Behavior Bridges Biology and Society:Toward Systems Integration.

(ATransdisciplinary and Translational Challenge)

David B. Abrams, Ph.D.Director, Office of Behavioral and Social Sciences

Research. Office of the Director, NIH

abramsd@od.nih.gov… http://obssr.od.nih.gov

1995-2005OBSSR

OBSSR at NIH

OBSSRprogram office

Other Scientificand Administrative

Units

ExtramuralPrograms

IntramuralPrograms

Institutes andCenters

Office of the DirectorNew OPASI Division

OPASIOPASIDirectorDirector

Division of Evaluation Division of Evaluation and Systematic and Systematic

AssessmentsAssessments(DESA)(DESA)

Division of Strategic Division of Strategic CoordinationCoordination

(DSC)(DSC)

Division of Resource Division of Resource Development Development and Analysisand Analysis

(DRDA)(DRDA)

Steering Committee Steering Committee OPASI OPASI

Working GroupWorking Group

NIH NIH DirectorDirector

Structure of OPASIStructure of OPASI

Develop and use analytic tools, like:

Knowledge management

Public health need/burden of illness

Strategic coordination of NIH-wide planningProvide an “incubator space” for trans-NIH initiatives Facilitate the exploitation of emerging scientific opportunities

Plan, conduct, coordinate, and support program evaluations for:

ICsTrans-NIH initiativesGPRAPART

OBSSR’s Vision at NIHTo mobilize the biomedical, behavioral, and social science research communities as partners in interdisciplinary research to solve the most pressing health challenges faced by our society.

Programmatic Directions to Achieve the Vision:

– Transdiciplinary science

– “Next generation”, basic science

– Problem-based, outcomes oriented tostrengthen the science of dissemination

– Systems - thinking for population impact

The Importance of Partnership for OBSSR

Adapted from Glass, McAtee (2006). Soc. Sci. Medicine, 62: 1650-1671

Health as a continuum between biological, behavioral and social factors across the lifespan and across generations

“Next Generation” Basic Science

OBSSR will support and facilitate the next generation of basic behavioral and social science research informed by breakthroughsin complementary areas such as genetics, informatics, and multilevel analyses.

IOM report : Genes, Behavior and the social environment 2006

IOM Report : New Horizons Singer and Ryff. 2003

ACD Report: Support for Basic BSSR at NIH, 2004

Moffitt, TE, Caspi, A., Rutter M. (2006).

Perspectives on Psychological Science, 1(1): 5-27

Epigenetics

Gosden & Feinberg, NEJM 2007 356: 731-733,

Overarching Themes1. Stress biology can influence tumor biology

• 1.5 – 3-fold effects observed2. Mechanisms are being elucidated*

• Neuroendocrine regulation of:• Angiogenesis• Invasion• Cell-mediated immunity• Apoptosis• Tumor gene expression• Viral replication

3. Opportunity to test adjuvant interventions

A Systems Perspective

• Nervous, endocrine and immune systems operate interdependently:

• Common chemical “language”• Feedback dependent• Opponent processes

• Dynamic process•Acute response•Recovery/healing•Chronic dysregulation•Reciprocal determinism

Future Research: Key Questions

• Classical Perspective: What causes what?

– This ignores system processes.

• Systems Perspective: What informs/regulates what?

– What are the processes and the agents of those processes?

• What are the processes linking stress to pathology?

– Failed wound closure, chronic pain, etc.

• What are the structures linking stress to pathology?

– Neural, endocrine and immune, working in concert

It's not just about the sequence of your genes, but how that sequence is turned on and off by

environmental exposures that is likely to determine whether you will be healthy

Announcements and References• Title: Studying Interactions Among Social,

Behavioral, and Genetic Factors in Health.

• Purpose: To allow new hypotheses to be tested at the intersection of genetics, behavioral and social sciences research. Priority will be given to gene-environment-behavior interaction studies by (1) social and/or behavioral science oriented studies adding consideration of genetic factors, (2) genetic focused studies adding social and/or behavioral factor components, and (3) other investigators using existing data sets to study gene X social X behavioral interactions.

• Roadmap Initiative: Epigenetics, GEI, GWAShttp://nihroadmap.nih.gov/roadmap15update.asp.

