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Robin Feldman, MBA & Joy Esterlitz, MS NINDS CDE Team

The Emmes CorporationRockville, MD USA

Thursday, September 14, 2017

The National Institute of Neurological Disorders and Stroke (NINDS) and American Academy of Cerebral Palsy and Developmental Medicine

(AACPDM) Cerebral Palsy Common Data Elements (CDE) Recommendations

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Disclosure InformationAACPDM 71st Annual Meeting | September 11-16, 2017

Speaker Name: Joy Esterlitz, MS

Disclosure of Relevant Financial Relationships: I have no financial relationships to disclose.

Disclosure of Off-Label and/or investigative uses: I will not discuss off label use and/or investigational use in my presentation

Disclosure InformationAACPDM 71st Annual Meeting | September 11-16, 2017

Speaker Name: Robin Feldman, MBA

Disclosure of Relevant Financial RelationshipsI have no financial relationships to disclose.

Disclosure of Off-Label and/or investigative uses: I will not discuss off label use and/or investigational use in my presentation

Presentation Overview Presentation Overview

• What is the National Institute of Neurological Disorders and Stroke (NINDS) Common Data Element Project?

• What are the Common Data Elements (CDEs) and associated Case Report Forms (CRFs)?

• What information does the NINDS CDE Website contain?

• What was the process to develop the Cerebral Palsy CDEs?

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What is the CDE Project?What is the CDE Project?

• NINDS initiated the development of CDEs as part of a project to develop data standards for funded clinical research in neuroscience.

• The CDEs are content standards that can be applied to various data collection models and are intended to be dynamic and may evolve over time.

• CDEs are not a database.

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What are the goals of the CDE Project?What are the goals of the CDE Project?

• Develop common definitions and standardize case report forms (CRFs) and other instruments

• Help investigators conduct clinical research through the development of these uniform formats by which clinical data can be systematically collected, analyzed and shared across the research community

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What are the objectives of the CDE Project?What are the objectives of the CDE Project?

Identify or develop CDEs used in clinical research

(age, gender, race, etc.) Present data elements in a standard format available to all

Identify common definitions

(including permissible values, range checks, etc.)Standardize CRFs and other data collection instruments

Provide information to researchers for clinical data collection and sharing

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Reduce the time and Reduce the time and cost needed to develop cost needed to develop

data collection toolsdata collection tools

Promote standardized, Promote standardized, consistent and consistent and universal data universal data

collectioncollection

Improve data quality Improve data quality and facilitate data and facilitate data

sharingsharing

Improve opportunities Improve opportunities for metafor meta--analysis and analysis and comparison of results comparison of results from various studiesfrom various studies

CDE GoalsCDE Goals

Overall Impact of the CDE ProjectOverall Impact of the CDE ProjectOverall Impact of the CDE ProjectOverall Impact of the CDE Project

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NINDS’ Collaborative Effort for CDE NINDS’ Collaborative Effort for CDE Development and ImplementationDevelopment and Implementation

Expertise from hundreds of disease specialists worldwide

Other NIH institutes and federal agencies such as the National Library of Medicine

International data standards (e.g., ISO)

Clinical Data Interchange Standards Consortium (CDISC)

Non-profits / FoundationsPharmaceuticals

NINDS CDE Current DiseasesNINDS CDE Current Diseases

Amyotrophic Lateral SclerosisCerebral Palsy

Chiari MalformationCongenital Muscular Dystrophy

Duchenne Muscular Dystrophy/Becker Muscular

DystrophyEpilepsy

Facioscapulohumeral Muscular Dystrophy

Friedreich’s AtaxiaHeadache Version 2.0Huntington’s DiseaseMitochondrial Disease

Multiple SclerosisMyasthenia Gravis

Myotonic DystrophyNeuromuscular Diseases

Parkinson’s DiseaseSpinal Cord Injury and Pediatric

SCISpinal Muscular Atrophy

Sports Related ConcussionStroke

Traumatic Brain InjuryUnruptured Cerebral Aneurysms and Subarachnoid Hemorrhage

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NINDS CDE Collaboration and PartnershipsNINDS CDE Collaboration and Partnerships

