NIH Precision Medicine Initiative:

Turning Discovery into Health

Gary H. Gibbons, M.D.

Director
National Heart, Lung, and Blood Institute
National Press Foundation Precision Medicine Meeting
Mayo Clinic
Rochester, MN
May 18, 2015

NIH Precision Medicine Initiative (PMI):

Turning Discovery into Health

NIH Precision Medicine Initiative (PMI)

Overview and Implementation
The PMI and the Nations Health
NHLBI Scientific Vision for PMI

What is the Precision Medicine Approach?

An emerging approach to disease prevention,
diagnosis and treatment
Considers the unique genes and environment of
each patient
Provides the right treatment, at the right time,
tailored to a patients individual needs

Precision Medicine
Concept is not new
Consider prescription eyeglasses, blood transfusions
Prospects for broader application raised by recent advances
in basic research, technology development, genomics,
proteomics, metabolomics, EHRs, Big Data, mHealth, etc.
Reinforced by 2011 National Research Council report

What is needed now

Development of rigorous research program to provide
scientific evidence to turn concept into reality
Recruitment of the best and brightest from multiple disciplines

Current Approach to Patient Care:

Annual Physical Exams and One-Size-Fits-All Care

What If? Diagnose and Treat an Individual Patient

Based on Refined Patient Classification and Treatment Outcomes
Diagnostic Precision -- Refining the Clinical Classification of Disease

Moving beyond -- One-Size-Fits-All

What If? Diagnose and Treat an Individual Patient

Based on Refined Patient Classification and Treatment Outcomes
Events
Response/Death
NoAdverse

What If? Diagnose and Treat an Individual Patient

Based on Refined Patient Classification and Treatment Outcomes
No
Response/Death
NoAdverse
Response/Death
Events

What If? Diagnose and Treat A Patient

Based on Refined Patient Subsets and Treatment Outcomes
Marked
Response
to Lowest Dose
NoAdverse
Response/Death
Events

What If? Diagnose and Treat an Individual Patient

Based on Refined Patient Classification and Treatment Outcomes
Precision
Medicine
Approach
NoAdverse
Response/Death
Events

Right
Drug

Right
Dose

Right
Time

Right
Person

Why Now? Recent Developments Make This

The Right Time

Patient Partnerships

Electronic Health Records

Technologies

Genomics

Data Science

PMI: Timing is Everything

Ten Years Ago

Now 2014
(most recent data)

Cost of Sequencing a Human

Genome

$22,000,000

$1000 - $5000

Amount of Time to Sequence

a Human Genome

2 years

<1 day

Number of Smart Phones in

the United States

1 million (<2%)

160 million (58%)

EHR Adoption, (% providers)

20-30%

>90%

n x 16

Computing Power

Precision Medicine and State of the Union

.Sotonight,ImlaunchinganewPrecision
MedicineInitiativetobringusclosertocuring
diseaseslikecanceranddiabetes,andtogive
allofusaccesstothepersonalizedinformation
weneedtokeepourselvesandourfamilies
healthier.Wecandothis.

Cystic Fibrosis and Precision Medicine

Discovery Science that Transforms Lives
CF epitomizes the promise of precision medicine discovery of disease mechanisms;
refined diagnostic disease classification; individualized, mutation-specific therapies.

New combination therapy targeting the most

common CFTR mutations is transforming the
lives of patients living with CF.
NIH-funded research revealed CFTR mutations
& resulting cellular actions that cause impaired
lung function
CFTR gene identified; led to earlier diagnosis
and improved symptom management

www.nih.gov/precisionmedicine

PMI: Vision and Goals

Vision: Build a broad research program to
encourage creative approaches to precision
medicine, test them rigorously, and,
ultimately, use them to build the evidence
base needed to guide clinical practice.
Near Term: apply the tenets of precision medicine to a
major health threat cancer
Longer Term: generate the knowledge base necessary to
move precision medicine into virtually all areas of health
and disease

PMI Proposed Support:

Presidents Budget FY16
Agency

$ Million

NIH
Cancer
Cohort

$200

FDA

$10

Office of the National

Coordinator for Health
Information Technology

$5

TOTAL

$70
$130

$215

NIH PMI Planning

Longer term focus on range of health issues & diseases
Longitudinal cohort of 1M or more Americans
Mix of existing cohorts and new volunteers
NIH Advisory Committee to the Director PMI Working Group
planning meetings

Building a consortium of cohorts cohort identification

and participant recruitment
Participant engagement, data privacy, and novel ways of
returning information to participants
Data collection including mobile health technologies
Data science, informatics; Electronic Health Records

Near-Term Timelines
NIH Advisory Committee to the Director PMI WG
Public workshops to inform September 2015 report

NIH with White House, FDA, other agencies

Seeking input from:
-

Potential participants
Leaders of current cohorts
mHealth technology developers
EHR developers
Potential international partners

Oct. 1, 2015PMI launch!