Basic Mechanisms in GxBxSxE

• Genes, Behavior, and the Social Environment: Moving Beyond the Nature/Nurture Debate

• Committee on Assessing Interactions Among Social, Behavioral, and Genetic Factors in Health, Lyla M.Hernandez and Dan G. Blazer, Editors

• ISBN: 978-0-309-10196-7, 384 pages, 6 x 9, paperback (2006)

• http://www.nap.edu/catalog/11693.html

Basic BSSR initiatives at NIH• Bio-behavioral stress measures and

mechanisms for disease and prevention• Social Neuroscience• Motivation and Behavior change• Networks and Analysis• New sensors, measures, markers, methods• Intermediate phenotypes, endophenotypes• Epigenetics - intra and inter-generational

Basic BSSR initiatives at NIH• http://www.genome.gov/26022424

• The Exposure Biology Program, will support interdisciplinary teams of basic scientists, bioengineers, physician-scientists and others working to: 1) develop environmental sensors for measuring toxins, dietary intake, physical activity, psychosocial stress and addictive substances; 2) identify biomarkers in the human body that indicate activation of disease mechanisms such as oxidative stress, inflammation and DNA damage; and 3) integrate sensor and biomarker technologies so that they can be applied to genome-wide association studies to better understand gene-environment interaction

Adapted from Glass, McAtee (2006). Soc. Sci. Medicine, 62: 1650-1671

Health as a continuum between biological, behavioral and social factors across the lifespan.

Emerging public health threats:• Unsustainable cost of quality healthcare• Obesity, Diabetes epidemic• Natural & human-made disasters, • Aging population,degeneration,disability

Persistent public health challenges:• Disparities, stereotype,health literacy,

quality of life, wellbeing• Tobacco use, stress, ……• Unhealthy built environment• Chronic disease management / support• Health Care Delivery Systems and Policy

Many Challenges Remain

NIH’s vision for the future: PesonalizedMedicine (Pharmacogenetics)

PreemptivePersonalizedPredictive

Participatory

NIH MedlinePlus Magazine,

Winter 2007

Hood (2003) Environmental Health Perspectives, 111(11) published by NIEHS, NIH

The FDA acknowledges a large variation in response rates to treatments for a variety of conditions

Frueh FW. (2006). Pharmacogenomics: Patient selection for clinical trial participation and enrichment strategies. Available at www.fda.gov/cder/genomics

Science, 302: 386-388. 2003

1057 consecutive births in Dunedin, New Zealand followed for 26 years with evaluation every 2-3 years beginning in first year.

At age 26, 17% met criteria for major depressive disorder. Neither life stress alone nor serotonin transporter genotype predicted depression.

Serotonin Gene, Experience, & Depression Age 26

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A. Caspi, Science, July 2003, Vol 301.

Early Childhood

Social neuroscience

Adolphs. Nature Rev Neuroscience 4:165-178, 2003

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Mental Health Care in the Pre-Genomic Era??

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OBSSR VISION: Systems Integration

“The idea of a sharp distinction between health and disease is a

medical artifact for which nature, if

consulted, provides no

support.”

Pickering (1937)

1. Capitalize on new discoveries and new tools

• Informatics, Computer technology• Gene-Environment Interaction• Predict, pre-empt, personalize

2. Conduct interdisciplinary science

3. Partner to solve problems whose

scope overwhelms single paradigms

• Translation, Dissemination, Policy

• Systems integration, problem-based

• Population Outcomes focus

Prepared,Proactive

Practice Team

Informed,Informed,ActivatedActivatedPatient & Patient &

FamilyFamily

Productive Interactions

Functional and Clinical Outcomes*E. Wagner, MD, W.A.MacColl Institute, Group Health Cooperative of Puget Sound

Health SystemOrganization of Health CareSelf-

Management Support

DecisionSupport

DeliverySystemDesign

ClinicalInformation

Systems

CommunityCommunityResources and PoliciesResources and Policies

A Model for Planned Care*

Interdisciplinary & TransdisciplinaryResearch

OBSSR will facilitate collaborative research across the full range of disciplines and stakeholders necessary to fully elucidate the complex determinants of health and health systems challenges… … such collaborations will yield new conceptual frameworks, methods, measures, and technologies that will speed the improvement of population health.

•Roadmap to Common Fund. New Division OPASI - DPCPSI

Director designate : Dr. A. Krensky, Stanford University.

