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An Overview of Marshfield Clinic’s Research Program Exploring Opportunities for Collaboration in the “Real” World. Dr. Humberto Vidaillet Director of Medical Research, Marshfield Clinic Director, Marshfield Clinic Research Foundation Clinical Professor of Medicine, UW SMPH September 14, 2011.

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An Overview of Marshfield Clinic’s Research Program Exploring Opportunities for Collaborationin the “Real” World

Dr. Humberto Vidaillet

Director of Medical Research, Marshfield Clinic

Director, Marshfield Clinic Research Foundation

Clinical Professor of Medicine, UW SMPH

September 14, 2011

objectives purpose of forum
Objectives: Purpose of Forum
  • Provide an opportunity for research networks and other research groups to learn about each other and the projects they conduct.
  • Learn about operational and project barriers, and successful methods to overcome barriers.
  • Facilitate networking and connections between people and groups with similar interests.
welcome to marshfield clinic
Welcome to Marshfield Clinic*

*Ranked by Forbes in 2010 as the “5th best small city in the country to raise a family.” Designated in 2008 by Demographics Daily as one of the nation’s top 20 “Dream Towns”

marshfield clinic
Marshfield Clinic

Mission: To serve patients through accessible, high quality health care, research and education

501(c)(3) organization

Largest private group practice in WI:

  • 52 centers in >35 communities
  • >770 physicians (102 family practice
  • physicians) in >85 specialties
  • 6,600 additional personnel
  • ~3.5 million patient encounters/year ~365,000 unique patients/year

Marshfield Labs (Human & Veterinary)

Lakeview Medical Center, Rice Lake, WI

Security Health Plan (HMO)

why marshfield clinic engages in research education
Why Marshfield Clinic Engages in Research & Education
  • Core elements of Marshfield Clinic’s Mission, its status as a nationally recognized Academic Medical Center, and its Charitable Trust
  • Contribute to knowledge leading to advances in patient care, quality metrics and public health, improves the quality of human existence and the lives of our patients and their loved ones
  • Contribute to recruitment of high quality physicians and other professionals who want to work in an academic environment
  • Differentiate Marshfield Clinic from competitors; patients rightly conclude that care is better at centers involved in research & education
  • For clinicians who do research and teach, it adds another dimension to their contributions to medicine and improves their clinical practice; for virtually all Marshfield Clinic employees, a sense of shared pride!

Research and Education have been integral to the

Clinic’s culture, sustained growth and quality of care since 1916!

research program at marshfield clinic
Research Program at Marshfield Clinic

~400 active studies

~125-150 clinical investigators and 30 MD/PhD scientists

Major external sponsors: NIH,CDC,NIOSH,AHRQ,Industry,Philanthropy

Academic structure: IRB, Research Comm., Research Compliance,ConflictofInterest,Biosafety,etc.

Tenure program and Endowed positions

Marshfield Clinic Research Foundation (MCRF)

Mission: To discover and communicate scientific knowledge that substantially improves human health and well-being

- 200 staff

St. Joseph’s Hospital

Laird Center for

Medical Research

Lawton Center

for Research

& Education

Main Clinic


East Wing

research program structure
Research Program Structure

Marshfield Clinic Research Foundation

Humberto Vidaillet, MD, Director

Steve Wesbrook, PhD, Deputy Director

Research Support


Core Laboratory

Research Centers

Sponsored Programs

& Fiscal Affairs

Research Integrity &


Biomedical Informatics

Research Center (BIRC)

Simon Lin, M.D.

Center for Human Genetics

Murray Brilliant, Ph.D.

Scientific Writing

& Publications

Health Systems


Clinical Research Center

Steven Yale, M.D.

Associate Director

Adedayo Onitilo, M.D.

Epidemiology Research Center

Edward A. Belongia, M.D.

