drug safety evidence aggregation pv - advera health safety data to...the first order of business is...

SPECIALREPORT

DrugSafetyDatatoSupporttheEntireLife-Cycle:

AnIntroductiontoDrugSafetyEvidenceAggregationPlatforms

May2017

www.adverahealth.com

©Copyright.2017AdveraHealthAnalytics.Allrightsreserved.ThismaterialMAYNOTBEREPRODUCED,DISPLAYED,MODIFIED,DISTRIBUTEDorLINKEDTOwithouttheexpresspriorwrittenpermissionofthecopyrightholder.AdveraHealthAnalytics’research

maybecitedbutnotexcerptedinitsentirety.Forpermission,[email protected].

www.adverahealth.com ©2017AdveraHealthAnalytics 2

Contents

Chapter1:WhatisaDrugSafetyEvidenceAggregationPlatform?..............................................................................3

Chapter2:HowisanEvidenceAggregationPlatformDifferentfromTraditionalSignalDetectionSoftware?...........3

Chapter3:CaseStudy-SignalDetectionUtilizingFAERSData......................................................................................5

Chapter4:CaseStudy-AnalyzingtheSafetyLandscapeofOralvs.InjectableDrugs...................................................5

Chapter5:CaseStudy-EstablishingDrugSafetyBenchmarksforaClinicalStageProduct.........................................6

Chapter6:WhychooseAdveraHealth’sEvidex™asYourDrugSafetyEvidenceAggregationPlatform.....................7


Chapter1:WhatisaDrugSafetyEvidenceAggregationPlatform?

Anevidenceaggregationplatformisawebbasedsoftware-as-a-service(SaaS)applicationthattakesdisparatesourcesofdata,orevidence,andcombinesthosedatatogetherusinganalyticstocreatenewinsight.

Adrugsafetyevidenceaggregationplatformcanreadadverseeventdatapointsfrommultipleclinicaltrialresultsandperformon-demandmeta-analysestobetterunderstandsideeffectratesfordrugs.TheplatformcanthencomparesideeffectratesfromclinicaltrialresultstosideeffectratesfoundinrealworlddatasuchastheFDAAdverseEventReportingSystem(FAERS)database,anorganization’sinternalsafetydata,and/ormulti-payerclaimsdata.

Thiscombinationofdatasourceshelpstosupportpharmacovigilanceandsafetyscienceteamsbyprovidingclean,standardized,andlinkableclinicalandrealworlddataonbothapprovedandpipelineproducts.Theinsightgainedfromanevidenceaggregationplatformaidesinsignaldetection,epidemiologicalresearch,andevidencegenerationandsupportsorganizationwidedecisions.

Thebestdrugsafetyevidenceaggregationplatformsprovideuniquedatasetsthatauserwouldnotbeabletogatherthemselves,aswellasofferthebenefitofcustomization.Anexamplewouldbeonethatpresentsvendorcurateddata,suchasannotateddatafromcuratedclinicaltrialresults,FDAAdverseEventReportingSystem(FAERS)data,andthenalsoincorporatesinternalsafetydatafromadatabasesuchasARGUS®orclientlicensedclaimsdata.

Chapter2:HowisanEvidenceAggregationPlatformDifferentfromTraditionalSignalDetectionSoftware?

Thekeydifferencebetweentraditionalsignaldetectionsoftwareandadrugsafetyevidenceaggregationplatformcomesdowntothetypesofdatatheyeachsupport,theflexibilityinwhichthosedataaresupported,andthemuchbroaderusecasesavailablethroughanevidenceaggregationplatform.

Drugsafetydatafromvarioussourcesareneededthroughoutadrug’slifecycletosupportawiderangeofregulatoryrequirements,clinicaldecisionsandplanning,aswellascommercialpositioningandevidencegeneration.Thesedatacanbecategorizedintothreebuckets:companyowned,vendorcurated,andlicenseddata.

Companyowneddataincludethosecapturedinaclinicalsafetydatabaseorthedatathatarereceivedpost-marketingfromspontaneousreportingthatarestoredindatabasessuchasARGUS.Overlayingafront-endonthesedatabaseshasbeenattheheartoftraditionalsignaldetectionsoftware.Theprocesswithlegacysoftwareprovidersislongandcomplicated,withasignificantinvestmentneededintermsofbothbudgetandtime.Thelargestorganizationshavetheresourcesneededtomakethisinvestment,howeverthe

Drug SafeyDept.

