Cro

1. CONTRACT RESEARCH
ORGANISATIONS
(CRO)
PRESENTED BY –SHAHBAZ KHAN
PHARMACOLOGY -2
ND
SEM
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2. INTRODUCTION
•AContractResearchOrganization(CRO)isaservice
organizationwhichprovidessupporttothepharmaceutical
industry.
•Itoffersvariouspharmaceuticalresearchthatisessentialfor
conductingclinicaltrialsinthepresentboom,whenvarious
complicationsareinvolvedinthedrugdiscoveryprocess.
•Variouscompaniesareinvolvedinhistypeofdevelopmentmany
examplesarethelikeLupin,Quintil,Cipla,Zydus,Cadeila.
•Theyarealsoconductthesetypeoftrailswiththe
collaborationofmanymultinationalcompaniesandthese
Indiancompaniesaremakingspaceinforeign.
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3. BACKGROUND
•Thereisagrowingreliancebysponsorsoncontractingoutpartor
alloftheworkoftheclinicaltrialtoasub-contractor.
•Manufacturersoftenfindthattheycannotorganizeeveryclinical
trialthattheyrequire.
Thereasonsaremany,butcommonlyreflect;
•limitedstaffresources
•pressuresoftime.
•Subsequently,thefieldhasexpandedtoincludefirmsintheareasof;
–formulationdevelopment
–stabilityprograms
–pharmacokineticstudies
–biostatistics
–datamanagement
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4. An Overview of CROs
•Traditionally,aCROwasviewedbypharmaceuticalindustry
somethingas;
•anun-acceptablerisk,becauseof
•lackofconfidenceinittermsoftheirqualification,experienceand
capabilities.
•However,themodernviewisthatthein-housestaffcanbekept
for“coreneeds”e.g.,
•designingofstudy
•selectionofCRO.
•AlistofqualifiedCROsisdevelopedbasedon;
–Thesponsorsneeds
–TherangeofservicesprovidedbyCRO
–ThetherapeuticareaofexpertiseofCRO,and
–Thecompatibilitywiththesponsor 4

5. MARKET STRUCTURE OF CRO
Top 10 CROs-75%Revenue
Avg revenue /company $1.3
ue
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Top 10 CROs-75%Revenue
Avg revenue /company $1.3
billion
Next 10 CROs -11% revenue
Avg revenue/company-$220
Million
Niche segment 14% revenue
Avg Revenue /company-$3.1
Million

6. WHEN TO USE A CRO?
•StrategiesforusingCROstypicallyfallintothreecategories:
–Tacticaloutsourcing
–Maximaloutsourcing
–Strategicoutsourcing
TacticalOutsourcing
•Individualstudiesorselectedactivitieswithinastudyare
contractedtoaCROonlywhenin-houseresourcesbecome
inadequatebecauseofanunfore-seenstudyorareductioninstaff.
MaximumOutsourcing
•Withthisstrategythesponsoroutsourcesnearlyallofitsclinical
developmentactivitiestoCROs.
StrategicOutsourcing
•ThesponsorconductsPhaseIandearlyPhaseIIstudies,andhires
CROstoconductlargerandroutinestudies.
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7. FREQUENT CAUSES OF
SPONSOR/CRO PROBLEM
•Problemswithcontractstudiescanoftenbetracedby;
–ThewrongCROisselected.
–SponsorsoftenmakethemistakeofassumingthataCROthat
hasperformedwellononestudywillbeequallycapableof
conductingastudyinadifferenttherapeuticarea.
SomesponsorsmistakenlyassumethatallCROsarethesame.
–Thesponsorfailstoarticulateitsneedsclearly.
–Sponsorssometimesissuearequestforproposal(RFP)with
littlemorethanaprotocoloutline,andexpectCROstoguess
whatservicesandresourcesarerequired.
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8. •Inordertoensuresuccessfuloutsourcing,thesponsorshouldfocus
onthreecriticalsteps:
–Determineaccuratestudyspecifications
–SelecttherightCRO
–Managethestudy
THREE CRITICAL STEPS TO
ENSURE SUCCESS WITH A CRO
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9. DETERMINE STUDY
SPECIFICATIONS
•Studyspecificationsarealistofactivitiesrequiredtoinitiate,
conduct,analyze,andreporttheresultsofaclinicalstudy.
•Theyincludetasksthatwillbeperformedin-houseandthosetobe
contractedouttooneormoreCROs.
ImportanceofAccurateStudySpecifications
•Studyspecificationsareanessentialelementofthesponsor’s
requestforproposal(RFP)andtheCRO’sproposal.
•AccuratestudyspecificationsalsoenabletheCROtoperforma
‘realitycheck’onthesponsor’sexpectations.
•Thisanalysisalsoprovidesusefulcriteriaforselectingtheright
CRO.
