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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 #



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




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.




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




Baseline: Human Health and Transition to Disease




Baseline Study: Transition to Disease




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




The Baseline Consortium

The Baseline Study




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




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







Baseline Study Participant Timeline




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




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




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




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




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




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




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




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




Wearable Physiometric Medical Devices




Big Data




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?




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




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

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