Discoverafaster,simplerpathtopublishinginahigh-qualityjournal.PLOSONEpromisesfair,rigorouspeerreview,broadscope,andwidereadership–aperfectfitforyourresearcheverytime.
ClickthroughthePLOStaxonomytofindarticlesinyourfield.
OpenAccess
Peer-reviewed
ResearchArticle
Theallegedefficacyofpharmaceuticalindustryself-regulationhasbeenusedtorepudiateincreasedgovernmentoversightoverpromotionalactivity.EuropeanpoliticiansandindustryhavecitedSwedenasanexcellentexampleofself-regulationbasedonanethicalcode.ThispaperconsidersantidepressantadvertisinginSwedentouncoverthestrengthsandweaknessesofself-regulation.
WeanalyzedallantidepressantadvertisementsintheSwedishMedicalJournal,1994–2003.Theregulationoftheseadvertisementswasanalyzedusingcasereportsfromself-regulatorybodies.Theauthorsindependentlyreviewedthismaterialtoinvestigate:(1)extentofviolativeadvertising;(2)patternofcodebreaches;(3)rateatwhichthesystemreactedtoviolativeadvertising;(4)prevalenceofandoversightoverclaimsregardingantidepressantefficacyanddiseasecausality,and(5)costsformanufacturesassociatedwithviolativeadvertising.
Self-regulatorybodiesidentifiednumerouscodebreaches.Nonetheless,theyfailedtoprotectdoctorsfromunreliableinformationonantidepressants,sinceasmanyas247of722(34%)advertisementsbreachedtheindustrycode.Self-regulatorybodiesrepeatedlyfailedtochallengeinflatedclaimsofantidepressantefficacy,lendingevidenceoflaxoversight.Onaverage,15weekselapsedbetweenprintingandcensureofawrongfulclaim,andin25%ofcases47weeksormoreelapsed.Industrypaidroughly€108000infinesforviolativeadvertising,addinganestimatedadditionalaveragecostof11%toeachpurchasedviolativeadvertisement,oramountingtoaslittleas0.009%oftotalantidepressantsalesofaround€1.2billion.
Laxoversight,combinedwithlagsinthesystemandlowfinesforviolations,mayexplaintheSwedishsystem’sfailuretopressurecompaniesintoprovidingreliableantidepressantsinformation.Iftheseshortcomingsprovetobeconsistentacrossself-regulatorysettings,andifappropriatemeasuresarenottakentoamendshortcomings,manycountriesmaywanttoreconsiderthecurrentbalancebetweenself-regulation,andlegislativecontrolwithgovernmentoversight.
Editor:BarbaraMintzes,UniversityofBritishColumbia,Canada
Received:June6,2012;Accepted:March26,2013;Published:May1,2013
Competinginterests:Theauthorshavedeclaredthatnocompetinginterestsexist.
(A)OutlineoftheSwedishself-regulatorysystem.ThePharmaceuticalIndustry’sInformationExaminer(IGM)monitorsindustrypromotionalmaterialforpotentialcodebreaches.TheIGMalsohandlescomplaintsfromhealthprofessionals(HP),pharmaceuticalcompaniesandthegeneralpublic.OffendingcompaniesaresanctionedbytheIGM.BesideshandlingappealsofIGMdecisions,theInformationPracticesCommittee(NBL)considerscomplaintsfrompublicauthorities,suchastheMedicalProductsAgency(MPA),andsanctionscodebreaches.(B)OverviewoftheflowofcasesconcerningantidepressantadvertisingintheSwedishMedicalJournalin1994–2003includingnumberofcasesinstigatedbyvariousactors.Ofthe24casesconsideredbytheIGM/NBL,23werefoundtobeinviolation.
WeusedantidepressantadvertisementsprintedintheSwedishMedicalJournaltoinvestigatetheworkingsoftheSwedishself-regulatorysystemofmedicinespromotion.
