cLRT‐Mod : An efficient methodology for pharmacometric model‐based analysis of longitudinal phase II dose finding studies under model uncertainty

2021 ◽  
Author(s):  
Simon Buatois ◽  
Sebastian Ueckert ◽  
Nicolas Frey ◽  
Sylvie Retout ◽  
France Mentré
Keyword(s):  
Phase Ii ◽  
Model Uncertainty ◽  
Dose Finding ◽  
Model Based ◽  
Longitudinal Phase ◽  
Model Based Analysis

Model-Based Bayesian Adaptive Dose-Finding Designs for a Phase II Trial

2011 ◽  
Vol 3 (2) ◽  
pp. 276-287 ◽  
Author(s):  
Byron Jones ◽  
Gary Layton ◽  
Helen Richardson ◽  
Neal Thomas
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Dose Finding ◽  
Model Based

scholarly journals TRAFIC: Statistical Plan for a Pragmatic Early Phase 1/2 Bayesian Adaptive Dose Escalation Trial in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Michael Cole ◽  
Christina Yap ◽  
Christopher Buckley ◽  
Wan-Fai Ng ◽  
Iain McInnes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Decision Making ◽  
Phase I ◽  
Phase Ii ◽  
Early Phase ◽  
Phase I Trial ◽  
Dose Finding ◽  
Model Parameters ◽  
Model Based ◽  
Transition Pathways

Abstract Background: Adaptive model-based dose-finding designs have demonstrated advantages over traditional rule-based designs but have increased statistical complexity resulting in slow uptake especially outside of cancer trials. TRAFIC is a multi-centre, early phase trial in Rheumatoid Arthritis incorporating a model-based design.Methods: A Bayesian adaptive dose-finding phase I trial rolling into a single arm, single stage phase II trial. Model parameters for phase I were chosen via Monte Carlo simulation evaluating objective performance measures under clinically relevant scenarios and incorporated stopping rules for early termination. Potential designs were further calibrated utilising dose transition pathways.Discussion: TRAFIC is an MRC funded trial of a re-purposed treatment demonstrating that it is possible to design, fund and implement a model-based phase I trial in a non-cancer population within conventional research funding tracks and regulatory constraints. The phase I design allows borrowing of information from previous trials; all accumulated data to be utilised in decision-making; verification of operating characteristics through simulation; improved understanding for management and oversight teams through dose transition pathways. The rolling phase II design brings efficiencies in trial conduct including site and monitoring activities, and cost.TRAFIC is the first funded model-based dose-finding trial in inflammatory disease demonstrating that small phase I/II trials can have an underlying statistical basis for decision-making and interpretation.Trial Registration: ISRCTN 36667085

scholarly journals Model-based dose finding under model uncertainty using general parametric models

2013 ◽  
Vol 33 (10) ◽  
pp. 1646-1661 ◽  
Author(s):  
José Pinheiro ◽  
Björn Bornkamp ◽  
Ekkehard Glimm ◽  
Frank Bretz
Keyword(s):  
Model Uncertainty ◽  
Parametric Models ◽  
Dose Finding ◽  
Model Based

scholarly journals TRAFIC: statistical design and analysis plan for a pragmatic early phase 1/2 Bayesian adaptive dose escalation trial in rheumatoid arthritis

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
M. Cole ◽  
C. Yap ◽  
C. Buckley ◽  
W. F. Ng ◽  
I. McInnes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Decision Making ◽  
Phase I ◽  
Phase Ii ◽  
Early Phase ◽  
Phase I Trial ◽  
Dose Finding ◽  
Model Parameters ◽  
Model Based ◽  
Transition Pathways

Abstract Background Adaptive model-based dose-finding designs have demonstrated advantages over traditional rule-based designs but have increased statistical complexity but uptake has been slow especially outside of cancer trials. TRAFIC is a multi-centre, early phase trial in rheumatoid arthritis incorporating a model-based design. Methods A Bayesian adaptive dose-finding phase I trial rolling into a single-arm, single-stage phase II trial. Model parameters for phase I were chosen via Monte Carlo simulation evaluating objective performance measures under clinically relevant scenarios and incorporated stopping rules for early termination. Potential designs were further calibrated utilising dose transition pathways. Discussion TRAFIC is an MRC-funded trial of a re-purposed treatment demonstrating that it is possible to design, fund and implement a model-based phase I trial in a non-cancer population within conventional research funding tracks and regulatory constraints. The phase I design allows borrowing of information from previous trials, all accumulated data to be utilised in decision-making, verification of operating characteristics through simulation, improved understanding for management and oversight teams through dose transition pathways. The rolling phase II design brings efficiencies in trial conduct including site and monitoring activities and cost. TRAFIC is the first funded model-based dose-finding trial in inflammatory disease demonstrating that small phase I/II trials can have an underlying statistical basis for decision-making and interpretation. Trial registration Trials Registration: ISRCTN, ISRCTN36667085. Registered on September 26, 2014.

Model based analysis and control of a cementation process

1997 ◽  
Vol 21 (1-2) ◽  
pp. S1099-S1103 ◽  
Author(s):  
K Stole-Hansen
Keyword(s):  
Model Based ◽  
And Control ◽  
Model Based Analysis

MODEL-BASED ANALYSIS OF EFFECTIVENESS OF ENGINEERING SOLUTIONS DESIGNED TO INCREASE COOLING CAPACITY OF TASHLYK WATER RESERVOIR OF SOUTHUKRAINIAN NUCLEAR POWER PLANT

2012 ◽  
Vol 13 (1-4) ◽  
pp. 39-51
Author(s):  
Roman V. Bezhenar ◽  
Volodymyr I. Koshebutsky ◽  
Ivan V. Kovalets ◽  
Vladimir S. Maderich ◽  
Mark J. Zheleznyak
Keyword(s):  
Power Plant ◽  
Nuclear Power Plant ◽  
Nuclear Power ◽  
Water Reservoir ◽  
Cooling Capacity ◽  
Model Based ◽  
Model Based Analysis

Model-Based Analysis of Biological Tissue Heating by Point Ultrasound Sources

2010 ◽  
Vol 42 (2) ◽  
pp. 44-50
Author(s):  
Sergey I. Lyashko ◽  
Dmitriy A. Klyushin ◽  
V. V. Pavlychko
Keyword(s):  
Biological Tissue ◽  
Model Based ◽  
Tissue Heating ◽  
Model Based Analysis
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