Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors’ Network

www.elsevier.es/revcolcar

Revista Colombiana de

Cardiología

EDITORIAL

Data Sharing: A New Editorial Initiative of the

International Committee of Medical Journal Editors.

Implications for the Editors’ Network

Fernando Alfonso (MD)

, Karlen Adamyan (MD)

, Jean-Yves Artigou (MD)

, Michael Aschermann (MD)

, Michael Boehm (MD)

, Alfonso Buendia (MD)

, Pao-Hsien Chu (MD)

, Ariel Cohen (MD)

, Livio Dei Cas (MD)

, Mirza Dilic (MD)

, Anton Doubell (MD)

, Dario Echeverri (MD)

, Nuray Enc ¸ (MD)

,

Ignacio Ferreira-González (MD)

, Krzysztof J. Filipiak (MD)

,

Andreas Flammer (MD)

, Eckart Fleck (MD)

, Plamen Gatzov (MD)

, Carmen Ginghina (MD)

, Lino Goncalves (MD)

, Habib Haouala (MD)

, Mahmoud Hassanein (MD)

, Gerd Heusch (MD)

, Kurt Huber (MD)

, Ivan Hulín (MD)

, Mario Ivanusa (MD)

, Rungroj Krittayaphong (MD)

, Chu-Pak Lau (MD)

, Germanas Marinskis (MD)

, Franc ¸ois Mach (MD)

, Luiz Felipe Moreira (MD)

, Tuomo Nieminen (MD)

, Latifa Oukerraj (MD)

, Stefan Perings (MD)

, Luc Pierard (MD)

, Tatjana Potpara (MD)

,

Walter Reyes-Caorsi (MD)

, Se-Joong Rim (MD)

, Olaf Rødevand (MD)

, Georges Saade (MD)

, Mikael Sander (MD)

, Evgeny Shlyakhto (MD)

, Bilgin Timuralp (MD)

, Dimitris Tousoulis (MD)

, Dilek Ural (MD)

, J.J.

Piek (MD)

, Albert Varga (MD)

, Thomas F. Lüscher (MD)

, on behalf of the Editors’

Network European Society of Cardiology Task Force

aChairmanEditors’Network

bEditorinChiefArmenianJournalofCardiology

cEditorinChiefArchivesdesmaladiesducœuretdesvaisseauxPratique

dEditorinChiefCoretVasa

eEditorinChiefClinicalResearchinCardiology

fEditorinChiefArchivosdeCardiologiadeMexico

gEditorinChiefActaCardiologicaSinica

hEditorinChiefArchivesofCardiovascularDiseases

iEditorinChiefJournalofCardiovascularMedicine

jEditorinChiefMedicinskiZurnal

kEditorinChiefSAHeart

lEditorinChiefRevistaColombianadeCardiologia

夽 ThisisajointsimultaneouspublicationinitiativeinvolvingallinterestedNationalandAffiliatedCardiovascularJournalsoftheEuropean SocietyofCardiology.

∗Correspondingauthorat: DepartmentofCardiology. HospitalUniversitario deLa Princesa.Institutode Investigaciónsanitaria IIS-IP.

UniversidadAutónomadeMadrid.C/DiegodeLeón62.Madrid28006.Spain.

E-mailaddress:[email protected](F.Alfonso).

http://dx.doi.org/10.1016/j.rccar.2017.06.001

0120-5633/©2017PublishedbyElsevierEspa˜na,S.L.U.onbehalfofSociedadColombianadeCardiolog´ıayCirug´ıaCardiovascular.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

mEditorinChiefKardiyovaskulerHemsirelikDergisi

nEditorinChiefRevistaEspa˜noladeCardiología

oEditorinChiefKardiologiaPolska

pEditorinChiefCardiovascularMedecine

qEditorinChiefCardioNews

rEditorinChiefBulgarianJournalofCardiology

sEditorinChiefRomanianJournalofCardiology

tEditorinChiefRevistaPortuguesadeCardiologia

uEditorinChiefCardiologieTunisienne

vEditorinChiefTheEgyptianHeartJournal

wEditorinChiefBasicResearchinCardiology

xEditorinChiefAustrainJournalfoCardiology

yEditorinChiefCardiologyLetters

zEditorinChiefCardiologiaCroatica

AAEditorinChiefThaiHeartJournal

BBEditorinChiefJournaloftheHongKongColleageofCardiology

CCEditorinChiefSeminarsinCardiovascularMedicine

DDEditorinChiefCardiovascularMedecine

EEEditorinChiefArquivosBrasileirosdeCardiologia

FFEditorinChiefSydänääni(HeartBeat)