Drug safety data to support entire lifecycle…

EXPLO

RAT

ION

CLINICAL

POST-APPROVA

L

Defining epidemiologic profile of comparators

Market segmentation and sizing

Evidence generation planning

Reviewing clinical trial protocols

Detecting, refining, evaluating, and managing safety signals

Pre-approval evidence dissemination

Detecting, refining, evaluating and managing safety signals

Implementing risk mitigation strategies

Supporting life-cycle management

…all with different needs


configurationisnotflexibleandthesoftwareitselfistypicallyusedbyonlyahandfulofexperts.Smallerorganizationswhohaveaneedforsignalingontheirowndataareoftenforcedtorelyon3rdpartyconsultantstoeitheradministerthesoftwareortorunthenecessaryanalyticsonbehalfoftheorganization.

Bycontrast,adrugsafetyevidenceaggregationplatformisagileandflexible,whilestillmaintaininganalyticalrigor.Iftheplatformhasaneasytousefrontend,thenusersdonothavetobe“experts”oreventechnicallytrained.Duringimplementationoftheevidenceaggregationplatform,usersareon-boardedusingthecurateddatapreloadedintheplatform.

VendorcurateddataincludesFDAAdverseEventReportingSystem(FAERS),WHO’sVigibase,andthevarious,unstructureddatathatexistsuchasclinicalstudyresultsthatarepublishedingovernmentregistrieslikeclinicaltrials.govorfoundinpublications,abstracts,andposterpresentations.FAERSdatahavelongbeenincludedintraditionalsignaldetectionsoftware,butit’susehasbeenlimitedtocertainpowerusersordedicatedinformaticsteams.Anevidenceaggregationplatformmakesthesedataandtherelatedanalyticseasyandprovidesforarobustsourceofinsight.

Curatedstudyresultsdatahavelongbeenrestrictedtotimeconsumingliteraturereviewsandmanualcollectionprocesses.Safetyscienceandepidemiologyteamshavehistoricallyminedthesedatabyhand,butmanuallyscalingandupdatingthesedataisnearlyimpossible.

Databasesofstudyresultsnowexistthatcanbepre-loadedintoanevidenceaggregationplatform.Analyticsincludedintheplatformcanprovideforon-demandpooledmeta-analysesattheAElevel,andthenmappedandmatchedbacktobothcompanyownedandcuratedFAERSdata.

Licenseddataarethosedataassetsthatanorganizationlicensesfromdifferentvendors.Examplesofthesedataincludemulti-payerclaims,sociallistening,searchquerylogs,andprovidertranscripts.Thesesourcesvarywidelyinstructureandusecaseandcanoftensitindifferentareasoftheorganization.Forexample,multi-payerclaimsdata,whilehavingaclearbenefitfordrugsafetyteams,areoftenheldbyoutcomesgroups,andthedataarenoteasilyaccessedorsharedoutsideofthegroup.

Evidenceaggregationplatformscancorraltheselicenseddataintooneinterfacebymatchingandstandardizingoutputstomapbacktobothcompanylicensedandpublicdata.Thisallowsforinvestigationintothedataacrossdisparatedatasourcesand360°viewintosafetyissues.

Drugsafetyevidenceaggregationplatformsarebecomingavitaltoolforpharmacovigilancedepartmentsatpharmaceuticalmanufacturers.ThroughoutthenextchaptersinthiseBook,specificusecasesforwillbeprovidedforadrugsafetyevidenceaggregationplatformdesignedforallfunctionswithinadrugsafetydepartment,includingsignaldetection,safetyscience,andepidemiology.

