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