garrett fitzgerald - clinical and translational research in the usa - 2009
TRANSCRIPT
ClinicalandTransla,onalResearchintheUSA
G.A.FitzGeraldIns,tuteforTransla,onalMedicineandTherapeu,cs
www.itmat.upenn.edu
IPPOSI SYMPOSIUM DUBLIN 2010
BasicandClinicalResearchareInterdependent
Translation from basic science to human studies
Translation of new knowledge
into clinical practice
Basic Research
Clinical Research
Improved Health
Adapted from Sung et al. (2003) JAMA, 289, 1278-89. Copyright © (2003) American Medical Association. All Rights reserved.
Financial Times Apr. 11th 2009
Merger: A Response to Crisis
Short Term Response - Merger
The Academic Gerontocracy
FixingtheProblem
• Addressingthedeficitinhumancapitalwithinterdisciplinarytransla,onalskillsetsper,nenttodrugac,on
• Enlargingtheprecompe,,vespacebyaddressingoutmodedandunrealis,cexpecta,onsbasedonIP
• Crea,ngtheinforma,cssubstrateforsecure,compliant,heterogeneousdatasharingacrosssectorsandcountries
AnAppealtoReason
“If we don’t change the business models, we’re not going to survive as an industry”.
Richard Clarke, Merck CEO Financial Times, Oct 22nd 2008
Research Continuum: BASIC TRANSLATIONAL CLINICAL POPULATION OUTCOMES
Basic Science Departments CCEB
LDI
Disease-based Centers and Institutes
Clinical Departments
Basic Science Centers/Institutes
ITMAT
Creation of the Penn Institute for Translational Medicine and Therapeutics
(ITMAT)
MT
WY
ID
WA
OR
NV
UT
CA
AZ
ND
SD
NE
CO
NM
TX
OK
KS
AR
LA
MO
IA
MN
WI
IL IN
KY
TN
MS AL GA
FL
SC
VA WV
MI NY
PA
MD
DE
NJ CT
RI MA
ME
VT NH
AK
HI
BuildingaNa+onalCTSAConsor+um
New members 2009 Members
Participating Institutions
NC
OH
NIHSpendingonClinicalResearch
http://officeofbudget.od.nih.gov/ui/2008/tabular%20data.pdf http://www.nih.gov/news/fundingresearchareas.htm#content
Total NIH Budget FY 2008
$29.5 Billion
Non-Clinical Research
$19.8 Billion (67.3%)
Other Clinical Research $6.1 Billion
(20.6%)
Clinical Trials $3.6
Billion (12.1%)
SponsorsofBiomedicalResearch(BasicandClinical)
Moses et al. (2005) JAMA, 294, 1333-42
ChallengestoAcademia
1.HUMANCAPITAL
• Disintegra,onofTransla,onalTherapeu,cs• Incen,vespoorlyalignedforteamscience
• Fewincen,vestointerdisciplinaryresearch• Timelinesofpromo,onandfunding
• Specificdeficitsinmedicinalchemistry• Trainee/Exper,semismatch
ITMATResponse
• Diversifiededuca,onalofferingsinclinicalandtransla,onalresearch;mastersandcer,ficateprograms,farmteams,workshops
• Mul,plefundingini,a,vestofostertrulyinterdisciplinarytransla,onalresearch
• Fosteringcommercializa,onandaddressingIPbarriers
*Half year
*Half year
TemporaldynamicsofITMAT
ChallengestoAcademia
INFRASTRUCTURE
• AccesstoHTSandmedicinalchemistry
• AccesstoseedfundingforcommercialPOC
• Informa,csinfrastructure–datasharingandmining,sampletracking,scanningforcollabora,on
• Analy,calbiochemistry,kine,csandmodeling
• POCinhumans
ITMATResponse• ClinicalandTransla,onalResearchCenterandLaboratory
• Inves,ga,onalDrugServiceandKine,csandModelingCore
• Co‐investmentininforma,cs,proteomics,genomics,imagingandbiotherapeu,csinfrastructure
• Discountedaccesstoexper,se–stats,trialdesign,databases
