The Job Demands-Job Control Model and absence behaviour: results of a 3-year longitudinal study

Empirical results of earlier studies only marginally supported the relevance of Karasek's Job Demands-Job Control Model for absence behaviour. Since longitudinal studies with respect to these relations were largely lacking, a four-wave panel study was carried out using data from 1755 male employees of a technical maintenance firm in the public sector. Job demands, job control, physical working conditions, and the employee's age, education, and health were measured in one year and absenteeism in the same year and in the next 3 years. Data were analysed with linear regression and Poisson regression techniques. The Poisson regression technique was superior to the linear regression technique in explaining absence. Age, health and prior absence were the best predictors of later absence behaviour. With respect to the Job Demands-Job Control Model, the main findings of the study were (1) that job control was significantly associated with a low number of simultaneous and later absence days, and (2) that, contrary to expectations, job demands were also related to a low number of simultaneous and later absence days. These results hold when age, health, education, prior absence, and working conditions are controlled for. Job control and job demands did not predict later absence frequency. In the discussion it is suggested that a high level of job demands may not only be harmful for the well-being of employees but also work as 'a pressure to attend'.     

Interval estimation for log-linear models with one variable subject to non-ignorable non-response

Summary.  Log-linear models for multiway contingency tables where one variable is subject to non-ignorable non-response will often yield boundary solutions, with the probability of non-respondents being classified in some cells of the table estimated as 0. The paper considers the effect of this non-standard behaviour on two methods of interval estimation based on the distribution of the maximum likelihood estimator. The first method relies on the estimator being approximately normally distributed with variance equal to the inverse of the information matrix. It is shown that the information matrix is singular for boundary solutions, but intervals can be calculated after a simple transformation. For the second method, based on the bootstrap, asymptotic results suggest that the coverage properties may be poor for boundary solutions. Both methods are compared with profile likelihood intervals in a simulation study based on data from the British General Election Panel Study. The results of this study indicate that all three methods perform poorly for a parameter of the non-response model, whereas they all perform well for a parameter of the margin model, irrespective of whether or not there is a boundary solution.     

Choice of the primary analysis in longitudinal clinical trials

Missing data, and the bias they can cause, are an almost ever‐present concern in clinical trials. The last observation carried forward (LOCF) approach has been frequently utilized to handle missing data in clinical trials, and is often specified in conjunction with analysis of variance (LOCF ANOVA) for the primary analysis. Considerable advances in statistical methodology, and in our ability to implement these methods, have been made in recent years. Likelihood‐based, mixed‐effects model approaches implemented under the missing at random (MAR) framework are now easy to implement, and are commonly used to analyse clinical trial data. Furthermore, such approaches are more robust to the biases from missing data, and provide better control of Type I and Type II errors than LOCF ANOVA. Empirical research and analytic proof have demonstrated that the behaviour of LOCF is uncertain, and in many situations it has not been conservative. Using LOCF as a composite measure of safety, tolerability and efficacy can lead to erroneous conclusions regarding the effectiveness of a drug. This approach also violates the fundamental basis of statistics as it involves testing an outcome that is not a physical parameter of the population, but rather a quantity that can be influenced by investigator behaviour, trial design, etc. Practice should shift away from using LOCF ANOVA as the primary analysis and focus on likelihood‐based, mixed‐effects model approaches developed under the MAR framework, with missing not at random methods used to assess robustness of the primary analysis. Copyright © 2004 John Wiley & Sons, Ltd.     

Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

A Hybrid Geometric Phase II/III Clinical Trial Design based on Treatment Failure Time and Toxicity

The problem of comparing several experimental treatments to a standard arises frequently in medical research. Various multi-stage randomized phase II/III designs have been proposed that select one or more promising experimental treatments and compare them to the standard while controlling overall Type I and Type II error rates. This paper addresses phase II/III settings where the joint goals are to increase the average time to treatment failure and control the probability of toxicity while accounting for patient heterogeneity. We are motivated by the desire to construct a feasible design for a trial of four chemotherapy combinations for treating a family of rare pediatric brain tumors. We present a hybrid two-stage design based on two-dimensional treatment effect parameters. A targeted parameter set is constructed from elicited parameter pairs considered to be equally desirable. Bayesian regression models for failure time and the probability of toxicity as functions of treatment and prognostic covariates are used to define two-dimensional covariate-adjusted treatment effect parameter sets. Decisions at each stage of the trial are based on the ratio of posterior probabilities of the alternative and null covariate-adjusted parameter sets. Design parameters are chosen to minimize expected sample size subject to frequentist error constraints. The design is illustrated by application to the brain tumor trial.     

Efficient likelihood-free Bayesian Computation for?household epidemics

Considerable progress has been made in applying Markov chain Monte Carlo (MCMC) methods to the analysis of epidemic data. However, this likelihood based method can be inefficient due to the limited data available concerning an epidemic outbreak. This paper considers an alternative approach to studying epidemic data using Approximate Bayesian Computation (ABC) methodology. ABC is a simulation-based technique for obtaining an approximate sample from the posterior distribution of the parameters of the model and in an epidemic context is very easy to implement. A new approach to ABC is introduced which generates a set of values from the (approximate) posterior distribution of the parameters during each simulation rather than a single value. This is based upon coupling simulations with different sets of parameters and we call the resulting algorithm coupled ABC. The new methodology is used to analyse final size data for epidemics amongst communities partitioned into households. It is shown that for the epidemic data sets coupled ABC is more efficient than ABC and MCMC-ABC.     

Modelling spatially correlated data via mixtures: a Bayesian approach

Summary. The paper develops mixture models for spatially indexed data. We confine attention to the case of finite, typically irregular, patterns of points or regions with prescribed spatial relationships, and to problems where it is only the weights in the mixture that vary from one location to another. Our specific focus is on Poisson-distributed data, and applications in disease mapping. We work in a Bayesian framework, with the Poisson parameters drawn from gamma priors, and an unknown number of components. We propose two alternative models for spatially dependent weights, based on transformations of autoregressive Gaussian processes: in one (the logistic normal model), the mixture component labels are exchangeable; in the other (the grouped continuous model), they are ordered. Reversible jump Markov chain Monte Carlo algorithms for posterior inference are developed. Finally, the performances of both of these formulations are examined on synthetic data and real data on mortality from a rare disease.