•CTSA’s -- Clinical Translational Science Awards: 2 levels of Translational research bench to bedside to community dissemination/implementation/community participatory

•Clinical Research Network (NCRR); PBRN, Crowley et al ‘04

Welcome from the CTSASubcommittee for CTSA Translation

Subcommittee Mission and Vision StatementOverview on Conceptual Translational Definition and Scope

William Martin, M.D.National Institute of Environmental Health Sciences

•The mission of the Subcommittee for CTSA Translation is to facilitate advancements of novel translational research and technologies. It aims to foster improvements in translational technologies through bidirectional integration of basic and clinical research to improve health and patient care. It will operate within the realm of the CTSA consortium as the NIH contribution to the CTSA Steering Committees.

National CTSA Consortium Evaluation Multiple Inputs into Planning Process

National CTSA Consortium Evaluation

CTSA Evaluation Steering Committee

Other CTSA Steering Committees (i.e., Informatics,

Translation, Education, etc.)Professional Evaluators

(The Madrillon Group)

External Advisors

National CTSA Consortium EvaluationRoles & Responsibilities

• Coordinate institutional evaluation efforts with National CTSA Consortium Evaluation

• Develop and build consensus for national metrics

• Identify and define baseline characteristics

• Adopt common terms and definitions across CTSA consortium as early as possible

• Exchange information (best practices, challenges, approaches, etc.)

• Manage public expectations: participants, stakeholders, Congress

• Recognize the novelty of CTSA program

Improving Medical and Research Education

• Physicians must be equipped with the knowledge and skills from the behavioral and social sciences needed to recognize, understand,and effectivelyrespond to patients as individuals, not just to their symptoms.

» IOM

Clinical Research Scientist: train in BSS research theory, methods, measures, including population sciences, economics, health services and policy research

IOM Report RecommendationsThe Committee identified six behavioral and social science domains

• Mind-body interaction in health and disease

• Patient behavior

• Physician role and behavior

• Physician-patient interactions

• Social and cultural issues in health care

• Health policy and economics

Syndemics and “Populomics”Linked epidemics.

New solutions may soon permit the real-time integrative utilization of vast amounts of behavioral-, biological-, and community-level information in ways not previously possible. Behavioral algorithms and decision support tools for scientists could facilitate the analysis and interpretation of population level data to enable the development of “community (population) arrays” or community-wide risk profiles, which in turn could form the foundation of a new “populomics.”

Gibbons, 2005A historical overview of health disparities - potential of eHealth solutions. J Med Internet Res, 7(5), e50.

The Atkins Report - NSF

The opportunity is here to create cyber-infrastructure that enables more ubiquitous, comprehensive knowledge environments that become functionally complete for specific research communities in terms of people, data, information, tools, and instruments

and that include unprecedented capacity for computational, storage, and communication…

They can serve individuals, teams and organizations in ways that revolutionize what they can do, how they do it, and who participatea.

St. Louis, Missouri

Tobacco Billboards

in St. Louis

Luke et al. Tobacco Control. 2000 9:16-23.

Eight Americas: Health Disparities

C. J. L. Murray, et al., 2006.

Eight Americas: Investigating Mortality Disparities across Races, Counties, and Race-Counties in the United States.

PLoS Medicine: Vol 3, Issue 1513 9, e260 www.plosmedicine.org

C. J. L. Murray, et al., Eight Americas: Investigating Mortality Disparities across Races, Counties, and Race-Counties in the United States. PLoS Medicine: Sept.2006. Vol. 3, Issue 1513 9, e260 www.plosmedicine.org

From gene chips to behavioral and population arrays

Personalized predictive, pre-emptive

at biological, socio-behavioral

and population levels

Proteomics

Nanotechnology

Populomics

Genomics

Adding “Populomics” to the “Grid”

Personalized Medicine

Personalized Health Care Systems

Announcements and References

Behavioral and Social Science Research on Understanding and Reducing Health Disparities:

PAR-07-379 (R01); PAR-07-380 (R21)http://grants.nih.gov/grants/guide/pa-files/PAR-07-379.html

Proposals that utilize an interdisciplinary approach, investigate multiple levels of analysis, incorporate a life-course perspective, and/or employ innovative methods such as system science or community-based participatory research are particularly encouraged.

PAR: Strengthening the Science of dissemination/ implementation - OBSSR, NCI, NIMH…..others

BSSR on �Understanding and Reducing Health Disparities

• http://grants.nih.gov/grants/guide/pa-files/PAR-07-379.html

• Application Submission/Receipt Date(s): September 19, 2007, September 19, 2008, September 18, 2009 �Peer Review Date(s): February-March of 2008, 2009, and 201

• To encourage BSSR on the causes and solutions to health disparities in the U. S. population. Emphasis is placed on research in three broad areas of action: 1) Public policy, 2) health care, and 3) disease/disability prevention. Proposals that utilize an interdisciplinary approach, investigate multiple levels of analysis, incorporate a life-course perspective, and/or employ innovative methods such as system science or community-based participatory research are particularly encouraged.

