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PowerPoint Presentation
November 2014
Kristin Newby, MD, MHS
DTMI
Baseline
Heart Disease, Cancer, Big Data and Google:
The Baseline Study
Duke Translational Medicine Institute
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
1
The Premise
Health and disease reflect the complex interplay of biology, environment, socioeconomic and cultural influences, and time
Characteristics that result in transitions between health and disease or herald the coming of these transitions, are poorly understood and only superficially characterized
A more profound understanding of health and disease state transitions will
allow more focused preventive measures
provide opportunities for monitoring and targeted preemptive interventions
inform the development of new therapeutics and diagnostics
enable learning systems and continuous quality improvement at the individual, neighborhood, county and state level
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Big Challenges in Biomedicine
Lack of significant information over the time dimension - Measurements to assess biology and human health are made periodically in visits to healthcare or research
Missing systems biology - When developing concepts of human biology or drug development we make limited measurements focused on specific mechanismswere looking under the lamppost
Missing the ability to measure the interactions of biology, sociology, environment and decision-making that could enable optimization of individualized and population health - Although we know that health and disease are the product of the interactions of genes, multiple derivative biological systems, environment, social context and personal decisions, we tend to look at one part of the time
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline Study
A comprehensive study of human health and the transition to disease
A longitudinal cohort study to extensively characterize participants at baseline and serially using a battery of clinical, imaging, psychosocial, behavioral, socioeconomic, geospatial, physiometric, and molecular tools.
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Objectives of the Baseline Study
Characterize human systems biology by measuring multiple systems simultaneously and longitudinally
Define normal values for a given parameter in the context of the other measured parameters
Predict outcomes that are meaningful to participants (cardiovascular events, new onset or recurrence of cancer, and functional status and quality of life)
Validate wearable human monitoring devices against well-characterized physiological measurements and clinical, quality-of-life, and functional outcomes
Characterize disease state transitions for cardiovascular disease and cancer, including quality-of-life and functional status
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline: Human Health and Transition to Disease
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline Study: Transition to Disease
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
The Ultimate Goals
Integrate personal and external information to enable individuals, neighborhoods and populations to:
optimize health
prevent disease
monitor treatment
enable people to be as functional as possible
Use a more profound understanding of health and disease to inform development of new therapeutics and diagnostics
Leverage an infrastructure of well characterized individuals for future studies
Provide these opportunities at a very low cost per individual at a large-scale
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
The Baseline Consortium
The Baseline Study
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline Pilot Study
N=200
Terry Shaack, California Health and Longevity Institute (CHLI)
Primary LOGISTICAL aims
complex schedule of assessments, including patient questionnaires, physical performance tests, imaging
determine optimal biospecimen collection strategy for stable sampling and reproducible assays
determine optimal assay methodology
validate quality control methods
ASSAY and DATA aims
primary stability, cross-validation, and reliability of all assays
determine variability of assays in challenge interventions
develop and validate data input, reduction, and analytical pipelines
validate device data against surrogate and primary endpoints
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline Study Sites and Participants
Sites at Duke (Kannapolis and Durham) and Stanford
10,000+ total participants
5000 cancer / 5000 CVD
3 risk buckets, defined by existing risk algorithms (CV) and family history and/or known genetic or exposure risk (Ca) or known disease (CV and Ca)
Stratified by age and representative of US race/ethnicity
Screen existing cohorts (MURDOCK, DCRU volunteer reg.), Duke and Stanford patients, high risk cancer clinics
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline Study Participant Timeline
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline StudyClinical Assessments
Schedule of AssessmentsYearEnrollment/Baseline1234EventsHistory and Physical ExamMeTree family history toolxEnvironmental exposure questionnairexxxxxCV risk score determinationxComplete clinical history (includes current medications and supplements) xxxxxaComplete physical exam (includes height, weight, waist circumference, BP and HR)xxxxxaAnkle-brachial indexxxxxx
a=data from clinical testing collected
c=continuous
x=specific testing for Baseline Study
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline StudyRoutine Laboratories
Clinical laboratoriesEnrollmentYear 1Year 2Year 3Year 4EventsComplete blood countxxxxxaComplete metabolic panelxxxxxaLiver function testsxxxxxMagnesiumxxxxxaCalciumxxxxxLipid profilexxxxxaHbA1cxxxxxThyroid profilexxxxxNT-proBNPxxxxxa4th generation troponin IxxxxxaHigh sensitivity troponin T or IxxxxxxHigh sensitivity C-reactive proteinxxxxxHepatitis C AbxxxxxHepatitis B sAg, sAb, cAbxxxxxHIV serologyxxxxxHPV serologyxxxxxProstate specific antigen (PSA)xxxxxUrinalysis xxxxxUrine microalbuminxxxxxUric acidxxxxxUrine drug screenxxxxxaUrine cotininexxxxxVitamin DxxxxxHormone panel (estradiol, progesterone, LH, FSH [women]; testosterone [men])xxxxxMercury, other heavy metals/trace elementsxxxxx