COMPANY OWNED CURATED LICENSED

EXAMPLE DATA:Clinical safety database and spontaneous reports (ex. ARGUS)

ISSUES:Complicated, legacy software and hard to get at analysis

Location, both on-prem and 3rd party hosted present issues

EXAMPLE DATA:FAERS, Vigibase, clinical trial results, publications

ISSUES:Difficult to collect, standardize, and map to other data

No centralized source, and data accessibility issues

EXAMPLE DATA:Claims, social, search query logs, transcripts, other

ISSUES:Disparate systems licensed by various departments

No common data model and expensive

Safety data is often “stuck” in proprietary systems within various departments


Chapter3:CaseStudy-SignalDetectionUtilizingFAERSData

Oneofthekeybenefitsofadrugsafetyevidenceaggregationplatformisthedatasourceflexibilityitprovides.Historically,smallerorganizationshaveputoffautomatingaggregatesignaldetectiontoavoidthecostandtimecommitmentneededtoimplementtraditionalsignaldetectionsoftware.Andthoseorganizationsthatdohavetraditionalsoftwareinstalled,havetypicallylimitedusetospecificfunctionalareaswithindrugsafetyand“expert”users,makingaccesstoFAERSdataandanalyticshardtoaccess.

However,withaneasy-to-useevidenceaggregationplatform,smallerorganizationsnolongerneedtoputoffautomatingaggregatesignaldetection.Theresourcesneededtogetupandrunningareminimal,andtheplatformallowsforeasyscalabilitywhentheteamisreadytoincreaseitsefforts.Inlargerorganizationswithestablishedworkflows,adrugsafetyphysicianwouldnothavetorequestananalysisofFAERSdatatouseasabenchmark.Rather,shewouldbeabletoaccessthedataherselfon-demand.

Adrugsafetyevidenceaggregationplatformisagreatsolutionforthesetwoscenariosasitcanprovideaneasy-to-useinterfacetoaccessbothqualitativedatasuchaslabelinginformation,seriousness,anddiseaserelatedclassifications,aswellassophisticateddatamininganalyticssuchasreportingoddsratios(ROR),proportionalreportingratios(PRR),andothersafetyspecificstatisticalcalculations.Theflexibilityoftheplatformallowsforon-demandadd-onsofotherdatasetssuchascuratedclinicalstudyoutcomesdata,theirowninternaldatafromsafetysystems,orotherrealworlddatalikeclaimsandsociallistening.

Chapter4:CaseStudy-AnalyzingtheSafetyLandscapeofOralvs.InjectableDrugs

Onceapproved,anoraldrugindevelopmentwillcompetewithcurrentlymarketedinjectabledrugs.Therewasaneedbytheoraldrug’smanufacturertounderstandsafetydifferencesbetweencurrentlymarketedoralvs.injectableproductstofullyunderstandthepotentialsafetyconcerns,identifypointsofdifferentiationbetweenproducts,andpinpointspecificfutureevidencegenerationopportunities.

Theevidenceaggregationplatformwasusedtoidentifyproductsonmarketwiththesameactiveingredientthathadbothoralandinjectabledelivery,andthentoprobeadverseeventreportingdifferencesbetweenactiveingredientsthatareadministeredbothorallyandbyinjection.

Theplatformwasabletoquicklyshowallofthespontaneouslyreportedadverseevents,aswellascalculateddisproportionalreportingrates,andreportingrates,itwassimpletoselectspecificMedDRApreferredterms(PT)andbroaderStandardizedMedDRAQuery(SMQ)topicsthatwereseentoshowthelargestdifferencesbetweenformulationsofthesamedrug.

Thrombocytopeniaandthrombocytopenia-relateddisorderswerereportedtoFAERSdisproportionatelyhigherwithinjectableproductsonthemarketcomparedtooralformulations.SincetheevidenceaggregationplatformbeingusedforthisexamplehadembeddedMedDRAàICD-9/10mapping,validationofthedifferencesinthesetypesofeventscouldbeseenusingactivesurveillancewithclaimsdata.

Next gen technology allows non-technical users to build on disparate data sources…

… and allows organizations to access, what they need, when they need it…

FAERS DATA

LITERATURE & PUBLICATIONS

INTERNAL SAFETY DATA

CLAIMS

Company A Company B Company C


Theresultofthisdatacollectionwasdeepunderstandingofhowtheoralproduct’sadverseeventcouldbecharacterized.Withthisinsightinhand,themanufacturercouldmoreeffectivelydevelopstrategytotakeadvantageofthesafetydifferentiation.

Chapter5:CaseStudy-EstablishingDrugSafetyBenchmarksforaClinicalStageProduct

ApipelineproducthasbeenputonclinicalholdbyFDAduetoanunexpectedseriousadverseeventinatrial.Thetrial’ssponsorneededtoactfasttolessentheimpactofthedelay.Isthissomethingthatshouldbeexpected?Docompetitordrugshavesimilarprofiles?Willtheadverseeventimpactmarketpotential?

