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

Drug R&D TrendsDrug R&D Trends

from Innovation or Stagnation, FDA Report March 2004

from Innovation or Stagnation, FDA Report March 2004

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

Exchange

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.

Thank YouThank You