Multiplicity and flexibility in clinical trials

Flexible designs offer a large amount of flexibility in clinical trials with control of the type I error rate. This allows the combination of trials from different clinical phases of a drug development process. Such combinations require designs where hypotheses are selected and/or added at interim analysis without knowing the selection rule in advance so that both flexibility and multiplicity issues arise. The paper reviews the basic principles and some of the common methods for reaching flexibility while controlling the family-wise error rate in the strong sense. Flexible designs have been criticized because they may lead to different weights for the patients from the different stages when reassessing sample sizes. Analyzing the data in a conventional way avoids such unequal weighting but may inflate the multiple type I error rate. In cases where the conditional type I error rates of the new design (and conventional analysis) are below the conditional type I error rates of the initial design the conventional analysis may, however, be done without inflating the type I error rate. Focusing on a parallel group design with two treatments and a common control, we use this principle to investigate when we can select one treatment, reassess sample sizes and test the corresponding null hypotheses by the conventional level alpha z-test without compromising on the multiple type I error rate.     

Value orientations and social attitudes in the holistic milieu

Based on a representative population survey for Germany this article investigates whether engagement in holistic activities is associated with privatized lifestyles and lack of social responsibility or with countercultural orientations and base‐democratic political commitment. To analyse this question, respondents who are engaged in holistic activities are divided into three groups that are compared with each other as well as with Christians and non‐religious people. The findings show that the three holistic groups are characterized by clearly different attitudinal patterns: Respondents engaged in body‐mind‐spirit activities have an affinity to self‐directed ways of life, post‐materialism and environmentalism. Holistic Christians try to combine the Christian ideal of altruism and post‐materialist orientations. Those who are attracted only to magical‐occult practices are primarily concerned with individualistic self‐improvement and correspond more to the image of the hedonist consumer at the esoteric marketplace.     

Parent,carer, person: future plans and the identities of parent carers for people with disabilities

Parent carers are often central in future planning for their children with disability; however, little is known about the implications of planning for parents’ futures and aspirations. In understanding these, parents’ own identities are important, but how these identities intersect with their planning is not well understood. This study explored how parents were positioned in discussions about planning. Interviews with parents and planning service staff highlighted three positions among parents – carer, parent, and person – representing multiple, intersecting identities. These impacted on and were impacted by planning in particular ways. Understanding these processes may assist programmes to support parents more effectively.     

Students’, caretakers’ and decision-makers’ perception of support in higher education for students with in-care experience

Students with in-care experiences overcome different life challenges, risks factors and use their strengths to get into higher education. During the study period they face different difficulties, so the state as ‘institutional’ parent should provide support. This paper presents results of a qualitative study that aimed to explore support system to students with in-care experience in Croatia from three perspectives: care leavers with studying experiences, caretakers and professionals who are involved in decision-making and implementing activities on national and local levels. Focus groups and interviews were conducted with 23 students, 5 professionals and 11 caretakers in 5 Croatian cities. Three basic themes from all three perspectives are presented: currently available support, difficulties in the support system and guidelines for supporting in-care students. All groups of participants are informed about support that is currently available for students with in-care experiences and describe financial and accommodation support. Perceptions of difficulties in delivering support differ between professionals and students and caretakers. Students also explain reasons for seeking support. Resolving existential issues is the first step in support system building according to students’ and caretakers’ perceptions. Participants suggest different incentive activities, so finally recommendations for forming and delivering support system for in-care students are presented.     

The Brain’s Reward Response Occurs Even Without Actual Reward!

What if the brain’s response to reward occurs even when there is no reward? Wouldn’t that be a further concern for people prone to problem gambling and other forms of addiction, like those related to eating? Electroencephalography was employed to investigate this possibility using probabilistic feedback manipulations and measures of known event-related potentials (ERPs) related to reward processing. We tested the hypothesis—that reward-based ERPs would occur even in the absence of a tangible reward and when manipulations on expectation are implicit. The well-known P300 response potential was a key focus, and was assessed in non-gambling volunteer undergraduates on a task involving experimentally-manipulated probabilities of positive or negative feedback comprising three trial types—80, 50, or 20% positive feedback. A feedback stimulus (F1) followed a guess response between two possible outcomes (implicit win/loss), and then a second feedback stimulus (F2) was presented to confirm an alleged ‘win’ or ‘loss’ (explicit win/loss). Results revealed that amplitude of the P300 in F1-locked data (implicit manipulation) was larger (more positive) on average for feedback outcomes that were manipulated to be less likely than expected. The effect is pronounced after increased time on task (later trials), even though the majority of participants were not explicitly aware of our probability manipulations. For the explicit effects in F2-locked data, no meaningful or significant effects were observed. These findings point to the existence of proposed success-response mechanisms that operate not only explicitly but also with implicit manipulations that do not involve any direct indication of a win or loss, and are not associated with tangible rewards. Thus, there seems to be a non-explicit form of perception (we call ‘implicit’) associated with an internal experience of wins/losses (in the absence of actual rewards or losses) that can be measured in associated brain processes. The potential significance of these findings is discussed in terms of implications for problem gambling.     

