1May 25, 2009

Office of Science Policy, NIH

Stefano Bertuzzi, Ph.D.

Office of Science Policy

Office of the Director

National Institutes of Health

Behind Medicine: Science and Policy

May 25, 2009

5th European Drug Policy ForumMadrid May 25, 2009

2May 25, 2009

NIH is the Steward of Medical and Behavioral Research for the U.S.

“Science in pursuit of fundamental knowledge about the nature and behavior of living systemsand the application of that knowledge to extend healthy lifeand reduce the burdens of illness and disability.”

3May 25, 2009

The NIH it is a “Federation” of 27 Institutes and Centers

NEI

NCI

NHLBI

NLM NINDS

NIMH

NIAMS

NINR

NCCAM

CIT

CC

NHGRI

NIANIAAA

NIAIDNICHD

NIDCD

NIDCR

NIDDK

NIDA

NIEHSOD

NIBIB

NCMHDCSR

NCRR

NIGMSFIC

4May 25, 2009

Note: FY08 enacted level does not reflect additional $150 million from supplemental appropriation.

SpendingSpendingOutside NIHOutside NIH

$24.8 B$24.8 B

RM&S and OD Oversight

$1.5B4.92%

B&F$0.1B0.43%

10,000 intramuralintramuralscientists & research

personnel

$3.1B10.42%

ExpenditureAmount84.2%84.2%

84.2% of the total NIH budget supports over 325,000 extramuralextramural scientists and research personnel at more than 3,000 institutions nationwide.

15.8%15.8%SpendingSpending

at NIHat NIH$4.7 B$4.7 B

NIH Budget in FY 2008: $29.5 Billion

5May 25, 2009

American Recovery and Reinvestment Act of 2009: $10.4 Billion (2 year appropriation)

Scientific Research Priorities

78%

Capital Equipment3%

NIH Building and Facilities

5%

Comparative Effectiveness

Research4%

Extramural Construction

10%

6May 25, 2009

Tremendous Progress: OECD All-Cause Mortality Rates….0

05.0

1.0

15.0

2.0

25

1950 1960 1970 1980 1990 2000Year

Males 50-64

.005

.01

.015

.02

.025

1950 1960 1970 1980 1990 2000Year

Females 50-64

7May 25, 2009

Office of Science Policy, NIH

Four Main Challenges

• Public Health Challenge• Health Care Challenge• Science Challenge• Industry Challenge

8May 25, 2009

Office of Science Policy, NIH

Public Health Challenge

9May 25, 2009

Shift from Acute to Chronic Conditions

Health Disparities

Emerging and Re-emerging Infectious Diseases

Health of an Aging Population

Emerging Non-communicable Diseases, e.g., Obesity

Public Health Challenge

Biodefense

Public Health Challenge

10May 25, 2009

Epidemiologic Transition: Worldwide Rise of Chronic Disease Death (%) of World Total

Chronic diseases:

Heart disease30.2

Cancer15.7Diabetes1.9Other chronic diseases15.7

Tuberculosis 2.4

Malaria 1.5

OtherInfectiousDiseases

20.9

Infectious diseases:HIV/AIDS 4.9

Injuries 9.3

Source: The Economist, WHO, 2005

Public Health Challenge

11May 25, 2009

A Different Kind of Evolution?

12May 25, 2009

World Population by Age, years 1950, 2005 and 2050 (projected)

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

0-4

5-9

10-

14

15-

19

20-

24

25-

29

30-

34

35-

39

40-

44

45-

49

50-

54

55-

59

60-

64

65-

69

70-

74

75-

79

80-

84

85-

89

90-

94

95-

99

100

+

Age groups

Popu

latio

n (in

thou

sand

s)

1950 2005 2050

Source: UN, World Population Prospects

Public Health Challenge

13May 25, 2009

Health Disparities: The Millennium Preston Curve

0 10,000 20,000 30,000 40,000

40

50

60

70

80

life

expe

ctan

cy, 2

000

gdp per capita, 2000, current PPP $

USA

Japan

Germany

FranceItaly

UK

Spain

Korea

Argentina

South Africa

Equatorial Guinea

Mexico

Russia

Brazil

Botswana

Namibia

Gabon

China

India

Indonesia

PakistanBangladesh

Nigeria

Public Health Challenge

14May 25, 2009

Office of Science Policy, NIH

Health Care Challenge

• Cost• Efficiency • Access and affordability• Comparative effectiveness evidence• Resource allocation strategies • Manage the full life cycle of the disease process• Decision making process

