Type I error rate control in adaptive designs for confirmatory clinical trials with treatment selection at interim

Interest in confirmatory adaptive combined phase II/III studies with treatment selection has increased in the past few years. These studies start comparing several treatments with a control. One (or more) treatment(s) is then selected after the first stage based on the available information at an interim analysis, including interim data from the ongoing trial, external information and expert knowledge. Recruitment continues, but now only for the selected treatment(s) and the control, possibly in combination with a sample size reassessment. The final analysis of the selected treatment(s) includes the patients from both stages and is performed such that the overall Type I error rate is strictly controlled, thus providing confirmatory evidence of efficacy at the final analysis. In this paper we describe two approaches to control the Type I error rate in adaptive designs with sample size reassessment and/or treatment selection. The first method adjusts the critical value using a simulation-based approach, which incorporates the number of patients at an interim analysis, the true response rates, the treatment selection rule, etc. We discuss the underlying assumptions of simulation-based procedures and give several examples where the Type I error rate is not controlled if some of the assumptions are violated. The second method is an adaptive Bonferroni-Holm test procedure based on conditional error rates of the individual treatment-control comparisons. We show that this procedure controls the Type I error rate, even if a deviation from a pre-planned adaptation rule or the time point of such a decision is necessary.     

Buchbesprechungen / Book reviews

Literatur / Books

Buchbesprechungen / Book reviews     

What Atypical Adults Can Teach Us about Development

In my presidential address, I described the early trap I fell into of describing the super‐baby capable of one after another adult perceptual ability, then how I discovered that two atypical populations of adults allowed me to study developmental mechanisms, namely, the role of early sensory input in sculpting the nervous system and the biological preparedness that constrains the experiential effects. Specifically, studies of adults who had dense central cataracts during childhood revealed that there are multiple critical periods during which visual input alters the potential of the nervous system for later refinement. Studies of adults with synesthesia generated novel hypotheses, subsequently supported experimentally, about the details of the biological preparedness that bias the child's early learning. Nevertheless, later studies indicated that considerable residual plasticity remains in adulthood.     

Democratic Participation in Voluntary Associations: A Multilevel Analysis of Sports Clubs in Europe

VOLUNTAS: International Journal of Voluntary and Nonprofit Organizations - Non-profit associations are usually democratically organized, and this feature plays a legitimizing role for the public...     

Content Audit for p-value Principles in Introductory Statistics

ABSTRACT

Longstanding concerns with the role and interpretation of p-values in statistical practice prompted the American Statistical Association (ASA) to make a statement on p-values. The ASA statement spurred a flurry of responses and discussions by statisticians, with many wondering about the steps necessary to expand the adoption of these principles. Introductory statistics classrooms are key locations to introduce and emphasize the nuance related to p-values; in part because they engrain appropriate analysis choices at the earliest stages of statistics education, and also because they reach the broadest group of students. We propose a framework for statistics departments to conduct a content audit for p-value principles in their introductory curriculum. We then discuss the process and results from applying this course audit framework within our own statistics department. We also recommend meeting with client departments as a complement to the course audit. Discussions about analyses and practices common to particular fields can help to evaluate if our service courses are meeting the needs of client departments and to identify what is needed in our introductory courses to combat the misunderstanding and future misuse of p-values.     

Parenthood, Marital Status, and Well-Being in Later Life: Evidence from SHARE

Using pooled cross-sectional data from the first two waves of the Survey of Health, Ageing and Retirement in Europe, we address the question of whether and how parenthood and marital status are associated with various dimensions of elders’ well-being, which we define by elements of the individual’s economic situation, psychological well-being, and social connectedness. The results of our multivariate analysis suggest that childless individuals do not generally fare worse than parents in terms of their economic, psychological, or social well-being. Although there is some indication for a ‘protective effect’ of marriage, having a partner does not per se contribute to greater psychological well-being: only those reporting satisfaction with the extent of reciprocity in their relationship report lower numbers of depression symptoms than their unmarried counterparts. We observe no systematic associations between parenthood (marriage, respectively) and individuals’ propensity to participate in social activities. These findings are fairly stable, that is, they hold for both men and women as well as across various cohorts, and they do not vary systematically between countries.     

The liquidity crisis of German open-end real estate funds and their impact on optimal asset allocation in retirement

In course of the recent turmoil in the financial markets, several open-end real estate funds froze redemption of their units, resulting in unanticipated and unprecedented liquidity and performance shocks for investors. Against this background, we analyze the long- and short-term risk and return profiles of open-end real estate funds and their role in efficient multi-asset retirement portfolios. To this end, we introduce the Retirement Efficient Frontier, describing those investment strategies that minimize the lifetime probability of ruin for specific levels of periodic withdrawals from a given retirement wealth. We find that for low to moderate periodic withdrawals, efficient portfolios consist of up to 85% real estate fund investments in case fund units are continuously redeemable. Moreover we show that even if there is a monthly probability of 2.5% that redemption of fund units is temporarily suspended, the allocation into real estate funds in risk-efficient portfolios is only slightly affected. Yet, if funds additionally face a high risk of having to depreciate their property portfolio during a liquidity crisis, their share in efficient retirement portfolios is reduced significantly.