(pending FY2016 appropriations)

PMI Near Term: Cancer

Apply tenets of precision medicine to cancer
Build on The Cancer Genome Atlas (TCGA) that has
characterized genomic features of many cancers in 11,000
patients
Use NCI clinical trials as models (e.g., NCI-Match, Lung-MAP) to:

Identify new cancer subtypes and therapeutic targets

Screen tumors for certain genomic features
Administer therapies specific for a genomic signature
Test precision therapies, with private sector partners

Apply these approaches to:

A wide spectrum of adult and pediatric cancers
Early stage to advanced disease

PMI and Cancer Research:

Possible Near-Term Applications
Evaluating use of liquid biopsies for non-invasive detection
of tumor response
Understanding, counteracting development of resistance to
targeted therapies
Determining prospects of combination targeted therapy based
on individual tumor genome analysis

PMI Longer Term

Generate knowledge base needed to move precision medicine
into the whole range of health and disease
To reach this goal, the PMI will support research to:
Create new approaches for detecting, measuring, analyzing a
wide array of biomedical variables: molecular, genomic,
cellular, clinical, behavioral, physiological, and environmental
Test these approaches in small, pilot studies
Utilize the most promising approaches in greater numbers of
people over longer periods of time to collect data of great value
to both researchers and participants

PMI Longer Term:

National Research Cohort of 1 million

PMI National Research Cohort

Will comprise:
>1 million U.S. volunteers
Numerous existing cohorts (many funded by NIH)
New volunteers

Participants will be:

Centrally involved in design, implementation
Able to share genomic data, lifestyle information, biological
samples all linked to their electronic health records

Will forge new model for scientific

research that emphasizes:
Engaged participants
Open, responsible data sharing
with privacy protections

Toward Creating a National PMI Research Cohort:

Potential Contribution of Existing NHLBI Cohorts

CVDinFamilyCohorts:
MexicanAmerican
OldOrderAmish

DiverseHLBS
ClinicalCohorts:
AsthmaandCOPD

Meta-Cohort
NHLBI Core
Cohorts

National Research Cohort: Possible Uses

Facilitate research on therapeutic safety/efficacy/metabolism
Study resilience by finding people who should be ill but arent
Uncover therapeutic targets by identifying rare variants
protective against disease
Provide unbiased quantitative determination of risk
Offer powerful test bed for:

Incorporating patient-reported outcomes

Improving utility of EHRs
Evaluating wide array of mHealth applications

What If? We Created a Large-Scale Precision Medicine

Information Commons Reflective of Our Diverse Nation

iPSCs

Astute Clinicians
Phenotyping

Cohort Datasets

Integrate omics, clinical

imaging, and health
outcome data in the
Information Commons

Proteomics/Metabolomics

Genomics

Big Data- Ontologies

Computational Models

Biorepositories

Mobile Health

Imaging

NIH Precision Medicine Initiative:

Turning Discovery into Health

NIH Precision Medicine Initiative (PMI)

Overview and Implementation
The PMI and the Nations Health
NHLBI Scientific Vision for PMI

The Emergence of Precision Medicine:

A NHLBI Success Story An Integrative Approach
Framingham Predictive Risk Factors

Public Health
Implementation
Science

Observational
Studies

Value of Lifestyle Interventions

Intramural Research Program:

Frederickson, Stadtmans

Collaboration/
Role of
Industry

Basic
Research

Roy Vagelos: Statins

Clinical Research:
Tangiers Disease
(HDL Cholesterol)

Clinical
Research

Brown and Goldstein: Nobel Prize

(LDL Cholesterol)

NHLBI Trial: Lowering Cholesterol Cuts CHD Risk

Discovery Science and Precision Medicine:

Linking Large & Small Scale Science and Public-Private Partnerships

Raal F et al. Circulation 2012;126:2408-2417

What If? Apply Precision Medicine to Address

Health Disparities
Asthma-related
Emergency Room Visits

Incident Chronic Kidney Failure

By Race

Reducing Asthma Health Disparities:

A Multi-pronged, Patient-Centric Precision Medicine Approach
Moving beyond -- One-Size-Fits-All

