Optimal sampling times in population pharmacokinetic studies

We propose a simulation-based approach to decision theoretic Bayesian optimal design. The underlying probability model is a population pharmacokinetic model which allows for correlated responses (drug concentrations) and patient-to-patient heterogeneity. We consider the problem of choosing sampling times for the anticancer agent paclitaxel, using criteria related to the total area under the curve, the time above a critical threshold and the sampling cost.     

Monitoring point patterns for the development of space–time clusters

Existing statistical methods for the detection of space–time clusters of point events are retrospective, in that they are used to ascertain whether space–time clustering exists among a fixed number of past events. In contrast, prospective methods treat a series of observations sequentially, with the aim of detecting quickly any changes that occur in the series. In this paper, cumulative sum methods of monitoring are adapted for use with Knox's space–time statistic. The result is a procedure for the rapid detection of any emergent space–time interactions for a set of sequentially monitored point events. The approach relies on a 'local' Knox statistic that is useful in retrospective analyses to detect when and where space–time interaction occurs. The distribution of the local Knox statistic under the null hypothesis of no space–time interaction is derived. The retrospective local statistic and the prospective cumulative sum monitoring method are illustrated by using previously published data on Burkitt's lymphoma in Uganda.     

Cancer treatments

Cancer is of particular importance to gerontology due to the changing nature of the disease. Survival rates are at all time highs as a result of technological advances in early detection and treatment of cancer. Some less aggressive or invasive forms of cancer are now seen as chronic illnesses rather than acute, terminal diseases. As a result, demand is increasing for evidence-based psychosocial interventions designed to improve the health and well-being of people living with cancer. This article reviews evidence-based psychosocial interventions designed to address the needs of persons with cancer and their family members. Traditional and technology enhance interventions are discussed as are complementary and alternative therapies designed to augment traditional interventions.     

Handling drop-out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches

This study compares two methods for handling missing data in longitudinal trials: one using the last-observation-carried-forward (LOCF) method and one based on a multivariate or mixed model for repeated measurements (MMRM). Using data sets simulated to match six actual trials, I imposed several drop-out mechanisms, and compared the methods in terms of bias in the treatment difference and power of the treatment comparison. With equal drop-out in Active and Placebo arms, LOCF generally underestimated the treatment effect; but with unequal drop-out, bias could be much larger and in either direction. In contrast, bias with the MMRM method was much smaller; and whereas MMRM rarely caused a difference in power of greater than 20%, LOCF caused a difference in power of greater than 20% in nearly half the simulations. Use of the LOCF method is therefore likely to misrepresent the results of a trial seriously, and so is not a good choice for primary analysis. In contrast, the MMRM method is unlikely to result in serious misinterpretation, unless the drop-out mechanism is missing not at random (MNAR) and there is substantially unequal drop-out. Moreover, MMRM is clearly more reliable and better grounded statistically. Neither method is capable of dealing on its own with trials involving MNAR drop-out mechanisms, for which sensitivity analysis is needed using more complex methods.     

The cost of not knowing the radius

Robust Statistics considers the quality of statistical decisions in the presence of deviations from the ideal model, where deviations are modelled by neighborhoods of a certain size about the ideal model. We introduce a new concept of optimality (radius-minimaxity) if this size or radius is not precisely known: for this notion, we determine the increase of the maximum risk over the minimax risk in the case that the optimally robust estimator for the false neighborhood radius is used. The maximum increase of the relative risk is minimized in the case that the radius is known only to belong to some interval [r _l ,r _u ]. We pursue this minmax approach for a number of ideal models and a variety of neighborhoods. Also, the effect of increasing parameter dimension is studied for these models. The minimax increase of relative risk in case the radius is completely unknown, compared with that of the most robust procedure, is 18.1% versus 57.1% and 50.5% versus 172.1% for one-dimensional location and scale, respectively, and less than 1/3 in other typical contamination models. In most models considered so far, the radius needs to be specified only up to a factor , in order to keep the increase of relative risk below 12.5%, provided that the radius–minimax robust estimator is employed. The least favorable radii leading to the radius–minimax estimators turn out small: 5–6% contamination, at sample size 100.      

Problematic emotions and maternal grief

The study was an empirical examination of the relation of personality proneness to "problematic social emotions"--envy (Dispositional Envy Scale), jealousy (Interpersonal Jealousy Scale), and shame and guilt (Personal Feelings Questionnaire-2)--to maternal grief (Perinatal Grief Scale-33) following miscarriage, stillbirth, neonatal death, or infant/child death. The 441 women who participated in the study were enrolled from the Website, e-mail contact lists, and parent support groups of an organization that offers information and support to bereaved parents. All four problematic emotions were positively correlated with maternal grief. Envy, jealousy, and guilt made significant unique contributions to the variance in maternal grief. Overall, time lapse since the loss and the four problematic emotion predispositions explained 43% of the variance in maternal grief following child bereavement.     

Analysis of exacerbation rates in asthma and chronic obstructive pulmonary disease: example from the TRISTAN study

Recurrent events in clinical trials have typically been analysed using either a multiple time-to-event method or a direct approach based on the distribution of the number of events. An area of application for these methods is exacerbation data from respiratory clinical trials. The different approaches to the analysis and the issues involved are illustrated for a large trial (n = 1465) in chronic obstructive pulmonary disease (COPD). For exacerbation rates, clinical interest centres on a direct comparison of rates for each treatment which favours the distribution-based analysis, rather than a time-to-event approach. Poisson regression has often been employed and has recently been recommended as the appropriate method of analysis for COPD exacerbations but the key assumptions often appear unreasonable for this analysis. By contrast use of a negative binomial model which corresponds to assuming a separate Poisson parameter for each subject offers a more appealing approach. Non-parametric methods avoid some of the assumptions required by these models, but do not provide appropriate estimates of treatment effects because of the discrete and bounded nature of the data.     

A Smooth Model of Decision Making under Ambiguity

We propose and characterize a model of preferences over acts such that the decision maker prefers act f to act g if and only if 𝔼_μφ(𝔼_πu○f) 𝔼_μφ(𝔼_πu○g), where 𝔼 is the expectation operator, u is a von Neumann–Morgenstern utility function, φis an increasing transformation, and μis a subjective probability over the set Πof probability measures πthat the decision maker thinks are relevant given his subjective information. A key feature of our model is that it achieves a separation between ambiguity, identified as a characteristic of the decision maker's subjective beliefs, and ambiguity attitude, a characteristic of the decision maker's tastes. We show that attitudes toward pure risk are characterized by the shape of u, as usual, while attitudes toward ambiguity are characterized by the shape of φ. Ambiguity itself is defined behaviorally and is shown to be characterized by properties of the subjective set of measures Π. One advantage of this model is that the well‐developed machinery for dealing with risk attitudes can be applied as well to ambiguity attitudes. The model is also distinct from many in the literature on ambiguity in that it allows smooth, rather than kinked, indifference curves. This leads to different behavior and improved tractability, while still sharing the main features (e.g., Ellsberg's paradox). The maxmin expected utility model (e.g., Gilboa and Schmeidler (1989)) with a given set of measures may be seen as a limiting case of our model with infinite ambiguity aversion. Two illustrative portfolio choice examples are offered.     

Public Procurement and Public Financial Management in Africa: Dynamics and Influences

Public Organization Review - How do public procurement practices influence effective public financial management (PFM) in Africa? Notwithstanding the several public procurement reforms to improve...