National Farm Medicine Center

(Rural, Agricultural Health & Safety)

Barbara Lee, RN, PhD

mcrf board of trustees
MCRF Board of Trustees

Oversees MCRF, providing policy direction, financial oversight, and counsel to MCRF leadership in a wide range of areas associated with research structure, process, and resources

  • Physician Members
  • Jaime Boero, MD. Vice - Chair
  • Michael Caldwell, MD, PhD
  • Christopher Cold, MD
  • Rezwan Islam, MD
  • Ram Pathak, MD
  • Kent Ray, DO
  • Shereif Rezkalla, MD, Treasurer
  • Karl Ulrich, MD
  • Matthias Weiss, MD
  • Scientist Member
  • Po-Huang Chyou, Ph.D.
  • Community Members
  • Rene Daniels
  • John Hutchinson
  • Brian Kief
  • Patricia Kleine, Ph.D.
  • John Laird
  • Scott Larson, Secretary
  • Mark T. Nelson
  • Mark Nook, Ph.D., Chair
  • Jim Schuh
  • James Weber, PhD

Mark Nook, PhD

UW System,


Senior Vice President for Academic Affairs

Publish Clinical Medicine & Research

Publish Journal of Agromedicine

With Division of Lab Medicine, part of State Laboratory Response Network and CDC’s Select Agent Program; provide Laboratory Medicine facilities for its R&D

With Clinic Information System, develop new clinical medical informatics tools

Other Capacities


research strategy and guiding principles
Research Strategy and Guiding Principles
  • Integration of research into clinical practice and clinical practice into research.
  • Collaboration with other top-tier medical centers, especially UWSMPH (now ICTR) and MCW.
  • Dedication to achieving excellence in translational research, which requires close collaboration among physicians and scientists to bring scientific advances into clinical care and public health.
Founded jointly in 2007 by UW and MC

Has become framework of strengthening research ties between the two institutions

Awarded a Clinical and Translational Science Award by NIH; now waiting for renewal

Unprecedented level of collaboration: 14 funded pilot projects with UW-Madison investigators working together with 23 Clinic investigators from 16 different departments

Likely to impact Clinic’s clinical and translational research for decades

Institute for Clinical and Translational Research (ICTR)


Schools of

Medicine and Public Health



Veterinary Medicine and

College of Engineering

Strength of the Marshfield Clinic - UW Research PartnershipCollaboration & Integration of Administrative Activities
the marshfield uw partnership
The Marshfield-UW Partnership

Leverage unique resources & shared Interests

To Conduct research not otherwise possible …

Foster Collaborations


Wisconsin IRB Consortium (WIC)


Facilitate collaboration among member institutions' Institutional Review Boards (IRBs) in order to provide more effective and efficient oversight of multi-site human subject research protocols In Wisconsin and reduce costs and duplication of effort among the Member institutions and affiliated investigators.

One Agreement

Allows any member institution to serve as the IRB of record for another, eliminating the need to draft individual, study-specific IRB authorization agreements for each study reviewed.

WIC is in its development/pilot phase ,and as such, is limited to the following participants:

Aurora Health Care IRB, Milwaukee

Marshfield Clinic IRB, Marshfield

Medical College of Wisconsin IRB, Milwaukee

University of Wisconsin-Madison Health Sciences IRB, Madison

clinical research center
Clinical Research Center
  • Established in 1998 to provide centralized research support for clinician-led research throughout system
  • Built on a strategy of integrating research and clinical practice
  • More than 350 active clinical trials
  • 125-150 clinician investigators
  • >40 research coordinators and research nurses as well as other administrative support staff
  • Community Clinical Oncology Program (CCOP) is the longest-running clinical research project
type 2 translational research
Type-2 Translational Research

The Role of Pharmacist Evaluation in Asthma

Local PI

Suzanne N. Havican, RN, RPh, BCPS


Henry N. Young, PhD

UW Madison

  • Study Goal
    • To conduct a pilot test of a telepharmacy-based intervention to improve asthma control through medications and disease management in an underserved, rural patient population.
  • Aims
    • To assess the feasibility of providing a telepharmacy intervention
    • To determine whether a telepharmacy intervention is acceptable
    • To assess the intervention’s impact on patients’ asthma control, adherence to medications, and patient activation
    • To examine the facilitators and barriers associated with implementing the intervention.
Type-2 Translational ResearchTailored Approach to Genetic Counseling for Cystic Fibrosis Newborn Screening: A New Model

Received additional/outside funding

type 2 translational research20
Type-2 Translational Research
  • Creating Healthy Workplaces: An intervention to Improve Outcomes for Providers and Patients

Study Goal

  • Test the impact of a novel quality improvement strategy on care quality. The quality improvement intervention (QIIs) will create “healthy workplaces” by addressing adverse primary care work conditions (workflow, work control, and organizational culture).