Cerebral Palsy–American Academy for Cerebral Palsy and Developmental Medicine (AACPDM)

Chiari I Malformation–Chiari & Syringomyelia FoundationUnruptured Cerebral Aneurysms and Subarachnoid Hemorrhage (SAH)–National Library of Medicine

Sports-Related Concussion (SRC)–U.S. Department of Defense

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What is a CDE?What is a CDE?

• Standardized question and potential answers• Semantic value with a CDE name, definition and permissible

values• Example: CDE name: “Clinical event or milestone type”Question Text: “Milestone”Definition: “Type of clinical event or milestone pertinent

to the disease or disorder”Data Type: “Alphanumeric” Input Restriction: “Multiple Pre-Defined Values

Selected”

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CDE Details (subset of attributes of the CDE shown below):CDE Details (subset of attributes of the CDE shown below):

Question on CRF:Question on CRF:

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CDE Development ProcessCDE Development Process

• CDEs are identified, developed, and vetted by experts in the scientific community• Development is transparent and inclusive• NINDS and NINDS CDE Team provide continuous support and guidance• Oversight Committee (OC) will be formed to help maintain disease-specific CDEs• Process is iterative – Steering Committee meets to annually review and update CDEs

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CDE DCDE DEVELOPMENTEVELOPMENT: P: PROCESSROCESS ((CONTCONT.).)CDE DCDE DEVELOPMENTEVELOPMENT: P: PROCESSROCESS ((CONTCONT.).)

DEVELOPMENT STEPTYPICAL

TIMEFRAME

NINDS invites Working Group (WG) members and WG Chair(s) 2 - 4 weeks

NINDS works with Chair(s) to divide WG into subgroups and to nominate subgroup Chair(s) 2 - 4 weeks

Introductory meeting of WG at national conference or via web conference 1 - 2 hours

Subgroups meet every 3 - 5 weeks via conference call to develop CDEs for assigned areas 6 - 9 months

Internal WG ReviewInternal WG Review of all subgroups’ CDEs 1 month

Subgroups revise CDEs based on feedback from internal WG review 1 - 2 months

Public ReviewPublic Review of WG’s CDEs 6 - 8 weeks

Subgroups review CDEs based on feedback from Public Review 1 month

Post version 1.0 of CDEs on the website 2 - 4 weeks

Total 12 - 18 months

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Version 1.0 of the CDEs is not the end Version 1.0 of the CDEs is not the end –– CDEs are CDEs are dynamic and will evolve over timedynamic and will evolve over time

NINDS has created oversight committees to NINDS has created oversight committees to continually review the general and disease specific continually review the general and disease specific

CDEsCDEs

CDE DCDE DEVELOPMENTEVELOPMENT:: PPROCESSROCESS ((CONTCONT.).)CDE DCDE DEVELOPMENTEVELOPMENT:: PPROCESSROCESS ((CONTCONT.).)

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CDE Terminology CDE Terminology –– ClassificationsClassifications

Exploratory

Supplemental

Supplemental -Highly

Recommended*

Disease Core

General

Core* Classification term of “Basic” used for Traumatic Brain Injury CDEs

NINDS CDE Disease Areas NINDS CDE Disease Areas –– over 13,000 CDEs & 900 Instrumentsover 13,000 CDEs & 900 Instruments

Chiari I Malformation (new)Cerebral palsy (new)Epilepsy*Headache (version 2.0 new)Mitochondrial disorders*Movement disorders

–Parkinson’s disease–Huntington’s disease

Multiple sclerosisSpinal cord injury (SCI)*Stroke*

–Unruptured Cerebral Aneurysms and Subarachnoid hemorrhage (new)

