Ida Sim, MD, PhD
Associate Professor of Medicine
Associate Director for Medical Informatics
Program in Biological and Medical Informatics
University of California, San Francisco, CA
R01-LM-06780
Copyright 2006, Ida Sim

• Background
• Trial Bank Project
• DBP Goals
Copyright 2006, Ida Sim

• Want to advance clinical science and practice evidence-based medicine
» based on results from scientific experiments, e.g., from randomized controlled trials (RCTs)
Drug A Death at 1 year
Placebo
Death at 1 year
»
» randomization equalizes known and unknown confounders between intervention arms any observed differences in outcome should be due only to the intervention
Copyright 2006, Ida Sim

• Two controversial areas of HIV with conflicting
RCT evidence
» Prevention of mother-to-child-transmission (MTCT)
» Structured Treatment Interruption
• Very complex heterogenous trials
» need computational support to visualize, analyze, apply these trials
Copyright 2006, Ida Sim

• RCT journal articles not ideal
» key descriptors of experimental method not always reported
» not easily computable
• KB of information on RCT
»
» design execution
» results
• would allow for better computer support for advancing clinical science and practice
Copyright 2006, Ida Sim

• Background
• Trial Bank Project
• DBP Goals
Copyright 2006, Ida Sim

• Bank-a-Trial
» web-based program for entering trials into RCT Bank (annotation)
» clinical descriptions of trial features (slot values) are in UMLS terms
• RCT Presenter
»
» web-based browser of RCT Bank entries
SecurePresenter for browsing restricted-access entries
Bank-a-Trial RCT Presenter
RCT Bank
(SecurePresenter)
Copyright 2006, Ida Sim

• Models clinical trials
» instantiated using UMLS terms to describe clinical concepts
• Frame-based model (in Ocelot)
» 7 levels deep
• 188 frames, 601 unique slots
» average 9.8 slots/frame
» 13 frames (7%) have multiple parents
» 187/601 slots (31%) take other frames as values
• Available at http://rctbank.ucsf.edu/
Copyright 2006, Ida Sim

• RCT Presenter is open access
» http://rctbank.ucsf.edu/Presenter/
Copyright 2006, Ida Sim

• http://rctbank.ucsf.edu/BaT/
Copyright 2006, Ida Sim

• Background
• Trial Bank Project
• DBP Goals
Copyright 2006, Ida Sim

• Trial Bank instances
» visualizing collections of related but heterogenous clinical trial instances
» using sample HIV medical record to select
“applicable” MTCT and STI trials in RCT Bank
» meta-analysis
• RCT Schema
» towards a reference ontology for clinical trials
Copyright 2006, Ida Sim

Interventions
XRT and tamoxifen
Outcomes
5 year survival
1 year local recurrence
Stage III
Breast CA tamoxifen only
5 year local recurrence
XRT only
5 year metastatic dissemination
5 year quality of life
Copyright 2006, Ida Sim

Bank-a-Trial
MTCT/STI trials
Core 1
Core 2
Visualization meta-model
Degree of Interest model
Interventions Outcomes survival
XRT and tamoxifen
1 year local recurrence
RCT Bank
WHO/
CDISC XML
OBD
Stage III
Breast CA tamoxifen only
5 year local recurrence
5 year metastatic dissemination
XRT only
• interventions
• conditions
• outcomes
• number of participants
5 year quality of life
Visualizations!
Presenter
Copyright 2006, Ida Sim

• Use case
»
»
I have an HIV patient, which STI trials are applicable?
– patients in STI trials are “like” this patient want to “drag and drop” EHR onto Trial Bank to pull out applicable trials
» visualize these applicable trials, explore specific details of trials
• Terminological matching required
» sample EHR coded in SNOMED
» RCT Bank trials coded in UMLS
Copyright 2006, Ida Sim

STI trials
Bank-a-Trial
Core 1
Core 2
Visualization meta-model
Degree of Interest model
Interventions Outcomes survival
XRT and tamoxifen
1 year local recurrence
RCT Bank
WHO/
CDISC XML
OBD
Stage III
Breast CA tamoxifen only
5 year local recurrence
5 year metastatic dissemination
UMLS XRT only
5 year quality of life
LexGrid
Applicability
Engine
Visualizations!
SNOMED
EHR
Core 1
Presenter
Copyright 2006, Ida Sim

• Given set of related trials, use statistical routines
» explore statistical heterogeneity
» perform quantitative meta-analysis
Copyright 2006, Ida Sim

Bank-a-Trial
STI trials
Core 2
RCT Bank
UMLS
LexGrid
SNOMED
EHR
WHO/
CDISC XML
OBD
Applicability
Engine
Core 1
Core 2?
Meta-analysis
Stage III
Breast CA
Interventions
XRT and tamoxifen
Outcomes survival tamoxifen only
1 year local recurrence
5 year local recurrence
XRT only
5 year metastatic dissemination
5 year quality of life
Visualizations!
Core 1
Presenter
Copyright 2006, Ida Sim

• Harmonize RCT Schema with CDISC, caBIG,
WHO, etc. through BRIDG (outside cBIO)
• Put into OWL
• Deposit into OBO
• Join the “OBO Collaboratory”
Copyright 2006, Ida Sim

• Dec 2006
» Visualization
• Year 2-3
» applicability
» meta-analysis
» moving towards OBO
Copyright 2006, Ida Sim

• Clinical trials are valuable source of biomedical knowledge
• Trial Bank captures RCTs to support understanding, analyzing, applying RCT evidence
• Drives cBIO on
» Core 1: visualization, terminology mapping,
Ocelot->OWL, RCT reference ontology
» Core 2: OBD, data interchange standard, metaanalysis
Copyright 2006, Ida Sim

• To group
Copyright 2006, Ida Sim