W3C HCLS Task Force on Drug Safety and Efficacy Kerstin Forsberg, Bo Anderson - AstraZeneca Jim McGurk - Merck Ted Slater - Pfizer Eric Neumann - Teranode Uwe Trinks - Sentrx

Focus Areas Translational Science Perspective Subject State Thinking (biomarkers) Safety dimensions Efficacy (disease models) Animal  Human (CDISC’s SEND, SDTM/ODM) Clinical Observations and their relation to biomarkers (+ mechanisms) and pharmacogenomics Connecting back to Discovery Targets Biomarkers Therapeutic Knowledge Leads, Candidates selection Mechanisms of Action BioPAX… 8 April 2019 Internal Information

Domain Semantics Clinical Semantics Patient/Subject  Disease state Diagnostics  Findings Findings  Inferred (proposed) Disease state Disease state  Patient Classification / Segmentation Design  Clinical trial arm / treatment Observation  POC, safety, mechanism 8 April 2019 Internal Information

“Protocol” and the Semiotic Triangle Doug Fridsma (U Pitt) “We need to sign off on the protocol by Friday” Concept 1 Thing 1 Document Study “Protocol XYZ has enrolled 73 patients” Thing 2 Concept 2 Symbol “Protocol” “Per the protocol, you must be at least 18 to be enrolled” Concept 3 Thing 3 Plan 8 April 2019 Internal Information Source: John Speakman/Charlie Mead

July 2004 Announcement of CDISC/SDTM as a standard format CDISC Clinical Data Interchange Standards Consortium RCRIM Regulated Clinical Research and Information Management, technical committee Relationship HL7/CDISC HL7 “Health Level Seven” 8 April 2019 Internal Information

During 2006-2007 Relationship HL7/CDISC SDTM variables as Common Data Elements & Controlled Terminologies In OWL format NCI Thesaurus CDISC Clinical Data Interchange Standards Consortium UMLS RCRIM Regulated Clinical Research and Information Management, technical committee Relationship HL7/CDISC BRIDG Biomedical Research Integrated Domain Group Model HL7 “Health Level Seven” 8 April 2019 Internal Information

Ongoing work at FDA Announcement of CDISC/SDTM as a standard format CDISC Clinical Data Interchange Standards Consortium RCRIM Regulated Clinical Research and Information Management, technical committee Relationship HL7/CDISC "The FDA has the largest pool of randomized clinical trial data in the world, but it cannot be analyzed now because it is inaccessible" Dr. Janet Woodcock, Deputy Commissioner for Operations and Chief Operating Officer, FDA 27 January 2006 Janus Model and Data Warehouse HL7 “Health Level Seven” “… populate a cross-study database and do more comprehensive analyses for the benefit of patients.” 8 April 2019 Internal Information

FDA’s JANUS Full Model one visual representation 8 April 2019 Internal Information

Proposed Notes and Activities Notes planned SDTM and JANUS from a SW perspective Semantic enriched evolvable recombinant clinical observations DEMO: Table and XML models ala RDF Retrospective DBs (JANUS) and SW + power of annotations and links DEMO: using URI code and RDBM Provenance and trust (non-reputability) ACL? 8 April 2019 Internal Information