garrett fitzgerald - clinical and translational research in the usa - 2009

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