## Tuesday, 5 February 2013

### The gradient function as an exploratory goodness-of-fit assessment of the random-effects distribution in mixed models

Geert Verbeke and Geert Molenberghs have a new paper in Biostatistics. The paper proposes the use of the gradient function (or equivalently the directional derivatives) of the marginal likelihood with respect to the random effects distribution, as a way of assessing goodness-of-fit in a mixed model. They concentrate on cases related to standard longitudinal data analysis using linear (or generalized linear) mixed models, however the method can be extended to other mixed models, such as clustered multi-state models with multivariate (log)-normal random effects.

If we consider data from units i with observations x_i, given a mixing distribution G, we can say the marginal density is given by .

The gradient function is then taken as where N is the total number of independent clusters

The use of the gradient function stems from finite mixture models and in particular the problem of finding the non-parametric maximum likelihood estimate of the mixing distribution. At the NPMLE the gradient function has a supremum of 1. If instead we assume there is a parametric mixing distribution, under correct specification the gradient function should be close to 1 across all values of u. Verbeke and Molenberghs use this property to construct an informal graphical diagnostic of the appropriateness of the proposed random effects distribution.

An advantage of the approach is that essentially no additional calculations are required to compute the measure, above and beyond those already needed for estimation of the parametric mixture model itself. A current limitation of the approach is that there is no formal test to assess whether the observed deviation is statistically significant. It is stated that this is ongoing work. It seems reasonably straightforward to show that the gradient function will tend to a Gaussian process with mean 1 but with a quite complicated covariance structure. Obtaining some nice asymptotics for a statistic based either on the maximum deviation from 1 or some weighted integral of the distance from 1 therefore seems unlikely. However, it may be possible to obtain a simulation based p-value by simulating from the limiting Gaussian process.

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