• HCLSIG
• Drug Safety and Efficacy

Task Force on Drug Safety and Efficacy

Mission

This HCLSIG task force focuses on the topic of “applying semantics to R&D Informatics efforts in support Drug Safety and Efficacy” within clinial trials, as well as post-market surveillance. We also intend to demonstrate how Semantic Web standards can be applied to issues related to these in the near-term. Specifically, the task force focuses on the following areas for scenarios and activities:

• Identify/address challenges and needs regarding Biomarkers and Pharmacogenomics in coordination with FDA guidelines
• Semantic applications around Drug Safety: Signals and Notification
• Possible applications of Semantic Web in Clinical Trial planning, management, analysis, and reporting (e.g., EDC and EHR Single-Source, data security, integrity)

• Facilitating electronic submissions as per the Common Technical Document (eCTD) specifications, http://www.fda.gov/cder/guidance/7087rev.htm )

(For non-experts, see the separate Glossary page)

Task Objectives

This task force has the following objectives and deliverables:

1. Develop and document Scenarios for some of the above identified areas
2. Identify and validate some initial Best Practices for handling safety and efficacy information through semantics, which incorporate current vocabulary conventions

3. Create one or more public Semantic Web-based Demonstrations (see Clinical Trial Demo)

4. Coordination and collaboration with relevant organizations, possibly CDISC, ICH, HL7-RCRIM, EMEA, FDA, NCI-caBIG

Rationale

The use of information to improve the development of Efficacious and Safe Drugs rests on the proper and timely utilization of diverse information sets, and the adoption and compliance of well-defined policies. As information becomes more diverse and policies more central to the pharmaceutical industry, the development of information systems that are better suited to handle multiple information types (data and ontologies) while complying with defined policies (rules and actions) will become essential. Semantic Web technology standards offer potential solutions for:

• Aggregating Study Datasets, around Biomarkers (and following eCTD guidelines)
• Enhancing management of non-clinical and clinical controlled vocabularies that will be certainly expanding and evolving (adaptability)
• Providing fast access to current safety information though semantic-enabled channels (Pharmacovigilance)
• Applying Rules, Integrity, and Security in support of policy compliance and management (HIPAA, CFR21Part11 and Sarbanes-Oxley)

Scope

• Pre-Clinical and Clinical Information Management
• Support for Translational Medicine
• Definition and use of all foms of Biomarkers and Pharmacogenomic Diagnostics
• Modes of representing and relaying information between clinical centers, sponsors, regulatory agencies, and CRO's

Active Participants

1. eneumann@teranode.com Eric Neumann (Teranode)

2. ted.slater@pfizer.com Ted Slater (Pfizer)

3. jmcgurk@daiichisankyo-us.com Jim McGurk (Daiichi Sankyo)

4. Bo.H.Andersson@astrazeneca.com Bo Andersson (AstraZeneca)

5. Kerstin.L.Forsberg@astrazeneca.com Kerstin Forsberg (AstraZeneca)

6. Stephen.Dobson@pfizer.com Stephen Dobson (Pfizer)

Proposed Focus Activities

• Biomarkers and Pharmacogenomics Capture, Analysis, and Document Prep -- inline with FDA proposed guidelines (EricN)

• Scenario and Task Activtity for Converting CDISC's SDTM into an RDF based model -- to be demo'ed to CDISC/RCRIM (EricN)

• Identification and selection of basic UI technology for RDF based clinical trials data (see: Clinical Trial demo)

Current Activities

• Amsterdam F2F workspace

• Clinical Trial Demo

Use case context

The Study Data Tabulation Model (SDTM) is used to define the study components in terms of domains and observations for a given clinical trial study. However, the ability to use it for sets of biomarkers that serve to define surrogate endpoints and/or evidence ofd mechanism is not currently possible. We intend to propose an augmented SDTM model using RDF-OWL that will support the inclusion of biomarker data from subjects, associated with known mechanisms and endpoint descriptors.

Problem statement for this use case

SDTM needs to be extended using a flexible mode to incorporate key elements of translation medicine.

Working Drafts

• SDTM Notes Draft 1.0

• SDTM-RDF 'sandbox' example in N3

• Genetic Diagnostic Clinical Trial Scenario

Deliverables

1. (F2F defined) STDM Table and XML models using RDF (early 2007)
2. (F2F defined) Retrospective DB (ala JANUS) with annotations and cross-references

Minutes

• 2007-3-23 Minutes

• 2007-3-2 Minutes

• 2007-2-9 Minutes

• 2007-1-12 Minutes

• 2006-12-15 Minutes

• 2006-12-1 Minutes

• 2006-11-17 Minutes

• 2006-11-3 Minutes

• 2006-9-15 Minutes

Related resources

• Clinical Trial Demo using Exhibit

• Demog, vitals, adverse treatment EXHIBIT files Stephen Dobson

• dummy data SDTM format Stephen Dobson

• dummy data Stephen Dobson

• VALID genomic biomarkers - Stephen Dobson

• John Senior - Liver Injury (potential biomarkers) Stephen Dobson

• CDISC SDTM and related initiatives - Kerstin Forsberg, Astra-Zeneca

• DSE Scenario Space (Amsterdam)

• Slides from Amsterdam F2F

• Case Report Tabulation Data Definition Specification - CDISC doc

• CDISC-SDTM Overview - Kerstin

• CDISC-SDTM Basics - Kerstin

• Reserved SDTM Codes

• CDISC-PG-Domain-V4

• CDISC-PG-Testdata Findings

• CDISC VSTEST Names

• Workshop on Clinical Trial Ontology

• From XML to RDF: how semantic web technologies may change the design of clinical standards?

Task supports and dependencies

• F2F Action Items

Tools and Services

• Viewing of clinical data using RDF-aware technologies, e.g. Tabulator

Timeline for Task Completion

• Stage 1 (3 month goals)
  • Notes on adapting SDTM model for the Semantic Web
  • Defining a Semantic Web based annotations model for JANUS
• Stage 2 (6 months goals)
  • Demonstration of adapted SDTM model

  • Definition of a GUI model that matches most CDM expectations while showing the advantages of Semantic Web structures Clinical Trial Demo using Exhibit