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10. SELECTING THE RIGHT CRO
•ThethreemostimportantcriteriaforselectingaCROare:
–Capability
–Compatibility
–Cost
MANAGING THESPONSOR-CRORELATIONSHIP
•Thesponsorshouldfollowthreeprinciplesformanagingan
outsourcesproject:
–ClarifytheroleandresponsibilitiesofthesponsorandCRO.
–Defineanduse‘performancemetrics’tomeasurestudy
progress.
–Ensureefficientcommunicationbetweenthesponsorand
CRO.
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11. SponsorRolesandResponsibilities
–Definethestudyspecifications
–ProvideinformationtotheCRO
–Monitorresults
–Recognize‘redflags’
–Resolveproblems
–Approvechangesin‘scope’
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12. CRO Roles and Responsibility
•Ifthesponsorhasprovideddetailedstudyspecificationsandthe
CROisexperiencedinthetargettherapeuticarea,itwillbe
possiblefortheCROto;
•compareitspastexperienceswiththesponsor’sprojections.
•CROrolesandresponsibilitiesare…
–Evaluatefeasibility
–Provideadequate,wellmanagedstaff
–Conductstudyactivities
–Manageprocesses
–Bringproblemsandproposedsolutionstothesponsor’s
attention
–Ensurethatthesolutionsarecost-effective
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13. Performance Metrics
•Theirvalidityisestablishedbydemonstratingthattheyarerelated
toachievingquality,ensuringtimelines,andmanagingcost.
•Performancemetricsshouldbenegotiatedbetweenthesponsorand
CROpriortothestudy.
•WhenperformancemetricsdemonstratethattheCROisfailingto
meettheobjectives,thesponsorandCROhaveashared
responsibilitytoexaminetheprocessandagreeonanappropriate
solution.
•MostinteractionsbetweenthesponsorandtheCROwilltakeplace
betweentheindividualteammembersandtheirtechnicalcounter-
parts.
•DiscussionsbetweensponsorandCROtechnicalstaffshouldfocus
oninformationexchangeandissueidentification.
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14. Sponsor-CRO Study Initiation Meeting
•ThesponsorandCROteamsshouldholda‘kick-off’meetingprior
toinitiationofthestudy.
•Thegoalsofthemeetingare:
–Topromoteownershipofthestudyamongteammembers
–ToclarifytherolesandresponsibilitiesofthesponsorandCRO
–ToidentifytheprimarysponsorandCROcontacts
–Topresenttheagreedtoperformancemetricsandaudit
procedures
–Todefinetheapproachtoproblemresolution
–Todefinethosechangesthatcanbeagreeduponinformallyand
thosethatrequireaformalchangeorder
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15. •Theyshouldbeidentifiedatanearlystage,sothattheyhave
minimalimpactonstudycost,timing,andquality.
•Itisimportantforateammembertoinformtheprojectmanagerof
anyissuebeforeattemptingtoresolveit.
•Thisinformationwillenabletheprojectmanagertodetermine;
–whethertheproblemisanisolatedcase.
–ispartofalargerproblemthatneedstobeaddressedwiththe
correspondingprojectmanager.
IDENTIFYING AND RESOLVING
PROBLEMS
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16. Ten ‘Red Flags’
•Redflagsareearlywarningthatmaynotrequireimmediateaction,
butshouldbeevaluatedtodeterminewhetherasignificant
underlyingproblemexists.
•Eachteammembermaywishtopreparealistofredflagsfor
his/herindividualtechnicalarea.
Typicalredflagsandthepossiblesignificantunderlyingproblems
are:
–Selectionofin-experiencedinvestigatorsbytheCRO:theCRO
monitoringstaffmaybeinexperienced.
–Questionsfromthestudysitedirectedtothesponsor:theCRO
maynothaveprovidedadequatetrainingtositepersonnel.
–In-adequatemonitoringreportsfromtheCRO:theCRO
monitoringstaffmaynotbereceivingadequatetrainingand
supervision.
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17. CONTRACT RESEARCH
LegalBackground
•Thearrangementsmadefortheconductofclinicalresearchwill
usuallygiverisetoanumberoflegalcontracts.
•Forexample,therewillbeacontractbetweenasponsorandany
appointedclinicalresearchorganization(CRO);betweenthe
sponsororCROandtheinvestigatorortheinstitutioninwhichthe
investigatorworks.
•Itwouldbeunusualtohaveacontractbetweenapatientparticipant
andthesponsororinvestigator,althoughthismayarisewherethe
participantisaprivatepatientoftheinvestigator.
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18. •Incontractsrelatingtoclinicalresearchbetweenasponsor,CROor
investigator/institutionmuchofthedetailedprovisionsconcerning
preciselyhowtheresearchwillbeconductedwillbecontainedin
thetrialprotocol.
