Home Economics



A Formal Basis for the TwoStage ApproachAs was explained in Section 4.3, an alternative strategy (not based on MI) that can be used to avoid the computational problems that arise in the estimation of the variance components of Model (15.1), consists of replacing the mixedeffects model representation by its fixedeffects (twostage) counterpart (Tibaldi et al., 2003). The twostage approach is based on the original paper by Laird and Ware (1982). Details can be found in Verbeke and Molenberghs (2000). Tibaldi et al. (2003) obtained very good results with the twostage approach, confirmed in various chapters of this text. Of course, the question remains as to whether the method is formally valid, i.e., whether it leads to a consistent estimator. A first observation is that the twostage approach is consistent when the number of patients per trial approaches infinity, whereas the number of trials is either bounded, or increases sufficiently slowly. A first observation is that the twostage approach is consistent when the number of patients per trial approaches infinity, whereas the number of trials is either bounded, or increases sufficiently slowly. Second, as shown in Hermans et al. (2015), with a compoundsymmetry structure, or one related to it (i.e., where patients within a trial are exchangeable), weights that are proportional to the trial size can be used, while equal weights may not perform too badly, either. This is because there is a so called finite information limit in compoundsymmetrytype structures (Nas siri, Molenberghs, and Verbeke, 2016). Third, it is technically possible to derive a closedform estimator for each of the trials separately, which implies that the weighted twostage approach can be constructed with high computational efficiency, even in a bigdata context. 
<<  CONTENTS  >> 

Related topics 