2017 CDISC INTERNATIONAL INTERCHANGESession 7: Data Standards for Patient-Focused Research

November 16, 2017 |2:00 – 3:30 PM CT

Allyson Gage, PhD

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Agenda

WCN-RAPID Dx Launch Meeting 2

01. 02. 03.About CVB PTSD Need for Data Standards

Mission PrevalenceDiagnosisTreatment

Data CollectorsData Types

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About Cohen Veterans Bioscience

We are a national, nonpartisan 501(c)(3) research organization dedicated to fast-tracking the development of diagnostic tests and personalized therapeutics

for the millions of veterans and civilians who suffer the devastating effects of trauma-related and other brain disorders.

To realize our mission, we have spearheaded a brain health roadmap

that capitalizes on new technologies and innovative approaches

to foster Wellness & catalyze Precision Biomarker, Diagnostics and Therapeutics

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Low Likelihood of Approval in CNS

BioMed Tracker Report 2006-2015

Psychiatry 6.2%

Exaggerated for Trauma-related Brain Disorders

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What is brain trauma?

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What Are Trauma-related Brain Disorders?

• Post-traumatic Stress Disorder (PTSD) • Mental health condition developed after experiencing or witnessing a life-threatening event

• Eg, combat, a natural disaster, a car accident, domestic violence, or sexual assault• Complicating factors

• Requires an interaction with the external environment• Only a small percentage (8-20%) of people who have that interaction develop the disorder• Symptoms can start right after the interaction or months later and the symptoms may come and go.

• Highly prevalent• ≥80% of people will suffer a trauma in their lifetime• 8% of the US population (8.6 million) suffers from PTSD during their lifetime• 20% of OEF/OIF service members have PTSD (1 in every 5)• 30% of Vietnam veterans suffered PTSD at some point after the war

• Traumatic Brain Injury (TBI)• Depression, Suicide, Anxiety, Substance Use Disorders, Cognitive DeficitsOverlapping symptoms – same mechanisms or different? Additive or synergistic?

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PTSD Diagnosis and Treatment Report Card

• Diagnosis• No objective laboratory tests; Clinical interview – subjective• DSM-V – endorsement of symptoms across several criteria categories

• What happens when you combine data that used different DSM or ICD criteria?

• Whew! Similar prevalence: DSM-IV & V • Uh-oh… Lower prevalence: ICD-11 & DSM-V • Ugh – Substantial portions of patients meet diagnosis with one, but not the other

• Result: Not only is an individual study starting with a very heterogeneous population, analyses combining study data are doing so with phenotypically different populations

The British Journal of Psychiatry (2014) 205, 230–235Perspectives on Psychological Science (2013) 8(6) 651–662

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PTSD Diagnosis and Treatment Report Card

• Treatment• Psychotherapy, but under-prescribed / utilized / completed• 2 therapeutics: Paxil and Zoloft – both SSRIs• No FDA-approved PTSD therapeutics in 16 years

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The Ultimate Goal is Prevention & Personalized Medicine for Brain Health

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Innovation Incubator: Improving Diagnosis & Treatment on a Precision Medicine Platform

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ExpertiseCVB expertise + CVB SME network

Due DiligenceCommercialLegalScientificRegulatory

ResourcesAccess to CVB platform

Bridge FundingStage-gated funding for FIH, PoP, PoC…

Clinical Trial Accelerator

INCUBATOR

IMPACT

Increase probability of success

Reduce development time

Improve precision & effectiveness

Diagnostic Pipeline

Small MoleculePipeline

Biologics Pipeline

ElectroceuticalsPipeline

Devices Pipeline

Alternative Therapy Pipeline

Stem Cell Pipeline

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Bio-typing using Biomarkers

Subtype 1

Subtype 2

Subtype 3

All Patients

Class predictionClass discovery Biological Mechanisms/ Treatments

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Biotype 1

Biotype 2

Biotype 3

IMAGING

BODY FLUIDS

METABOLOMICS

LIPIDOMICS

PROTEOMICS

TRANSCRIPTOMICS

GENOMICS

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CVB Program Portfolio w/ Multiple Partners

