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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:

Challenging times!!!!!

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 (%)

National Institutes of Health Funding 1990-2041

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)

Research Project Grants: Competing Applications, Awards, and Success Rates

NIH Budget Authority: FY 2013 Actual

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

Finding the Right Fit for Your Research Idea

Opportunities

Training Grants

Fellowships

Career Development Awards

Research Grants

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

grants.nih.gov/grants/grants_process.htm

Policy & Program News

Patient released from Clinical Center

Zmapp(no randomized control trial

limited supply)

VaccinesNIAID & GSK – Phase I in CC

PHA Canada & New Link Genetics

EBOLA

Learning the Language of the Brain

BRAIN Initiative“The Next Great American Project”

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

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

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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

Myriad Data Types

Other ‘Omic

Imaging Phenotypic

Clinical

Genomic

Exposure

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

Greater Diversity in Research Workforce is Needed

Award Probability – Institution and Race/Ethnicity*

*Courtesy of Dr. Donna Ginther

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

Webpage of Grants and Funding

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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.

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