GGEditorinChiefLaRevueMarocainedeCardiologie

HHEditorinChiefDerKardiologie

IIEditorinChiefActaCardiologica

JJEditorinChiefHeartandBloodVessels

KKEditorinChiefRevistaUruguayadeCardiologia

LLEditorinChiefKoreanCirculationJournal

MMEditorinChiefHjerteforum

NNEditorinChiefHeartNews

OOEditorinChiefCardiologiskForum

PPEditorinChiefRussianJournalofCardiology

QQEditorinChiefAnatolianJournalofCardiology

RREditorinChiefHellenicJournalofCardiology

SSEditorinChiefArchivesoftheTurkishSocietyofCardiology

TTEditorinChiefNetherlandsHeartJournal

UUEditorinChiefCardiologiaHungarica

VVEditorinChiefEuropeanHeartJournal Availableonline11June2017

KEYWORDS Editorialethics.

Scientificprocess;

Datasharing;

Clinicaltrial;

Trialregistration;

Authorship;

Conflictofinterest;

Big-data;

ScientificJournals

Abstract The InternationalCommittee ofMedical Journal Editors (ICMJE) providesrecom- mendationstoimprovethe editorialstandardsandscientificquality ofbiomedical journals.

Theserecommendationsrangefromuniformtechnicalrequirementstomorecomplexandelu- siveeditorialissuesincludingethicalaspectsofthescientificprocess.Recently,registrationof clinicaltrials,conflictsofinterestdisclosure,andnewcriteriaforauthorship-emphasizingthe importanceofresponsibilityandaccountability-,havebeenproposed.Lastyear,anewedito- rialinitiativetofostersharingofclinicaltrialdatawaslaunched.Thisreviewdiscusses this novelinitiativewiththeaimofincreasingawarenessamongreaders,investigators,authorsand editorsbelongingtotheEditors’NetworkoftheEuropeanSocietyofCardiology.

©2017PublishedbyElsevierEspa˜na,S.L.U.onbehalfofSociedadColombianadeCardiolog´ıa yCirug´ıaCardiovascular.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://

creativecommons.org/licenses/by-nc-nd/4.0/).

PALABRASCLAVE Éticaeditorial;

Procesocientífico;

Compartirdatos

;Registrodeestudios clínicos;

Intercambiodedatosenred:unanuevainiciativaeditorialdelComitéInternacional deEditoresdeRevistasMédicas.ImplicacionesparalaReddeEditores

Resumen ElComiteinternacionaldeeditoresderevistasmédicas(CIERM)proponerecomen- daciones para mejorar los estándares editoriales y la calidad científica de las revistas biomédicas. Estas recomendaciones abarcan desde requerimientos técnicos uniformados a temaseditorialesmáscomplejosyevasivos,comolosaspectosbioéticosrelacionadosconel proceso científico.Recientementese hanpropuestoalgunas iniciativas editoriales, como el registrodelosensayosclínicos,ladeclaracióndelosconflictosdeinterésylosnuevoscriterios

Autoría;

Conflictodeinterés;

Bigdata;

Revistascientíficas

paraautoría(quedestacanlaresponsabilidaddelosautoressobreelestudio).Ela˜nopasado sepresentóunanuevainiciativaeditorialpararesaltarlaimportanciadecompartirlosdatos generadosenlosestudiosclínicos.Enesteartículosediscuteestanuevainiciativaeditorial,con laideadedifundirsuconocimientoentreloslectores,investigadores,autoresyeditoresdela reddeeditoresderevistascardiovascularesnacionalesdelaSociedadEuropeadeCardiología.

©2017PublicadoporElsevierEspa˜na,S.L.U.ennombredeSociedadColombianadeCardiolog´ıa yCirug´ıaCardiovascular.Esteesunart´ıculoOpenAccessbajolalicenciaCCBY-NC-ND(http://

creativecommons.org/licenses/by-nc-nd/4.0/).

