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PhenX Measures for Sickle Cell Disease Research

Hemoglobinopathy Uniform Medical Language (HUML) Project Meeting September 18, 2014

Carol M. Hamilton, PhenX PITabitha Hendershot Co-I

Wayne Huggins, Co-ISeptember 18, 2014

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PhenX: consensus measures for Phenotypes and eXposures

• PhenX is funded by the National Institute of Human Genomics (NHGRI), Project Scientist, Dr. Erin Ramos

• NHGRI recognized that including standard measures in genome-wide association studies (GWAS) would have significant impact on biomedical research and released an RFA

• In September 2007, RTI International was awarded a cooperative agreement (U01) to select and define high priority measures for GWAS

• In July 2013, RTI International was awarded a genomics resource grant (U41) to maintain and expand the Toolkit and extend beyond GWAS

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Why Use Standard Measures?

• Study findings require validation • Initial findings need to be replicated, standard measures aid comparisons

• Increased sample size provides greater statistical power• For GWAS, to identify moderate associations and more complex interactions• For other types of studies, increases statistical confidence in results

• Cross-study analyses increase the impact of individual studies• Many diseases and conditions share common risk factors• Use of standard (common) measures facilitates cross-study analyses

PhenX – Driven by the Scientific Community

• A Steering Committee (SC) provides overarching guidance

• Working Groups (WGs) of experts are engaged to select measures

• Outreach to the scientific community– Raises awareness of PhenX measures– Gives the scientific community the opportunity to provide

feedback– Provides the WGs with comments and suggestions for their

consideration– Increases willingness to adopt PhenX measures

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PhenX Approach

• The approach was to select 15 high-priority measures for each of 21 research domains – Domains were selected by the PhenX Steering Committee – Measures and protocols were chosen by Working Groups which are

assembled for each domain– Scientific community had the opportunity to review and comment on

initial set of up to 25 measures for each domain

• Measures are made available to the research community via the PhenX Toolkit

• The PhenX Toolkit facilitates broad use of standard measures by the research community, and promotes collaboration

• The PhenX Toolkit is Web-based and available for use at no cost

PhenX Definitions

• DOMAIN: Topical area with a unifying theme

Psychiatric

• MEASURE: A certain characteristic of, or related to, a study subject

Depression

• PROTOCOL: Standard procedure recommended by a Working Group to collect and record a PhenX measure• Center for Epidemiological Studies Depression Scale for

Children (CES-DC)• Composite International Diagnostic Interview - Short Form

(CIDI-SF) - Adults• Quick Inventory of Depressive Symptoms (QIDS) - Adults

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What the PhenX Toolkit Is and Is Not

What the PhenX Toolkit is

• a catalog of recommended measures for inclusion in new studies or when expanding existing studies

• a database that allows researchers to browse, search, and select measures

• cross-referenced to Cancer Biomedical Informatics Grid (caBIG) Common Data Elements

What the PhenX Toolkit is not

• not a new set of standards• not a new ontology of phenotypes• not a data repository• not a biobank• not restrictive• not a proprietary resource

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Criteria for Selecting PhenX Measures

• The measures should be: • Clearly defined• Well established• Broadly applicable• Validated• Reproducible• Specific• Reliable• Standard measurement protocols exist

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PhenX - Initial 21 Research Domains

• Alcohol, Tobacco, and Other Substances• Anthropometrics• Cancer• Cardiovascular• Demographics• Diabetes• Environmental Exposures• Gastrointestinal• Infectious Diseases and Immunity• Neurology

• Nutrition and Dietary Supplements• Ocular• Oral Health• Physical Activity and Physical Fitness• Psychiatric• Psychosocial• Reproductive Health• Respiratory • Skin, Bone, Muscle, and Joint• Social Environments• Speech and Hearing

PhenX - depth and breadth

• PhenX Measures for Substance Abuse and Addiction Research – funding provided by the National Institute on Drug Abuse (Feb 2012, release)

• PhenX Measures for Mental Health Research – funding provided by the National Institute of Mental Health (NIMH)

• PhenX Measures for Tobacco Regulatory Research - funding provided by the Tobacco Regulatory Science Program (TRSP)

• PhenX Measures for Sickle Cell Disease Research – funding provided by the NIH Heart Lung and Blood Institute (NHLBI)

• Common Measures for Clinical Trials – funding provided by the US Food and Drug Administration Center for Drug Evaluation and Research (FDA CDER)

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Sickle Cell Disease – Project Organization

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PhenXSteering Committee (SC)

RTI

SCD WG2

NHLBI

Sickle Cell Disease Research and Scientific Panel (SRSP)

NHGRI

SCD WG1

Role of the Sickle Cell Disease Research and Scientific Panel (SRSP)

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• Define the scope to be addressed by the SCD Working Groups WGs

• Help identify individuals to serve as members of the WGs

• Identify a Research Panel member to serve as SRSP liaison to each SCD WG

• Identify a Core set of measures for use by all SCD researchers

Working Group Process

• Introductory Call • Refine scope

– Assignments for in-person meeting mini-presentations• In-person meeting

– Members present measures for consideration– Identify preliminary measures for outreach

• Datasheet preparation • Outreach • Teleconference to review results, make final decisions • WG Chairs present to SRSP for approval• Measures released in PhenX Toolkit

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Sickle Cell Disease – project timeline

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PhenX Measures for Sickle Cell Disease

