas"negative"forcompanies'medicinesarepublishedinscientificliterature;–whetherpublishedstudiesaccuratelyreflecttheconductofthestudy;–whethersomejournalarticlesare"ghost-written"(wheredoctorsputtheirnametoarticleswrittenbypharmaceuticalcompanies);–thelackofaccesstotheunderlyingpatientleveldatathatiscollectedduringthestudy.
ThispaperoutlinesGSK'sapproachtoaddressingtheseissues.
Itisanapproachthatdatesbackto2004whenwebecamethefirstcompanytolaunchaninternet-basedclinicalstudyregisterhttp://www.
gsk-studyregister.
com/providingresultsummariesfromourclinicaltrialsofmarketedmedicines(i.
epharmaceuticalsandvaccines)irrespectiveofthestudyoutcome.
Ithasevolvedsignificantlyaswehavesoughtnewwaysofenhancingthetransparencyofourclinicalresearch,includingthatconductedbyourconsumerhealthcaredivision.
GSK'sdisclosurepolicygoesbeyondwhatisrequiredbylawsandregulations.
GSK'sPosition–Beforethefirstsubjectisenrolledinastudy,wepostprotocolsummariesofGSK-sponsoredinterventionalandnon-interventionalstudiesoninternetregisters.
ThisincludesphaseI-IVclinicaltrialsofbothinvestigationalandmarketedmedicinesandconsumerhealthcareproducts.
Thiscommitmentalsoincludespooledanalyses/meta-analysesthatevaluateourproducts.
–WepostourinterventionalstudiesonClinicalTrials.
gov(http://www.
clinicaltrials.
gov).
Wepostournon-interventional,observationalstudiesonourGSKStudyRegister(http://www.
gsk-studyregister.
com).
–Irrespectiveoftheoutcomeofthestudy,wepostresultsummarieswithin12monthsofprimarycompletiondateforinterventionalstudiesand12monthsfromthecompletionofanalysisfornon-interventionalstudies.
Wedonotwaituntilapprovalorterminationofthemedicinebeforepostingresultsummaries.
Atthetimeofresults'registration,wealsopostthefullprotocolandthestatisticalanalysisplan.
–Ourcommitmentincludespostingresultsfromstudiesofterminatedcompoundsinordertohelpinformthescientificcommunityaboutnon-productiveareasofresearchandtoreduceunnecessaryexposureofstudyparticipantstosimilarcompoundsinotherclinicaltrials.
–GSK'scommitmenttopostprotocolsummaries,analysisplansandresultsummariesforallPhaseIstudies(inadditiontoPhasesII-IV)toClinicalTrials.
gov,goesbeyondwhatiscurrentlyrequiredbylawsandregulationsintheUSandEU.
Equally,ourpolicyofpostingasimilarlevelofdetailforallournon-interventionalstudiestoGSK'sStudyRegistergoesbeyondcurrentlegalandregulatoryrequirements.
–Inordertosupportabroaderunderstandingofourclinicalresearch,in2017webegancreating"plainlanguage"summariesofsomeclinicaltrialresults.
Aswegainexperienceandfeedback,wemayincreasinglycreatethesesummaries.
Wepostourplainlanguagesummariesonwww.
trialsummaries.
com.
GSKPublicpolicypositionsApublicationofGlaxoSmithKlineCommunicationsandGovernmentAffairs2–Weconsidertheabovepostingsontheinternettobesupplementaryto,andnotareplacementfor,theneedtopublishstudiesinpeerreviewedjournals.
Ourapproachistosubmitstudiesasmorecomprehensivemanuscriptsforpublicationinpeerreviewedjournals,withanincreasingfocusonopenaccessjournals,thatareindexedbyonlinesearchenginessuchasMedlineandEmbase.
Themanuscriptsaresubmittedwithin18monthsofstudycompletion,regardlessofmarketauthorisationortermination.
