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.     

Wage and Non-Wage Compensation Among Young Alcoholic and Heavy Drinking Women: A Preliminary Analysis

The association between drinking and selected job characteristics among women aged 24 to 31 is examined. Using the 1989 NLSY, women are classified as alcohol abusers or dependent based on DSM-III-R criteria or as heavy drinkers based on reported frequency of six or more drinks. Heavy drinking is negatively associated with wage and non-wage compensation. These effects diminish when human capital measures are controlled. Current alcoholism and current and past heavy drinking are strongly negatively associated with years of schooling. The association between alcoholism and job compensation and characteristics is not as strong as that seen for heavy drinking. It is not known if this is a consequence of errors in identifying alcoholic women in population-based surveys.     

A NOTE ON EVANESCENT PROCESSES

This note examines the connection between μ-invariant measures for the transition function of a continuous-time Markov chain and those of its q-matrix, Q. The major result establishes a necessary and aufficient condition for a convergent μ-invariant measure for Q to be μ-inhant for the minimal transition function, P, under the assumption that P is honest. This corrects Theorem 6 of Vere-Jones (1969) and the first part of Corollary 1 of Pollett (1986), both of which assert that the above conclusion holds in the absence of this condition. The error was pointed out by E.A. van Doom (1991) and the counterexample which be presented provides the basis for the present arguments. In determining where the error occurred in the original proof, we are able to identify a simple sufficient condition for μ-invariance.     

Don't mention Stonehenge!

It rises massive and magnificent above Salisbury Plain. The extraordinary monoliths of Stonehenge leave us as impressed today as ever—and as baffled. Archaeologists argue about how it was made. Can statisticians tell the answer? Chris Jones thinks they can be of considerable assistance.     

Female Victim Perceptions of the Causes of Male Spouse Abuse*

Victims of spouse abuse were interviewed concerning their views of why their husbands were abusive. It was hypothesized that by concentrating on one specific characteristic of this kind previously undocumented patterns of response would be elicited from the subjects. It was concluded that the women's reasons for the violence perpetrated by their spouses serve as justification for the abusers’actions and legitimize maintenance of the relationship.     

Asymptotic bias in the linear mixed effects model under non-ignorable missing data mechanisms

Summary.  In longitudinal studies, missingness of data is often an unavoidable problem. Estimators from the linear mixed effects model assume that missing data are missing at random. However, estimators are biased when this assumption is not met. In the paper, theoretical results for the asymptotic bias are established under non-ignorable drop-out, drop-in and other missing data patterns. The asymptotic bias is large when the drop-out subjects have only one or no observation, especially for slope-related parameters of the linear mixed effects model. In the drop-in case, intercept-related parameter estimators show substantial asymptotic bias when subjects enter late in the study. Eight other missing data patterns are considered and these produce asymptotic biases of a variety of magnitudes.     

African American Children's Adjustment: The Roles of Maternal and Teacher Depressive Symptoms

This study examined the unique and interactive roles of mother and teacher depressive symptoms in child adjustment in 277 African American single mother‐headed families, as well as whether the associations differed depending on the age and gender of the child. Findings revealed a significant association between maternal depressive symptoms and child depressive symptoms in girls, but not boys. Moreover, the combination of higher levels of both mother and teacher depressive symptoms was associated with the highest level of child depressive symptoms and, for younger children, externalizing symptoms. The importance of considering the multiple social contexts in which children interact is discussed.     

Classifying At‐Risk High School Youth: The Influence of Exposure to Community Violence and Protective Factors on Academic and Health Outcomes

Using cluster analysis, 789 predominately Latino and African American high school youth were classified into varying academic at‐risk profiles using self‐reported levels of academic confidence, motivation to attend school, perceived family support, connections with teachers and peers, and exposure to violence. Six clusters emerged, 5 of which were identified as “at‐risk.” The clusters were examined in relation to academic stress, health status, grades, and school retention. Exposure to violence was one distinguishing feature of youth identified as most vulnerable, vulnerable, and resilient; however, youth identified as resilient recorded better academic outcomes.     

D-efficient window experimental designs

In the paper we present a new method of calculating sampling intervals, so-called windows, allowing an experimenter some flexibility in timing the sample collection, while a minimum required design efficiency for parameter estimation is assured. The method is based on the Equivalence Theorem for D-optimality what makes the length of each window related to the parameter sensitivities. An example of calculating the windows in a pharmacokinetic study is presented. Some other methods of calculating efficient sampling windows are briefly discussed.