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.     

The Story of Belle, Minnie, Louise and the Sovjets: throwing light on the dark side of an institution

Our post-modernist story is composed as a narrative analysis of the lived experiences of Belle and Louise--two women with 'learning difficulties'--and our ethnographic field notes while doing narrative inquiry. The narratives mirror a shared construction of meaning and broaden our understanding--throwing light on the dark side of an institution. The narrative analysis points out a clear illustration of power dynamics and discourses in their lives, and shows how the women boast of resilience and offer (hidden) resistance. This paper particularly illuminates the individual, personal and even private celebration of activism and self-empowerment of Belle and Louise. Their vivid stories take us on an enthralling journey, getting to know their world through their eyes.     

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.     

‘Democracy always comes first’: adolescents’ views on decision-making in everyday life and political democracy

Research shows adolescents to be positively oriented towards democracy, but little is known about what it actually means to them and what their views are on decision-making in both everyday situations and political democracy. To gain insight into these aspects of adolescents’ democratic views, we have interviewed 40 Dutch adolescents from second grade of different types of high school. Potential conflict between various democratic principles prevalent in everyday life situations was discussed and compared to how they view decision-making in political democracy. The results of our qualitative study showed that adolescents’ views on issues concerning collective decision-making in everyday situations are quite rich and reflect different models of democracy (majoritarian, consensual, and deliberative). Moreover, how adolescents deal with tensions between democratic principles in everyday life situations varies. While some adolescents combine several principles (for instance, majority rule as a last resort after trying to find broader consensus), other adolescents tend to strictly focus on only one of these principles. Adolescents’ views on political democracy, however, are rather limited and one-dimensional. Those adolescents who seemed to have a more explicit picture of political democracy often preferred a strict focus on majority rule, neglecting minority interests.     

Integrated nested Laplace approximation for the analysis of count data via the combined model: A simulation study

The combined model accounts for different forms of extra-variability and has traditionally been applied in the likelihood framework, or in the Bayesian setting via Markov chain Monte Carlo. In this article, integrated nested Laplace approximation is investigated as an alternative estimation method for the combined model for count data, and compared with the former estimation techniques. Longitudinal, spatial, and multi-hierarchical data scenarios are investigated in three case studies as well as a simulation study. As a conclusion, integrated nested Laplace approximation provides fast and precise estimation, while avoiding convergence problems often seen when using Markov chain Monte Carlo.     

Testing variance components in balanced linear growth curve models

It is well known that the testing of zero variance components is a non-standard problem since the null hypothesis is on the boundary of the parameter space. The usual asymptotic chi-square distribution of the likelihood ratio and score statistics under the null does not necessarily hold because of this null hypothesis. To circumvent this difficulty in balanced linear growth curve models, we introduce an appropriate test statistic and suggest a permutation procedure to approximate its finite-sample distribution. The proposed test alleviates the necessity of any distributional assumptions for the random effects and errors and can easily be applied for testing multiple variance components. Our simulation studies show that the proposed test has Type I error rate close to the nominal level. The power of the proposed test is also compared with the likelihood ratio test in the simulations. An application on data from an orthodontic study is presented and discussed.     

Predictors of Antisocial and Prosocial Behavior in an Adolescent Sports Context

This study examined antisocial and prosocial behavior of N = 439 adolescent athletes between 14 and 17 years of age (67 teams). Multi‐level analyses showed that team membership explained 20 and 13 percent of the variance in antisocial and prosocial behavior in the sports context, respectively. The team effects suggest that aggregating antisocial or prosocial adolescents within teams may partially explain differences in antisocial and prosocial behavior among athletes in the sports context. A trend was found toward a relation between higher levels of moral reasoning within teams, and less antisocial behavior in the sports context. Favorable moral atmosphere was positively associated with more prosocial behavior in the sports context. Finally, supportive coach–athlete relationships were associated with both less antisocial and more prosocial behavior in the sports context.