• AcceleratedCTRC/IRBapproval
Physician‐Scien,st
BasicResearch
ClinicalResearch
ResearchPlan
LC‐MS/MSCore
Developmentofunbiasedmarkers
ResearchPlan
IACUC
SampleAnalysis
inmice
inhumans
BiomedicalLab
AnimalFacili,es
ExternalScien,ficAdviserandIndustry
Bionutri,onalResearchCore
ClinicalTransla,onalResearchCenter
BiochemistryCoreLabResearchNurseCore
Biosta,s,csCore
Ins,tu,onalReviewBoard
CTRCAdvisoryCouncil
Administra,on/OfficeofHumanResearch
ITMATClinicalTrialsUnit
FoodandDrugAdministra,on(IND)
Bioinforma,csCoreCRCUDataManagement
CenterforClinicalEpidemiologyandBiosta,s,cs
Inves,ga,onalDrugService
Post‐Doc
Kine,csModelingandSimula,on
USAcademicCentersandIndustrySponsoredRandomizedClinicalTrials
• Studyini+a+onatacademiccentersis49dayslongerthanatprofessionalandcommunitysites
• Onceupandrunning,academicsitesareroughly10%slowerinenrollmentthandedicatedandprofessionalsites
• Manycentersfailtoenrollasinglepa+ent
17 Source: Harvard Business School/
RapidTrials Consortium
2.5 0 1.0
PA to FSFV 82 480 200
239 0 88
243
95th perc. mean
%of Enrollment Goal
Enrollment Index .89
75.8
Enrollment Rate (wk) .02 .82
Screen Failure Rate 78.1 31.1 30.7
Drop Out Rate 0 83.3 .26 37.3
5th perc.
.9
Academic Medical Centers Summary Metrics Report
Academic Medical Centers
0
2.9
ChallengestoCTSACONSORTIUM1.Fes+naLente–ShiLingEmphasisfromSpeedto
Quality
• DetailedphenotypinginsmallnumbersinsingleCenterscloselyintegratedwithpreclinicalresearch
• Muchmoreemphasismechanismandvariabilityindrugresponseasabasisforpersonalizeddoseselec,on
• Projectedtoscaleamongstsimilarcenters• Tradi,onalPhase3–someCTSAs,butmostlynonCTSAenvironments
2.LAUNCHINGANEWDISCIPLINE
• Developandprojectmechanismbasedquan,ta,vebiomarkersfrommodelsystemsintohumans.
• Evokingphenotypicresponsesinhumanstoguideindividualiza,onofra,onaldoseselec,on
• Harnesstheunbiasedtechnologiestoselectamongstmoleculesdirectedagainstasingletarget
• Anunintendedconsequenceofnomenclature
3.ExpandthePrecompe++veSpace
• ExampleoftheNotforProfitSector
• FDA:createasafehavenforSystemsPharmacologyandPhysiology
4.Enhanceinterac+onwiththeFDAAJPLfortheFDA
• ResourceFDAtoincentacademiccenterstoaffordexper,seinemergingscienceandasitetopursueques,onsrelevanttodrugac,onbeforeanda_erapproval
• Fostercollabora,veandeduca,onalinterac,onsbetweenofFDAandAcademicscien,sts
• Rewardinnova,on• Staggeredapprovalanddrugwithdrawl
FDA Science and Mission at Risk Science Board Report Nov. 2007
It’sallabouttheMoney
5.ShowmetheMoney
• CTSAcutscompoundedbyins,tu,onalretrenchment
• Shi_toconsor,alac,vi,esatexpenseofindividualcenterresource
• Complementwithinvestmentinbasicandinves,gatorini,atedscience
• SustainandexpandpublicfundingfortheTransla,onalenterprise;the17yearrule
SummaryTheHealthandWealthofaNa,on• Thequalityofclinicalresearchdependsonbasicandtransla,onalresearch.
• Thisispar,cularlysoaswemovetowardsamorepersonalizedapproachtomedicine.
• Sustainedfundingiscrucialforalltheseinterdependentelements;it’snotazerosumgame.
• Pa,entswillandshouldplayanincreasingroleaspartnersinthisprocess.
ProgressinTransla,onalMedicineandTherapeu,cs