Cover of "The Economist", Dec. 13Cover of "The Economist", Dec. 13--19, 200319, 2003.

1991

1996

Obesity Trends* Among U.S. Adults: BRFSS1991, 1996, 2004

(*BMI ≥30, or about 30 lbs overweight for 5’4” person)

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

2004

Modeling Obesity Trends: Contributors

Project funded by CDC/DNPA May 2005 – April 2006

Core Design Team (CDC)• Dave Buchner• Andy Dannenberg• Bill Dietz• Deb Galuska• Larry Grummer-Strawn• Anne Haddix• Robin Hamre• Laura Kettel-Khan• Elizabeth Majestic • Jude McDivitt• Cynthia Ogden• Michael Schooley

System Dynamics Consultants• Jack Homer• Gary Hirsch

Time Series Analysts (CDC)• Danika Parchment• Cynthia Ogden• Margaret Carroll• Hatice Zahran

Project Coordinator• Bobby Milstein (CDC)

Workshop Participants• Atlanta, GA: May 17-18 (N=47)• Lansing, MI: July 26-27 (N=55)

An Ecological Framework for Organizing Influences on Overweight and Obesity

Prevention of Overweight and Obesity Among Children, Adolescents, and Adults

Individual Factors

Behavioral Settings

Social Norms and Values

Home and Family

School

Community

Work Site

Healthcare

Genetics

Psychosocial

Other Personal Factors

Food and Beverage Industry

Agriculture

Education

Media

Government

Public Health Systems

Healthcare Industry

Business and Workers

Land Use and Transportation

Leisure and Recreation

Food and Beverage Intake

Physical Activity

Sectors of Influence

Energy Intake Energy Expenditure

Energy Balance

Adapted from: Koplan JP, Liverman CT, Kraak VI, editors. Preventing childhood obesity: health in the balance. Washington, DC: Institute of Medicine, National Academies Press; 2005.

Obesity Diabetes: Systems Integration from cells to society

A Broad View of Causal Forces

LEGEND: Blue arrows indicate same directionlinks; Green arrows indicate opposite directionlinks; R loops indicate reinforcing processes;

B loops indicate balancing processes

NOTE: All parameters vary by social position (e.g.,age, sex, race/ethnicity, income, geography) DRAFT 5/8/05

Healthiness of Diet& Activity Habits

Effective HealthProtection Efforts

R6

Disease CareCosts Squeeze

PreventionB4

Creating BetterMessages

R4Options ShapeHabits Shape

OptionsPrevalence ofOverweight &

Related Diseases

-

Costs of Caringfor Overweight-

Related Diseases

-

Options Available atHome, School, Work,

Community InfluencingHealthy Diet & Activity

Costs of Developing &Maintaining HealthProtection Efforts

B5Creating Better

Options inBehavioral

Settings

-B8

Up-front CostsUndercutProtection

Efforts

Observation ofParents' andPeers' Habits

R2Parents/PeersTransmission

Media MessagesPromoting Healthy

Diet & Activity

Wider Environment(Economy, Technology,

Laws) Influence on Options

B1

Self-Improvement

B6

Creating BetterConditions in the

Wider Environment

Health ConditionsDetracting from

Healthy Diet & Activity

-

Perceived ProgramBenefits Beyond Weight

Reduction

Resistance andCountervailing Effortsby Opposed Interests

-

B9

DefendingStatus Quo

Cost Implicationsof Overweight inOther Spheres

B10Potential Savings

Build Support

Genetic MetabolicRate Disorders

B7

AddressingRelated Health

Conditions

Healthcare Servicesto Promote Healthy

Diet & Activity

B2Medical Response

R1

Spiral of PoorHealth and Habits

B3

ImprovingPreventiveHealthcare

R5Society ShapesOptions Shape

Society

Broader Benefits ofHealth Protection

Efforts

R7Broader Benefits

Build Support

R3MediaMirrors

Source: Jones, A.P., Homer, J.B., et al., (2006). American Journal of Public Health, Vol. 96, No. 3, 488-494

Alternative FuturesObesity in Adults (20-74)

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AnnouncementsPAR : “Systems Science Methodologies.