–Weaimtopublishallinterventionalandnon-interventionalstudiesthatevaluatetheefficacy,safety,oreffectivenessofourproductsinhumans.
Wealsoaimtopublishotherhumansubjectresearchwhentheresultsprovideimportantscientificknowledgeorarerelevantforpatientcare.
–GSK'spolicyprohibits"ghostwriting"ofjournalmanuscriptsandabstractsbyrequiringauthorshipandacknowledgementsforscientificpublicationsconsistentwiththerequirementsoftheInternationalCommitteeofMedicalJournalEditors(ICMJE).
GSKandexternalmedicalwritersareeithernamedasauthorsorincludedintheacknowledgementsectionofmanuscripts.
–SinceDecember2013,wehavemadeClinicalStudyReports(CSRs1)publiclyavailablethroughourClinicalStudyRegister,oncethemedicinebeingstudiedisapprovedorterminatedfromdevelopment.
WehavealsopostedCSRsforinterventionalclinicaltrials(phaseI-IV)forapprovedandterminatedmedicinesdatingbacktotheformationofGSKin2000,aswellallnon-interventionalstudiesconductedsince2009thathaveevaluatedthesafetyandefficacyofourmedicines.
–ThenamesoftheinvestigatorswhoparticipateinourclinicalstudiesthatwereinitiatedafterJanuary2009areavailableonourClinicalStudyRegister.
GSKalsodisclosespaymentsmadetohealthcareprofessionals(HCPs)andhealthcareorganisations(HCOs)involvedinGSK-sponsoredclinicaltrialsinmarketsincludingtheUSA,Europe,JapanandAustralia.
ThiscommitmentbeganinMarch2011,withdisclosureofindividualpaymentsmadetoUSHCPsandtheirHCOsforresearchstudiesinitiatedfromJanuary2010onwards.
WhileinEurope,wehavepublishedourtransfersofvaluemadetoHCPsandtheirHCOsforresearchactivitiesasanaggregatefiguresince2016.
–InMay2013,GSKlaunchedanonlinesystemtoenableresearcherstorequestaccesstoanonymisedpatientleveldatafromgloballyconductedGSKclinicaltrials(phaseI-IV)ofmedicinesstartedsince2000.
Studiesarelistedonthissystemwithinsixmonthsofpublication.
RequestsforaccesstoparticipantleveldatafromConsumerHealthcarestudiesmayalsobesubmitted.
Thissystemisnowaconsortiumofseveralindustrysponsorsandnon-industryresearchfunders.
Itcanbefoundatwww.
clinicalstudydatarequest.
com.
–Wereinforcethesecommitmentsbycontinuallyassessingourperformance.
Amonthlydashboardofmetricsonourtransparencyactivitiesismaintainedaspartofourinternalbusinessmonitoring.
BackgroundTheClinicalDevelopmentProcessEvaluationofaninvestigationalproductisdonethroughinterventionalclinicaltrialsandisusuallyconductedinfourmainphases.
Eachphaseaddressesdifferentquestionsthatdetermineiftestingshouldproceedtothenextphase.
PhaseI:PhaseIstudiesareprimarilyconcernedwithassessingtheinvestigationalproduct'ssafetyusuallyinasmallnumberofhealthyhumanvolunteers(typicallybetween20and100people)andaredesignedtodeterminewhathappenstotheinvestigationalproductinthehumanbody.
1CSRsareformalstudyreportsthatprovidemoredetailsonthedesign,methodsandresultsofclinicaltrialsandformthebasisofsubmissionstotheUSFDA,EMAandotherregulatoryagencies.
PatientdataintheCSRsandappendiceswithpatientdatalistingsareremovedtoprotectpatientconfidentiality.
GSKPublicpolicypositionsApublicationofGlaxoSmithKlineCommunicationsandGovernmentAffairs3PhaseII:AninvestigationalproductthatpassesPhaseItestingthenmovesontoPhaseII,whichusuallyincludesthe"proofofconcept"stage.