•Thereisnoprescribedformatforclinicalresearchcontracts.
•Astandardformmustalwaysbeadaptedtofittheparticularstudy.
•However,thefollowingareanon-exhaustivechecklistofpoints
thatmightbeconsideredforinclusioninacontract.
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19. Study details
•Theprotocolshouldbeincorporatedbyreferenceintothe
contract
•Theprotocolmustnotbedeviatedfrom,except;
1.Asagreedinwritingbetweenthepartiesandapprovedbythe
ethicscommittee.
2.Intheopinionoftheinvestigator,itisnecessarytodoso
immediatelyinordertoprotectthehealthandsafetyofa
researchsubject.
•A‘keyperson’clauseshouldbeconsidered.Thismightspecify
thatidentifiedindividuals,oracertainnumberofstaffspecified
minimumqualifications,willworkonthestudy.
•ThecontractshouldaddresswhethertheCROorinvestigatoris
allowedtosubcontractanyoftheirobligationsand,ifso,which
ofthem.
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20. Compliance
•Aspecifiedpartymustholdorobtain(andmaintain)allnecessary
authorizations.
•Alllegalandregulatoryrequirements(includinglabeling)mustbe
compliedwith.
•CompliancewiththeICH,GoodClinicalPracticeGuidelinesor
equivalentshouldberequired.
•Theinvestigatormustobtainethicalapprovalfromrelevantethics
committeesbeforebeginningthestudyandreferallamendments.
•Thestudymustbecarriedouttothehighestprofessionalstandards.
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21. Timing
•Startdate,duration/enddateshouldbeidentified.
•Thenumberofsubjectstoberecruitedbyspecifieddatesshouldbe
addressed.
•Theoptionsiftherecruitmentrateisnotontarget.
•Provisionformakingstatusreports,providinginterimanalysis
reportsandsubmittingthefinalreportbyspecifieddateshouldbe
made.
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22. Data
•Exceptforthepurposesofthestudyandasrequiredbylaw,the
datamustbekeptconfidential.
•Retentionoftitlebyspecifiedparties(inparticularthesponsor)in
identifieddocumentsandmaterialsshouldspelledout.
•Protectionofintellectualpropertyrightsofthesponsormustbe
covered.
•Arrangementsformaintainingsafetyandsecurityofdata,
documentsandtrialsuppliesshouldbeidentified.
•Theinvestigatorwillmaintainallrecordsrelatingtothestudy,
includingcasereportforms,foraslongasispracticable.
•ResponsibilityandprocedurefornotificationofAdverseDrug
Reactions(ADRs)orotherunexpectedorunusualoccurrencesin
compliancewiththelegislationneedstobedescribed.
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23. Payment
The contract should specify:
•Theamountsandtiming(advance,stageorinterimandfinal)of
paymentsandthepaymentofreasonableexpenses.
•Whetherseparateaccountsaretobeestablished.
•Provisionforalterationofbudgetintheeventofamendmentofthe
protocol,orextentofservicestobeprovided,andearly
termination.
Materials
•Supplyoftheinvestigatorbrochure,updates,productand
documentationbysponsor.
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24. Product Liability
•Inrelationtoliabilityissues,thecontractshouldcover:
1.Indemnitytobeprovidedbythesponsorforanyliability
costsandexpensesoftheinvestigatorarisingoutofpersonal
injuryclaims,subjecttoconditions.
2.IndemnitybytheCROorinvestigatorinfavorofthesponsor
inrespectofnegligence,breachofcontractbytheCROor
investigator.
3.Observanceofapplicablelocalguidelines
4.Financialprovisionforhandlingofclaims(e.g.,insurance
arrangements).
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25. Termination
•Appropriateprovisionfortermination,especiallyearly
termination,isessential:
1.Onspecifiedgrounds;sensibletoprovideforterminationby
thesponsoronnoticewithoutreason,butsubjecttothe
obligationtopayforworkdoneatthatpoint.
2.Therightsoftermination,ifany,consequentuponabreachof
contractbyeitherpartyshouldbedescribed.
3.Terminationupontheinsolvency,administrationor
liquidationofeitherparty,orlong-termsuspensionofthe
agreement(i.e.circumstancesbeyondthecontrolofeither
party)shouldbeaddressed.
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26. CONCLUSION
•Moreeffectivecontractingofclinicaldrug-developmentactivities
toCROscanbeachievedbyapplyingthefollowingmethods:
–Useastrategicapproachtooutsourcing
–FollowthethreeprinciplesforachievingsuccesswithCROs:
defineaccuratestudyspecifications;selecttherightCRO;and
managethestudy.
–SelectCROsaccordingtothethreeCs:capability,compatibility
andcost.
–EvaluatetheCRO’sresourceallocations
–Definetheperformancemetrics
–EnsureefficientcommunicationwithCRO
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27. THANK YOU
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