From Bench to Bedside: Applications to Drug Discovery and Development

1
From Bench to BedsideApplications to Drug
Discovery and Development

• Eric Neumann W3C HCLSIG co-chair Teranode
  Corporation
• HCLSIG F2F
• Cambridge MA

2
Knowledge--is the human capacity (both
potential and actual) to take effective action in
varied and uncertain situations.
3
Drug Innovation and the Technology Gap
4

Drug RD Trends
from Innovation or Stagnation, FDA Report March
2004
5
from Innovation or Stagnation, FDA Report March
2004
6
New Regulatory Issues Confronting Pharmaceuticals
ADME Optim
from Innovation or Stagnation, FDA Report March
2004
7
Translational Medicine

• Enable physicians to more effectively translate
  relevant findings and hypotheses into therapies
  for human health
• Support the blending of huge volumes of clinical
  research and phenotypic data with genomic
  research data
• Apply that knowledge to patients and finally make
  individualized, preventative medicine a reality
  for diseases that have a genetic basis

8
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.

9
Challenges for Drug DD

• 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

10
Drug Discovery Development Knowledge
KD
11
Drug Discovery Development Knowledge
Qualified Targets
Molecular Mechanisms
Lead Generation
Toxicity Safety
Lead Optimization
Pharmacogenomics
Biomarkers
Clinical Trials
Launch
12
Communities 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

13
Multiple Ontologies Used Together
UMLS
OMIM
SNP
Drug target ontology
FOAF
UniProt
BioPAX
PubChem
Patent ontology
Extant ontologies
Under development
Bridge concept
14
Potential Linked Clinical Ontologies
SNOMED
CDISC
ICD10
Clinical Trials ontology
RCRIM (HL7)
Disease Models
Pathways(BioPAX)
Tox
Genomics
Extant ontologies
Under development
Bridge concept
15
Drug Safety Knowledge

• 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?

Human Hepato-Toxicity Study
Hepato-Toxicity Lens
16
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

17
Developing Standards
Exchange
Design
Implementation
18
Developing Standards
Design
Implementation
Exchange
19
Support 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.

20
Thank You
21
(No Transcript)