TheEditors’Network oftheEuropeanSocietyof Cardi- ology(ESC)iscommittedtopromotingtheimplementation ofhigh-qualityeditorialstandardsamongESCNationalSoci- etiesCardiovascularJournals(NSCJ).^1---4NSCJplayamajor roleindisseminatinghigh-qualityscientificresearch.How- ever, they also play a relevant role in education and harmonization of clinical practice.³ Most NSCJ are pub- lished in local languages, but many have English editions andhavegainedinternationalscientificrecognition.^1---4NSCJ well complements official ESC journals and, altogether, provide an effective means to disseminateEuropean car- diovascularresearch.Inaglobalizedandhighlycompetitive editorialenvironment,promotinghighqualityeditorialstan- dards remains of paramount importance to increase the scientificprestigeofNSCJ.^1---4Fromitsconception,theEdit- ors’Networkstrongly advocatedfor theadherencetothe uniformrecommendations ofthe International Committee ofMedicalJournalEditors(ICMJE).¹Initsmissionstatement documentthe Editors’Network committedto adapt NSCJ tofollow thesegeneraleditorial recommendations.¹How- ever,NSCJarehighlyheterogeneousinscopeandcontents andthesenewrecommendationsshouldbeembracedpro- gressively,considering currently existingeditorial policies andtheeditorialfreedomoftheNSCJ.^1---4Ethicalissuesplay agrowing rolein ensuring thecredibility ofthe scientific process.^5---13 Biomedical researchrelies ontrust. However, transparencyalsorepresentsamajortenetinthescientific process.^5---8 This review willdiscussthe neweditorial rec- ommendationsondatasharingissuedbytheICMJE.¹⁴ Novel ICMJErecommendationsalwaysappearasprovocative,and oftenastooambitious,wheninitiallypresented.Moreover, implementation of editorial changes is rather demanding from a technical and logistical viewpoint. Adherence to novel editorial initiativesis challenging notonly for edit- ors,butalsofortheentirescientificcommunity.Therefore, many Editors have a natural tendency to avoid stepping aheadasearlyadoptersofnew‘‘editorialexperiments’’and usuallyprefertokeepmovingwithintheircomfortzoneuntil the ‘‘sea change’’ has matured.^1---4 However, experience hastaughtusthatalleditorialinitiativesdevelopedbythe ICMJEeventuallyprevailedandplayedacriticalroleinmain- taining the credibility of the scientific process.^9---13 Highly successfulrecentexamplesincludetrialregistration,acon- flicts of interest initiative and the new requirements for authorship.^9---13The novel ICMJE recommendations on data sharing¹⁴ arediscussed hereinfroma didacticperspective withtheaim toprovide neweditorial insights and,hope- fully,tobeprogressivelyadoptedandimplementedbythe NSCJ.

Sharing Clinical Trial Data: The New ICMJE Proposal.

The ICMJE considers that there is a moral obligation to responsiblysharethedatageneratedbyclinicaltrials.¹⁴The rationale underlying this global endeavor is that patients have assumedariskbyaccepting toparticipateinatrial.

Accordingly, making the obtained data publicly available representsaresponsibleinitiativetofacilitatetheadvance- mentofscience.Sharingthedatawouldincreasetrustinthe conclusions reached by trials.Indeed,data sharingallows confirmationoftheresultsbyindependentresearch.¹⁴Fur- thermore, new hypotheses may be pursued by different groupsofinvestigators.Thisinitiativemayfosterthelever- aging of data to answer different research questions not contemplated in the original study. If science becomes an open process,then manyresearcherswould benefitby taking advantage of reliable data generated somewhere else. Therefore,data sharingemergesasthe bestwayto ensurethat alltheinformationgatheredbytrialsis made freely andwidelyavailable,sothatit canbereadilyused to advance scientific knowledge.¹⁴ The use of previously collecteddatatofurtheradvancescienceisdifficulttocrit- icize. As discussed, this honours the volunteerism of the patients whosigned up andconsented to participatein a trial.