Thesetypesofquestionscanonlybeansweredwhenvariousstakeholderscometogethertoprovideinsight.Thefirstorderofbusinessistoensuretheproperdataareavailable.Thesponsorneedstoestablishabenchmarkrateofadverseeventoccurrenceacrossalldrugsforthesameindicationinpastclinicaltrialsaswellasinrealworlddata.Thisiswhereadrugsafetyevidenceaggregationplatformisextremelybeneficial.

First,acuratedclinicalstudyoutcomesdatabaseallowsthesponsortoquicklyidentifyalltrials,foralldrugsintheindicationthatpresentedthesameorsimilaradverseevent.Withanevidenceaggregationplatform,datareportingdelays,non-standardizationofresultsdata,andotherincongruitiesarecorrected,providingforeasysearchandretrievalofdatapoints.

Second,giventhatresultsdataarecapturedasmetadatafromeachtrial,pooledratesfortheadverseeventsforeachdrugwerecalculatedtoidentifyincidenceratesdrug-by-drug,ratherthantrial-by-trial.Anevidenceaggregationplatformcanthencombinedrug-by-drugratestoacombinedpooledanalysistoestablishanindication-widebaselineadverseeventrate,asseeninclinicaltrials.

Next,theseclinicaltrialresultsdatacanbematchedtospontaneousreportinginFAERS,combinedwithpatientutilizationnumbers,toestablisharealworldadverseeventreportingrate.Usingcustomizedanalyticsonclaimsdata,alsoloadedintotheevidenceaggregationplatform,allowsforanadditional“versionofthetruth,”givingthesponsora360⁰view,andatruebaselineratefortheadverseevent.

Theresultoftheuseofanevidenceaggregationplatformallowsforthekeyquestionstobeansweredquickly,helpstoacceleratetheliftingoftheclinicalhold,andprovidesabetterunderstandingofhowtheadverseeventimpactspotentialmarketshare.

Scalable, flexible, and agile platform exists…

…to bring together the data and the analytics that you need


Chapter6:WhychooseAdveraHealth’sEvidex™asYourDrugSafetyEvidenceAggregationPlatform

AdveraHealth’sEvidex™isadrugsafetyevidenceaggregationplatformthatmakesdisparatedrugsafetydataactionablethoughasimpletouseyetpowerfulweb-basedapplication.Evidexprovidesproprietarycurateddataandanalyticswhileallowingforcustomdataintegrations.

QuicksearchesandanintuitiveuserinterfaceempoweruseofEvidexatallorganizationallevelswithouttheneedfordatascientists.Theplatformenablesquickcomparisonsofdrugsacrossdatasourcesbyindication,class,ormechanismofaction,providingeasyidentificationofdifferencesinsafetythatpreviouslycouldnotbeknown.

ProprietaryDataAssetsincludedinEvidex™

CuratedFDAAdverseEventReportingSystem(FAERS)

AdveraHealthprovidesthegoldstandardforcleaned,standardized,andcuratedFAERSdata,usingproprietaryRxFilter®technology.Withroughlytenmillioncasereports,coveringroughly2,300FDAapproveddrugs,everythingiscoveredincludingin-patient,out-patient,andspecialtytherapies.

AllFAERSdatainEvidexisfullymappedtoclinicaltrialresultsdata.

FAERSdatainEvidexspans690indicationsand389mechanismsofactionmatchedviaVA-NDFRTandissegmentedbyage,gender,andcondition.ThedatabaseissearchablebyeveryFAERSfieldavailable,includingover100,000literaturereferenceadverseevents.

Datamininganalyticsareprovidedout-of-the-boxforsignaldetectionandproprietarysafetysignalingisincludedwiththepeer-reviewedandpublishedRxSignal®analytic.

COMPANY OWNED

PROPRIETARY TO ADVERA HEALTH

CURATED LICENSED

Data standardization with RxFilter

FAERS RCT Outcomes

Proven algorithm + human intelligence for 100% clean and standardized FDA Adverse Event Reporting System (FAERS) database.