AN ADAPTIVE DECISION SUPPORT SYSTEM FOR ACADEMIC RESOURCE PLANNING

Institutions of higher learning are growing increasingly interested in the use of model-based approaches to their resource allocation problems. Recent modeling approaches, however, have failed to consider that resource allocation planning is not a well-structured decision process. Additionally, many decision makers are necessarily involved in the academic planning process and may assume dissimilar perspectives on the importance of achieving different goals and objectives. Furthermore, satisfactory allocation solutions can be expected to vary considerably from decision maker to decision maker as the individual's cognitive processes, perceptions, and evaluations are taken into consideration. This paper describes a decision support system (DSS) approach that attempts to adapt to a variety of academic decision makers with differing planning views in an environment of multiple conflicting objectives. This DSS, which was successfully tested on four academic decision makers in a large midwestern university, shows considerable promise for providing decision support to decision makers with varied problem-solving styles.     

Predictive Accuracy Gain From Disaggregate Sampling in ARIMA Models

We compare the forecast accuracy of autoregressive integrated moving average (ARIMA) models based on data observed with high and low frequency, respectively. We discuss how, for instance, a quarterly model can be used to predict one quarter ahead even if only annual data are available, and we compare the variance of the prediction error in this case with the variance if quarterly observations were indeed available. Results on the expected information gain are presented for a number of ARIMA models including models that describe the seasonally adjusted gross national product (GNP) series in the Netherlands. Disaggregation from annual to quarterly GNP data has reduced the variance of short-run forecast errors considerably, but further disaggregation from quarterly to monthly data is found to hardly improve the accuracy of monthly forecasts.     

Panel Unit Root Tests in the Presence of Cross-Sectional Dependencies: Comparison and Implications for Modelling

Several panel unit root tests that account for cross-section dependence using a common factor structure have been proposed in the literature recently. Pesaran's (2007 Pesaran , M. H. ( 2007 ). A simple panel unit root test in the presence of cross section dependence . Journal of Applied Econometrics 22 : 265 – 312 .[Crossref], [Web of Science ®] , [Google Scholar]) cross-sectionally augmented unit root tests are designed for cases where cross-sectional dependence is due to a single factor. The Moon and Perron (2004 Moon , H. R. , Perron , B. (2004). Testing for a unit root in panels with dynamic factors. Journal of Econometrics 122:81–126.[Crossref], [Web of Science ®] , [Google Scholar]) tests which use defactored data are similar in spirit but can account for multiple common factors. The Bai and Ng (2004a Bai , J. , Ng , S. ( 2004a ). A PANIC attack on unit roots and cointegration . Econometrica 72 : 1127 – 1177 .[Crossref], [Web of Science ®] , [Google Scholar]) tests allow to determine the source of nonstationarity by testing for unit roots in the common factors and the idiosyncratic factors separately. Breitung and Das (2008 Breitung , J. , Das , S. ( 2008 ). Testing for unit roots in panels with a factor structure . Econometric Theory 24 : 88 – 108 .[Crossref], [Web of Science ®] , [Google Scholar]) and Sul (2007 Sul , D. ( 2007 ) . Panel Unit Root Tests Under Cross Section Dependence with Recursive Mean Adjustment . Mimeo : University of Auckland . [Google Scholar]) propose panel unit root tests when cross-section dependence is present possibly due to common factors, but the common factor structure is not fully exploited.

This article makes four contributions: (1) it compares the testing procedures in terms of similarities and differences in the data generation process, tests, null, and alternative hypotheses considered, (2) using Monte Carlo results it compares the small sample properties of the tests in models with up to two common factors, (3) it provides an application which illustrates the use of the tests, and (4) finally, it discusses the use of the tests in modelling in general.