A re-evaluation of random-effects meta-analysis

Summary.  Meta-analysis in the presence of unexplained heterogeneity is frequently undertaken by using a random-effects model, in which the effects underlying different studies are assumed to be drawn from a normal distribution. Here we discuss the justification and interpretation of such models, by addressing in turn the aims of estimation, prediction and hypothesis testing. A particular issue that we consider is the distinction between inference on the mean of the random-effects distribution and inference on the whole distribution. We suggest that random-effects meta-analyses as currently conducted often fail to provide the key results, and we investigate the extent to which distribution-free, classical and Bayesian approaches can provide satisfactory methods. We conclude that the Bayesian approach has the advantage of naturally allowing for full uncertainty, especially for prediction. However, it is not without problems, including computational intensity and sensitivity to a priori judgements. We propose a simple prediction interval for classical meta-analysis and offer extensions to standard practice of Bayesian meta-analysis, making use of an example of studies of 'set shifting' ability in people with eating disorders.     

Using relative utility curves to evaluate risk prediction

Summary.  Because many medical decisions are based on risk prediction models that are constructed from medical history and results of tests, the evaluation of these prediction models is important. This paper makes five contributions to this evaluation: the relative utility curve which gauges the potential for better prediction in terms of utilities, without the need for a reference level for one utility, while providing a sensitivity analysis for misspecification of utilities, the relevant region, which is the set of values of prediction performance that are consistent with the recommended treatment status in the absence of prediction, the test threshold, which is the minimum number of tests that would be traded for a true positive prediction in order for the expected utility to be non-negative, the evaluation of two-stage predictions that reduce test costs and connections between various measures of performance of prediction. An application involving the risk of cardiovascular disease is discussed.     

Nonparametric density deconvolution by weighted kernel estimators

Nonparametric density estimation in the presence of measurement error is considered. The usual kernel deconvolution estimator seeks to account for the contamination in the data by employing a modified kernel. In this paper a new approach based on a weighted kernel density estimator is proposed. Theoretical motivation is provided by the existence of a weight vector that perfectly counteracts the bias in density estimation without generating an excessive increase in variance. In practice a data driven method of weight selection is required. Our strategy is to minimize the discrepancy between a standard kernel estimate from the contaminated data on the one hand, and the convolution of the weighted deconvolution estimate with the measurement error density on the other hand. We consider a direct implementation of this approach, in which the weights are optimized subject to sum and non-negativity constraints, and a regularized version in which the objective function includes a ridge-type penalty. Numerical tests suggest that the weighted kernel estimation can lead to tangible improvements in performance over the usual kernel deconvolution estimator. Furthermore, weighted kernel estimates are free from the problem of negative estimation in the tails that can occur when using modified kernels. The weighted kernel approach generalizes to the case of multivariate deconvolution density estimation in a very straightforward manner.     

Automating and evaluating reversible jump MCMC proposal distributions

The reversible jump Markov chain Monte Carlo (MCMC) sampler (Green in Biometrika 82:711–732, 1995) has become an invaluable device for Bayesian practitioners. However, the primary difficulty with the sampler lies with the efficient construction of transitions between competing models of possibly differing dimensionality and interpretation. We propose the use of a marginal density estimator to construct between-model proposal distributions. This provides both a step towards black-box simulation for reversible jump samplers, and a tool to examine the utility of common between-model mapping strategies. We compare the performance of our approach to well established alternatives in both time series and mixture model examples.     

Cemetery locus as a mechanism of socio-cultural identity

In cultural studies of cemetery locus there is a very important aspect of understanding the cemetery as a tool for the formation of the socio-cultural identity of living people. I adhere to the point of view that the cemetery has always produced, and continues to produce, a variety of identities. While during the pre-Modern period the cemetery was a necessary element of individual self-understanding as a member of a certain community, in the Modern era the cemetery produces more particularistic identities. Modernity generates some universal and abstract schemes of identification, and by means of the repression of death from public consciousness, cemeteries lose their role as a focal point in social communication. I draw attention to the radical utopian ideas of the Russian philosopher Nikolai Fedorov, who not only considered the cemetery as a locus of memory, but also proclaimed the task of the transformation of cemeteries into a base for universal work on resurrection of dead ancestors and the restoration of brotherly relations in all mankind.     

Effects of unmeasured heterogeneity in the linear transformation model for censored data

We investigate the effect of unobserved heterogeneity in the context of the linear transformation model for censored survival data in the clinical trials setting. The unobserved heterogeneity is represented by a frailty term, with unknown distribution, in the linear transformation model. The bias of the estimate under the assumption of no unobserved heterogeneity when it truly is present is obtained. We also derive the asymptotic relative efficiency of the estimate of treatment effect under the incorrect assumption of no unobserved heterogeneity. Additionally we investigate the loss of power for clinical trials that are designed assuming the model without frailty when, in fact, the model with frailty is true. Numerical studies under a proportional odds model show that the loss of efficiency and the loss of power can be substantial when the heterogeneity, as embodied by a frailty, is ignored. An erratum to this article can be found at     

A computationally simple bivariate survival estimator for efficacy and safety

Both treatment efficacy and safety are typically the primary endpoints in Phase II, and even in some Phase III, clinical trials. Efficacy is frequently measured by time to response, death, or some other milestone event and thus is a continuous, possibly censored, outcome. Safety, however, is frequently measured on a discrete scale; in Eastern Cooperative Oncology Group clinical trial E2290, it was measured as the number of weekly rounds of chemotherapy that were tolerable to colorectal cancer patients. For the joint analysis of efficacy and safety, we propose a non-parametric, computationally simple estimator for the bivariate survival function when one time-to-event is continuous, one is discrete, and both are subject to right-censoring. The bivariate censoring times may depend on each other, but they are assumed to be independent of both event times. We derive a closed-form covariance estimator for the survivor function which allows for inference to be based on any of several possible statistics of interest. In addition, we derive its covariance with respect to calendar time of analysis, allowing for its use in sequential studies.     

Is the Study of Happiness a Worthy Scientific Pursuit?

This paper critiques the view that the study of happiness is not a worthy scientific pursuit. The happiness set point and hedonic treadmill theories denote the complexity of increasing happiness levels due to genetic limitations and adaptation, however, there is mounting evidence to suggest that with the use of appropriate measures and specific interventions aimed at fostering strengths and virtues, happiness can be increased. Furthermore, the benefits of investigating methods for increasing happiness include improvements in physical, psychological and social health and well-being. It is concluded that approaching human needs from a top down or holistic standpoint where individuals can use their strengths to overcome life’s challenges, is beneficial to health and well-being. Hence, the study of happiness is a worthy scientific pursuit.     

The Extent of Economic Vulnerability in the Canadian Labour Market and Federal Jurisdiction: Is There a Role for Labour Standards?

This paper characterizes vulnerable workers in Canada and the federal jurisdiction, based upon characteristics such as employment status, demographic characteristics, and job characteristics, and identifies areas in which labour standards may have a role. Based on this analysis, the paper evaluates the potential for labour standards to address economic vulnerability, focusing on labour standards policies aimed at wages and benefits, hours, and employment arrangements. In addition, the analysis considers the extent to which labour standards are likely to reach vulnerable workers. The results suggest several potential roles for labour standards and highlights policy implications.