* Includes pediatric-specific recommendations

Traumatic brain injury*–Sports-Related Concussion (new)

Neuromuscular disorders*– Amyotrophic lateral sclerosis – Friedreich’s ataxia– Muscular dystrophies

◊Congenital, Duchenne/Becker, Facioscapulohumeral, Myotonic

– Myasthenia gravis– Spinal muscular atrophy

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (in development)

Biomechanical Sensors in Traumatic Brain Injury (in development)

Disease Listing

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How were How were the CP CDEs the CP CDEs developed?developed?

CP CDE DCP CDE DEVELOPMENTEVELOPMENT:: PPROCESSROCESSCP CDE DCP CDE DEVELOPMENTEVELOPMENT:: PPROCESSROCESS CP CDE TCP CDE TIMELINEIMELINEInitial CP CDE Project meeting held in October 2015

Individual working groups met via teleconference monthly for 6–9 months

CP CDE working groups internally reviewed all the working groups in June 2016

CP CDEs posted to NINDS CDE Website for public review from September 2016 to October 2016

Version 1.0 CP CDEs were posted on NINDS CDE website (www.commondataelements.ninds.nih.gov) on December 15, 2016

Collaboration between the National Institutes of Neurological Disorders and Stroke (NINDS) and the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM)

Seven Working Groups and a Steering Committee

Participant Characteristics and Disease/Injury Related Events Health, Growth, Genetics, Comorbidities, and Labs Neuroimaging Diagnostics Neuromotor Skill and Functional Assessments Neurocognitive, Social, and Emotional Assessments Engagement and Quality of Life Assessments Integrated Across WGs

CCEREBRALEREBRAL PPALSYALSY CDE PCDE PROJECTROJECT

CP CDE PCP CDE PROJECTROJECT –– WWORKFLOWORKFLOW ANDAND CONCEPTUALCONCEPTUAL FRAMEWORKFRAMEWORK**

* Schiarti et al. (Submitted for publication)

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CP CDE PCP CDE PROJECTROJECT OOVERALLVERALL PURPOSEPURPOSEStandardize data collection and assessment in studies of children and

youth by:

Indentify valid and reliable measures – including assessment and evaluative tools – to be recommended for routine use in research studies and clinical practice in all types of studies

Recommend a set of CDEs and measures that comprehensively represent functional profiles across all domains of the International Classification of Functioning, Disability and Health (ICF)

Identify CDEs/ measurement gaps that could be addressed in future research initiatives

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CCEREBRALEREBRAL PPALSYALSY SSELECTIONELECTION CCRITERIARITERIA

Selection criteria applied by all the working groups:

Applicable to children and youth aged 0 to 18 yearsand

Represents a relevant areas of study in CPand

Has documented validity and reliability testing

CDEs and instruments had to meet all selection criteria in order to be included in the CP CDEs set

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NINDS CP CDE CNINDS CP CDE CLASSIFICATIONLASSIFICATION CCRITERIARITERIA

CDEs Classification Definitions

Core

A data element for recording essentialinformation applicable to any CP studyincluding therapeutic areas and studydesigns. Consistent with all NINDS disease-specific CDE sets

Supplemental – Highly RecommendedA data element which is recommended foruse whenever applicable

Supplemental

A data element that has some evidence ofvalidity and is commonly collected inclinical studies in CP. Use depends uponthe study design

ExploratoryA data element that is emerging or thatrequires further validation in CP

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CCEREBRALEREBRAL PPALSYALSY DDOMAINOMAIN WWORKINGORKING GGROUPSROUPSDDEVELOPMENTEVELOPMENT PPROCESSROCESS

All WGs reviewed existing CDEs and instruments defined from other diagnostic groups in the NINDS CDE project including:Friedrich’s AtaxiaStroke EpilepsySpinal Muscular Atrophy Duchenne Muscular Dystrophy/

Becker Muscular Dystrophy Traumatic Brain Injury

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IINTEGRATEDNTEGRATED AACROSSCROSS WWORKINGORKING GGROUPSROUPSReviewed all the instruments recommended by the six domain Working Groups recommended:

226 measures were identified by the Working Groups 122 (54%) were proposed for inclusion in Version 1.0 CP CDEs.

