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The primary efficacy analysis will assess average treatment group differences for the primary outcome measure (MADRS) over the entire study period and use a likelihood based mixed-effects model, repeated measures (MMRM) approach at each time point.
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This method first estimates the generation time distribution using a likelihood based method.
We used a likelihood based approach to determine evolutionary relationships of the N. vectensis NRs with bilaterian NRs.
This is a standard approach in the context of meta-analysis [ 10] and by using a likelihood based approach we can easily fit models with the flexible variance structure we require.
For example, purifying selection on synonymous sites was found in 9.4% of all yeast genes and 5.1% in all worm genes using a likelihood based model that distinguishes between synonymous substitutions between preferred and unpreferred codons [ 12].
The use of a likelihood based on the L1-norm derived from biological replicate data makes fewer assumptions than a Gaussian error model (Johnson et al., 2014; Vyshemirsky and Girolami, 2008), and is less computationally complex than a transitional likelihood function derived from reaction propensities (Aitken and Akman, 2013; Heron et al., 2007).
Mixed-effects models use a likelihood-based approach to estimation and therefore made use of all available data without directly imputing missing outcome values.
We use a likelihood-based phylogeographic history estimation method (Phylomapper [ 32]) to test hypotheses of the geographic location of the origins of clades.
The primary analysis method will use a likelihood-based mixed model, which accommodates incomplete observations and operates under the assumption that the missing data is missing at random (MAR).
An alternative for rooting without an outgroup is to use a likelihood-based approach with a nonreversible transition state matrix (Barry and Hartigan 1987a , 1987; Ferretti et al. 1994; Hendy and Penny 1996; Evans and Zhou 1998).
A strength of this study is that the results are a synthesis of 5 models and use a likelihood-based approach, in which the models are weighted according to their ability to fit the sentinel data.
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