Copyright 2006, Ida Sim Ida Sim, MD, PhD Associate Professor of Medicine Associate Director for Medical Informatics Program in Biological and Medical Informatics

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


Outline

• Background

• Trial Bank Project

• DBP Goals


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


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


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


Outline

• Background


• DBP Goals


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)


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/


RCT Presenter Demo

• RCT Presenter is open access» http://rctbank.ucsf.edu/Presenter/


Bank-a-Trial Demo

• http://rctbank.ucsf.edu/BaT/


Outline

• Background


• DBP Goals


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


Goal 1: Visualization

Stage IIIBreast CA

XRT and tamoxifen

XRT only

tamoxifen only

5 year survival

1 year local recurrence


5 year metastatic dissemination

5 year quality of life

OutcomesInterventions


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






Presenter


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


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






EHR

LexGrid

UMLS

SNOMED

Applicability Engine

Core 1

Presenter


Goal 3: Meta-Analysis

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


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






EHR

LexGrid

UMLS

SNOMED

Applicability Engine

Core 1

Presenter

Meta-analysis

Core 2?


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”


Timelines

• Dec 2006» Visualization

• Year 2-3» applicability» meta-analysis» moving towards OBO


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


Questions

• To group

Documents

Copyright 2006, Ida Sim Ida Sim, MD, PhD Associate Professor of Medicine Associate Director for Medical Informatics Program in Biological and Medical Informatics