Hoffman KB, Dimbil M, Kyle RF, Tattonetti NP, Kyle R. (2016) A Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports (Drug Safety, 39(3) 0114-5916)


AswithalldatasetsincludedinEvidex,MedDRA,ICD-9,RXNORM,andOHDSICDMmappingsallowforusewithclientprovideddrugdatabasesandrealworlddatasuchasclaims.

ClinicalTrialSafetyOutcomes

AdveraHealthprovidesanannotateddatasetfromcuratedclinicaltrialresultsextractedfromgovernmentregistriessuchasClinicaltrials.gov,publishedresearch,abstracts,andposterpresentations.Thedistinctdatafieldsareextractedintodatatablesincludingbasictrialinformation,studyarms,interventions,baselinecharacteristics,participantflow,reportedadverseevents,outcomemeasures.

ThosedataarematchedandstandardizedusingproprietaryRxFilter®technologyplustrainedanalystwork.Newdataareupdatedwithinoneweekofbeingreleased.

AswithalldatasetsincludedinEvidex,MedDRA,ICD-9,RXNORM,andOHDSICDMmappingsallowforusewithclientprovideddrugdatabasesandrealworlddatasuchasclaims.

CustomDataIntegrations

Evidex’scustomdataintegrationsallowsclientstoBYOD…BringYourOwnData.Withflexibleback-endmethodologiessupportinganydatasetandexperiencewithbothstandardizedandunstructureddata,thepossibilitiesofwhatcanbeaggregatedandlinkedarevirtuallyendless.

WithallFAERS-reportedadverseeventsinMedDRAmappedtoICD-9/10,thereisnoneedtopredeterminewhattolookfor.Ongoing,activeAEdetectionacrossmultipledatasetsprovideforahypothesis-generatingformatthatsupportsmultiplefunctionswithintheorganization.

Standardized,yetflexibledesignallowsforcustomized,pre-definedcohortdevelopmentforstandardizedtrackingalongwiththeflexibilitytoadjustobservationprotocolbasedonnewdata.

AswithalldatasetsincludedinEvidex,clientprovideddatabasesandotherrealworlddataaremappedtobothclinicaltrialresultsandFAERSdataassetsthroughMedDRA,ICD-9,RXNORM,andOHDSICDMmappings.

First of its kind safety focused clinical trial outcomes database, only available via Evidex.

Extensive data mappings and flexible back-end technology allows virtually any other dataset to be

included in Evidex™

Claims Data Social Search Logs Transcripts


“Weusedtodoin-depthliteraturereviewstogatherdatafromclinicaltrials,butwithresourceconstraintsitsbecomeimpossible.HavingAdverakeepupwiththesedata,havingtheabilitytoperformad-hocanalysesonthem,andcomparetospontaneousreportingandotherRWDhasbeenagamechanger.WeexpecttokeeptheAdverateambusyforalongtime!”

-VPofSafetyScienceandEpidemiology,Top10Pharma

“WithonedrugonmarketandanotheronefinishingphaseIII,wehadanimmediatebusinessneedtoputasignaldetectionplatforminplacetomeetregulatoryrequirementsaswellasdrivecommercialdecisions.However,thebudgetimpact,implementationtimeandinternalresourcesrequiredtosetuplegacyvendorswasprohibitiveandlimitedinscope.Evidexwasanidealsolutionthatcouldscaletomatchwherewewereinourlifecycle”

-DirectorofClinicalIT,Mid-SizedBiotech

Data to support every drug safety function…

Sig

nal M

anag

em

ent

Ep

idem

iolo

gy

Evi

dence G

enera

tion

Data mining for aggregate signal detection (FAERS and Internal)

Benchmark and characterize AEs through pooled meta-analysis from external study results

Refine signals and generate hypotheses utilizing multiple data sources

Support clinical trial design and decision making with databased safety results from clinical studies

Easy to use spontaneous reporting metrics and signal characterization

Hypothesis generating data sources lead to further epidemiological evaluation

Support medical affairs and HEOR with validated and peer-reviewed data

Ensure safety data from various sources are properly characterized and understood

Easily share analyses and data points with other functional areas with easy to use platforms


Welcome to pharmacovigilance 2.0

Jim Davis, EVP

617.877.6530 | [email protected]

Please don’t hesitate to contact us if you have questions

drug safety evidence aggregation pv - advera health safety data to...the first order of business is...

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