Search

Frailty models have been developed to quantify both heterogeneity as well as association in multivariate time-to-event data. In recent years, numerous shared and correlated frailty models have been proposed in the survival literature allowing for different association structures and frailty distributions. A bivariate correlated gamma frailty model with an additive decomposition of the frailty variables into a sum of independent gamma components was introduced before. Although this model has a very convenient closed-form representation for the bivariate survival function, the correlation among event- or subject-specific frailties is bounded above which becomes a severe limitation when the values of the two frailty variances differ substantially. In this article, we review existing correlated gamma frailty models and propose novel ones based on bivariate gamma frailty distributions. Such models are found to be useful for the analysis of bivariate survival time data regardless of the censoring type involved. The frailty methodology was applied to right-censored and left-truncated Danish twins mortality data and serological survey current status data on varicella zoster virus and parvovirus B19 infections in Belgium. From our analyses, it has been shown that fitting more flexible correlated gamma frailty models in terms of the imposed association and correlation structure outperforms existing frailty models including the one with an additive decomposition.

Bivariate binary response data appear in many applications. Interest goes most often to a parameterization of the joint probabilities in terms of the marginal success probabilities in combination with a measure for association, most often being the odds ratio. Using, for example, the bivariate Dale model, these parameters can be modelled as function of covariates. But the odds ratio and other measures for association are not always measuring the (joint) characteristic of interest. Agreement, concordance, and synchrony are in general facets of the joint distribution distinct from association, and the odds ratio as in the bivariate Dale model can be replaced by such an alternative measure. Here, we focus on the so-called conditional synchrony measure. But, as indicated by several authors, such a switch of parameter might lead to a parameterization that does not always lead to a permissible joint bivariate distribution. In this contribution, we propose a new parameterization in which the marginal success probabilities are replaced by other conditional probabilities as well. The new parameters, one homogeneity parameter and two synchrony/discordance parameters, guarantee that the joint distribution is always permissible. Moreover, having a very natural interpretation, they are of interest on their own. The applicability and interpretation of the new parameterization is shown for three interesting settings: quantifying HIV serodiscordance among couples in Mozambique, concordance in the infection status of two related viruses, and the diagnostic performance of an index test in the field of major depression disorders. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was only possible, thanks to the financial support of the Flemish Interuniversity Council (VLIR-UOS) in collaboration with Eduardo Mondlane University (UEM) through the DESAFIO Program. NH acknowledges funding from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programme (grant no. 682540 TransMID) and the Special Research Fund of Hasselt University.

There are several generalized linear mixed models to combine direct and indirect evidence on several diagnostic tests from related but independent diagnostic studies simultaneously also known as network meta-analysis. The popularity of these models is due to the attractive features of the normal distribution and the availability of statistical software to obtain parameter estimates. However, modeling the latent sensitivity and specificity using the normal distribution after transformation is neither natural nor computationally convenient. In this article, we develop a meta-analytic model based on the bivariate beta distribution, allowing to obtain improved and direct estimates for the global sensitivities and specificities of all tests involved, and taking into account simultaneously the intrinsic correlation between sensitivity and specificity and the overdispersion due to repeated measures. Using the beta distribution in regression has the following advantages, that the probabilities are modeled in their proper scale rather than a monotonic transform of the probabilities. Secondly, the model is flexible as it allows for asymmetry often present in the distribution of bounded variables such as proportions, which is the case with sparse data common in meta-analysis. Thirdly, the model provides parameters with direct meaningful interpretation since further integration is not necessary to obtain the meta-analytic estimates.

Network meta-analysis (NMA) allow combining efficacy information from multiple comparisons from trials assessing different therapeutic interventions for a given disease and to estimate unobserved comparisons from a network of observed comparisons. Applying NMA on diagnostic accuracy studies is a statistical challenge given the inherent correlation of sensitivity and specificity. A conceptually simple and novel hierarchical arm-based (AB) model which expresses the logit transformed sensitivity and specificity as sum of fixed effects for test, correlated study-effects and a random error associated with various tests evaluated in given study is proposed. We apply the model to previously published meta-analyses assessing the accuracy of diverse cytological and molecular tests used to triage women with minor cervical lesions to detect cervical precancer and the results compared with those from the contrast-based (CB) model which expresses the linear predictor as a contrast to a comparator test. The proposed AB model is more appealing than the CB model in that it yields the marginal means which are easily interpreted and makes use of all available data and easily accommodates more general variance-covariance matrix structures., Comment: 27 Pages, 6 figures

The vast majority of settings for which frequentist statistical properties are derived assume a fixed, a priori known sample size. Familiar properties then follow, such as, for example, the consistency, asymptotic normality, and efficiency of the sample average for the mean parameter, under a wide range of conditions. We are concerned here with the alternative situation in which the sample size is itself a random variable which may depend on the data being collected. Further, the rule governing this may be deterministic or probabilistic. There are many important practical examples of such settings, including missing data, sequential trials, and informative cluster size. It is well known that special issues can arise when evaluating the properties of statistical procedures under such sampling schemes, and much has been written about specific areas (Grambsch P. Sequential sampling based on the observed Fisher information to guarantee the accuracy of the maximum likelihood estimator. Ann Stat 1983; 11: 68–77; Barndorff-Nielsen O and Cox DR. The effect of sampling rules on likelihood statistics. Int Stat Rev 1984; 52: 309–326). Our aim is to place these various related examples into a single framework derived from the joint modeling of the outcomes and sampling process and so derive generic results that in turn provide insight, and in some cases practical consequences, for different settings. It is shown that, even in the simplest case of estimating a mean, some of the results appear counterintuitive. In many examples, the sample average may exhibit small sample bias and, even when it is unbiased, may not be optimal. Indeed, there may be no minimum variance unbiased estimator for the mean. Such results follow directly from key attributes such as non-ancillarity of the sample size and incompleteness of the minimal sufficient statistic of the sample size and sample sum. Although our results have direct and obvious implications for estimation following group sequential trials, there are also ramifications for a range of other settings, such as random cluster sizes, censored time-to-event data, and the joint modeling of longitudinal and time-to-event data. Here, we use the simplest group sequential setting to develop and explicate the main results. Some implications for random sample sizes and missing data are also considered. Consequences for other related settings will be considered elsewhere. IAP research Network of the Belgian Government (Belgian Science Policy) - NIH