A strong law of large numbers for independent random variables under non-additive probabilities

Abstract

Under non‐additive probabilities, cluster points of the empirical average have been proved to quasi-surely fall into the interval constructed by either the lower and upper expectations or the lower and upper Choquet expectations. In this paper, based on the initiated notion of independence, we obtain a different Marcinkiewicz-Zygmund type strong law of large numbers. Then the Kolmogorov type strong law of large numbers can be derived from it directly, stating that the closed interval between the lower and upper expectations is the smallest one that covers cluster points of the empirical average quasi-surely.     

Exploring Parameter Relations for Multi‐Stage Models in Stage‐Wise Constant and Time Dependent Hazard Rates

Single cohort stage‐frequency data are considered when assessing the stage reached by individuals through destructive sampling. For this type of data, when all hazard rates are assumed constant and equal, Laplace transform methods have been applied in the past to estimate the parameters in each stage‐duration distribution and the overall hazard rates. If hazard rates are not all equal, estimating stage‐duration parameters using Laplace transform methods becomes complex. In this paper, two new models are proposed to estimate stage‐dependent maturation parameters using Laplace transform methods where non‐trivial hazard rates apply. The first model encompasses hazard rates that are constant within each stage but vary between stages. The second model encompasses time‐dependent hazard rates within stages. Moreover, this paper introduces a method for estimating the hazard rate in each stage for the stage‐wise constant hazard rates model. This work presents methods that could be used in specific types of laboratory studies, but the main motivation is to explore the relationships between stage maturation parameters that, in future work, could be exploited in applying Bayesian approaches. The application of the methodology in each model is evaluated using simulated data in order to illustrate the structure of these models.     

Inference in Semi‐Parametric Dynamic Models for Repeated Count Data

This paper deals with a longitudinal semi‐parametric regression model in a generalised linear model setup for repeated count data collected from a large number of independent individuals. To accommodate the longitudinal correlations, we consider a dynamic model for repeated counts which has decaying auto‐correlations as the time lag increases between the repeated responses. The semi‐parametric regression function involved in the model contains a specified regression function in some suitable time‐dependent covariates and a non‐parametric function in some other time‐dependent covariates. As far as the inference is concerned, because the non‐parametric function is of secondary interest, we estimate this function consistently using the independence assumption‐based well‐known quasi‐likelihood approach. Next, the proposed longitudinal correlation structure and the estimate of the non‐parametric function are used to develop a semi‐parametric generalised quasi‐likelihood approach for consistent and efficient estimation of the regression effects in the parametric regression function. The finite sample performance of the proposed estimation approach is examined through an intensive simulation study based on both large and small samples. Both balanced and unbalanced cluster sizes are incorporated in the simulation study. The asymptotic performances of the estimators are given. The estimation methodology is illustrated by reanalysing the well‐known health care utilisation data consisting of counts of yearly visits to a physician by 180 individuals for four years and several important primary and secondary covariates.     

Nonparametric Estimation of the Number of Drug Users in Hong Kong Using Repeated Multiple Lists

We update a previous approach to the estimation of the size of an open population when there are multiple lists at each time point. Our motivation is 35 years of longitudinal data on the detection of drug users by the Central Registry of Drug Abuse in Hong Kong. We develop a two‐stage smoothing spline approach. This gives a flexible and easily implemented alternative to the previous method which was based on kernel smoothing. The new method retains the property of reducing the variability of the individual estimates at each time point. We evaluate the new method by means of a simulation study that includes an examination of the effects of variable selection. The new method is then applied to data collected by the Central Registry of Drug Abuse. The parameter estimates obtained are compared with the well known Jolly–Seber estimates based on single capture methods.     

Addressing potential prior‐data conflict when using informative priors in proof‐of‐concept studies

Bayesian methods are increasingly used in proof‐of‐concept studies. An important benefit of these methods is the potential to use informative priors, thereby reducing sample size. This is particularly relevant for treatment arms where there is a substantial amount of historical information such as placebo and active comparators. One issue with using an informative prior is the possibility of a mismatch between the informative prior and the observed data, referred to as prior‐data conflict. We focus on two methods for dealing with this: a testing approach and a mixture prior approach. The testing approach assesses prior‐data conflict by comparing the observed data to the prior predictive distribution and resorting to a non‐informative prior if prior‐data conflict is declared. The mixture prior approach uses a prior with a precise and diffuse component. We assess these approaches for the normal case via simulation and show they have some attractive features as compared with the standard one‐component informative prior. For example, when the discrepancy between the prior and the data is sufficiently marked, and intuitively, one feels less certain about the results, both the testing and mixture approaches typically yield wider posterior‐credible intervals than when there is no discrepancy. In contrast, when there is no discrepancy, the results of these approaches are typically similar to the standard approach. Whilst for any specific study, the operating characteristics of any selected approach should be assessed and agreed at the design stage; we believe these two approaches are each worthy of consideration. Copyright © 2015 John Wiley & Sons, Ltd.     