  • Increase clinician and staff interest in participating in QIIs by addressing primary care work conditions
  • Improve care quality in hypertension and diabetes by improving work conditions
  • Improve clinician and staff satisfaction, decrease stress, and reduce intention to leave

Local PI

Steven H. Yale, MD

epidemiology research center
Epidemiology Research Center
  • Consequential epidemiology: focus on applied research questions that make a difference in the lives of people
    • Vaccine safety & effectiveness
    • Antibiotic resistance
    • Cancer surveillance
    • Cardiovascular care and outcomes
  • Unique resources & network collaborations:
    • Marshfield Epidemiology Study Area (MESA)
    • HMO Research Network (HMORN)
      • Cancer Research Network (NCI)
      • Cardiovascular Disease Research Network (NHLBI)
    • Vaccine Safety Datalink (CDC)
  • In 2011, Dr. Laura Coleman joined as tenure-track scientist
Key Features:

Defined geographic region (24 zip codes)

Nearly all residents choose to receive health care from Marshfield Clinic and affiliated hospitals

Dynamic cohort tracked since 1991

Links to sophisticated electronic medical record system and data warehouse archive

Low population mobility

High population coverage and health event capture, in MESA Central:

97% population coverage

99% deaths captured

95% hospitalizations captures

90% outpatient visits captured

Marshfield Epidemiologic Study Area (MESA)

25,000 people

60,000 people

marshfield epidemiologic study area mesa
Marshfield Epidemiologic Study Area (MESA)
  • There are more than 25 active consults in the current year, with many early and mid-career stage recipients, including:
    • a UW Shapiro scholar,
    • an ICTR scholar,
    • UW Population-Health students,
    • UW faculty and medical residents, &
    • Marshfield faculty and medical residents.
collaborations mesa
Collaborations: MESA

“Mortality & Cardiovascular Events Among Rural

Systemic Lupus Erythematosus Patients”

  • Goal: To examine the actual mortality burden and rates of cardiovascular events among a rural population-based cohort of lupus patients
hmo research network
HMO Research Network
  • Mission: Use collective scientific capabilities to integrate research and practice for the improvement of health and health care among diverse populations.
  • Consortium of 16 HMO organizations
  • MCRF leveraged the MESA cohort and Security Health Plan enrollees to facilitate membership in the HMORN.
  • Focus is on cancer, cardiovascular disease, diabetes, genomics, vaccine safety, medical product surveillance, health care quality, and comparative effectiveness.
  • MCRF co-hosted the National HMORN meeting in 2008, at which the NCRR Director was a plenary keynote speaker.
  • MCRF investigators are currently leading efforts on more than 20 active collaborative research projectswithin the HMORN.
survey of the health of wisconsin
Survey of the Health of Wisconsin
  • First statewide research survey to systematically gather data on health status and health disparities among Wisconsin adults.
  • Marshfield Clinic became the home of a new, third recruitment and enrollment center for SHOW, joining Madison (Middleton) and Milwaukee.
  • MCRF assists SHOW data collection, including: face-to face interviews, self administered questionnaires, and physical exams.
  • In the first year of the MCRF, 30 scheduled weeks of rural Wisconsin data collection were completed in three months due to Marshfield Clinic’s presence in rural WI communities.
  • The data collected from SHOW will address critical and novel research questions to accelerate translation into evidence-based policies and health care practices, and improve health and reduce health disparities in Wisconsin.
center for human genetics
Center for Human Genetics
  • A long history of important discoveries in human genetics (short tandem repeat polymorphisms, Marshfield linkage maps)
  • Mission: “To conduct translational research in medical genetics that substantially improves patient care”
  • In 2009, recruited Dr. Murray Brilliant (Center Director, tenured Senior Research Scientist and James Weber Endowed Chair)
  • in 2010, recruited Dr. Steve Schrodi and Dr. Deana Cross as tenure-track scientists
  • In 2011, joint recruitment of Dr. Brautbar
  • Major programs and unique resources:
    • Personalized Medicine Research Project (PMRP)
    • Wisconsin Genomics Initiative (WGI)
    • Electronic Medical Records and Genomics (eMERGE) Network
personalized medicine research project pmrp
Personalized Medicine Research Project (PMRP)
  • In September 2002, Governor McCallum and the leadership of MC and MCRF announced enrollment of the first research subject
  • Initial funds: State government ($2 million), Federal government ($800K), and Marshfield Clinic ($1 million)
  • Ultimate Goal: Translate genetic data into specific knowledge about disease that is clinically relevant & will enhance patient care
  • Key Features:
    • Nation’s largest population-based biobank
    • Stable population of approximately 20,000 adults
    • DNA, plasma and serum samples on each subject
    • Access to longitudinal electronic health record
    • 99% of PMRP cohort has agreed to be re-contacted
    • All genotyped for 50 medically relevant markers, ~5K high-density genotyped samples
pmrp community advisory group
PMRP Community Advisory Group
  • The Community Advisory Group (CAG) provides advice and guidance from the community perspective on the continued development, implementation and on-going operations of the Personalized Medicine Research Project
ongoing studies

