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The Future of Biomedical Research: A View from NIH
Sally J. Rockey, PhDDeputy Director for Extramural ResearchNational Institutes of Health
October 2014
NIH: Steward of Biomedical & Behavioral Research for the Nation
NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems…
…and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.
U.S. Dept. of Health & Human Services
Administration forChildren and Families
(ACF)
Food and DrugAdministration
(FDA)
Health Resourcesand Services
Administration(HRSA)
Secretary of Health and
Human Services
Administration onAging(AoA)
Center for Medicare & Medicaid Services
(CMS)
Indian HealthServices
(IHS)
National Institutesof Health
(NIH)
Agency for Healthcare Research
and Quality(AHRQ)
Centers for Disease Controland Prevention
(CDC)
Substance Abuse andMental Health Services
Administration(SAMHSA)
Agency for ToxicSubstances and
Disease Registry(ATSDR)
4
National Instituteon Alcohol Abuseand Alcoholism
National Instituteof Arthritis andMusculoskeletal
and Skin Diseases
National CancerInstitute
National Instituteon Aging
National Instituteof Child Health
and HumanDevelopment
National Instituteof Allergy and
Infectious Diseases
National Instituteof Diabetes andDigestive and
Kidney Diseases
National Instituteof Dental andCraniofacial
Research
National Instituteon Drug Abuse
National Instituteof EnvironmentalHealth Sciences
National Institute onDeafness and Other
CommunicationDisorders
National EyeInstitute
National HumanGenome Research
Institute
National Heart,Lung, and Blood
Institute
National Instituteof Mental Health
National Instituteof NeurologicalDisorders and
Stroke
National Instituteof General
Medical SciencesNational Institute
of Nursing Research
National Libraryof Medicine
National Centerfor Complementary
and AlternativeMedicine
FogartyInternational
Center
National Centerfor AdvancingTranslational
Sciences
National Instituteof Biomedical Imaging and
Bioengineering
No funding authority
NIHClinical Center
Centerfor Information
Technology
Center for Scientific
Review
National Center on Minority Health
and Health Disparities
Office of the Director Office of Extramural Research
National Institutes of Health
Understanding the Dual Nature of NIH
NIH supports institutions & people(Extramural Research)
• >2,500 institutions• >400,000 scientists & research
personnel• Approx. 70,000 applications and 40,000
awards annually• Approx. 81% of the NIH budget
NIH is an institution(Intramural Research)
• Approx. 6,000 scientists• Approx. 11%
of NIH’s budget
Fiscal Year 2012 Extramural Research Grants by Institution
NIH Leadership
1. NIH Director as of August 17, 2009
2. Former Director of the National Human Genome Research Institute, NIH
3. Leader of the Human Genome Project
4. Dr. Collins’ own lab discovered a number of important genes, including those responsible for cystic fibrosis, neurofibromatosis, Huntington's disease and more
5. New York Times best selling book author
6. Interested in the interface of science and faith
7. Musician and Rock Star of Science
8. Believes the value of the NIH community is one where hard work, laughter, and compassion allow the imagination to soar
Francis S. Collins, Ph.D., M.D.