Month Sept Oct Nov Dec Jan Feb Mar AprSRSP X XSCD WG1 XSCD WG2 XDevelop Core Collection (SCP)Release Measures in Toolkit

20152014

Types of PhenX Measures

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Data Sharing and Data Interoperability

• National Library of Medicine (NLM) – National Center for Biotechnology Information (NCBI) database of

Genotypes and Phenotypes (dbGaP)– Logical Observation Identifiers Names and Codes (LOINC)– Unified Medical Language System (UMLS)

• National Cancer Institute (NCI) – Cancer Data Standards Registry and Repository (caDSR)

Common Data Element (CDE)– Grid Enabled Measures (GEM)

• National Center for Biological Ontologies (NCBO) BioPortal– NCBO mapped PhenX to BioPortal ontologies using Lexical OWL

Ontology Matcher (LOOM) 20

PhenX and Existing Standards

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Collaborations - highlights

• Beginning to release PhenX measures in REDCap (Oct 2014) http://www.project-redcap.org/

• Mapping PhenX measures to study variables in the database of Genotypes and Phenotypes (dbGaP)

• PhenX Toolkit database download page (coming soon)

• PhenX protocols translated into Chinese (coming soon)

• Other measures initiatives: PROMIS, NIH Toolbox, Neuro-QoL, NINDS CDEs

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PhenX Toolkit Statistics

• Number of Toolkit Registered Users: 1,586 • Number of Countries that have Accessed the PhenX

Toolkit: 155 • Number of Visits: 607,148 • Number of Unique Visits (August, 2014): 4,384 • Average Visits Per Day: 299 • PhenX Publications: 17• Publications citing PhenX: 65 • Number of Funding Opportunity Announcements

mentioning PhenX: 9523

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Resources

• www.phenxtoolkit.org– Find PhenX measures for inclusion in your study– Quick Start guide– Tutorial – Video and PowerPoint archive https://

www.phenxtoolkit.org/index.php?pageLink=resources.presentations• www.phenx.org

– Provides general information about the PhenX project– Register to receive periodic updates via e-mail of the PhenX Newsletter and

notification of new surveys• www.genome.gov/gwastudies/

– A catalog of published Genome-Wide Association Studies

(Hindorff et al. PNAS 2009)• http://www.nlm.nih.gov/cde/

• NIH Common Data Element (CDE) Resource Portal

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Acknowledgements

• NHGRI – Erin M. Ramos (Project Scientist)– Iglesias, Brenda (Program Analyst

• PhenX Steering Committee– Mary Marazita, Co-Chair– Cathy McCarty, Co-Chair

• WG Chairs / Members

• NIH Liaisons• DoD, CDC, FDA, VA Liaisons

• NIDA lead – Kevin Conway• TRSP lead – Kay Wanke• NIMH lead – Greg Farber• NHLBI lead – Ellen Werner

• Collaborators

• RTI Team– Carol M. Hamilton (Principal

Investigator)– Tabitha Hendershot (Co-Investigator)– Amanda Riley (Project Manager)– Darigg Brown– Beth Bullard– Wayne Huggins– Debbie Maiese– Destiney Nettles– Helen Pan– Mike Phillips– Toolkit team– Communications team– Logistics team

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Toolkit Features

• Search or Browse– Browse by domain, collection or measure– Search using “Smart Query Tool”

• Add measures to “My Toolkit”– Recommends related measures– Registration allows users to save and share multiple Toolkits

• Provides information about selected measures– Reports, download, review, print or save

– Custom Data Collection Worksheets (DCW)

– Data Dictionaries (DD) support data submission to dbGaP

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Cross-reference table for PhenX measures and variables

PhenX variable

PhenX ID dbGaP variable

LOINC code

Current Age PXV010101020000 phv00023938.v1phv00024004.v1

21612-7

EthnicityPXV010501010000 phv00023941.v1

phv00024007.v156050-8

GenderPXV010701010000 phv00023939.v1

phv00024005.v146607-8

P3G variable*

Age

Ethnicity

Gender

eMERGE variable

caDSR CDE

Age 2423393

Ethnicity 2200284

Gender 2179640

* P3G DataShaPER doesn’t distinguish between “exact” and “similar” mappings to PhenX measures

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Facilitating Cross-Study Analysis

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PhenX Toolkit

• Researchers will visit the Toolkit to:– Add standard measures to ongoing studies– Consider PhenX measures when planning new studies– Obtain high quality measures outside of their area of expertise– Review PhenX measures that relate to their primary research focus

• By selecting some of the PhenX measures:– Ensure that their study will be compatible with others that also incorporate

PhenX measures– Combine studies to increase statistical power and the ability to identify

genes associated with complex diseases– Potential to cumulatively combine with future studies

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PhenX Toolkit Contents

• Recommended measures for each research domain

• Detailed protocols for collecting the measures

• Information about the measures – Rationale for inclusion– References– Supplemental Information

• User support – Quick Start guide– Tutorial– Glossary of terms– Frequently Asked Questions (FAQs)– Feedback tool

PhenX Smart Query Tool

• Search with Filters– Filter search results using protocol characteristics (Data Collection Mode,

Lifestage, Time to Complete, and Language) Smart Search

– Searches through measure names, aliases, and keywords; high specificity Text Search

– Searches through full text of measures and protocols; high sensitivity

• Supplemental Information– Searchable in the full-text search only

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