Efficacy and safety of statins

Efficacy of metformin in patients with type II diabetes

Pharmacogenetics of tamoxifen for breast cancer

Pharmacogenetics underlying response to beta blockers in patients with glaucoma

Pharmacogenetics of warfarin metabolism

Sulfa hypersensitivity

ACE and angioedema

Genetic Basis of Disease

Atrial fibrillation/flutter



Hypertensive heart disease


Macular degeneration

Multiple sclerosis

Myocardial infarction

Obesity, genetics and risk of diabetes and abnormal lipids

Prostate cancer

Venousthromboembolism Dz.

Ongoing Studies
wisconsin genomics initiative wgi
Wisconsin Genomics Initiative (WGI)
  • Announced by Governor Doyle in October 2008
  • Received $2 million in State FY10-11 budget
  • A historic collaboration of Wisconsin’s three academic medical centers and its major urban university created to advance predictive and personalized health care
  • Vision: to be able to predict for individual patients in a clinical setting the risk of disease susceptibility and treatment response using the combined power of cutting edge genetic, phenotypic, and environmental analyses
wisconsin genomics initiative
Wisconsin Genomics Initiative


  • MCRF
  • Rural Cohort Comprised of 20,000 Adults
  • Biomedical Informatics
  • Phenotyping
  • MCW
  • Genetic & Genomic Analysis
  • Diverse Urban & Pediatric Patient Populations
  • High Through-Put Genotyping
  • UW-Milwaukee
  • Urban & Environmental Health
  • Community Engagement
  • School of Nursing
  • Regenerative Medicine
  • Statistical & Computational Analysis
  • Super-Computing Capability



building accurate predictive models










Building Accurate Predictive Models
  • Complex combinations of variables are required for accurate prediction
  • The more we know about individual patients, greater the probability of prediction
wgi funded demonstration projects 1
WGI Funded Demonstration Projects (1)

Integrating Genomic Data into a Computational Model for Improved Breast Cancer Diagnosis

  • PIs: Elizabeth Burnside, MD4; David Page, PhD4
  • Collaborators: Cathy McCarty, PhD, MPH1; Peggy Peissig, MBA1; Adedayo Onitilo, MD1

Improving the Predictive Modeling of Atrial Fibrillation/Flutter (AF/F) and Its Outcomes

  • PI: Humberto Vidaillet, MD1
  • Collaborators: Bess Berg, MS4; David Page, PhD4; Peggy Peissig, MBA1; Percy Karanjia, MD1

Feasibility of Modular High Throughput Electronic Phenotyping

  • PI: Peggy Peissig, MBA1

WGI Infrastructure Project Proposal: Expand the Current Informatics Architecture in Order to Capitalize on the Available EMR and Genetic Data

  • PI: Justin Starren, MD, PhD1

WGI Exome Sequencing to Identify Coding Variants for Myocardial Infarction

  • PI: Ulrich Broeckel, MD2
  • Collaborators: Cathy McCarty, PhD, MPH1; David Page, PhD4