15May 25, 2009

Projected Spending on Health Care Under an Assumption That Excess CostGrowth Continues at Historical Averages

0

10

20

30

40

50

60

70

80

90

100

2007

2010

2013

2016

2019

2022

2025

2028

2031

2034

2037

2040

2043

2046

2049

2052

2055

2058

2061

2064

2067

2070

2073

2076

2079

2082

Perc

ent o

f GD

P

Medicare Medicaid All Other

Source: CBO, The Long-Term Outlook for Health Care Spending

Health Care Challenge

16May 25, 2009

Relationship Between Quality of Care and Medicare Spending, by State, 2004

Com

posi

te m

easu

re o

f qua

lity

of c

are,

10

0 =

max

imum

State-Level Medicare Spending per Beneficiary(Thousands of Dollars)

Source: CBO, Congressional Budget Office based on data from the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality

Health Care Challenge

17May 25, 2009

37.0 36.1

8.4 8.7 9.4 8.9

34.6 35.6

2004 2005 2006 2007

ChildrenAdults

43.0 44.446.5

45.0

Number of Nonelderly Uninsured Americans, 2004 – 2007(in millions)

Source: Kaiser Commission on Medicaid and the Uninsured/Urban Institute analysis of March CPS for each year

Health Care Challenge

18May 25, 2009

Office of Science Policy, NIH

Science Challenge

• Complexity of biological systems• Interdisciplinary collaborations• Modeling of human disease • Molecular understanding of diseases• Functional reclassification of diseases• Translational strategies

19May 25, 2009

A Fundamental Challenge

Today, a fundamental scientific barrier is our limited ability to study complex and dynamic

biological systems in health or disease

Science Challenge

20May 25, 2009

The Complexity of Biological Networks

• Multiple levels of cross-talk between receptor systems

• Many drug targets part of intricate signaling network

• Multidimensional functional approach needed

Science Challenge

21May 25, 2009

The Complexity of Biological Networks

Science Challenge

• Burkitt’s lymphoma and diffuse large B-cell lymphoma look alike histopathologicallybut require different treatments

• Genetic signatures defined for Burkitt’s and DLBCL

• Expert histopathologistsmisdiagnosed 17% of cases

• Molecular profiling was more accurate for differential diagnosis

Source: Dave S. et al. N Engl J Med 2006;354:2431-2442

22May 25, 2009

Consilience

The “jumping together” of knowledge by linking facts and fact-based theory across disciplines to create a common groundwork of explanation

William Whewell, 1840The Philosophy of

Inductive Sciences

Science Challenge

23May 25, 2009

A Rapidly Changing Landscape

• Unraveling of the molecular mechanisms of disease and disease pathways

• Genomics discoveries suggest that disease pathways are not always the same even when phenotypes are similar

Patient stratificationGenotype-biomarker associationDifferent treatments for different disease stagesHighly effective treatments for smaller strata of patientsHigher patient complianceVirtual Networks of patientsPost-marketing surveillance

• Training the appropriate workforce

Science Challenge

24May 25, 2009

Time Magazine March 23, 2009

Folks at the National Cancer Institute (NCI) are heading up an effort to establish the U.S.'s first national biobank — a safe house for tissue samples, tumor cells, DNA and, yes, even blood — that would be used for research into new treatments for diseases…. By fall, the group hopes to have mapped out a plan for a national biobank; the recent stimulus showered on the government by the Obama Administration might even accelerate that timetable.

8. BiobanksBy ALICE PARK

Inside Huntsman Cancer Institute's vaults: Pancreatic tumors on ice.Lance W. Clayton for TIME

Science Challenge

25May 25, 2009

New Pathways to Discovery

Re-engineering theClinical Research Enterprise

Research Teamsof the Future

Science Challenge

26May 25, 2009

NIH Roadmap Initiative: Human Microbiome Project

• Will generate resources, support development of new technologies and computational approaches to facilitate characterization of highly complex human microbiome

• Will improve our knowledge of how changes in microbiome correlate with changes in human health

• Some questions to be asked:What microbes live in humans?

