bayesian clinical trials: software and logistics
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Bayesian Clinical Trials:
Software and Logistics
John D. Cook, PhD
Head of Software Development
M. D. Anderson Cancer Center
Division of Quantitative Sciences
JSM 2007
Software developers
• Hoang Nguyen
• Kyle Wathen
• Leiko Wooten
• Clift Norris
• Odis Wooten
• John Cook
Outline
• Software for designing trials
• Software for running trials
Software for designing trials
Basic utilities Safety monitoring
Randomized trials Dose finding
Parameter Solver
• Solve from quantiles or mean & variance
• May also enter parameters
• Self-validating
• Graphics options
Parameter solver
Inequality Calculator
• Included inside several other applications
• Supports common distributions
• Allows a slippage term
• Customizable plots of density function
• Can specify parameters via
ParameterSolver tool
Inequality calculator
Multc Lean
• Original software Multc99, developed by
Hsi-Guang Sun
• Greatly simplified, added Windows UI
• Well-tested
• Added trial duration simulation
Multc Lean
TTEDesigner and TTEConduct
• Safety monitoring for single-arm trials withtime-to-event outcomes
• Doesn’t artificially dichotomize data
• Takes advantage of partial information
• Very robust
TTEDesigner and TTEConduct
TTE Stopping boundaries
Stop for futility:
Predictive Probability
• Supports binary and time-to-event outcomes
• What is likely to happen given what has
happened? Predictive probability
• Three decisions: A, B, neither
• If P(neither) is large, stop for futility
• See PP tutorial on download site
Predictive Probability
Adaptive Randomization
• Supports binary and TTE outcomes
• Up to 10 arms
• Support for covariates in development
• Separate software for conduct
Adaptive Randomization
CRMSimulator
• Emphasis on ease-of-use, not generality
• Contains features commonly used at MDACC, and no more
CRMSimulator
EffTox dose-finding
• Minimize toxicity, maximize efficacy
• Investigator specifies trade-off
• Uses twice as much data per patient
• Uses dose values, not just dose order
EffTox dose-finding
Trial conduct software design
• Store data on server, not on desktops
• Maintain audit trail
• Organize by protocol, not statistical method
• Hide statistical detail from nurses
• Expose statistical detail to statisticians
• Label doses with dimensional units, not ordinal numbers
• Design for sporadic use
Complications
• Nurses can change jobs during a trial
• Patients can withdraw from trial
• Patients can be discovered to be ineligible after being treated
• Trials may be redesigned mid-stream
• Cohorts can be complicated
• Nurses will forget to update data
• Researchers may question software output
MDACC trial conduct software
• Multc Lean requires no software
• Simple TTE requires no software
• TTE (Weibull with covariates)
• CRM dose-finding
• EffTox dose-finding to be added
• Pocock-Simon
• Adaptive Randomization (including covariates)
Resources
• http://biostatistics.mdanderson.org/SoftwareDownload/
• Watch RSS feed for news
• http://www.johndcook.com
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