Governments,fundingagencies,scientificsocieties,the industryand eventhelaysociety growinglydemand shar- ing clinical trial data.Therefore, the ICMJEsuggests that editors should help to meet this ethical obligation by devising neweditorial policies specificallyaddressing this issue.¹⁴ Proponentsof ‘‘open science’’ should be pleased by this new editorial requirement of sharing clinical trial data.¹⁴

Thefirstconsiderationistoclarifywhataclinicaltrialis exactly.AccordingtotheICMJEdefinition,aclinicaltrialisa studythatprospectivelyassignspeopletoaninterventionin ordertoassessthecause-and-effect relationship between thatinterventionandtheensuinghealthoutcome.⁵

The ICMJE considers that sharing ‘‘de-identified’’

individual patient data should become part of the pub- lication process of clinical trials.¹⁴ This strategy protects patient’sconfidentialityrights.Therequirement,however, isrestrictedtotheindividual-patientdataunderpinningthe results presented in the published article. Importantly, a clearplanfordatasharingshouldbedisclosedatthetime ofinitialtrial registrationandshouldbealsopresentedat the timeof manuscriptsubmission. The proposal requires clinical trialists todeclare that theywillshare their data

publicallyasaprerequisiteforpublishingthetrial.¹⁴ They shouldpromisetofreelyreleaseindividualpatientrawdata atthetimetheysubmitthemanuscriptforconsideration.

It is important to keep in mind that clinical trial reg- istration was a previous ICMJE editorial initiative aimed to address problems related to publication bias (selec- tivepublicationofpositivetrials),endpointsinconsistency andredundantresearch.^9,10 Potentially,publicrepositories provide an optimal tool not only for initial trial registra- tionbutalsoforindividual-patientdatasharing.Fromnow on the plan for data-sharing would be an important step of the clinical trial registration initiative.^9,10,14 Details on whetherthedatawouldbefreely available uponrequest, or only after a formalapplication thateventually will be approvedafteran agreementis reached ondatausecon- ditions,shouldbepresented.Finally,ithasbeen proposed thatthedatashouldbemadepublicnomorethan6months afterpublicationoftheoriginal studyin thejournal.^9,10,14 Clinicaltrials.com, a widely used non-for profit scientific repository,^9,10 hasalreadyadapteditsregistrationplatform tospecificallyclarifydata-sharingplansatthetimeofclin- icaltrialregistration.

Obviously,thiseditorialinitiativemayhaveprofoundcon- sequences on the planning, conduction and reporting of clinical trials and,in fact, maydeeply influence research andpublicationstrategies.¹⁴Asaresult,theideaistoimple- mentthis requirementfor anyclinical trialthat beginsto enrollpatients1yearaftertheofficialadoptionofthisedi- torialpolicybythecorrespondingjournal.¹⁴ Theinitiative willalsohavemajorimplicationsfortheeditorialprocess.

Indeed, Editors are supposed to monitor the data shar- ingprocessand,eventually,addresspotentialirregularities.

Thesemightincluderequestsofclarificationtotheauthors, notificationtoacademicinstitutions,publicationofexpres- sionsofconcernorevenretractions.

Finally, the ICJME acknowledges that the rightsof the investigatorsandsponsorsshouldbeprotected.¹⁴Moreover, credittotheoriginalreportshouldbegrantedbyincludinga uniqueidentifierofthedataset.Itisemphasizedthatcredit should be always given to the original investigators that postedthedataafterpublicationoftheirresearch.Further- more,additionalinvestigatorsusingthesedatabasesshould requestcollaborationoftheinvestigatorsthatoriginallycol- lected the data to ensure adequate data interpretation, managementandanalysis.

ChallengesofDataSharing:

Although it appears clear that this initiative will further improvetransparencyandtheoverallintegrityofthescien- tificliterature,someremainingissuesneedtobeaddressed.

Thereisinherentresistancetoembraceopenscienceinitia- tivesfromsomeacademicinstitutionsorinvestigatorsthat defendtheideaof exploitingtheir‘‘own’’ data.^15,16 Until now clinical researchers were discouraged from working withclinicaltrialdatatheydidnotgeneratethemselves.^15,16 Likewise, trialists tended to see trial data as their per- sonalpropertyandwouldroutinelyrefuserequestsfordata sharing. In fact,until very recentlymost researchers and pharmaceutical industry groups were opposed to making raw data available after trial publication. This practice, however, differs from other disciplines (as genomics or

economics)wheredatasharinghasbeencommonplacefor alongtime.^15,16

Obtainingreliable,high-qualityoriginal datarequiresa majorresearcheffort.Allowingasufficientperiodof time fromthetime ofarticle publication totheneed toshare the raw data would give original investigators the possi- bilityofpublishingadditionalsubgroupanalysesfromtheir owndata.¹⁴Thisnewproposalwillfurtherincreasethepres- sureonacademicinvestigatorsthatfrequentlydonothave therequired resources to publish theirsubsequent analy- sesandrequiretimetopreparethenewthemanuscripts.¹⁴ Notably,mostresearchershavenoexperiencewiththepro- cessofreleasingordealingwithpublicdata.Furthermore, theeffortandresourcesrequiredtoorganizetherawdata inawaythatwouldbecomprehensibletootherinvestiga- torsremainacauseofmajorconcern.¹⁴ Thiswouldrequire technicalsupportandadequatefunding.