A win ratio approach to comparing continuous non‐normal outcomes in clinical trials

Clinical trials are often designed to compare continuous non‐normal outcomes. The conventional statistical method for such a comparison is a non‐parametric Mann–Whitney test, which provides a P‐value for testing the hypothesis that the distributions of both treatment groups are identical, but does not provide a simple and straightforward estimate of treatment effect. For that, Hodges and Lehmann proposed estimating the shift parameter between two populations and its confidence interval (CI). However, such a shift parameter does not have a straightforward interpretation, and its CI contains zero in some cases when Mann–Whitney test produces a significant result. To overcome the aforementioned problems, we introduce the use of the win ratio for analysing such data. Patients in the new and control treatment are formed into all possible pairs. For each pair, the new treatment patient is labelled a ‘winner’ or a ‘loser’ if it is known who had the more favourable outcome. The win ratio is the total number of winners divided by the total numbers of losers. A 95% CI for the win ratio can be obtained using the bootstrap method. Statistical properties of the win ratio statistic are investigated using two real trial data sets and six simulation studies. Results show that the win ratio method has about the same power as the Mann–Whitney method. We recommend the use of the win ratio method for estimating the treatment effect (and CI) and the Mann–Whitney method for calculating the P‐value for comparing continuous non‐Normal outcomes when the amount of tied pairs is small. Copyright © 2016 John Wiley & Sons, Ltd.     

Distribution of the two‐sample t‐test statistic following blinded sample size re‐estimation

We consider the blinded sample size re‐estimation based on the simple one‐sample variance estimator at an interim analysis. We characterize the exact distribution of the standard two‐sample t‐test statistic at the final analysis. We describe a simulation algorithm for the evaluation of the probability of rejecting the null hypothesis at given treatment effect. We compare the blinded sample size re‐estimation method with two unblinded methods with respect to the empirical type I error, the empirical power, and the empirical distribution of the standard deviation estimator and final sample size. We characterize the type I error inflation across the range of standardized non‐inferiority margin for non‐inferiority trials, and derive the adjusted significance level to ensure type I error control for given sample size of the internal pilot study. We show that the adjusted significance level increases as the sample size of the internal pilot study increases. Copyright © 2016 John Wiley & Sons, Ltd.     

Group sequential monitoring based on the weighted log‐rank test statistic with the Fleming–Harrington class of weights in cancer vaccine studies

In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log‐rank tests with the Fleming–Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming–Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long‐term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log‐rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.     

A Note on the Large Sample Properties of Estimators Based on Generalized Linear Models for Correlated Pseudo‐observations

Pseudo‐values have proven very useful in censored data analysis in complex settings such as multi‐state models. It was originally suggested by Andersen et al., Biometrika, 90, 2003, 335 who also suggested to estimate standard errors using classical generalized estimating equation results. These results were studied more formally in Graw et al., Lifetime Data Anal., 15, 2009, 241 that derived some key results based on a second‐order von Mises expansion. However, results concerning large sample properties of estimates based on regression models for pseudo‐values still seem unclear. In this paper, we study these large sample properties in the simple setting of survival probabilities and show that the estimating function can be written as a U‐statistic of second order giving rise to an additional term that does not vanish asymptotically. We further show that previously advocated standard error estimates will typically be too large, although in many practical applications the difference will be of minor importance. We show how to estimate correctly the variability of the estimator. This is further studied in some simulation studies.     

Linear Increments with Non‐monotone Missing Data and Measurement Error

Linear increments (LI) are used to analyse repeated outcome data with missing values. Previously, two LI methods have been proposed, one allowing non‐monotone missingness but not independent measurement error and one allowing independent measurement error but only monotone missingness. In both, it was suggested that the expected increment could depend on current outcome. We show that LI can allow non‐monotone missingness and either independent measurement error of unknown variance or dependence of expected increment on current outcome but not both. A popular alternative to LI is a multivariate normal model ignoring the missingness pattern. This gives consistent estimation when data are normally distributed and missing at random (MAR). We clarify the relation between MAR and the assumptions of LI and show that for continuous outcomes multivariate normal estimators are also consistent under (non‐MAR and non‐normal) assumptions not much stronger than those of LI. Moreover, when missingness is non‐monotone, they are typically more efficient.