Adaptive and repeated cumulative meta‐analyses of safety data during a new drug development process

During a new drug development process, it is desirable to timely detect potential safety signals. For this purpose, repeated meta‐analyses may be performed sequentially on accumulating safety data. Moreover, if the amount of safety data from the originally planned program is not enough to ensure adequate power to test a specific hypothesis (e.g., the noninferiority hypothesis of an event of interest), the total sample size may be increased by adding new studies to the program. Without appropriate adjustment, it is well known that the type I error rate will be inflated because of repeated analyses and sample size adjustment. In this paper, we discuss potential issues associated with adaptive and repeated cumulative meta‐analyses of safety data conducted during a drug development process. We consider both frequentist and Bayesian approaches. A new drug development example is used to demonstrate the application of the methods. Copyright © 2015 John Wiley & Sons, Ltd.     

The financial practices and perceptions behind separate systems of household financial management

Qualitative research in the UK has revealed a diversity of financial arrangements underlying separate systems of household financial management. One factor, identified in previous work, is perceived ownership of money, with financial practices differing according to whether couples have distinct, blurred or shared ownership perceptions. The present work aims to build on and extend this research, using data from an online survey study with 190 cohabitants in the UK. The findings reveal that ownership perceptions transcend separate money management categories, and can be a significant predictor of the type of contribution cohabitants make towards joint household expenses.     

A case study in identifying targeted patients population in major depressive disorder by enhanced enrichment design

Despite advances in clinical trial design, failure rates near 80% in phase 2 and 50% in phase 3 have recently been reported. The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high‐placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm. This approach led to a redefinition of an ongoing, blinded phase 3 trial algorithm for patient inclusion (1) to eliminate further randomization of transient placebo responders and (2) to exclude previously randomized transient responders from the primary analysis of the double blind phase of the trial. It is illustrated for a case study for the comparison between brexpiprazole + antidepressant therapy and placebo + antidepressant therapy. Analysis of the primary endpoint showed that efficacy of brexpiprazole versus placebo could not be established statistically if the original algorithm for identification of placebo responders was used, but the enhanced enrichment approach did statistically demonstrate efficacy. Additionally, the enhanced enrichment approach identified a target population with a clinically meaningful treatment effect. Through its successful identification of a target population, the innovative enhanced enrichment approach enabled the demonstration of a positive treatment effect in a very challenging area of depression research.     

Money in marriage: how patterns of allocation both reflect and conceal power

This paper examines perceptions of money within marriage, focusing upon the concepts of control and ownership. It considers the criteria involved in Pahl's (1983; 1989) typology for the allocation of income, and their ability to capture the dynamic perceptual elements associated with change. These issues were explored by means of data from semi-structured interviews, using mainly middle-class couples (thirteen women and nine of their partners) in the 30–50 year age-range. Most of the women were in the process of returning to the labour market following an absence of at least eight years. The findings demonstrate, on the one hand, that Pahl's revised typology (1989), which includes an emphasis on the person possessing overall control, can be used to trace major shifts in the balance of economic power as a function of the life-cycle and associated changes in the source of income. On the other hand, the findings also show that a couple's report of their financial arrangements, concerning the Spooling’ of income, can yield the erroneous impression that resources are equally shared. In particular, the ‘rights’ of ownership associated with having earned the income may remain hidden, and lead to patterns of overall control with potential consequences for a non-earning, dependent partner.     

The Structure of Mental Health: Higher-Order Confirmatory Factor Analyses of Psychological Distress and Well-Being Measures

Social Indicators Research - This paper addresses the question of whether psychological distress and subjective well-being are the opposite poles of the same axis of mental health or independent...     

Reconnecting Past,Present and Future Lives: Therapy with a Young Person who Experienced Severe Childhood Privation

This case study describes therapy over a three year period with a young adopted person who presented as highly suicidal, with a childhood background characterised by severe privation and abuse. The paper describes the use of a visual Life line, designed to assist the young person in reconnecting and honouring different parts of her life. A flexible and client centred therapeutic approach is also described.