1MCRF ♦ 2MCW ♦ 3UW-Milwaukee ♦ 4UWSMPH

wgi funded demonstration projects 2
WGI Funded Demonstration Projects (2)

Risk Modeling Post-Hospitalization Venousthromboembolism in a Population-Based Cohort

  • PI: Steve Yale, MD1
  • Collaborators: Mark Craven, PhD4; Deanna Cross, PhD1; Stephen Talsness, BA1; Peggy Peissig, MBA1; Joseph Mazza, MD1

Sustained Community Engagement in Genetics and Genomics Research to Improve Health and to Increase Health Equity

  • PIs: Aaron Buseh PhD, MPH3; Sandra Underwood, PhD, RN, FAAN 3

Development of a Predictive Algorithm for Age-related Macular Degeneration

  • PI: Murray Brilliant, PhD1
  • Collaborators: David Page, PhD4; Joe Carroll, PhD4; Cathy McCarty, PhD, MPH1; Gary Pesicka, MD1; Robert Valenzuela1

Investigation of Genomic Association Between Heart Failure & Diabetes Mellitus

  • PI: Nancy Sweitzer, MD, PhD4
  • Collaborators: Cathy McCarty, PhD, MPH1; Orly Vardeny, PharmD4; Zhan Ye, PhD1

Membrane Metaloproteinase-9 Genotype and Aortic Aneurysm

  • PI: Jay Yang, MD, PhD4
  • Collaborators: Sijan Wang PhD4; Martha Wynn MD4; Charles Acher, MD4; Peggy Peissig, MBA1; Ulrich Broeckel, MD2

1MCRF ♦ 2MCW ♦ 3UW-Milwaukee ♦ 4UWSMPH


WGI Project: Sustained Community Engagement in Genetics & Genomic Research to Improve Health & to Increase Health Equity

  • Study Purpose
    • Determine effective ways to engage members of diverse urban communities in genetic and genomics research designed to improve health and achieve health equity.
  • Aims
    • Determine how characteristics of diverse ethnic, racial urban communities are related to their potential engagement in genetics and genomics research;
    • Describe knowledge and attitudes of members of diverse ethnic, racial urban communities toward genetics and genomics research for health;
    • Identify facilitators and barriers to sustained engagement of members of diverse ethnic, racial urban communities in genetics and genomics research for health.

PI: Aaron Buseh

UW Milwaukee

collaboration with uw waisman center
Collaboration with UW Waisman Center
  • Genetic/Complex Disorders
  • 1) To estimate the prevalence of premutation of FMR1 using the Wisconsin longitudinal Study (WLS) cohort (PMRP in the Marshfield cohort
  • 2) To describe natural history of premutation into adulthood and into old age (18 through 70 yrs.) with respect to family background, academic achievement, IQ, marital history, fertility, childbearing patterns, menopause, occupational stability, depression and anxiety, health and physical symptoms and cognition.
  • 3) To compare men and women with the premutation with a closely matched comparison group of WLS unaffected age peers. Because of the small size of the sample with the permutation, this will be an exploratory aim.

Marsha Seltzer, PhD

Waisman Center

Murray H. Brilliant, PhD



Marshfield Clinic



Type II diabetes

Group Health Cooperative


Coordinating center

Mayo Clinic

Peripheral artery disease


QRS duration

mcrf s oral systemic health research project 1
MCRF’s Oral & Systemic Health Research Project (1)
  • Goals:
  • Understand the causes of oral diseases, such as periodontal disease and caries (e.g., determining the effect of genetics, diet, water source [well/city + fluoridation], and microbiome).
  • Understand the connections between oral and systemic health, (e.g., mutual enhancement of periodontal disease and diabetes).
  • Understand how improving oral health aids systemic health (comparative effectiveness) and bring PHC to the dental arena.
mcrf s oral systemic health research project 2
MCRF’s Oral & Systemic Health Research Project (2)
  • Microbiome contribution to heath is an NIH priority and our investigators will be among the first to utilize oral microbiome data in personalized healthcare
  • Will create a unique research infrastructure to support the OSHRP:
    • Initial cohort of 2,000 participants with electronic dental and health records coupled with a comprehensive biobank (DNA, plasma, serum, urine and periodontal microbiome)
    • Questionnaire data on environment, diet, etc
  • OSHRP builds upon the Personalized Medicine Research Project (PMRP)
    • >1,000 participants in PMRP who are also dental patients of Marshfield Clinic; 2 MC dental facilities in PMRP recruitment area have been operating for 1 year
    • As the Clinic’s Electronic Health Record contains medical and dental care information, this research sub-cohort of PMRP can be used today to study the connections between oral and systemic health in a population-based cohort
  • National Institute of Dental and Craniofacial Research (NIDCR) Collaborative Grant: Data Extraction using Electronic Dental Record in Dental Practice Based Research Network
    • Collaborating with University of Pittsburgh

