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.     

Enoch Powell,empires, immigrants and education

2018 marks the 50th anniversary of Enoch Powell’s infamous ‘Rivers of Blood’ speech, an intervention that is still viewed as one of the most incendiary statements of the perceived decay and violence likely to follow legislation intended to assure minoritised British citizens of equal rights regardless of their ethnic origin. In this essay, Sally Tomlinson (one of Britain’s foremost multicultural theorists) reflects on Powell’s legacy and the contemporary scene where in the US, UK and across Europe, White resentment and fear is increasingly shaping ‘mainstream’ debates about nationhood, migration and education.     

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.     

Disability in Somaliland

Civil war lasting into the 1990s destroyed much of Somalia's economic, political and social structures, and conflict still continues in the southern areas of the country. In 1991, the northwest region declared itself the Independent Republic of Somaliland, established a government in Hargeisa and is struggling to rebuild an infrastructure. It is one of the poorest countries in the world, ranking high on the UN hunger index, and is the third most heavily land-mined country. One of the most disadvantaged groups of people are the disabled, although there is little general information about numbers and kinds of disability, and few social and medical services. This article presents some limited information about the extent of the nature of disability, and local efforts to improve the lives of disabled children and adults. It reports projects funded by non-government organisations, and concentrates on a seminar held in early 2002 attended by a group of disabled people who made their voices heard.     

Accommodation issues in the work place for people with disabilities: a needs assessment in an educational setting

The passage in the USA of the Americans with Disabilities Act (ADA) has mandated the private sector to provide a sweeping variety of accommodations to individuals with disabilities. Objections to ADA focused on costs in an era of scarcity. These assumptions have been presented with insufficient information about the actual needs of individuals with disabilities. This study is a needs assessment of employees with disabilities at a major university setting. In-depth interviews were conducted with a small number of individuals who described their work situations and accommodations. Findings challenge prevailing assumptions. Costs are often not large, many accommodations are simple, and much depends on the match between a person's disability and job duties. Additionally, informational needs, psychological concerns and the existing social climate provide a more balanced picture of the lives of these employees.     

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.