Hereforthefirsttime,itisgenerallyadministeredtocarefullyselectedpatientssufferingfromthediseasewhichtheproductwillpotentiallytreat.
Generally100–300patientsareenrolledinthesePhaseIIstudies.
Prophylacticvaccinetrialsenrolluptoseveralhundredhealthyvolunteers.
Therapeuticvaccinetrialsenrolvolunteerswhoarealreadyinfectedorhavethedisease.
Theaimofthestudiesistodetermineiftheinvestigationalproductaddressestheillnessitisintendedfor,aswellastheamountandfrequencyofdosingnecessarytoachievetheoptimalbenefitsforpatientswiththefewestsideeffects.
PhaseIII:InPhaseIIIstudies,theinvestigationalproductisgiventohundredsandfrequentlythousandsofpatients.
PhaseIIIstudiesrequiredifferingperiodsoftimetocomplete,dependingonthediseasebeingstudied.
PhaseIV:Trialsofaninvestigationalproductmaycontinueafterithasbeenapprovedformarketing.
KnownasPhaseIVtrials,theymayfurtherevaluatetheeffectoftheproductfortheapproveduse;assessotherpotentialuses;oryieldadditionalsafetydata.
Regulatoryagenciesmayrequirethesetrialstoaddressspecificquestions.
Othertypesofclinicalresearch,suchasnon-interventionalresearch(usingdatacollectedduringtheprovisionofroutinehealthcare)andanalysesofdatathatiscombinedfromanumberofclinicaltrials(e.
g.
meta-analyses),areincreasinglyseenasimportantevidenceintheevaluationoftherisksandbenefitsofproducts.
GSK&ClinicalResearchDataTheguidingprincipleforGSKistodisclosepubliclytheresultsofGSK-sponsoredclinicalresearchthatevaluatesourproducts,irrespectiveofwhethertheresultsarelikelytobeperceivedaspositiveornegative.
Likewise,werequireinvestigatorsponsoredstudiessupportedbyGSKtobeconductedandpubliclydisclosedconsistentwithourpolicies.
ToinforminvestigatorsoftheoutcomeofaGSK-sponsoredtrial,GSKaimstoprovidesthemwithasummaryoftheoveralltrialresultswhichweencouragethemtosharewithstudyparticipants.
Internet-basedRegistrationofOngoingClinicalTrialsPubliclyavailableinternet-basedregistrationofongoingclinicalresearchcanhelptoincreaseparticipation.
Italsoprovidesanimportantreferencepointsointerestedpartiescantrackthesubsequentpublicdisclosureoftheresults.
PublicationandInternet-basedPostingofClinicalResearchResultsTraditionally,researchresultshavebeenpubliclydisclosedviapublicationinpeerreviewedscientificliterature;however,therearewellrecognisedconstraintsassociatedwiththisapproach.
Withlimitedjournalcapacity,somestudiesoranalysesmaynotbeconsideredaprioritybysomejournals,andthereforemaynotbeacceptedforpublication.
Attimes,throughagovernancereviewprocess,wealsorecognisethatapublicationattemptwouldbefutileforreasonssuchasearlystudyterminationwithlimitedenrollment.
Postingresultsummariesoninternet-basedregistersispartofasolutionasitensuresthattheresultsofclinicalstudiesareavailableinthepublicdomainwhetherornottheyareacceptedforpublication.
Regulatoryrequirementstodiscloseresearchresultshavethereforearisenandnumerouspublicregisters[e.
g.
http://www.
clinicaltrials.
gov/]havebeenestablishedtoserveasrepositoriesforthisinformation.
Wherewearenotthesponsorofastudy,forexample,wherewesupportastudybyprovidingaGSKproduct,weseekagreementthatexternalresearcherswillpostprotocolandresultsummariesoninternet-basedregistersandsubmittheresultsforpublicationinasearchablepeer-reviewedjournal.