Plans for 2011 and 2012

Goals for the next 5 years

Searchable PMRP database

Sequence all 20,000 subjects in PMRP

Sequence genetic data linked to iEHR

with decision making tools

Pilot Personalized Health Care to clinical standard of care (AMD)

Create enhanced Personalized Health Care Resource Networks

Improve user interface for PMRP

Sequence 10 subjects

Stakeholders plan incorporation of genetic data in EHR

Pilot/Develop a clinically actionable predictive algorithm (Age-related Macular Degeneration - AMD)

Pilot/Develop Oral-Systemic Health Research Project (OHRP) and plan recruitment of a large OSRP cohort

Current cost $4K

Planned Transition to Personalized Health Care

“To visit the Marshfield Clinic, a longtime innovator in health information technology, is to glimpse medicine’s digital future. Across the national spectrum of health care politics there is broad agreement that moving patient records into the computer age, the way Marshfield and some other health systems have already done, is essential to improving care and curbing costs.”

By: Steve Lohr

Published: December 26, 2008

biomedical informatics research center birc
Biomedical Informatics Research Center (BIRC)

Established in 2005

7 PhDs and 38 other staff

Mission: to accelerate improvements in human health and well being through informatics research while providing integrated tools, services and reliable management of information assets in support of Marshfield Clinic missions

  • Organizational Structure:
    • Administrative Informatics Support
    • Biostatistics
    • Usability/ICDI (Interactive Clinical Design Institute)
    • Informatics Research
    • Infrastructure & Central Resource
    • Research Data & Analytics Management
birc multiple missions
BIRC: Multiple Missions

External Funders











Clinic IS

IT Planning



Foundation Administration

birc personnel growth
BIRC Personnel Growth

Does not include short term students



BIRC Expansion

  • Cost: $980,000
  • Accommodates 25 additional people in BIRC, increasing its staff to 65 by end FY 2012
  • Provides enhanced Biomedical informatics infrastructure support for increased collaboration with internal & external investigators
  • BIRC expansion will house personnel to support:
    • MCRF’s new tenure track hires & grants they will generate
    • Collaboration w/ MC’s IS (R&D: usability, decision support, etc.)
    • New Networks in Personalized Care and Population Research
    • Dental Informatics & Oral Systemic Health Research Networks
dental informatics research
Dental Informatics Research
  • It is a sub-discipline of biomedical informatics.
  • Dental informatics is the application of computer and information science to improve dental practice, research, education and management.

* Eisner J. The future of dental informatics. Eur J Dent Educ. 1999;3 Suppl 1:61-9.

major dental informatics research projects
Major Dental Informatics Research Projects
  • A Standard Information Model for General Dental Records
    • - Funded by National Institute of Dental and Craniofacial Research, NIH
    • - Goal is to develop a comprehensive, consensus-based Electronic Dental Record Information Model (EDRIM) as a reference standard for the content and structure of Electronic Dental Records
  • Multi-institutional Consortium for Comparative EffectivenessResearch in Diabetes Treatment and Prevention
  • - Funded by Agency for Healthcare Research and Quality, DHHS
  • - Goal is to build a national research network and a multi-system distributed database for conducting comparative effectiveness research (CER) in the treatment and prevention of diabetes mellitus
  • Personnel: Dr. AmitAcharya
  • Collaboration: University of Pittsburgh
objectives purpose of forum50
Objectives: Purpose of Forum
  • Provide an opportunity for research networks and other research groups to learn about each other and the projects they conduct.
  • Learn about operational and project barriers, and successful methods to overcome barriers.
  • Facilitate networking and connections between people and groups with similar interests.