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From Bench to Bedside:From Bench to Bedside:Applications to Drug Discovery and Applications to Drug Discovery and
Development Development
Eric Neumann W3C HCLSIG co-chair Teranode Corporation
HCLSIG F2F
Cambridge MA
KnowledgeKnowledge
““--is the human capacity (both --is the human capacity (both potential and actual) to take potential and actual) to take effectiveeffective action in varied and action in varied and uncertain situations.uncertain situations.””
Drug Innovation and the Technology GapDrug Innovation and the Technology Gap
Need to utilize Knowledge more
effectively
New Regulatory Issues New Regulatory Issues Confronting PharmaceuticalsConfronting Pharmaceuticals
from Innovation or Stagnation, FDA Report March 2004
Tox/EfficacyADME Optim
Translational MedicineTranslational Medicine
Enable physicians to more effectively translatetranslate relevant findings and hypotheses into therapies for human health
Support the blendingblending of huge volumes of clinical research and phenotypic data with genomic research data
Apply that knowledgeknowledge to patients and finally make individualized, preventative medicine a reality for diseases that have a genetic basis
Role of Informatics Role of Informatics
John Glaser, CIO Partners Healthcare Providing high quality and efficient health care isn't
possible anymore without a sophisticated marriage of information technology and state-of-the-art science.
Bringing these together to inform patient care is a tremendous undertaking… the full array of new information provided by genomic research must be harnessed and made real for doctors and patients
A Framework for conducting clinical research in and across large multidisciplinary academic medical centers is designed to establish a "new" biomedicine to "fully exploits the fruit of the genomic revolution for clinical practice and allows clinical care to be leveraged to advance basic biological research.
Challenges for Drug D&DChallenges for Drug D&D
Counteracting the legacy of “Silos” How to break away from the DD “conveyor belt
model” to the “Translation model” – gaining and sharing insights throughout the
process The Benefit of New Targets for New Diseases
How to best identify safety and efficacy issues early on, so that cost and failure are reduced
A D3 Knowledge-base: Drugability and Safety
Drug Discovery & Development KnowledgeDrug Discovery & Development Knowledge
Qualified Targets
Lead Generation
Toxicity & Safety
Biomarkers
PharmacogenomicsClinical Trials
Molecular Mechanisms
Lead Optimization
KD
Drug Discovery & Development KnowledgeDrug Discovery & Development Knowledge
Qualified Targets
Lead Generation Toxicity &
Safety
Biomarkers
Pharmacogenomics
Clinical Trials
Molecular Mechanisms
Lead Optimization
Launch
Communities and InteroperabilityCommunities and Interoperability
Semantic interoperability is directly tied to CoP:“Within a community or domain, relative homogeneity reduces interoperability challenges. Heterogeneity increases as one moves outside of a focal community/domain, and interoperability is likely [to be] more costly and difficult to achieve” Moen, 2001
Meanings encoded in a schema are usually useful for only one (original) community - difficult to extend to others!
Database utility more difficult if group is heterogeneous
Multiple Ontologies Used TogetherMultiple Ontologies Used Together
Drug targetontologyFOAF
Patentontology
OMIM
Person
Group
Chemicalentity
Disease
SNP
BioPAX
UniProt
Extant ontologies
Protein
Under development
Bridge concept
UMLS
DiseasePolymorphisms
PubChem
Potential Linked Clinical OntologiesPotential Linked Clinical Ontologies
Clinical Trialsontology
RCRIM(HL7)
Genomics
CDISC
IRB
Applications
Molecules
Clinical Obs
ICD10
Pathways(BioPAX)
DiseaseModels
Extant ontologies
Mechanisms
Under development
Bridge concept
SNOMED
DiseaseDescriptions
Tox
Drug Safety KnowledgeDrug Safety Knowledge
Human Hepato-Toxicity Study
Toxicity Indication
Hepato-Toxicity Lens
• Genomic Profile Standards set by Regulatory Agencies
• To be part of NDA (New Drug Applications)
•How will Reviewers be empowered to handle such large amaount sof new data?
CDISC and the Semantic Web?CDISC and the Semantic Web?
Reduce the need to write data parsers to any CDISC XML Schema
Make use of ontologies and terminologies directly using RDF
Easier inclusion of Genomic data
Use Semantic Lenses for Reviewers
Easier acceptance by industry with their current technologies
QuickTime™ and aTIFF (LZW) decompressor
are needed to see this picture.
Developing StandardsDeveloping Standards
Design Implementation
Semantic Web-basedSpecifications
Exchange
Support Full Information IntegrationSupport Full Information Integration
Integration: integrate and manage data from sources, EDC systems, Clinical Data Management Systems , labs and CROs
Analysis and reporting: Accurately and timely analytical reports from study data, for use in decision making; easier results sharing with researchers and reviewers
Discovery: Use expanding research information as a knowledge base for rapid investigations into critical drug safety issues, new marketing claims, and identify product-line extensions.
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