Data-accesstonon-trialresearchersmaydisclose prob- lemsnot recognizedby the initial investigators. Although thiswillincreasetransparencyand,therefore,trustintrial results, it might also generate confusion and undue sci- entific controversies. It is difficult to envision how the newresearcherswillgaintherequireddetailedknowledge of the complicated datasets enjoyed by the original trial investigators.¹⁴Areliableassessmentofthedatarequiresa deepknowledge on the study background and to beable to properly address many nuances and practical consid- erations. These include precise information on the way variables were defined,how data was collected and how resultswerefinally codedand enteredinto thedatabase.

The initiative might be fraught with problems related to incorrectanalysisresultingininaccurate resultsanderro- neousinterpretations,potentiallydamagingscience.¹⁴

Finally, Editors, already deluged with work, will need to check that all of the raw data of the published arti- cles eventually has been released as promised. Different results may emerge from misconceptions regarding what datashould beanalysed toanswer specific questions.¹⁴ If therearedifferencesinresults,itwillbedifficulttodecide whichanalysisprovidesthemostaccuratereflectionofthe data.This couldgenerate undue ‘‘scientific noise’’, with contradictoryresults andrectifications,which maygener- ateconfusion and frustration in thescientific community.

Finally, this may also promote the simultaneous publica- tioninseveraljournalsofconflictingresultsfromthesame databasebydifferentgroups.¹⁴

Asmanyissuesstillshouldbeclarified,theICMJEasked forfeedbackonitspreliminaryeditorialproposalonclinical trialdatasharing.¹⁴ Obviously,the initiativewillonlygain therequiredmaturityfromtheexperiencegainedduringits adoptionandimplementation.

PreviousinitiativesonDataSharing:

Severalleading academic entitiespreviously have worked inthisfield.TheBritishMedicalJournalpioneeredan edi- torialinitiative of datasharing.¹⁷ In 2012 thispolicy took effectonlyfortrialsondrugsanddevicesbut,in2015,the requirementofdatasharing‘‘onrequest’’wasextendedto allsubmittedclinicaltrials.¹⁷Ithasbeenproposedthatindi- vidualpatientdatamayalsobeofmajorvalueduringthe

‘‘peerreview’’processbypermittingindependentverifica- tionoftheresultsbeforefinalpublication.¹⁸ Althoughthis initiative might be of potential value most reviewers are alreadydelugedwithworkandthisextrataskcouldgener- atefatigueandburnoutphenomena.Inaddition,manygood clinicalreviewersdonothavetheexpertiserequiredtoman- agedataandtoperformconfirmatorystatisticalanalyses.¹⁸ Somejournals,asJAMA,previouslydevelopedsomerelated editorial initiativesincludingthe request for independent statisticalanalysesbyanacademicstatisticianofindustry- sponsoredtrials.¹⁹

TheWorldHealthOrganization(WHO)andtheInstitute ofMedicine (IOM) previouslymade importantdeclarations onclinicaltrialtransparency.Inthisregard,theIOMissued specific guidelines for trial data sharing.²⁰ WHO initially presentedastatementonpublicdisclosureofclinicaltrial resultsand, subsequently,encouragedsharing of research datasetswheneverappropriate.^21---23Morerecently,theWHO developedglobalnormsforsharingdataandresultsduring public health emergencies, with special focus on clini- cal,epidemiologic,andgeneticfeaturesofnewinfectious diseases and experimental therapeutics and vaccines. In emergency situations, data needs to be shared quickly beforetheinformationisformallypublished.²³

Finally, the National Health, Lung and Blood Institute (NHLBI)presenteddetaileddata-sharingpracticesallowing publicaccesstotrialrawdataanddevelopedadatarepos- itorycurrently includingover half a million patients from over100trialsandobservationalstudies.²⁴In2015theNHLBI discusseditsintenttomakepublicthedigitaldatafromits fundedtrials.²⁴

Platforms and Repositories.