Informationobtainedfromthesesourceswereusedto:
Toevaluatethestrengthofregulatoryoversight,weconsideredtwoclassesofpromotionalclaimsthathavebeenwidelycriticized:(1)claimspertainingtodrugefficacyinthetreatmentofdepression,and(2)claimspertainingtothebiologicalunderpinningsofdepression.Withrespecttoclaimsaboutdrugefficacy,weconsideredtwotypesofclaims:generalclaimsaboutantidepressantefficacythatdidnotmakedirectproductcomparisons,andcomparativeclaimsthatdid.AlladvertisementscontainingsuchclaimswereidentifiedandcomparedtoretrievedcasereportstoidentifybreachesuncoveredbytheIGM/NBLrelatedtotheseclaims.
Anotherwayofgaugingtheeconomiccostofpublishingmisleadingadvertisementsistoconsiderthemagnitudeoftheadministrativefinesinrelationtothecostofbuyinganadvertisement.Tothisend,weestimatedtheadditionalaveragecostaddedbyadministrativefinestoeachpurchasedviolativeantidepressantadvertisement.Inafirststep,weestimatedthecostofantidepressantadvertisingusingadvertisingratespublishedintheSwedishMedicalJournal.In1997,forexample,aregularone-pagecoloradvertisementcostroughly€3100.Wewereunabletoestablishadvertisingratesforeveryyear,andwhenqueried,thejournalfailedtoprovideuswiththemissingdata.Formissingyears,weestimatedratesbasedonoverallyearlyrateincrements.Tocalculatethecostofviolativeantidepressantadvertising,weusedtheserateestimatestogetherwiththecodedinformationontheratecategoryofeachviolativeadvertisement(seeabove).Inasecondstep,wedividedtotaladministrativefinesbythetotalcostofviolativeantidepressantadvertising.
Shiftsinvariablesovertheten-yearperiodweretestedusinglinearregression.Differencesbetweengroupswereanalyzedbynon-parametricMann–Whitneytest.StatisticalanalyseswereperformedusingGraphPadPrism5.0(Graphpadsoftware,LaJolla,CA,USA).
(A)Graphsshowantidepressantsales(inEURmillion)(dottedline)inSwedenin1991–2011andtotalantidepressantadvertisements(redunbrokenline)intheSwedishMedicalJournalin1994–2003.Spendingonantidepressantsrosesteeplybetween1993and1996,aswellasbetween1999and2001,butsubsequentlyplateauedandstartedfalling,coincidingwithadropinantidepressantadvertising.(B)Decliningantidepressantspending(dottedline)andadvertisingdidnotcoincidewithadropinprescriptions(unbrokenline),butinsteadcoincidedwithpricecutsduetomajorpatentexpiries.(C)Graphsshowtotal(redline)andviolative(blackline)antidepressantadvertisingintheSwedishMedicalJournalin1994–2003.
Graphsshowestimatedpurchasingcostsforunethicalantidepressantadvertisements(unbrokenline),accordingtoIGM/NBLstandards,intheSwedishMedicalJournalin1994–2003andtheadministrativefinesforoffendingcompanies(dottedline)overthesameperiod(inEURmillion).
Inappropriatelylowfinesrepresentyetanotherareaofmajorconcern.Strikingly,wefoundthatfinescorrespondedtoaslittleas0.009%oftotalantidepressantspendingovertheperiod,andthattheyaddedanestimatedadditionalaveragecostof11%toeachpurchasedviolativeadvertisementinoursamplewithnoevidenceofchangeovertime.Arguably,suchfinesmaymerelybeacceptedasthe“costofdoingbusiness”anddonotserveasasignificantdeterrentforcompanieswithsalesinthebillions.Presently,finesarecalculatedbasedonthecostofadministeringtheself-regulatorysystem.Thefactthatdelinquentcorporationspayadministrativefinesaimedatkeepingtheself-regulatorysystemafloat,ratherthanprovidingcompensationfordamagescausedby–andprofitsgeneratedasaresultof–misleadingdrugpromotionrepresentsamajorweaknessintheSwedishregulatorysystem.