How do they contribute to health? To disease?

Might the microbiota be manipulated to improve health?

Science Challenge

27May 25, 2009

Knock Out Gene Project (KOMP) and International Mouse KO Consortium• Complete nucleotide sequence of genome determined• A series of inbred strains available to control genetic background• Mammalian species with many functions quite similar to humans• Straightforward to manipulate the genetic background • An international effort to generate null alleles for most of the estimated 20,000 structural

genes discovered in the mouse genome (targeted deletions and gene trapping)• Resource currently at the level of embryonic stem cells, ready to be used to generate

embryos and live mice• Collaborative effort between EuComm, NorComm, TIGM, and NIH• Close coordination to avoid unproductive duplication of efforts in accomplishing this

ambitious goal as quickly as possible

Science Challenge

28May 25, 2009

MT

WY

ID

WA

OR

NV

UT

CA

AZ

ND

SD

NE

CO

NM

TX

OK

KS

AR

LA

MO

IA

MN

WI

ILIN

KY

TN

MS AL GA

FL

SC

VAWV

MINY

PA

MD

DE

NJCT

RIMA

ME

VTNH

AK

HI

Newest memberMembers

Participating Institutions

NC

OH

Building a National CTSA Consortium

Science Challenge

29May 25, 2009

UC DavisCTSC

School of Veterinary Medicine

UC Davis Cancer Center

Shriners Hospitals for Children–

Northern California

Lawrence Livermore National Laboratory

College of Agriculture andEnvironmental Sciences

College of Engineering

College of Biological Sciences

California National Primate Research Center

Department of Veterans Affairs Northern California

Health Care System

Formation of Local Networks

Science Challenge

30May 25, 2009

Office of Science Policy, NIH

Industry Challenge

• Pipeline management• Maintain innovation and productivity• Cost-effectiveness and incentives for innovation• Intellectual Property• Need for increased flexibility and network

formation• Shift from blockbuster drugs to molecules

effective for specific strata of patients• Vertical integration from basic R&D to post-

marketing surveillance IT research

31May 25, 2009

The Pharmaceutical Industry in the U.S.

Parameter 1996 2006

Sales (Billion of $) 102

17

35,000

74*

276

R&D Spending (Billion of $) 43

Average # of Employees 68,000

New Drug Applications to FDA 102**

* 1993** 2004

Industry Challenge

32May 25, 2009

Regions/Countries Where R&D Employment is Anticipated

Thursby & Thursby, 2006 Here or There? NAS Press

33May 25, 2009

The Pipeline Challenge

• Output of new molecular entities (NMEs)

• Efficiency of the R&D Process

• Knowledge management

• Replacing $65 billion worth of pharmaceuticals going off patent in the next five years

Source: PhRMA

Industry Challenge

34May 25, 2009

Innovation Reward

• Who captures the social value generated by biomedical innovation?

• Some studies argue that only 5% of the net social value of HIV/AIDS drugs has been captured by companies providing treatments. Not everybody agrees.

• A treacherous trade off: the decreased welfare of current patients resulting because of higher prices of drugs vs. the increased welfare of future patients who could benefit from the benefits of incentives to develop new drugs

Industry Challenge

35May 25, 2009

The Rapidly Evolving Industry Landscape

Industry Today Tomorrow

Products Few Many

Focus Phenotypes Genotypes

Sales Blockbusters Many Smaller Sales

Patient Target Diseased Prevention/Early Diagnosed

Partnerships Acquisitions of Biotech Wide Networks

Industry Challenge

36May 25, 2009

Genetic Association Information Network (GAIN)

• Create public-private partnership to support Genome Wide Association Studies

• Determine and make public all the genetic contributions to common diseases

• Provide “free” genotyping information to researchers forwell phenotyped cases and controls

Industry Challenge

37May 25, 2009

Collaborative Initiatives www.biomarkersconsortium.org

• FNIH, NIH, FDA, PhRMA, BIO partnership—the first of its kind—launched October 5, 2006