GSKPublicpolicypositionsApublicationofGlaxoSmithKlineCommunicationsandGovernmentAffairs4AuthorshipAuthorshipandacknowledgementsformanuscriptsfollowICMJEcriteria(http://www.
icmje.
org)andaredeterminedbasedonthelevelofintellectualcontributiontostudydesign,dataacquisition,analysisandinterpretation,andwritingorrevisingthemanuscript.
Somejournals,however,haveamorenarrowdefinitionofauthorshipandthisconventionisfollowedforsuchjournals.
Thenamedprimaryauthorforapapermustactivelyparticipateinthedraftingprocessandleadthecontentdevelopmentofmanuscripts.
Theprimaryauthorworkscloselywithco-authorsandtogethertheyhavefinalapprovalauthorityforthemanuscript.
AnyGSKstafforcontractorssuchasprofessionalmedicalwriterswhocontributetothedevelopmentofmanuscriptsforauthors(e.
g.
assistanceinassemblinginitialdrafts,tablesandfigures,collatingco-authorcommentsandrevisingthedocumentbasedonauthorinput)arenamedinthearticleeitherasauthorswhentheircontributionmeetsauthorshipcriteria,orbydescriptionoftheircontributionwithintheacknowledgementssection.
GSKwillprovideauthorsfullaccesstodatasupportingthepublicationincludingaccesstodatatables,finalstudyreports,casereportformsandrawdataasneeded.
Wedonotsuppressorvetosubmissionofmanuscripts;thoughthetimingofsubmissionsmayonoccasionneedtobedelayedtoallowGSKtheopportunitytoseeknecessaryintellectualpropertyprotection.
GSKgenerallydoesnotsupportpublicationofdatafromanindividualcentreinamulti-centretrial.
ItisGSK'spositionthattheresultsfromtheentiretrialshouldbepublishedbeforeinformationfromindividualcentresispublished,andthatindividualcentredatashouldalwaysreferencetheprimarypublicationoftheentirestudy.
AccesstoPatientLevelDataPublicationofclinicalstudiesinthescientificliteratureandresultsummariesonregisterstypicallyonlycontainaggregateddata.
Thesepublicationsthereforehavelimitationsforthosewhowishtoexaminethedatamorecloselyortocombineitwithotherstudiesinmeta-analyses.
Toaddresstheselimitations,thereneedstobegreateraccesstounderlyingpatientleveldata.
InMay2013,wethereforeestablishedanonlinesystemtoallowresearcherstorequestaccesstoanonymisedpatientleveldatafromGSKsponsoredclinicaltrials.
Clinicalstudiesforourmedicinesarelistedonthewebsitewithin6monthsofpublicationoftheprimaryendpointsofthestudy.
Studiesthathavenotbeenacceptedforpublicationandarenolongerbeingprogressedarealsoavailable,asarestudiesofapprovedmedicinesforindicationsthatareterminatedfromdevelopment.
AnonymisedpatientleveldataismadeavailablefromGSKmedicines'studiesprovidedthatanexternalIndependentReviewPanelapprovesanassociatedresearchproposalandtheinvestigatorsignsaDataSharingAgreement.
TheIndependentReviewPanelacceptsorrejectsproposalsbasedonthescientificrationaleandrelevancetomedicalscienceorpatientcare.
ThePanelalsoconsidersthequalificationsoftheinvestigators,themanagementofpotentialconflictsofinterestandpublicationplans.
Accesstothedataisprovidedinasecuremannertohelpensurepatientprivacyisprotectedandthedataisusedonlyfortheintendedpurpose.
Togetherwithothersponsorsofclinicaltrials,GSKisencouragingabroadersharingofclinicaltrialdatatoenableresearcherstocombinedatafrommultiplesponsors(bothindustryandnon-industry),andtohelpensurethatthecontributionofstudyvolunteerstomedicalinnovationisfullyrealised.
June2019