In this work a general semi-parametric multivariate model where the first two conditional moments are assumed to be multivariate time series is introduced. The focus of the estimation is the conditional mean parameter vector for discrete-valued distributions. Quasi-Maximum Likelihood Estimators (QMLEs) based on the linear exponential family are typically employed for such estimation problems when the true multivariate conditional probability distribution is unknown or too complex. Although QMLEs provide consistent estimates they may be inefficient. In this paper novel two-stage Multivariate Weighted Least Square Estimators (MWLSEs) are introduced which enjoy the same consistency property as the QMLEs but can provide improved efficiency with suitable choice of the covariance matrix of the observations. The proposed method allows for a more accurate estimation of model parameters in particular for count and categorical data when maximum likelihood estimation is unfeasible. Moreover, consistency and asymptotic normality of MWLSEs are derived. The estimation performance of QMLEs and MWLSEs is compared through simulation experiments and a real data application, showing superior accuracy of the proposed methodology.

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