PTSD Genetics

Partners: Broad, NIH

Global PTSD GWAS

CVC, Tau-Dx & RAPID - Dx

CVC, Tau-Dx& RAPID-Dx

Partners: NYU,

Stanford, DOD

Brain Bank

AMP-IT-UP

PTSD/TBI Brain Bank

Partners: McLean/

Harvard, VA

Partners: Columbia,

McLean/Harvard

AMP-IT-UP

Tau InsilicoModeling

Partners: InSilico Biosciences,

Tau Consortium

MAPTACDISC Standard &

Outcomes

Partners: CDISC

CDISC Standards & Outcomes

Imaging Library

TBI Imaging Library

Partners: ACR, Baylor

College, U Virginia

mHealth & Wearables

Partners: Early Signal, IMEC,

NeuroScios, MindStrong

Wearables & Mobile Health

Data Commons

Data Commons

Partners: Open Commons

Consortium, U Chicago

KnowledgeMap

Partners: Fraunhofer SCAI,

Exaptive

KnowledgeMap

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Our Alliance Partners

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Data Standards for Animal Models

2 hours restraint < 5 min Ether 7 day isolated housingForced swim

Control

SPS

BalancedGroup

AllocationArrival

Acclimation & Handling

5 days + 3 days

7 daysIsolation (Days 2-9)

FearConditioning

Fear ExtinctionTraining

ExtinctionRecall

Day 1 Day 10 Day 11(24 h later)

Day 12(24 h later)

Single Prolonged Stress (SPS)

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Data Standards for Animal Models

Belzung, C., & Lemoine, M. (2011). Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biology of Mood & Anxiety Disorders, 1(1), 9.

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Biomarkers & Diagnostics for PTSD & TBI

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We Collect Multi-modal Data

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Data Type Examples: Global PTSD Genome-wide Association Study

~15,000 cases, 55,000 controls = ~70,000 samples

56 Studies from around the Globe

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Data Type Examples: GWAS Freeze 2 Results

GWAS in European ancestry:• N cases: 12,813; N controls: 35,640; N total: 48,453; • N studies: 50• GWAS hits: 2

GWAS in African ancestry:• N cases: 4,289; N controls: 10,500; N total: 14,7893; • N studies: 30• GWAS hits: 1

GWAS in Latino ancestry:• N cases: 1,981; N controls:3,722; N total: 5,703; • N studies: 6• GWAS hits: suggestive 2

What about the phenotypic data?

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Data Type Examples: Mobile Health and Wearables

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Data Type Examples: Other Biomarkers

Eye-tracking“assess damaged eye-movement circuits”

The Task40 sec/cycle;

8 cycles

Ocular Coherence Tomography “looks at integrity of photoreceptors”

Voice-markers”evaluate semantics and patterns of speech”

Brain Circuit markers”measure connectedness of circuits”

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Data Type Examples: Cognitive City & KnowledgeMapTM

We are creating a collaborative network that is able to suggest tools, datasets, algorithms and even collaborations based on objective measures and usage of the assets that exist in the network. This cognitive city will grow and allow our partners and collaborators to learn from each others.

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RAPID-Dx Framework

Cohort 2

Cohort 1

Cohort 3

B.R.A.I.N Commons

StatisticalAnalysis Plans

Discovery

Data Mining of Existing Data

‘Omics Bio-assaying on High Performance Platforms

Large-scale Replication of candidate markers

Legacy & Prospective Cohorts

Cohort 4

Diagnostics

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What is the BRAIN Commons

The BRAIN Commons is a scalable, centralized big data cloud-based platform for computational innovation and data driven discovery By partnering with OCC we are leveraging Open Source data models &

continued investments in the community platform Integrates individual level data across data types (genomics, biomics,

imaging, wearables, etc.) Able to scale to work with large quantities of data Equipped with data-analysis and systems biology tools FISMA Moderate Security & HIPAA Compliant

(Brain Research and Innovation Network)

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Apply CDISC

Data Standards

Data PartnersControl Accessto their data

Multiple Sources of Data

Visualization & Analytics Built-In

Cloud-ArchitectureBig Data Capacity

Discovery Accelerated

THANK YOU

www.cohenveteransbioscience.org

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