To better understand the direction of NIH, here’s some known (and little known) facts about the NIH Director:
Compound Annual Growth Rate of Biomedical R&D Expenditures by Country, Adjusted for Inflation
2007–2012
CanadaUnited StatesEuropeTaiwanJapanIndiaAustraliaSingaporeSouth KoreaChina 32.8
11.4
10.0
6.9
6.7
5.7
5.2
-0.4
-1.9
-2.6
-5 0 5 10 15 20 25 30 35
Source: N Engl J Med. 2014 Jan 2;370(1):3-6
Compound Annual Growth Rate of Biomedical R&D Expenditures (%)
NIH Program Level in Nominal Dollars and Constant 1998 Dollars, FY1998 – FY2014
$0
$5
$10
$15
$20
$25
$30
$35
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Appropriation Appropriation in 1998 Dollars
(In B
illio
ns)
Basic Research 52.0%
Applied Research (Clinical)34.6%
Applied Research (Other) 10.5%
R&D Facilities 0.3%
Training & Overhead
2.6%
Percent Distribution of Basic and Clinical Research
Funding Opportunities
• Advertised through▫ Grants.gov▫ NIH Guide for Grants and Contracts
• Issued by ▫ Each IC▫ “Parent” announcements span the
breadth of the NIH mission, include many ICs
Types of Funding Opportunity Announcements (FOA)
Type of FOA Description
Program Announcements (PA, PAR, PAS)
• Highlights areas of focus• Usually ongoing (3 yrs)• Often use standard receipt dates
Requests for Applications (RFA)
• Narrowly defined scope• Usually single receipt date • Set aside funds• IC usually convenes review panel
Parent Announcements
• Type of program announcement• Generally span the breadth of NIH mission• By activity code (R01, R03, etc)• For “investigator initiated” or “unsolicited”
research ideas
How does a grant get funded?National Institutes of Health
Center for Scientific Review
Performs the Research
Institution
InvestigatorInvestigator
Great Research Idea! Submits
Application
Assigns to IC & IRG / Study Section
Study Section
Reviews for Scientific Merit
Institute
Evaluates for Relevance
Advisory Councils & Board
Recommends Action
Institute Director
Makes Funding Decision
Allocates Funds
Where to Start• Develop your research idea ▫ Should be important (have high impact)▫ Needs to align with an IC mission
• Identify a funding opportunity • If no FOA specific to your area, look for a
“parent” announcement.• Talk with NIH staff about your idea and where it
fits• Write a strong proposal that addresses review
criteria
Where to Start (cont.)• Complete/renew required registrations (Start now!)
• Institutions are required to register in multiple systems
• Investigators must register in the eRA Commons• Develop the application• Carefully read the funding opportunity and
application instructions!!• Download application from funding opportunity
announcement• Learn about the electronic application submission
process well before the application due date
Patient released from Clinical Center
Zmapp(no randomized control trial
limited supply)
VaccinesNIAID & GSK – Phase I in CC
PHA Canada & New Link Genetics
EBOLA
FY 2014 Investments
Government Agencies $ in MillionsNational Institutes of Health $40 .7
• Blueprint for Neuroscience Research $10M• NIMH $12.85M• NINDS $12.85M• NIDA $4M• NIBIB $1M
Defense Advanced Research Projects Agency $50National Science Foundation $20Food and Drug Administration N/A
+ Private Investments
Unraveling Life’s Mysteries through Basic Research: The BRAIN Initiative September 30: NIH’s first investment in a 12-year
scientific vision; awarded $46M to more than 100 researchers in 15 states and 3 nations
Among the 58 projects are efforts to:– Develop innovative technologies to advance basic neuroscience– Generate methods for classifying the brain’s diverse cells/circuits– Create/optimize technologies for recording and modulating
groups of cells that act together in circuits– Form interdisciplinary teams to develop new non-invasive tools
for human brain imaging
Accelerating Medicines Partnership (AMP)www.nih.gov/amp
Aims to distinguish targets of disease most likely to respond to new therapies
Will invest >$230M over five years on pilot projects:
– Alzheimer’s disease
– Type 2 diabetes
– Autoimmune disorders (systemic lupus erythematosus and rheumatoid arthritis)
Costs are shared equally between NIH and the private sector
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Accelerating Medicines Partnership
Government Industry Non-Profit Organizations
NIH
FDA
AbbVie
Biogen Idec
Bristol-Myers Squibb
GlaxoSmithKline
Johnson & Johnson
Lilly
Merck
Pfizer
Sanofi
Takeda
Alzheimer’s Association
American Diabetes Association
Arthritis Foundation
Foundation for the NIH
Geoffrey Beene Foundation
Juvenile Diabetes Research Foundation
Lupus Foundation of America
Lupus Research Institute / Alliance for Lupus Research
PhRMA
Rheumatology Research Foundation
USAgainstAlzheimer’s
Antimicrobial Resistance:Obama Administration Activities
Presidential Executive Order – September 18, 2014– Federal Government will work to detect, prevent and control illness and death
related to antibiotic-resistant infection • Reduce Emergence & Spread
• New and effective Therapeutics– Task Force co-chaired by Defense, Ag and HHS
CARB – National Strategy for Combating Antibiotic Resistant Bacteria– Rapid Diagnostic
– Surveillance
– Network
Big Data and Biomedical Research
The promise – and the challenges
Big Data and NIH
Partnerships: national, and international
Growth of Biological Databases
0
200
400
600
800
1000
1200
1400
1600
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Source: Michael Bell, Newcastle University, U.K.