• Purpose: Search for and validate biomarkers to accelerate discovery, development of new technologies and therapies

• Enables government, industry, and philanthropy to explore and develop common tools for everyone’s benefit

Industry Challenge

38May 25, 2009

Pharmaco-Genomics: Managing Human Variability

• Pharmaco-Genetics Research Network (PGRN)

National collaboration of scientists studying the effect of genes on people's responses to a wide variety of medicines

• Pharmaco-Genetics & Pharmaco-Genomics Knowedge Database (PharmGKB)

Integrated knowledge base for pharmacogenetics linking phenotypes and genotypes

Source: http://www.nigms.nih.gov/Initiatives

Industry Challenge

39May 25, 2009

NIH Intramural Research Program Selected Activities

Activity 2008

Invention Disclosures 402

176

343

Issued US Patents 88

Executed CRADAs 72

Executed Licenses 2592

Royalties ($ in millions) 97.2

New US Patent Applications1

Total US Patent Applications

1 Patent applications include only the first U.S. patent application for a new disclosure filed in the reporting period (data include CIP filings but not Divisional applications). 2 This number includes 26 administrative amendments that modify executed license agreements to correct or clarify non-substantive terms or obligations.Source: NIH Office of Technology Transfer

Industry Challenge

40May 25, 2009

NIH Top 20 Commercially Successful Inventions(2008, based on royalties on product sales)

Invention Description Inventor Rank

HPV Vaccines Based Upon Recombinant Papillomavirus Capsid Proteins Lowy et al. (NCI) 2

Monoclonal Antibody for Treatment of Respiratory Syncytial Virus Murphy et al. (NIAID) 3

Novel Protease Inhibitor for Treatment of Drug-Resistant HIV-1 Erickson et al. (NCI) 4

Proteosome Inhibitor for Treatment of Multiple Myeloma Gupta (NCI) 5

AIDS Drug ddI Mitsuya et al. (NCI) 7

Synthetic Thyrotropin as Adjuvant in Thyroid Cancer Wondisford et al. (NIDDK) 8

Paclitaxel as a Cancer Treatment Wilson et al. (NCI) 10

Nutritional Supplement to Treat Macular Degeneration Ferris et al. (NEI) 11

Hepatitis A Vaccine Daemer et al. / Funkhouser et al. (NIAID) 12

Vaccinia Virus Vector Used in Veterinary Vaccines Moss et al. (NIAID) 14

Palifermin for Treatment of Oral Mucositis Rubin et al. (NCI) 18

HIV-1 Diagnostic Kit Gallo et al. (NCI) / Montagnier et al. 6

Her-2 Diagnostic for Breast Cancer King et al. (NCI) 9

Genoyping of HIV Protease Gene Oroszlan et al. (NCI) 15

Norwalk-like Virus Diagnostic Kit Green et al. (NIAID) 16

HTLV-1/2 Diagnostic Kit Papas et al. (NCI) 20

Paclitaxel-Eluting Coronary Stent System Kinsella et al. (NIA) 1

Diffusion Tensor MRI Software Basser et al. (NICHD) 13

Software for MRI Enhancement Balaban et al. (NHLBI) 17

Purified Transforming Growth Factor Beta (TGF-beta) Sporn et al. (NCI) 19

VAC

CIN

ES A

ND

TH

ERA

PEU

TIC

SD

IAG

NO

STIC

SD

evis

esSo

ftwar

eR

esea

rch

Mat

eria

lsIndustry Challenge

41May 25, 2009

NIH Contribution to Pharmaceutical Development

Source: Lichtenberg and Sampat, 2008

Industry Challenge

42May 25, 2009

Factors in the selection of R&D Site Placement by Industry

Thursby & Thursby, 2006 Here or There? NAS Press

43May 25, 2009

The NIH is the Steward of Medical and Behavioral Research for the United States

“The NIH speaks the universal language of humanitarianism. It has been devoted throughout its long and distinguished history to furthering the health of mankind, in which service it has recognized no limitations imposed by international boundaries; has recognized no distinctions of race, of creed, or of color”

Franklin D. RooseveltDedication of the NIH Campus in Bethesda, MDOctober 31, 1940