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline StudySpecific Assessments
Study specific clinical testing and evaluationsEnrollmentYear 1Year 2Year 3Year 4EventsAll participants 12-lead electrocardiogramxxxxxa PA and lateral chest X-rayx Complete eye exam with visual and contrast acuity and wide field retinal imaging/OCTxxx PFTs with DLCOxx Audiometry (phone/web based)xxCardiology cohorts only Coronary calcium score (cohort 1, 2 only)x Echocardiogram (2D/Doppler)xxxa Stress echocardiogramxxxaCancer cohorts only (all standard of care) Whole body MRI (cohort 2 p53 mutation only)aaaaa Chest CT- nodules (cohort 2 lung CA only)aaaaa Breast MRI (cohort 2 breast CA only)aaaaa
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline StudySpecial Evaluations and Testing
Special study evaluations and testingEnrollmentYear 1Year 2Year 3Year 4EventsPhysiometric monitoring/wearable deviceccccccCognitive performance testingxxxxxSocioeconomic and level of education questionnairexxxxxFunctional status questionnaire (PROMIS[1])xxxxxxOther PROMIS questions (mood, etc.)xxxxxxBehavioral questionnaire/s (stable)xxxPhysical performance assessmentxxxDietxxxxxGeospatial referencingxQuantified self (volunteer subset)xxxxx
[1] www.nihpromis.org. Accessed July 11, 2014
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline StudyBiospecimen Collection
Protocol-specified biospecimen collectionEnrollmentYear 1Year 2Year 3Year 4EventsUrinexxxxxxSalivaxxxxxxTearsxxxBuccal swabxPlasmaxxxxxxSerumxxxxxxPaxgene RNA tubesxxxxxxWhole blood for DNA studiesxxxxxxPBMCs and hPSCs (flow cytometry)xxxxxxStoolxxxxxMicrobiome swabs (tongue, post-auricular)xxxxxExhaled breath (subset)xBiopsies (opportunistic if taken clinically)aa
300 mL of blood collected
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
GENOMIC ASSAYS(NGS)GENOMIC ASSAYS(Array based)PROTEOMIC ASSAYS(Mass spectrometry)CYTOMETRIC ASSAYSMETABOLOMIC ASSAYSPROTEOMICS- Whole Genome Sequencing (phased)- Whole Genome Methylation (bisulfite)- RNA-Seq, PBMC
- Targeted sequencing B&T Cells- Exosome + Circulating DNA Sequencing- Illumina HD exome- Illumina HD methylome-Nanostring Gene Expression Panels (cancer, cardiovascular, inflammation)- LC/MS MS MRM (Saliva, Serum, Plasma, Urine, Tear film (strip), Tear film (Capillary)
- LC MS/MS open-ended (Saliva, Serum, Plasma, Urine, Tear film (strip), Tear film (Capillary)- Immune Status Cytometry Panels
- Veridex Cellsearch CTC -LC/MS Metabolomics (Saliva, Serum, Plasma, Urine, Tear film (strip), Tear film (caplllary) (polar and lipids)- High density aptamer affinity array-Auto-antibody array- Antibody immunoassay- Curated MesoScale Assays- Curated Bioplex/Luminex Milliplex Assays
Microbiome; Oncology cohorts: extensive pathology, including genomic assays
Baseline StudyMolecular Assays
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Blood and peripheral
Baseline Study Big Data
RNA
DNA
PROTEIN
GENOME1.00 TB
EPIGENOME2.00 TB
TRANSCRIPTOME 0.70 TB
METABOLOME0.06 TB
PROTEOME 0.04 TB
STANDARD LAB TESTS ~1 MB
HUMAN3.75 TB
Create unique capabilities to process complex phenotypic, biochemical, and genomic data
METABOLITE
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Baseline Study Big Data
Processed images
Digital X-ray 8-32 MB
Chest CT 50-100 MB
MRI50-500 MB
depending on body area
2-D/Doppler echo 600 MB
Stress echo 300 MB
Raw datasets
Chest CT 1-3 GB
MRI 4-20 GB
Stress echo 50 GB
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Wearable Physiometric Medical Devices
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Big Data
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Preparing the Community for Baseline
Key Principles
Individual volunteers and the community as participants and partners not research subjects
Building trust
Community ownership of the study rather than just being studied
Yields pride in participation and in turn altruism
Common Questions
What happens after my study visit?
How will information collected about me be kept private?
How are my rights protected?
What are the benefits of participating?
How does the community benefit?
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
Locally based, Duke-employed clinical research team with an average of 7 years experience
18 full-time personnel
Certified clinical research coordinators, clinical trials assistants, project managers, regulatory staff, and data technicians
Spanish-speaking coordinators
On-the-ground recruiters closely engaged with local community
Clinical Assessments
Community Engagement and
Participant Recruitment
Labs
Clinical Trial Coordination
DTMI Strategy & Innovation Group #
SB/2012/DCRI Confidential and Proprietary
DUKE Translational Medicine Institute
FORMS &
QUESTION-
NAIRES
Human
Me
Tree
Pool
EDC
(eCOS)
LABCORP
CAROLINAS
EMR
(CANOPY)
STANFORD
EMR
(EPIC)
DCRU
REGISTRY
OPERATIONAL
ANALYTICS
BIOREPOSI-
TORY
DUKE
CALL CENTER
Log System
Footprints?
BIOSPECIMEN
VENDORS
CARDIAC
Electrocardio-
gram12-Lead
AUDIOMETRY/
AUDIOLOGY
MURDOCK
SITE
PAYMENTS
SYSTEM
DUKE DHTS
Geospatial
Coding
*Does not reflect actual process of transferring data.
Automated
Manual
Possible/
Unknown
Baseline Study
Context Diagram
Source and Destination Systems*
*DRAFT*
As of: 10/17/2014
DEVICES
DATA
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and imaging
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REGISTRY OF
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MRI
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Echocardio-
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6
VISION
Retinal
Imaging
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6
CARDIAC
Stress Echo-
cardiogram
6
X-RAY
3
5
6
PULMONARY
PFTS w/DLCO
(Lung
Diffusion)
2
5
6
EMR
19
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ON-SITE TESTS
(Cog.fx; BP;
HR; Blood, etc)
16
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