Upto30,000 clinical trialsareconductedannuallyworld- widegeneratingahugevolumeofpatient-levelrawdata.²⁵ Currently,however, available portalsfor data sharing are stillnot adequate. Most of them require a time consum- ing request, including a detailed research proposal with thestudy design, main endpoints anda statistical plan.²⁵ The submitted proposal is then reviewed by an indepen- dent researchpanel thatdecides whethertoapprove the request for data.^21,25,26 Currently, this process takes too longandwhen eventuallythedatais obtainedoftentimes it is not readily usable.²⁵ However, the means to facili- tate datasharing from the dataholder tothe researcher maybecumbersome andchallenging toimplement.Some systemsprovide an electronic formor template.²¹ Never- theless,whenthesearenotavailablea‘‘denovo’’proposal shouldbegenerated outlining thepurpose, the statistical analysis plan, the research team, and potential conflicts of interest. The review process maycome froman inter- nal or external review panel selected by the data holder orbyathirdparty.^25---27Finally,datacanbesharedthrough apublicwebsiteorby directcommunicationbetweenthe data holder and the researcher. In most cases, however, controlledaccessisrequired.Beforeanyanalysisisstarted reviewingalltheaccompanyingdocumentationtoassistthe researcherintheunderstandingoftheoriginalclinicaltrial andthemethodologyused,remains critical.Furthermore, thedataholdermayrequirealegallybindingdatasharing

agreementandshouldbeavailabletoprovidetherequired supportshouldquestionsarise.²⁷

Major care should be taken toprevent the perils that mayunderminethevalueofdatasharing.¹⁴Datafromtrials shouldberesponsiblyused.²⁸ArecentsurveyfromUKClini- calTrialUnitsdisclosedsomepotentialrisksassociatedwith datasharing.²⁹Thesebasicallyincludeda)misuseofdata,b) incorrectsecondaryanalyses,c)resourcerequirementsand d)identificationofpatients.^29,30Researchersareresponsible for presentingthedatainaformatamenableforexternal secondaryuse.Repositoriesshouldbepreparedtomakeraw dataavailableinstandardizedplatformsinafullycompre- hensive manner.Datasharingfromtrialswithanonymized patient-leveldatawithassociatedmetadataandsupporting informationshouldbemadeavailabletootherresearchers following an independent analysis of the research pro- posals. Developing and adopting standard approaches to protectingpatientprivacy areurgentlyrequired.¹⁴ Finally, anadequate infrastructureshouldbeorganizedtosupport effectivedatasharing.Inthisregard,theroleoftheindus- try issignificantly growingasdemonstratedby somejoint initiatives, such asthe Yale University Open Data (YODA) project.^16,31

Someacademic researchorganizationconsortiums par- ticularlyfocussedonthestudyofcardiovasculardiseases,³² have developed interesting tools for data sharing. This cardiovascular initiative requires presentation of a stan- dardized request in a Web portal. Proposals are to be analyzedbyascientificcommittee,includingmembersdes- ignatedbytheconsortiumandastatisticianalongwiththe trial’sprincipalinvestigator.The ideaistoensureanade- quateuseofthedatabaseandcorrectstatisticalanalyses, whileavertingtheproblemofmultipleinvestigatorspropos- ingthesameanalyses.³²

StatisticalIssues:

Statisticians play a key role in developing data sharing strategies.¹⁹ Theyshouldbeinvolvedfromtheverybegin- ning to organize the research strategy and the required analyticaltechniques.¹⁹Inthisscenariostatisticiansshould move fromtheir classical roleasdata ‘‘gate-keepers’’to thatofdata‘‘facilitators’’.¹⁹Adatasharingworkinggroup of medical research statisticians has been recently cre- atedfromthepharmaceuticalandbiotechnologicalindustry and from academia.The ideawas to address the techni- cal and statistical challenges of accessing research data forre-analyses.Specifictechniquesarerequiredtoensure adequate data manipulation to convert the data initially collected and entered in the data base into data that is analyticallyusable.Convertingraw dataintostandardized formatsmaybechallenging.Moreover,familiaritywiththe requiredstatisticalprograminglanguageisnecessary.Inde- pendentstatisticiansshouldplayamajorroleinguidingthe principlesofre-analysisbasedontheresearchers’request while,atthesametime,guardingagainstmisleadingconclu- sions. They shouldbe fully awarethat additionalanalysis mayyielddifferentresultscomparedwiththeoriginalanal- yses.Accordingly,theyshouldbepreparedtofacecriticism but,atthesametime,theyshouldbeabletoopenlychal- lengepreviousstatisticalmethods.¹⁹