34 classified as Supplemental – Highly Recommended 61 classified as Supplemental 31 classified as Exploratory

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NNUMBERUMBER OFOF IINSTRUMENTSNSTRUMENTS ANDAND CRFCRFSS RREVIEWEDEVIEWEDANDAND RRECOMMENDEDECOMMENDED BYBY WWORKINGORKING GGROUPSROUPS

Working Group Standardized Instruments

(Number)

Number of CRFs

(Number)Participant Characteristics and Disease/Injury Related Events

8 2

Health, Growth, Genetics, Comorbidities, and Labs

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Neuromotor Skill and Functional Assessments

92 6

Neurocognitive, Social, and Emotional Assessments

66 N/A

Engagement and Quality of Life Assessments

32 N/A

Neuroimaging N/A 1

Total 226 20

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NINDS CDE Website HomepageNINDS CDE Website Homepage

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NINDS CDE Website Navigation NINDS CDE Website Navigation

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Cerebral Palsy Data Standards PageCerebral Palsy Data Standards Page

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Cerebral Palsy Case Report FormCerebral Palsy Case Report Form

Case Report Form

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Cerebral Palsy Case Report FormCerebral Palsy Case Report Form

CDE

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Cerebral Palsy Case Report Form

CDE Details = Data Dictionary

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NeuroImagingNeuroImaging –– Cerebral Palsy Cerebral Palsy MRI CDE Details MRI CDE Details

Question Text

Permissible Value

CDE Name

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NINDS CDE CP Outcome Measures NINDS CDE CP Outcome Measures RecommendationsRecommendations

Notice of Copyright

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Cerebral Palsy: Notice of Copyright Cerebral Palsy: Notice of Copyright Instrument RecommendationInstrument Recommendation

Classification

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NINDS CDE CP Outcome Measures NINDS CDE CP Outcome Measures RecommendationsRecommendations

CDE Details = Data Dictionary

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CDE Detailed ReportCDE Detailed Report

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Cerebral Palsy Overview PageCerebral Palsy Overview Page

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Cerebral Palsy History and Acknowledgements PageCerebral Palsy History and Acknowledgements Page

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Feedback and Suggestions FormFeedback and Suggestions Form

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StartStart--UP Resource ListingUP Resource Listing

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Cerebral Palsy CDE StartCerebral Palsy CDE Start--Up Resource Listing Up Resource Listing DocumentDocument

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Cerebral Palsy CDE StartCerebral Palsy CDE Start--Up Resource Listing Up Resource Listing DocumentDocument

CP CDE Highlight SummaryCP CDE Highlight Summary

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Cerebral Palsy CDE Highlight Summary DocumentCerebral Palsy CDE Highlight Summary Document

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NINDS CDE Website NavigationNINDS CDE Website Navigation

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Cerebral Palsy : CRFCerebral Palsy : CRF

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NINDS CDE Website NavigationNINDS CDE Website Navigation

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Cerebral Palsy: CDE DetailsCerebral Palsy: CDE Details

CDE Name

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Cerebral Palsy: Notice of Copyright Cerebral Palsy: Notice of Copyright –– Instrument RecommendationInstrument Recommendation

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NINDS CDE Website Learn PortalNINDS CDE Website Learn Portal

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Questions?Questions?NINDSCDE@emmes.com

Support: This project was funded by HHSN271201200034C.

At the end of this month, there will be more than 20 disease areas with over 13,000 CDEs and 900

CRFs available for use through the NINDS CDE project website.