Num
ber o
f Dat
abas
es
Daily Data Processing at National Center for Biotechnology Information (NCBI)
InteractiveWeb
DataDownloads
365TB/day365TB/day
126 Petabytes/year126 Petabytes/year
3TB/day
35 TB/day
4 Terabytes (TB)/day
BD2K: Activities
Data sharing– Data Discovery Index– Data/metadata standards
Software development Training, including
– K01 Mentored Career Development awards; new training grants
Centers of Excellence– Applications have been received; reviewed– Awards FY 2014
Possible Causes for Difficulties Reproducing Data
• Poor experimental design: e.g., no blinding, randomization, insufficient power, variable experimental conditions, insufficient documentation of methods
• Errors in analysis & interpretation: lack of replication, inappropriate use of statistics, misinterpretation of findings
• Inadequate reporting of: detailed methods, failures to replicate, exclusion of outliers, changes to endpoints
• Overemphasis on the “exciting” or “big picture” finding sometimes results in publications leaving out necessary details of experiments performed
• Difficulty in publication of “negative” findings
• Underlying issues of poor training in experimental design and perverse reward incentives
Trans-NIH Actions
• Discussing reproducibility and transparency of research findings with stakeholder communities, such as journal editors
• Creating a new training module on research integrity and experimental design
• Implementing pilot studies to address key concerns, such as:▫ Developing a checklist to ensure more systematic evaluation of
grant applications▫ Determining approaches needed to reduce “perverse incentives,”
e.g., longer term support for investigators▫ Supporting replication studies
• Considering approaches to encourage applicants to:▫ Authenticate cell lines and other unique research resources▫ Analyze and report sex differences in preclinical research
Over the course of FY 2015, NIH plans to roll out policies that will require applicants to address inclusion of both sexes in biomedical research.
New Approaches to Supporting Science
• NIH is piloting the concept of awarding longer grants that provide more stable support for investigators at all career stages.
• Each Institute and Center will decide the appropriate size and duration of their awards.
• Applications will not require specific aims in the R01 format; investigators will describe their research plans and demonstrate how they will translate their prior accomplishments into future research approaches.
NIH Diversity Programs
• To ensure that we continue to attract the brightest minds to biomedical research, NIH is committed to increase the diversity of its workforce
• For over 30 years NIH has supported programs to achieve these goals▫ Institutional Programs (e.g. Minority-Serving and Hispanic-
Serving Institutions)▫ Individual Programs: target individuals from
underrepresented groups, including racial or ethnic minorities, persons with disabilities, or individuals from disadvantaged backgrounds
Race and Ethnicity of the 2010 U.S. Population and the 2010 NIH Principal Investigators on RPGs
Sources: US Census Report 2010; IMPACII
0.9% 4.8%
12.6%
72.4%
0.2%16.3%
9.1%
2010 U.S. Census 2010 NIH Principal Investigators on RPGs
0.2%
16.4% 1.1%
71.0%
0.1%3.5%
11.2%
NOTE: The charts add up to more than 100% as Hispanic/Latino population is double-counted
Greater Diversity in Research Workforce is Needed
NIH’s Plan for Action:• Evaluate current training programs• Phase out unsuccessful programs, expand
successful ones• Increase number of early career reviewers,
including those from underrepresented populations • Examine grant review process for bias and develop
interventions• Improve support for grant applicants• Gather expert advice on additional action steps
ACD Working Group on Diversity in the Biomedical Research Workforce Recommendations:
A Comprehensive Strategy
• Pipeline
• Mentoring
• Peer Review
• Infrastructure
Implementation Strategies
• Four interrelated approaches will be implemented: ▫ The NIH Building Infrastructure Leading to Diversity
(BUILD) Program Planning grant FOA http://grants.nih.gov/grants/guide/rfa-
files/RFA-RM-13-001.html. Applications due May 10, 2013.
▫ The National Research Mentoring Network (NRMN) Planning grant FOA http://grants.nih.gov/grants/guide/rfa-
files/RFA-RM-13-002.html. Applications due May 10, 2013.
▫ Ensuring Fairness in Peer Review ▫ Increased Engagement by All NIH Leadership
Finding Funded Research: http://RePORT.NIH.Gov
•Quick access to “Frequently Requested Reports” (e.g. Funding by State, Funding by Award Mechanism, etc.)
•Efficient search tools for locating data and reports•Links to funding estimates for certain research areas, conditions, & diseases.