copyright 2006, ida sim ida sim, md, phd associate professor of medicine associate director for...
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Copyright 2006, Ida Sim
Ida Sim, MD, PhDAssociate Professor of Medicine
Associate Director for Medical InformaticsProgram in Biological and Medical Informatics
University of California, San Francisco, CA
R01-LM-06780
Analysis of HIV TrialscBIO Driving Biological Project
Copyright 2006, Ida Sim
Domain Problem• Want to advance clinical science and practice evidence-based
medicine » based on results from scientific experiments, e.g., from
randomized controlled trials (RCTs)
» randomization equalizes known and unknown confounders between intervention arms
» any observed differences in outcome should be due only to the intervention
Drug A
Placebo
Death at 1 year
Death at 1 year
Copyright 2006, Ida Sim
HIV Trials
• 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
Need Computational KBs of RCTs• 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
Trial Bank Software• 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
RCT Bank
Bank-a-Trial RCT Presenter
(SecurePresenter)
Copyright 2006, Ida Sim
Ontology: RCT Schema• 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 Demo
• RCT Presenter is open access» http://rctbank.ucsf.edu/Presenter/
Copyright 2006, Ida Sim
DBP Goals
• 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
Goal 1: Visualization
Stage IIIBreast CA
XRT and tamoxifen
XRT only
tamoxifen only
5 year survival
1 year local recurrence
5 year local recurrence
5 year metastatic dissemination
5 year quality of life
OutcomesInterventions
Copyright 2006, Ida Sim
Visualization (cont.)
RCT Bank OBD
• interventions• conditions• outcomes• number of participants
Visualizations!
Visualization meta-modelDegree of Interest model
Core 2
Core 1Bank-a-Trial
MTCT/STI trials
WHO/CDISC XML
Stage IIIBreast CA
XRT and tamoxifen
XRT only
tamoxifen only
5 year survival
1 year local recurrence
5 year local recurrence
5 year metastatic dissemination
5 year quality of life
OutcomesInterventions
Presenter
Copyright 2006, Ida Sim
Goal 2: Identifying Applicable Trials
• 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
Identifying Applicable Trials
RCT Bank OBD
Visualizations!
Visualization meta-modelDegree of Interest model
Core 2
Core 1Bank-a-Trial
STI trials
WHO/CDISC XML
Stage IIIBreast CA
XRT and tamoxifen
XRT only
tamoxifen only
5 year survival
1 year local recurrence
5 year local recurrence
5 year metastatic dissemination
5 year quality of life
OutcomesInterventions
EHR
LexGrid
UMLS
SNOMED
Applicability Engine
Core 1
Presenter
Copyright 2006, Ida Sim
Goal 3: Meta-Analysis
• Given set of related trials, use statistical routines» explore statistical heterogeneity» perform quantitative meta-analysis
Copyright 2006, Ida Sim
Meta-Analysis
RCT Bank OBD
Visualizations!
Core 2
Core 1
Bank-a-Trial
STI trials
WHO/CDISC XML
Stage IIIBreast CA
XRT and tamoxifen
XRT only
tamoxifen only
5 year survival
1 year local recurrence
5 year local recurrence
5 year metastatic dissemination
5 year quality of life
OutcomesInterventions
EHR
LexGrid
UMLS
SNOMED
Applicability Engine
Core 1
Presenter
Meta-analysis
Core 2?
Copyright 2006, Ida Sim
RCT Reference Ontology?
• 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
Timelines
• Dec 2006» Visualization
• Year 2-3» applicability» meta-analysis» moving towards OBO
Copyright 2006, Ida Sim
Summary
• 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, meta-
analysis