Relatedtothis,healthprofessionalsandpublicauthoritiesmustreportpotentialbreachesinatimelyfashion.Theneedtoimproveswiftnessinreportingissupportedbythefindingthatcasesinitiatedfollowingvoluntarycomplaintswereassociatedwithsignificantlags,possiblyreflectingmajorgapsbetweendatesofprintingandreportingonaclaim.Whentakentogether,thispointstolimitationsinthevoluntarycomplaintsmechanismsand,consequently,itemphasizestheneedforactiveandefficientmonitoringofpromotionalmaterialbyexpertbodiessuchastheIGMtolimitphysicianexposuretomisleadingmedicinesinformation.
Finally,wewouldsuggestthatmeasuresbetakentofurtherenhancetransparencyandaccountabilityintheself-regulatorysystem.Specifically,wesuggestthatcasereportsnotonlyspecifyallclaim(s)inbreachofthecode,butalsoindicateallpublicationswheretheseclaimshadbeenprintedpriortotheviolationruling.Thiswouldfacilitateinvestigationsoflagsinthesystemandhelptoassesstheimpactofmisleadingpromotion.
Themainlimitationofthisstudyisitsrestrictiontoaspecificdrugclassinasinglejournal.Inregardtodrugclass,itispossiblethatthehighlycompetitivenatureoftheantidepressantmarketdrovecompaniestoparticularlyextravagantclaims.Rivalrybetweencompaniesisalsolikelytoincreasemotivationtocomplainaboutmisleadingclaims(e.g.comparativeefficacyclaims)thatareperceivedtoprovideanadvantagetocompetitors–butisunlikelytogeneratecomplaintsaboutmisleadingclaimsthataremutuallybeneficialtoallcompetitors(e.g.generalefficacyclaimsorclaimspertainingtomonoaminetheories,asaddressedbythispaper).Thus,futurestudiesmightappropriatelyaddressacomparisonofcaseswithandwithoutinter-companycompetition.
Concerningsinglejournal,itshouldbenotedthatalthoughtheSwedishMedicalJournalisthecountry’sprincipalmedicaljournal,thereareafewothermedicaljournalsprintedinSweden.ItisreasonabletobelievethatadvertisementsintheSwedishMedicalJournalatleastsometimesweresimultaneouslyprintedinthesejournals.Consequently,thefigurespresentedinthispaperregardingthenumberofmisleadingadvertisements,lagsinthesystemandthelowcostassociatedwithmisleadingadvertising,shouldbeconsideredunderestimates.Thisfact,however,merelyservestofurtherstrengthentheargumentthatpharmaceuticalindustryself-regulationinSwedenhasnotbeenworkingsatisfactorily.
TheSwedishself-regulatorysystemofmedicinespromotionlargelyfailedtomotivateindustryintoprovidingtruthfulinformationonantidepressantsinmedicaljournaladvertisements.Specifically,wedemonstratethatthisfailurewasassociatedwith:(1)laxoversight,(2)lagsintheregulatorysystem,and(3)lowfinesforviolations.Ifcurrentcorporateregulatoryregimesfailtodeterindustryfromprovidingunreliableinformation,wesuggestthatmanycountriesmaywanttoreconsiderthecurrentbalancebetweenself-regulation,anddirectlegislativecontrolwithgovernmentoversightovermedicinespromotion,inordertoensurerationaldrugprescribingpractices,providedthatsufficientfundingforpublicregulatorybodiesisguaranteed.
(TIF)
CompileddataonIGM/NBLcases.
(PDF)
FrequencyandexamplesofcodebreachesfoundbytheIGMorNBLinantidepressantadvertisementsintheSwedishMedicalJournalin1994–2003.CompleteTable.
Conceivedanddesignedtheexperiments:SM.Performedtheexperiments:SMAVZ.Analyzedthedata:SMAVZ.Wrotethepaper:SM.
PLOSisanonprofit501(c)(3)corporation,#C2354500,basedinCalifornia,US