WilliamBarsan,MDSIRENClinical

CoordinatingCenter

Evolutionnotcreation

Specificaims

1.diligentlyrecruit,efficientlyperform,andwidelydisseminatethemostscientificallyandclinicallyimportanttrialsinemergencypatientcare

2.createacultureofclinicaltrialsthatiscollaborative,multidisciplinary,diverseandinclusivethroughleadership,openness,andengagement

3.transformtheemergencyresearchenterprisethroughinnovativedesign,patientstakeholderengagement,betteroperationalstrategies

Designprinciplesandorganizationalvalues

• Focuson earlytreatment.

• Focusonmeaningfuloutcomesforpatients.

• Focuson efficiency.

• Focuson collaboration.

• Focuson transformingtheclinicaltrialsenterprise.

SIREN Grant Awards

Massachusetts General Hospital

Temple University

University of Pittsburgh

Wayne State University

University of Cincinnati

Emory University

Medical College of Wisconsin

University of Minnesota

University of Washington

Oregon Health Sciences University

University of California Los Angeles

Coordinating Centers

University of Michigan

Medical University of South Carolina

Clinical Trial Summaryand Rough Budget

Trial Ideas(from

anybody)

Scientifically and Clinically Important

Questions and Observations

InstitutePre-approval

to submit

Grant application(s)

Collaborative Grant Application

and Protocol Development with input from Sites,

Patients, and Others

NIH Study Section

Revise Grant Award

Grant Award to Scientific PI’s Institution with

major subaward to CCC

DCC may be paired grant or

subaward depending on IC

Begin discussions with NIH program

officers early

Begin discussions with SIREN leadership early as well.

SIREN leadership will evaluate fit for the network, contribute to concept, and relay to site PI’s

SIREN will NOT be a layer of scientific peer review

TrialRecruitmentandPipeline

AdaptableopenclinicaltrialinfrastructureCollaborativeleadership(typicallymultiplePI)Respectfulofinvestigators’ownershipandcontrolofthescienceSharingofoperationalandstatisticalresponsibilitiesFacilitatingsuccessfulimplementationanddataintegrity

TrialRecruitmentandPipeline

Effectivenessandefficiencyfromconsistentre-useof:establishedskilledresearchteamsandinterpersonalrelationshipspre-existingcontractual,regulatory,administrativeframeworksfamiliarandconsolidatedclinicaltrialmanagementtechnology.

Optimalstrategyforworkingwiththenetworkis:contactpriortorequestingpermissionfromtheinstitutetosubmitcollaborativedevelopmentoftrial,grantapplication,andbudget

ScopeofPortfolio

LatelearningphaseorconfirmatoryphasetrialsPatientorientedoutcomesControlledefficacytoregistrybasedRCTAppropriatesizedforourscalablenetwork

Primaryfocusonneurological,cardiac(lungandblood),(andtrauma?)SecondaryfocusonotherICportfolios,andhealthservices

QUESTIONS?

Innovationsintrialdesign

• Answeringthemostimportantquestionswiththemostappropriatetrialdesignforthatquestion

• AdaptiveDesigns• RegistryBasedRCT’s(AHAandACS/COT)

• GoodTrialDesignAffectsSubject Accrual

OrganizationalStructure

Specimen

Pharmacy

Imaging

Spokes

Hubs

CCC

NIH

DCC

MgmtComm

SteeringComm.

TrialPI

AHAACS

RegistryBasedRCTWG

CriticalCareWG

HSPWG

SurgicalWG

EMSWG

DSMB

Trial Comm

OperationsCommittee

FederalComm.

ER-CIRB

Innovationsintrialoperations

• StudyTeamsAffectTrialSuccess• CreatingaCultureofService• EngagingCommunityStakeholders

IllustrationofgrantrelationshipsinSIREN

Hubsandspokes(designatedbyrectangles)representenrollmentsites.Circlesarecoordinatingentities.

SuperHub SuperHub SuperHub SuperHub

SubHub SubHubSubHub AncillaryHub/Spoke

AncillaryHub/Spoke

TrialPrime

NIH

DCCCCC

Spoke Spoke SpokeSpokeSpokeSpokeSpokeSpoke Spoke SpokeSpoke Spoke Spoke

MultiplePILeadershipPlan- CCC

• Barsan• Silbergleit• Callaway

MultiplePILeadershipPlan- DCC

• Palesch• Durkalski

NIHProgramLeadership

• Brown• Mendoza-Puccini• Sopko• Culp

Keyassets

• People• StreamlinedFinancialManagement•PatientRecruitmentandEnrollment•OutstandingDataManagement

• QualityAssurance

IllustrationofproposedcontractualrelationshipsinSIREN

Hubsandspokes(designatedbyrectangles)representenrollmentsites.Circlesarecoordinatingentities.Dottedlinesrepresentoptionalrelationships.DashedlinesrepresentHub-spokecomplexes.Numberofblue“superhubs”isestablishedbynumberofindividualNIHenrollmenthubawards.SteeringCommitteeincludesall“superhub”PI’s(includingmultiplePI’s)withonlyonevotepersuper-hub.Green“subhubs”areaffiliatedwith“superhubs”buthavetheirownmasteragreementwiththeCCC.Whichsiteswithinahub-spokecomplexare“subhubs”isdeterminedlocally,butaretypicallydistinguishedbythe“subhub”beinganinstitutionthathasitsownspokes.AncillaryHub/spokesaretypicallycontractedbytheTrialPrimeifbroughtonforasingletrial,orbytheCCCifexpectedtoparticipateinmultipletrials(includingthosealreadyparticipatinginmultipletrials).

SuperHub SuperHub SuperHub SuperHub

SubHub SubHubSubHub AncillaryHub/Spoke

AncillaryHub/Spoke

TrialPrime

NIH

DCCCCC

Spoke Spoke SpokeSpokeSpokeSpokeSpokeSpoke Spoke SpokeSpoke Spoke Spoke

IllustrationofproposedcontractualrelationshipsinSIREN

PotentialSourcesofTrials

EarlyreferralsfromprogramofficersatNIHInvestigatorscontactingusdirectlySIRENinitiated/generatedtrials

(addressingneeds,portfoliogaps,ICpriorities)(retreats/workshops)

Industrypartnerships(SBIRs)

EmergencyResearchCentralIRB(ER-CIRB)

Site Site Site Site

CCC

CIRB

ER-CIRB

CTMS WebDCU

IRB-IT

• Closecollaborationwithvendor• Mostlyexistingrelianceagreements• IRBcommunicationallthroughCCC• InfoallsubmittedthroughWebDCU

• Expectsomegoodandsomebad

Outreach

• NetworkCollaborationPECARNPETALLITESStrokeNETOthers

• StakeholderEngagement