Worta McCaskill-Stevens, M.D., M.S.Director, NCORP
Chief, Community Oncology and Prevention Trials Research GroupDivision of Cancer Prevention
AlphabetSoup:TrialFundingandSupportMechanismsandHowtoUseThem
WithintheAllianceNCICommunityOncologyResearchProgram
(NCORP)May11,2017
DriversBiology
Technology
Economic and Demographics
New Generation of Clinical Trialsand Related Research
ChallengestothePhysician-ScientistTeam
• Demandforoncologyservicesisexpectedtoriserapidly,drivenbyaging,growthofthepopulationandimprovementsincancersurvivalrates
• Theoncologyworkforceisagingandretiringinincreasingnumbers
• Demandisexpectedtorise48%between2005and2020.Thistranslatesintoashortageof9.4to15.0millionvisits,or2,550to4,080oncologists—roughlyone-quartertoone-thirdofthe2005supply.
Clese Erikson,JOP2007
BiomedicalWorkforce(BMW)WorkingGroupJune2012ReportRecommendation
• Differenteconomicandeducationaldriversaffectthetrainingandcareerpathsofthephysician-scientistworkforcethanthePhDworkforce
• Changinglandscapeofhealthcareanditseffectsonacademicmedicalcenterswillaffectfuturephysician-scientistworkforce
ChargetothePhysician-ScientistWorkforce(PSW)WorkingGroup
• DevelopapproachesthatcaninformdecisionsaboutthedevelopmentoftheU.S.PSW
• AnalyzethesizeandcompositionofthePSW;considerimpactofNIHfundingpolicies
• AssessneedsandcareeropportunitiesforPS
• IdentifyincentivesandbarrierstoenteringthePSW
TrialFundingandSupportMechanismsToday’sDiscussion
• Overview:NCORPthroughyear3
• FundingofTrials/StudiesØNCORPResearchBasesØNCORPCommunity&Minority/UnderservedSitesØNon-NCORPResearchBaseMembers
• OtherNCIResources
BriefNCORPOverview
NCORP:3Components
Research Bases• Design and conduct multi-center trials in cancer
prevention, control, screening and post-treatment surveillance clinical trials and cancer care delivery studies
• Provide scientific and statistical leadership• Data management, administration, regulatory
compliance
Community Sites• Accrue participants to
NCORP trials/studies (may include providers, organizations) and to NCTN treatment/imaging trials
Minority/Underserved Community Sites• Accrue participants to NCORP
trials/studies (may include providers, organizations) and to NCTN treatment/imaging trials
• Communities are composed of 30% Minority/Underserved
NCICommunityOncologyResearchProgram(NCORP)isanAcademic/CommunityPartnership
ClinicalTrialsforprevention,control,health-relatedqualityoflife,comparativeeffectiveness,andscreening
• 7,527patientsinYear1and2combined(includesenrollmentstoQOLsub-studiestoTreatmentTrials)
Accrual toNationalClinicalTrialsNetwork(NCTN)treatmentandimagingtrials
• 6,742patientsinYear1and2combined
NCICommunityOncologyResearchProgram(NCORP)isanAcademic/CommunityPartnership
Cancercaredeliveryresearch focusedonpatient-providerandorganization-levelinfluencesoncanceroutcomes
NCICommunityOncologyResearchProgram(NCORP)isanAcademic/CommunityPartnership
Incorporationofcancerdisparitiesresearch intoclinicaltrialsandcancercaredeliveryresearch
• WakeForestU:ImprovingResectionRatesAmongAfricanAmericanswithNSCLC
• Earlyonsetmalignanciesin6cancerinracial/ethnicpopulations₋ Breast,colon,prostate,renal,liver,multiplemyeloma
• Expandeddemographicandaccrualdata:DCP001
12
PrecisionMedicineNCTNTrials:ALCHEMISTAccrualasof4/28/17
Accruals by Organization Type (Swim Lane)
Swim Lane
A151216
% of A151216
ptsA081105
% of A081105
ptsE4512
% of E4512
ptsEA
5142%
EA5142 pts
LAPS 461 25% 25 24% 9 26% 21 21%
NCORP 705 38% 39 38% 16 46% 40 41%
ROSTERED 692 37% 40 38% 10 29% 37 38%
Name Accrual
Kaiser Permanente NCI Community Oncology Research Program
99
Michigan Cancer Research Consortium NCORP 61
