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Model selection and averaging of nonlinear mixed-effect models for robust phase III dose selection

Overview of attention for article published in Journal of Pharmacokinetics and Pharmacodynamics, November 2017
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  • Good Attention Score compared to outputs of the same age and source (66th percentile)

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Citations

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22 Mendeley
Title
Model selection and averaging of nonlinear mixed-effect models for robust phase III dose selection
Published in
Journal of Pharmacokinetics and Pharmacodynamics, November 2017
DOI 10.1007/s10928-017-9550-0
Pubmed ID
Authors

Yasunori Aoki, Daniel Röshammar, Bengt Hamrén, Andrew C. Hooker

Abstract

Population model-based (pharmacometric) approaches are widely used for the analyses of phase IIb clinical trial data to increase the accuracy of the dose selection for phase III clinical trials. On the other hand, if the analysis is based on one selected model, model selection bias can potentially spoil the accuracy of the dose selection process. In this paper, four methods that assume a number of pre-defined model structure candidates, for example a set of dose-response shape functions, and then combine or select those candidate models are introduced. The key hypothesis is that by combining both model structure uncertainty and model parameter uncertainty using these methodologies, we can make a more robust model based dose selection decision at the end of a phase IIb clinical trial. These methods are investigated using realistic simulation studies based on the study protocol of an actual phase IIb trial for an oral asthma drug candidate (AZD1981). Based on the simulation study, it is demonstrated that a bootstrap model selection method properly avoids model selection bias and in most cases increases the accuracy of the end of phase IIb decision. Thus, we recommend using this bootstrap model selection method when conducting population model-based decision-making at the end of phase IIb clinical trials.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 27%
Unspecified 4 18%
Student > Ph. D. Student 4 18%
Professor > Associate Professor 2 9%
Librarian 2 9%
Other 4 18%
Readers by discipline Count As %
Unspecified 7 32%
Pharmacology, Toxicology and Pharmaceutical Science 4 18%
Medicine and Dentistry 4 18%
Mathematics 2 9%
Agricultural and Biological Sciences 2 9%
Other 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 November 2017.
All research outputs
#7,207,846
of 12,134,677 outputs
Outputs from Journal of Pharmacokinetics and Pharmacodynamics
#67
of 146 outputs
Outputs of similar age
#143,476
of 281,183 outputs
Outputs of similar age from Journal of Pharmacokinetics and Pharmacodynamics
#1
of 6 outputs
Altmetric has tracked 12,134,677 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 146 research outputs from this source. They receive a mean Attention Score of 2.1. This one has gotten more attention than average, scoring higher than 52% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 281,183 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them