•‘Systems Science’ perspective in which the problem space is conceptualized as a system of interrelated component parts. Offer insights into the nature of the whole system = cannot be gained by studying the component parts in isolation

•The relationships among the components give rise to the “emergent”properties of the system. those that can only be seen at the system level -

•Embedded in the system are feedback loops, stocks and flows, that change over time (i.e., dynamic complexity of the system).

•Advantages of utilizing systems approaches as a complementary method for addressing complex problems include the fact that non-linear relationships, unintended effects of intervening in the system, and time-delayed effects are often missed with traditional reductionist approaches, whereas systems approaches excel at detecting these.

Announcement Systems Science- Agent based modeling - System dynamics simulation - Network analysis, including social network analytic

methods - Discrete event simulation - Markov modeling - Stochastic modeling - Differential equation/compartmental modeling

Applicants are encouraged to learn more about systems methodologies and their role in behavioral and social science research at NIH by visiting the OBSSR Systems Science and Health webpage (currently under construction) at

• http://obssr.od.nih.gov/Content/AboutOBSSR/Activities/Systems_Science/

Systems Science Seminar Series and References

Patty Mabry (OBSSR) mabryp@od.nih.govhttp://videocast.nih.gov see "Past Events"- "Special”

Systems Methodologies for Solving Real-World Problems: Applications inPublic Health. John Sterman, Ph.D. & Kenneth McLeroy.

Network Analysis: Using Connections and Structures to Understand and Change Health Behaviors. Katherine Faust &Thomas W. Valenti

Agent Based Modeling: Population Health from the Bottom Up. Michael W. Macy Joshua M. Epsteih FRIDAY, JULY 13, 2007 10:00 AM – 12:00 PM

System Dynamics Modeling for Population Health. Jack Homer & George Richardson, Ph.D. Thursday, August 30, 2007, 1:00 p.m. - 3:00 p.m

Conference: U of Michigan “Complex Systems Approaches to Population Health” May 30-31, 2007 Note: Day 1 and Day 2 are listed separately and are next to each other on the list.

Funding announcements• BSSR on �Understanding and Reducing Health

Disparities��PAR-07-379

• three broad areas of action:– 1) Public policy – 2) health care – 3) disease/disability prevention

• Proposals that utilize an interdisciplinary approach, investigate multiple levels of analysis, incorporate a life-course perspective, and/or employ innovative methods such as system science or community-based participatory research are particularly encouraged

Influences of Genetics arefundamentally

dependent on context

Summary:Understanding the “Whole” System

Influences of Genetics are

fundamentallydependent on context

Reductionism

It’s reallygenetic!

It’s reallysocial

context!

It’s reallycognition!

A New Integrative Causal Loop Model

The Biomedical Model:

Causes of disease lie in genes, molecules,

proteins

The Social -Ecological Environmental Model:

Causes of disease are behavioral, social

Environmental factors

INTEGRATION OF BIOMEDICAL CAUSES & SOCIO-ECOLOGICAL “CAUSES OF CAUSES”

Group Individual

Situation Behavior

Phenotype Genotype

Environment Person

Context Agent

Systems Integration: Causal Loops

Adapted from Glass, McAtee (2006). Soc. Sci. Medicine, 62: 1650-1671

Health as a continuum between biological, behavioral and social factors across the lifespan.

From gene chips to behavioral and population arrays

Personalized, predictive, pre-emptive:

at biological, socio-behavioral

and population levels

Proteomics

Nanotechnology

Populomics

Genomics

Adding “Populomics” to the “Grid”

Personalized Medicine

Personalized Health Care Systems

COMPLEXITY • The world is complex, contextual, dynamic, multi-causal (causal loops),

multi-level, multiply determined…….

• For every complex problem there is a simple solution……….and its usually wrong

• Research designs, methods and measures should take this into account and capitalize on advances in computer sciences, technology, informatics, imaging, knowledge management, networking and communications

• Vertical integration: cells to society, special attention to the “filling-frosting” between the layers of the “cake”

• Solid basic behavioral and social science is needed as a firm foundation to build systems within systems models

• Aligned incentives at every level of the system can change populations

ConclusionBehavior is the bridge between biology and society

From Systems Biology to Systems Behavioral and Population Science

There is a person and a context to the new vision of personalized, predictive, preemptive (and preventive), medicine, health care and public health

Theory is the net man weaves to catch the world of observation, to explain, predict, and influence it.

Theories in Social PsychologyDeutsch & Krauss, 1965