CDISC Inclusion/Exclusion Standardized Coding Project:

1. CDISC Inclusion/ExclusionStandardized Coding Project: ASPIRE: Agreement on Standardized Protocol Inclusion Requirements for Eligibility

2. Joyce Niland, Lead City of Hopejniland@coh.org Elly Cohen, Co-Lead UCSFElly.cohen@ucsfmedctr.org Greg Eoyang, Admin Lead Digital Infuzion grege@digitalinfuzion.com Lakshmi Grama NIH lgrama@mail.nih.gov Cortney Hayflinger GSK Cortney.d.hayflinger@gsk.com Robert Wang ClinTrialStat clintrialstat@yahoo.com Jeffrey Suico LLCR suicoje@lilly.com Charles Barr Roche Laboratories Inc charles_e.barr@roche.com Allen Tien MD Logix allen@mdlogix.com Stanley Kaufman Epimetics skaufman@epimetrics.com Deborah Price NIH Priced@mail.nih.gov Valerie Dyer NIH dyerv@mail.nih.gov ASPIRE Project Participants

3. The Challenge We Face:Statistics from Oncology • According to the research literature: • Over 1.2 million patients are diagnosed with cancer in the U.S. each year • Somewhere between 12% and 44% of all cancerpatients are eligible for clinical trial enrollment • Only 1% to 3% of eligible patients actuallyparticipate • If only 10% of eligible patients participated inoncology clinical trials, trials could be completedmuch more rapidly than the current 3-5 years • Corresponding increased rates of new drugdevelopment and availability

4. Potential Questions to be Answered via Standardized Coded Eligibility Criteria • Patients/Providers/Family Members • Does a specific center have an open trial formy condition? • Investigators • Who and where are my potential collaborators and competitors? • Sponsors • Where can I run my new trial so that it doesn’toverlap with a center’s other trials? • Centers • How can we disseminate information to increase and/or expedite patient accrual?

5. Charter & Mission of the ASPIRE Subcommittee • Charter: • To serve as a subgroup of the CDISC Protocol Representation Committee, charged with developing proposed standardized method(s)of encoding protocol eligibility criteria, using accepted medical terminology and vocabulary standards • Mission: • To facilitate more rapid efficient screening of potential participants for available clinical trials worldwide, to help speed the discovery of new interventions to treat, prevent or screen for disease among patients, and to serve as the underpinning for various technical implementations to facilitate subject screening and recruitment

6. Key Deliverable: Pan-Disease and Disease-Specific Coded Core Eligibility Criteria • Agreement upon a core set of standardized eligibility codes, pan-disease and disease-specific, that cut across many studies • Not an attempt to fully code or automate full inclusion/exclusion criteria for protocols • Augments protocol registration data • Facilitates disease-specific coded searches to “filter” available protocols based on patient’s presenting characteristics

7. Sample Use Case: City of Hope Breast Cancer-Specific Protocol Search Filter

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12. Pros/Cons of Disease-Specific Coded Core Eligibility Criteria • Advantages: • Facile / practical to code new protocols; becomes part of electronic instantiation of protocol • Rapidly enhances patient/provider capability to identify potential trials while eliminating inappropriate studies, or data mining to ID patients (cast wide net, avoid “false negatives”) • Disadvantages: • Doesn’t automatically match patient to protocol (very difficult to achieve, timing of tests, experimental tests, etc.) • Requires much work to cover many diseases

13. Activities to Date and Future • To Date: • Submitted as official sub-project with HL7 RCRIM • Held numerous conference calls to discuss core eligiblity criteria • Completed pan-disease criteria, and disease-specific criteria for breast cancer and diabetes • Vetted twice with CDISC Protocol Representation Group • Harmonized with WHO registry elements, STDM, CDASH Pkg. 2 (and BRIDG in future)

14. Activities to Date and Future • Future: • Tackling pediatric hypertension as next disease (per CDISC pilot) • Joining HL7/OMG Clinical Research Filtered Query project to provide sample use case to exercise the filter message • Conducting an evaluation plan using breast cancer criteria: • Propose to code all breast cancer trials in PDQ for core eligibility • Requesting permission to utilize NCCN database of >30,000 coded breast cancer patients from last 10 years • Apply filter algorithm to “match” patients to open protocols and determine yield • Follow with “bootstrapping” technique to drop out one criterion at a timeand reevaluate protocol match yield

15. Form B Form C 3 Tiers of Clinical Trial Objects ProtocolRegistered Higher RiskProtocol Available for Accrual Available for Accrual ProtocolTier: ConceptApproved Consentmodification N – 1slots Available Registration Conditions met,N slots available Suggestedfor Protocol PatientRegistered FullyEligible Consented RXHeld Study ConductTier: On-Study …. Treatment & Monitoring AE Eligibility Screening ConsentingProcesses AccessioningProcesses Eligibility Filtering Data Tier: ConsentForm SAEReport Eligibility Checklist Form A City of Hope

16. Questions/Discussion