Southeast Clinical Oncology Research (SCOR) Consortium NCORP
53
Georgia NCI Community Oncology Research Program 50
Metro-Minnesota NCI Community Oncology Research Program 44
Catholic Health Initiatives NCORP 42
Heartland Cancer Research NCORP 41
Pacific Cancer ResearchConsortium NCORP 29
Main Line Health NCORP 27
Wichita NCORP 21
Stroger Hospital of Cook County Minority Underserved NCORP 19
Baptist Health System/Mid South Minority Underserved NCORP 15
NCORPCommunitySite,MUCommunitySiteandResearchBasesGeographicandOrganizationalDiversity
• Investigators(4,025)• Components/Subcomponents(938)
Community Sites (34)Distributed network (25)Integrated System (7)Small Network (2)
MU Community Sites (12)Academic (8)Non-Academic (4)
Research Bases (7)Research Bases
FundingMechanisms
NCORPStudyandEnrollmentFunding
LAPS,MainMembers,Affiliates,etc.PercasereimbursementfromResearchBasegrant
Concept&ProtocolDevelopment
ReimbursementforPatientEnrollments
NCORPCommunitySitesAnnualgrantawardfundscoverenrollments
FundingfromNCORPResearchBaseGrant
• StudyDevelopment• StatisticalSupport• CommitteeSupport• DataSafetyMonitoringCommittee(s)• Auditing• DataAnalysis
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Investigator-Initiated Grants in NCORP
• Must be conducted via the Research Base
• Federally grants are reviewed at the protocol level
• Non-Federally funded grants are reviewed at the concept level
• NCI has recently released guidance for the following:ØTime-line from grant approval to submission of protocolØStrategies to obtain feasibility and level of interest input from
NCORP community and academic investigators
FeasibilityofOmega-3SupplementationforCancer-RelatedFatigue(Peppone,R03CA175599)
PrimaryAims:1) Collectpreliminarystatisticaldata(meanchanges
&standarddeviations)ontwoOmega-3supplementationsvs.placeboforreducingCRF
SecondaryAims:1) Determineadherenceandadverseevents,and2) Collectpreliminarystatisticaldataonpossible
mechanismsofactiontoinformthedesignoffuturetrials
URCC13091– NIHfundingwasneededtopurchasetheagent
S1415CDAPragmaticTrialtoEvaluateaGuideline-BasedColonyStimulatingFactorStandingOrderInterventionForFebrileNeutropenia
PrimaryAim:TocomparetheuseofprimaryprophylacticcolonystimulatingFactoraccordingtorecommendedclinicalpracticeguidelinesamongptsregisteredatinterventioncomponentsvs.usualcarecomponentsSecondaryAims:Todeterminetheneutropeniarateamonglowriskpatients
PCORIFunding
A221505:PhaseIIIRandomizedTrialofHypofractionatedPostMastectomyRadiationwithBreastReconstruction
PrimaryObjective:Toevaluatewhetherthereconstructionthecomplicationrateat24mos.postradiationisnoninferior withhypofractionationcomparedtostandardfractionation
SecondaryObjective:Toevaluatetheincidenceofacuteandlateradiationcomplications
UseofIROC– mechanism- supplementtoNCTNU-24
BIQSFPFunding
• Goal:EnhancethescientificqualityofNCI-fundedclinicaltrialsbyimprovingprioritization,fundingandstandardizationofassociatedbiomarkerandqualityoflifestudies
• Initiative1:Assurethatadequatefundingisavailableforclinicaltrialsinvolvingbiomarkers,imaging,andqualityoflife
• Initiative2:EstablishqualitycontrolstandardsforlaboratoryassaysandimagingproceduresusedinassociationwithNCI-fundedclinicaltrials
2017Eligibility
• NCTNGroupsandNCORPResearchBases
• Phase2(≥100patients)and3treatmentclinicaltrialswithintegralorintegratedbiomarkerorimagingorQOL/PROstudies
• Phase3CancerPreventionclinicaltrialswithintegralorintegratedbiomarkerorimagingstudies
• RandomizedSymptomSciencetrialswithefficacyendpoints
• Cost-EffectivenessAnalysis(CEA)studies:randomizedphase3treatmentorpreventionclinicaltrialwithacomparatorarmorasymptomscience/supportivecareclinicaltrialwithacomparatorarm.
