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.     

Deliberate acquisition of competence in physiological breech birth: A grounded theory study

Problem

Research suggests that the skill and experience of the attendant significantly affect the outcomes of vaginal breech births, yet practitioner experience levels are minimal within many contemporary maternity care systems.

Absent bodies and present memories: marking out the everyday and the future in Eastern Sri Lanka

Drawing from ethnographic work carried out between 2005 and 2007, this article considers the ways in which a women’s network has developed strategies to find meaning around the absences of loved ones, killed or ‘disappeared’ during the decades of conflict in Sri Lanka. For most of these women, the fate of their husbands, brothers, sons and fathers is not known and the lack of answers means that they are unable to fully grieve and find closure. In order to survive, they must find ways to deal with the absent bodies and present memories of those who may never be located and accounted for. These strategies include tree-planting ceremonies carried out as a way of not only remembering and mourning loved ones but also asking questions about how one makes sense of loss and what it means to carry the burden of unanswered absences through everyday life and into the future.     

Generating random variates from D-distributions via substitution sampling

Laud et al. (1993) describe a method for random variate generation from D-distributions. In this paper an alternative method using substitution sampling is given. An algorithm for the random variate generation from SD-distributions is also given.