1. Key Foundational Layers Classification, Vocab, Web Stds –Classification Content Model (Taxonomy) –Web Std Tech Requirements W3C, cloud, online, offline Digital Signing - PKI x.509 Business Process model support Export / Import format »(XML, RDF/XML) Core Tech Architecture Discussion

2. Content Model = eTMF Domain Classification –Conceptual model –Supports vocabulary, relationships –Includes core metadata, domain metadata –W3C RDF/XML Data Model = eTMF Instance for a Study –Instance of digital content for a single study –Includes content model in use –Pointers to content resources –W3C XML Content Model and Data Model Content Model Data Model Metadata Study Digital Content eTMF Domain Classification eTMF Instance for Study

3. Ontology’s are used to define conceptual models for a domain –Related Domains using ontology and W3C RDF/XML to define their domain model: CDISC/FDA PhUSE project – Interoperable data standards initiativeCDISC/FDA PhUSE NCI Thesaurus – Published semantic concepts, vocabulary in National Center for BioMedical Ontology (NCBO)NCI Thesaurus HL7 Model Interchange Format — RIM, data types, and HL7 vocabularyHL7 Propose use of ontology and W3C RDF/XML to represent eTMF domain eTMF Content Model can be edited, validated with free open source editor, Protégé eTMF Data Model can be edited, validated with XML editors Proposed use of Ontology for eTMF Domain

4. Data model is used to define an instance of the content model Data model defines a single clinical trial study / archive Contains content model in use, metadata in use, links to content resources Can be used online / offline Supports viewing of data model in web browser Universally exchangeable, interoperable W3C XML format proposed (V1.0 encoding = UTF-8) Proposed eTMF Data Model

5. Use of Semantic technologies for representation of interoperable content models in Health Sciences: – HL7 Semantic Tech: http://www.genomeweb.com/informatics/qa-io-informatics- charles-mead-efforts-adopt-semantic-web-translational-medicine http://www.genomeweb.com/informatics/qa-io-informatics- charles-mead-efforts-adopt-semantic-web-translational-medicine –CDISC / FDA PhUSE: http://www.prweb.com/releases/PhUSECDISC/SemanticTechnology/prweb11065477.htm http://www.prweb.com/releases/PhUSECDISC/SemanticTechnology/prweb11065477.htm –NCI Thesaurus: http://purl.bioontology.org/ontology/NCIT -- CareLex – eTMF Content Model: http://purl.bioontology.org/ontology/CareLex/http://purl.bioontology.org/ontology/CareLex Proposed OASIS eTMF Standard Architecture: –http://carelex.org/downloads/ CareLex Content Model Spec – V1.03http://carelex.org/downloads/ Architecture is outlined in Section 2, Pg 4. Resources - Content Model, Arch