Funding&Review
NCORPLaunchtoPresent:AccrualSuccesses
A221303:EarlyPalliativeCarevsStandardOncologyCare
• 400+patients
Alliance221304- PhaseIIIPlacebo-Controlled,RandomizedThree-ArmStudyofDoxepinandaTopicalRinseintheTreatmentofAcuteOralMucositisPaininPatientsReceivingRTwith/withoutChemotherapy
• 272patientsECOG/ACRIN4112– ProspectiveStudyofMagneticResonanceImagingandMulti-parameterGeneExpressionAssayinDCIS
• 362patients
AdditionalNCIResources
NCIResources
• NCORPProgramDirectors
• DianeSt.GermainandImanMartin
• CoverageAnalysisandPartnershipwithCMS
• NCORPCCDRLandscapeData
• NCORPwillhavetrialspecificdataaboutaccrual(Log)
• https://ncorp.cancer.gov/
Summary from NCI DCP Cancer Prevention Think Tank Published in AACR Cancer
Prevention Research
WorkingGroups
RadiationOncology
AdolescentandYoungAdult
Non-OncologySpecialists
DisparitiesIntegration
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Non-Oncology Specialists WG GOALS
• Create and share strategies to engage primary care physicians and other non-oncology specialists (e.g. gastroenterologists, gynecologists, primary care practitioners) and connect with organizations (e.g. NMA, AAFP, etc.)
• Support these connections with researchers and other relevant organizations
• Invite member representatives from these organizations to act as champions for cancer prevention research trials across their organizations.
Thankyou!
SCConcept&BIQSFPReviewandApproval:
GenesisofaProtocol
Concept Approval S.C.
3-monthdeadline
Study Team/Research Basedevelops protocol
responding to outstanding issues from the concept
reviewSubmits to DCP
FDA submitin parallel if applicable
DCP reviewsSends response
Approve, Revise/resubmit,disapproval
Central IRB ReviewProtocol is
activated byresearch base
2-month deadlineRevise, responding to
review commentsSubmit to DCP
FDA finalizationIntervention prep Revise &
ResubmitApprove CIRB activate
Unlimited times, can also be disapprovedAccrue!
Delays can occur from:CIRB review pendingCIRB requested
changes
Integrative BIQSFP submitted and reviewed by SC
*Integral BIQSFP submitted and reviewed by SC along with initial concept and concept revisions
EvaluationofNCORPResearchConcepts
• Theconceptisthemostimportantdocumentfromwhichthescientificmeritforanideaisevaluated
• Allconceptsarereviewedinternally
• NCIhasaSteeringCommittee(SC)reviewprocessfordiseaseandnondisease concepts
• FollowingaconceptapprovalbyaSC,theprotocoldevelopmentismanagedinternally
NCORPConceptReview
ConceptReceivedinProtocolInformationOffice
SteeringCommitteeReviewor
InternalReview
DCPInternalReview
Chairperson,ReviewersandPIOTeamMedicalOfficersNurseConsultantsDCPBiometryExpertsfromDCCPS,DCTD,CRCHDOtherExpertise:NIH,NCICCR,
ExtramuralCommunity
• SymptomManagement&QOL• CancerCareDelivery• ClinicalImaging• Breast
NCICoordinatingCenterforClinicalTrials:ScientificSteeringCommittees
ConceptEvaluationProcess
SteeringCommitteeEvaluationofConcept
Approval
Concept may be revised &
submitted once
ProtocolDevelopmentbyResearchBase
ConsensusReview
Revise&ResubmitPendingDisapproval
WhatDoesNotGototheSteeringCommittees?
• Longitudinalstudies,surveys,cancerprevention
• Pediatriccancercontrol
• Studies≤100participants
• ResearchstudiesforwhichthereisnoestablishedscientificSC
• Studiesreviewed&fundedbyFederalAgencies– InvestigatorInitiatedStudiesarereviewedattheprotocollevel
• Phase0and1Trials
ProtocolReview
• Includesallinformationandproceduresnecessaryforconductingasuccessfultrial/study
• AssessesINDstatus,credits,rosters,accrualplans,non-federalfunding
• Evaluatestheinclusionofscientificinputfromtheconceptreview
ProtocolEvaluationProcess
DCPProtocolCommitteeEvaluation
Approval
CIRB
Disapproval Revise&ResubmitPending
Approval“onHold” ConsensusReview
CTSUReview&RBActivation
39
Investigator Initiated Grants§ Must Come through the Research Bases
§ Reviewed at the Protocol Level
§ No phase III RCTs for Prevention
Theworldwecreatedtodayhasproblemswhichcannotbesolvedbythinkingthewaywethought
whenwecreatedthem…..AlbertEinstein
3860640276
3531836672
32317 33021
40487
33649
3037932309
30172
8374 91847409 7460 7559
900511572 10652 9935 10210 10423
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
FY2003 FY2004 FY2005 FY2006 FY2007 FY2008 FY2009 FY2010 FY2011 FY2012 FY2013
Majority Minority Unknown
MinorityEnrollmenttoNCICooperativeGroupClinicalTrials
14% 16%17% 16% 17% 17%
19% 20% 19%21%17%
85% 83%82% 83% 82% 81%
79% 78% 79%77%81%
