Bayesian model averaging of longitudinal dose-response models
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作者:
Payne, Richard D.
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机构:
Eli Lilly & Co, Global Stat Sci, Indianapolis, IN USA
Lilly Corp Ctr, Global Stat Sci, Indianapolis, IN 46285 USAEli Lilly & Co, Global Stat Sci, Indianapolis, IN USA
Payne, Richard D.
[1
,3
]
Ray, Pallavi
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机构:
Eli Lilly & Co, Global Stat Sci, Indianapolis, IN USAEli Lilly & Co, Global Stat Sci, Indianapolis, IN USA
Ray, Pallavi
[1
]
Thomann, Mitchell A.
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机构:
Boehringer Ingelheim Pharmaceut Inc, Dept Biostat & Data Sci, Ridgefield, CT USAEli Lilly & Co, Global Stat Sci, Indianapolis, IN USA
Thomann, Mitchell A.
[2
]
机构:
[1] Eli Lilly & Co, Global Stat Sci, Indianapolis, IN USA
[2] Boehringer Ingelheim Pharmaceut Inc, Dept Biostat & Data Sci, Ridgefield, CT USA
[3] Lilly Corp Ctr, Global Stat Sci, Indianapolis, IN 46285 USA
Selecting a safe and clinically beneficial dose can be difficult in drug development. Dose justification often relies on dose-response modeling where parametric assumptions are made in advance which may not adequately fit the data. This is especially problematic in longitudinal dose-response models, where additional parametric assumptions must be made. This paper proposes a class of longitudinal dose-response models to be used in the Bayesian model averaging paradigm which improve trial operating characteristics while maintaining flexibility a priori. A new longitudinal model for non-monotonic longitudinal profiles is proposed. The benefits and trade-offs of the proposed approach are demonstrated through a case study and simulation.