Analysis of HIV Trials
cBIO Driving Biological Project
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
Outline
• Background
• Trial Bank Project
• DBP Goals
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)
»
»
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
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
Outline
• Background
• Trial Bank Project
• DBP Goals
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
Bank-a-Trial
RCT Presenter
RCT Bank
(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
Bank-a-Trial Demo
• http://rctbank.ucsf.edu/BaT/
Copyright 2006, Ida Sim
Outline
• Background
• Trial Bank Project
• DBP Goals
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
Interventions
XRT and tamoxifen
Outcomes
5 year survival
1 year local recurrence
Stage III
Breast CA
tamoxifen only
5 year local recurrence
5 year metastatic dissemination
XRT only
5 year quality of life
Copyright 2006, Ida Sim
Visualization (cont.)
Bank-a-Trial
MTCT/STI trials
Core 2
Core 1
Visualization meta-model
Degree of Interest model
Interventions
XRT and tamoxifen
RCT Bank
WHO/
CDISC XML
Outcomes
5 year
survival
1 year local
recurrence
OBD
• interventions
• conditions
• outcomes
• number of participants
Stage III
Breast CA
tamoxifen only
5 year local
recurrence
5 year metastatic
dissemination
XRT only
5 year quality of life
Visualizations!
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
Bank-a-Trial
Core 1
Visualization meta-model
Degree of Interest model
Core 2
STI trials
Interventions
XRT and tamoxifen
RCT Bank
WHO/
CDISC XML
1 year local
recurrence
OBD
UMLS
LexGrid
SNOMED
EHR
Outcomes
5 year
survival
Stage III
Breast CA
tamoxifen only
5 year metastatic
dissemination
XRT only
Applicability
Engine
5 year local
recurrence
5 year quality of life
Visualizations!
Presenter
Core 1
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
Bank-a-Trial
STI trials
Core 2?
Meta-analysis
Core 2
Interventions
XRT and tamoxifen
RCT Bank
WHO/
CDISC XML
1 year local
recurrence
OBD
UMLS
LexGrid
SNOMED
EHR
Stage III
Breast CA
tamoxifen only
Applicability
Engine
5 year local
recurrence
5 year metastatic
dissemination
XRT only
Core 1
Outcomes
5 year
survival
5 year quality of life
Visualizations!
Presenter
Core 1
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, metaanalysis
Copyright 2006, Ida Sim
Questions
• To group
Copyright 2006, Ida Sim