Translating cross-lagged effects into incidence rates and risk ratios: The case of psychosocial safety climate and depression

Longitudinal studies are the gold standard of empirical work and stress research whenever experiments are not plausible. Frequently, scales are used to assess risk factors and their consequences, and cross-lagged effects are estimated to determine possible risks. Methods to translate cross-lagged effects into risk ratios to facilitate risk assessment do not yet exist, which creates a divide between psychological and epidemiological work stress research. The aim of the present paper is to demonstrate how cross-lagged effects can be used to assess the risk ratio of different levels of psychosocial safety climate (PSC) in organisations, an important psychosocial risk for the development of depression. We used available longitudinal evidence from the Australian Workplace Barometer (N?=?1905) to estimate cross-lagged effects of PSC on depression. We applied continuous time modelling to obtain time-scalable cross effects. These were further investigated in a 4-year Monte Carlo simulation, which translated them into 4-year incident rates. Incident rates were determined by relying on clinically relevant 2-year periods of depression. We suggest a critical value of PSC?=?26 (corresponding to ?1.4 SD), which is indicative of more than 100% increased incidents of persistent depressive disorder in 4-year periods compared to average levels of PSC across 4 years.     

Re‐framing the Analysis: A 3‐dimensional Perspective of Prisoners’ Children's Well‐being

This article highlights three dimensions to understanding children's well‐being during and after parental imprisonment which have not been fully explored in current research. A consideration of ‘time’ reveals the importance of children's past experiences and their anticipated futures. A focus on ‘space’ highlights the impact of new or altered environmental dynamics. A study of ‘agency’ illuminates how children cope within structural, material and social confines which intensify vulnerability and dependency. This integrated perspective reveals important differences in individual children's experiences and commonalities in broader systemic and social constraints on prisoners’ children. The paper analyses data from a prospective longitudinal study of 35 prisoners’ children during and after their (step) father's imprisonment to illustrate the arguments.     

Towards Uniformly Efficient Trend Estimation Under Weak/Strong Correlation and Non‐stationary Volatility

In this paper, we consider the deterministic trend model where the error process is allowed to be weakly or strongly correlated and subject to non‐stationary volatility. Extant estimators of the trend coefficient are analysed. We find that under heteroskedasticity, the Cochrane–Orcutt‐type estimator (with some initial condition) could be less efficient than Ordinary Least Squares (OLS) when the process is highly persistent, whereas it is asymptotically equivalent to OLS when the process is less persistent. An efficient non‐parametrically weighted Cochrane–Orcutt‐type estimator is then proposed. The efficiency is uniform over weak or strong serial correlation and non‐stationary volatility of unknown form. The feasible estimator relies on non‐parametric estimation of the volatility function, and the asymptotic theory is provided. We use the data‐dependent smoothing bandwidth that can automatically adjust for the strength of non‐stationarity in volatilities. The implementation does not require pretesting persistence of the process or specification of non‐stationary volatility. Finite‐sample evaluation via simulations and an empirical application demonstrates the good performance of proposed estimators.     

Interval estimation for conformance proportions of multiple quality characteristics

A conformance proportion is an important and useful index to assess industrial quality improvement. Statistical confidence limits for a conformance proportion are usually required not only to perform statistical significance tests, but also to provide useful information for determining practical significance. In this article, we propose approaches for constructing statistical confidence limits for a conformance proportion of multiple quality characteristics. Under the assumption that the variables of interest are distributed with a multivariate normal distribution, we develop an approach based on the concept of a fiducial generalized pivotal quantity (FGPQ). Without any distribution assumption on the variables, we apply some confidence interval construction methods for the conformance proportion by treating it as the probability of a success in a binomial distribution. The performance of the proposed methods is evaluated through detailed simulation studies. The results reveal that the simulated coverage probability (cp) for the FGPQ-based method is generally larger than the claimed value. On the other hand, one of the binomial distribution-based methods, that is, the standard method suggested in classical textbooks, appears to have smaller simulated cps than the nominal level. Two alternatives to the standard method are found to maintain their simulated cps sufficiently close to the claimed level, and hence their performances are judged to be satisfactory. In addition, three examples are given to illustrate the application of the proposed methods.     

Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

Design selection for strong orthogonal arrays

Strong orthogonal arrays (SOAs) were recently introduced and studied as a class of space‐filling designs for computer experiments. An important problem that has not been addressed in the literature is that of design selection for such arrays. In this article, we conduct a systematic investigation into this problem, and we focus on the most useful SOA(n,m,4,2 + )s and SOA(n,m,4,2)s. This article first addresses the problem of design selection for SOAs of strength 2+ by examining their three‐dimensional projections. Both theoretical and computational results are presented. When SOAs of strength 2+ do not exist, we formulate a general framework for the selection of SOAs of strength 2 by looking at their two‐dimensional projections. The approach is fruitful, as it is applicable when SOAs of strength 2+ do not exist and it gives rise to them when they do. The Canadian Journal of Statistics 47: 302–314; 2019 © 2019 Statistical Society of Canada     

Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial.     

A Bayesian Analysis of Abundance,Trend, and Population Viability for Harbor Seals in Iliamna Lake,Alaska

Harbor seals in Iliamna Lake, Alaska, are a small, isolated population, and one of only two freshwater populations of harbor seals in the world, yet little is known about their abundance or risk for extinction. Bayesian hierarchical models were used to estimate abundance and trend of this population. Observational models were developed from aerial survey and harvest data, and they included effects for time of year and time of day on survey counts. Underlying models of abundance and trend were based on a Leslie matrix model that used prior information on vital rates from the literature. We developed three scenarios for variability in the priors and used them as part of a sensitivity analysis. The models were fitted using Markov chain Monte Carlo methods. The population production rate implied by the vital rate estimates was about 5% per year, very similar to the average annual harvest rate. After a period of growth in the 1980s, the population appears to be relatively stable at around 400 individuals. A population viability analysis assessing the risk of quasi‐extinction, defined as any reduction to 50 animals or below in the next 100 years, ranged from 1% to 3%, depending on the prior scenario. Although this is moderately low risk, it does not include genetic or catastrophic environmental events, which may have occurred to the population in the past, so our results should be applied cautiously.     

Inference and optimal design of multiple constant-stress testing for generalized half-normal distribution under type-II progressive censoring

The generalized half-normal (GHN) distribution and progressive type-II censoring are considered in this article for studying some statistical inferences of constant-stress accelerated life testing. The EM algorithm is considered to calculate the maximum likelihood estimates. Fisher information matrix is formed depending on the missing information law and it is utilized for structuring the asymptomatic confidence intervals. Further, interval estimation is discussed through bootstrap intervals. The Tierney and Kadane method, importance sampling procedure and Metropolis-Hastings algorithm are utilized to compute Bayesian estimates. Furthermore, predictive estimates for censored data and the related prediction intervals are obtained. We consider three optimality criteria to find out the optimal stress level. A real data set is used to illustrate the importance of GHN distribution as an alternative lifetime model for well-known distributions. Finally, a simulation study is provided with discussion.     

Modifications of sequential designs in bioequivalence trials

Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/ . Copyright © 2015 John Wiley & Sons, Ltd.