Environment

Socio-Cultural
Context
Health
Economy
Systems

Community
Parks
Quality
MedicalCare

Schools

Culture

Family
Behavior

Individual
Individual
Genetics

Precision Medicine -- Patient-Centric Care in Context:

The Interplay of Genes, Behavior and Environment
Home

Allergens

Asthma Health
Care System

Community

Genetics

School
Family

What If? Best diagnostics, best drug, best dose =

best outcomes for all asthma patients
Asthma-related ER Visits

Discovery of Mediators/Biomarkers
Are there distinctive biological factors that
drive racial/ethnic disparities in asthma?
Clinical Studies
Do health disparities reflect the right
drug/right dose problem?
Best African American Response to
Asthma Drugs (BARD)

mHealth

Patient-Centered
Asthma Control
Empowering Patient SelfManagement of Asthma
Geospatial air quality monitor
Inhaler use alerts
Patient-based breathing test
Patient-reported outcomes

What If? Bend the Curves of Racial Health Inequities

by Precisely Predicting and Pre-empting CKD
Rising Medicare Costs
For CKD

Incident Chronic Kidney Failure

By Race

Genomic Admixture Analysis:

African American
African ancestry
Shared African and
European ancestry
European ancestry

Genomics
CDC, 1996

The Ecosystems of Race-Ancestry Health Disparities:

The Exposome, Population History and Genomic Variation
Environment /Exposome
Environment

Infection Socio-Cultural
Context
Health
Economy
Systems

Community
Parks
Quality
MedicalCare

Schools

Immune Defense Systems

Host Genomic Variation

Culture

Family
Sickle Cell
Duffy Antigen
G-6-PD

Behavior

Individual
Individual
Genetics

What If? Reproduce Past Successes in Using Study Cohorts

to Identifying Molecular Mediators of Health Disparities
DiversityinNHLBI-fundedCohorts:SCTwasassociatedwithhigherriskof
CKDinAfricanAmericans.

JAMA. 2014;312(20):2115-2125

APOL1 Risk Variant for Kidney Failure in African-Americans:

Increased Risk of Chronic Kidney Disease and CVD
13 August 2010
Volume 329, Issue 5993

Association of Trypanolytic
ApoL1 Variants with Kidney
Disease in African-Americans

360

370

380

A A A T T T A A A T A CCC T T A TGT A A A A T A

G Genovese, DJ FriedmanJB
Kopp, E Pays, MR Pollack

> 5-fold increased risk of ESKD

Hypertension, HIVAN, SCD
12% of AARisk
have prediction
2 risk alleles (G1/G2)
Also 2-fold increased risk of CVD

Start antihypertensive and

statin treatment
at lower goal of
130/80 in at-risk
APOL1/SCT
carriers

Pharmacogenomics

Angiotensin
Blockers in AfricanAmericans with
high-risk
APOL1/SCT
genotype

New therapies

New drugs
targeting
mediators
downstream of
APOL1 /SCT to
prevent kidney
failure

Evolving Medicine as an Information Science:

Democratizing Data-2-Knowledge in the Digital Age

Participant-Patients: The Center of the

Precision Medicine Initiative

William Elder Jr.

Melanie Nix

Emily Whitehead

Hugh and
Beatrice Rienhoff

Elana Simon

Kareem
Abdul-Jabbar

Noah and
Alexis Beery

What If? We Actively Engaged and Empowereed the Public

in Citizen-Science for Healthier Communities
WearableMobileHealth
Technology:
Patient-centric data generation

ZEO: Sleep-Wake
Cycle Citizen Data

NestWatch: Enables citizens to

contribute data tracking bird
behavior in their area

PatientsLikeMe: Enables
patients to share experience;
knowledge and relationships
for change

Carlas Story in 2018

Volunteers to take part in National
Research Cohort
Cares for her mother who suffered a
stroke; but feels healthy.
Her DNA profile reveals a APOL1
variant that increases risk for kidney
and cardiovascular disease.
Offered opportunity to try out
wearable sensor to continuously
monitor blood pressure, physical
activity, diet, sleep patterns, etc.
Finds her blood pressure is
consistently high

Carlas Story in 2018

Doctor confirms hypertension;
prescribes diuretic drug, 7+ hrs sleep
and DASH diet (low salt; rich in
fruit/vegetables)
Obtains smart bottle that notifies her
smart phone if dose is missed
mHealth App monitors adherence to
DASH diet and sleep hygiene.
Blood pressure normalizes;
Carla remains healthy

The Power of 1 million

Questions