Statistical guidance may be required for appropriate interpretation of resultsfrom re-analyseswhere different methods have been utilized. In particular, it is important to keep in mind the inherent risk of over-interpretation of the results from multiple subgroup analyses.³³ Like- wise,documents forbestpractices indata anonymization have beendeveloped.³⁴ Statisticiansshould bealsofamil- iar withthis methodology. Risk to patientprivacy can be mitigated by datareduction techniques. Dataholders are responsible for generating de-identified datasets to offer protection for patient privacy through masking or gener- alization of main identifiers. In addition, legally binding datasharingagreements shouldincludeacompromisenot to attempt to identify patients.³⁴ In particular, it is rec- ommended that data use agreements are signed by the data holderand researchers. Only appropriately qualified

‘‘named’’researchersshouldbegrantedaccesstothedata.

Finally,highsecuritylevelsshouldbeimplementedfordata transferring.Resources,costsandeffortrequired tomake patient-leveldataavailableforthirdpartyresearchmaybe considerable and, therefore, adequate funding should be organized.³⁴

CredittotheOriginalAuthors

A clear motivation for researchers to conduct random- ized clinical trials is the opportunity to publish different studies in addition to the main manuscript with the pri- maryendpoint.Thesesecondaryanalysesmaybeofmajor valuetounravelnewfindingsfromtheoriginaldataset.^35,36 Many have proposed that the time to open the process of data sharing should be extended to 2 years, or even to5 years in selected complexor large studies. This will allow a precioustime for original investigatorsto further scrutinizeand analyze in depththeir own data.As blind- ing is necessary during trial execution, once the study is completed the research teams concentrate on publishing the primary findings as soon as possible. Following this, usually there is a series of pre-planned additional analy- ses.Thesestudies areorganizedbycollaborativeresearch teamsfromdifferentinstitutions,butusuallywithrelatively poor support. Secondary analyses are also very impor- tant for co-investigators and junior scientists. To respect this legitimate interest an extension from the 6 month- periodaftertheprimarydatahasbeenpublishedhasbeen advocated.^35,36

Academia rewards scientists withrecognition for mak- ing their discoveries public. Credit should be granted to the original researchers that create data sets that other investigatorsfinduseful.^14,15 Otherwise,originalinvestiga- tors may be tempted to consider ‘‘research parasites’’, thoseperformingsecondaryanalysesoftheirdata.Further- more,mechanismsarerequiredtoensurethattheexternal analysesareconductedadequatelyandnotmerelytounder- mine the original findings. Direct collaboration between primaryandsecondaryresearchersis,therefore,necessary toensure properdataanalysisandinterpretation.^14,15 The originalinvestigatorswhodesignedandconductedthetrial and obtained sources of founding deserve to receive the adequatescientificcredit.²⁸

Conclusions

The data transparency revolution is here to stay. This is justanotherstepaheadintoaculture of‘‘open science’’

anditis clearthat weareat thedawnof anewage.^37,38 SeveralEuropeanNationalSocietieshavealreadydeveloped registryprogramsinwhichtheregistriesdatabasesarepub- lic for the use of their members.³⁹ Major challenges and hurdles in the adoption and implementation of the new ICMJE recommendation should still be overcome.⁴⁰ Expe- rience gained by leading journals will eventually allow a balancedcompromisebetweentheinterestsoftheoriginal researchersandthatofthescientificcommunityasawhole.

NSCJshouldprogressivelyadapt their policies toincrease awarenessoftheimportanceofdatasharingandpromote policies designed to enhance transparency in biomedical research.

Disclosures

NoneoftheEditorsorauthorsofthispaperhasanypotential conflictofinterestthatneedstobedisclosedinrelationto thismanuscript.

Conflict of interest

None.

Acknowledgements

Wearegratefulfor thesupportandassistanceof Ismahen OuertaniandMichaelAlexanderfromtheESCPublications DepartmentattheEuropeanHeartHouse.

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