Approaches to sample size calculation for clinical trials in rare diseases

We discuss 3 alternative approaches to sample size calculation: traditional sample size calculation based on power to show a statistically significant effect, sample size calculation based on assurance, and sample size based on a decision‐theoretic approach. These approaches are compared head‐to‐head for clinical trial situations in rare diseases. Specifically, we consider 3 case studies of rare diseases (Lyell disease, adult‐onset Still disease, and cystic fibrosis) with the aim to plan the sample size for an upcoming clinical trial. We outline in detail the reasonable choice of parameters for these approaches for each of the 3 case studies and calculate sample sizes. We stress that the influence of the input parameters needs to be investigated in all approaches and recommend investigating different sample size approaches before deciding finally on the trial size. Highly influencing for the sample size are choice of treatment effect parameter in all approaches and the parameter for the additional cost of the new treatment in the decision‐theoretic approach. These should therefore be discussed extensively.     

Effects of an 8-week multimodal exercise program on strength, flexibility, and golf performance in 55- to 79-year-old men

Substantial research has indicated the beneficial effect of physical activity on physical fitness and activities of daily living in older adults, but none have investigated the effects on performance of recreational activities. This investigation studied the effect of an exercise program on fitness and golf-clubhead speed in older men. Thirty-one golfers (mean age 65.1 +/- 6.2 years) were randomly assigned to a treatment (n = 19) or control (n = 12) group. The treatment group completed an 8-week strength and flexibility program. Assessments included 10-RM muscle strength; selected range-of-motion (ROM) measurements; and golf-clubhead speed (CHS). ANCOVA revealed significant differences between groups (p <.005) for all strength measurements and several ROM measurements. CHS was significantly different (p <.05) between groups after the intervention. Mean CHS improved from 85.0 to 87.1 miles/hr (136.8 to 140.2 km/hr). These results indicate that a strength and flexibility program can improve golf performance in older adults.     

A comparison of mean squared error approximations for a small estimated state space model*

Summary: This paper investigates mean squared errors for unobserved states in state space models when estimation uncertainty of hyperparameters is taken into account. Three alternative approximations to mean squared errors with estimation uncertainty are compared in a Monte Carlo experiment, where the random walk with noise model serves as DGP: A naive method which neglects estimation uncertainty completely, an approximation based on an expansion around the true state with respect to the estimated parameters, and a bootstrap approach. Overall, the bootstrap method performs best in the simulations. However, the gains are not systematic, and the computationally burden of this method is relatively high.*This paper represents the authors personal opinions and does not necessarily reflect the views of the Deutsche Bundesbank. I am grateful to Malte Knüppel, Jeong-Ryeol Kurz-Kim, Karl-Heinz Tödter and a referee for helpful comments. The computer programs for this paper were written in Ox and SsfPack, see Doornik (1998) and Koopman et al. (1999). The used SsfPack version is 2.2.     

Adolescents' beliefs about marijuana use: a comparison of regular users, past users and never/occasional users

A questionnaire investigating adolescents' opinions and experiences regarding marijuana use was administered to 163 adolescents and young adults (96 boys and 67 girls) aged 13 to 20 (mean age = 16.8, s.d. = 1.5). Items referred to marijuana and other substances' dangerousness, representations regarding the positive and negative consequences of marijuana use. Responses were compared according to marijuana use status (classified into never/occasional use, current regular use and past regular use). Results show that adolescents' opinions differ according to their experience with marijuana use. Current regular users evaluate marijuana as less dangerous, but alcohol and heroin as more dangerous in comparison with never/occasional and past users. Current and past users are more likely to define marijuana as a medical drug and a plant used in agriculture, and less likely to define it as an illegal drug. Current and past users evaluate marijuana use as a way to cope with stress, to relax to a greater extent than do never/occasional users do. The latter attribute more negative consequences to marijuana use such as diminished driving ability and school performance and a pathway to hard drugs.     

The probability of inconsistencies in complex collective decisions

Many groups make decisions over multiple interconnected propositions. The doctrinal paradox or discursive dilemma shows that propositionwise majority voting can generate inconsistent collective sets of judgments, even when individual sets of judgments are all consistent. I develop a simple model for determining the probability of the paradox, given various assumptions about the probability distribution of individual sets of judgments, including impartial culture and impartial anonymous culture assumptions. I prove several convergence results, identifying when the probability of the paradox converges to 1, and when it converges to 0, as the number of individuals increases. Drawing on the Condorcet jury theorem and work by Bovens and Rabinowicz (2001, 2003), I use the model to assess the truth-tracking performance of two decision procedures, the premise- and conclusion-based procedures. I compare the present results with existing results on the probability of Condorcets paradox. I suggest that the doctrinal paradox is likely to occur under plausible conditions.The author wishes to express his gratitude to Luc Bovens, Matthew Braham, Steven Brams, Bruce Chapman, Philip Pettit, Wlodek Rabinowicz and two anonymous reviewers for helpful comments or discussion. A previous version of this paper was presented at the 2002 Annual Meeting of the European Public Choice Society, Belgirate, Lago Maggiore, Italy, April 2002, and at the Sixth International Meeting of the Society for Social Choice and Welfare, held at the California Institute of Technology, Pasadena, California, July 2002.     

Well-being and occupational roles among middle-aged women

One purpose of the present study is to explore the stability of the pattern of health/work and sickness absence among middle-aged women over a period of three years. This study tested two hypotheses: (a) that enduringly healthy working women would perceive more valued occupational roles and higher well-being than long-term sick-listed women; (b) that high levels of well-being at baseline would predict enduring health and occupational role value at a 3-year follow-up. Middle-aged women (n = 208) answered a postal survey with the Role checklist, a well-being scale and questions about work and sickness situation. The results showed that there was a considerable variability in the pattern of health/work and sickness absence. The variability was greatest among the women who were long-term sick-listed at baseline, and the internal drop out was great among them. The results showed that the enduringly healthy women experienced a more valued worker role and higher well-being than the long-term sick-listed women. Furthermore, high levels of well-being concerning health and work predicted enduring health in the studied sample, and high well-being concerning work was predictive of a valued worker role. Interventions that enable women to develop valuable worker and leisure roles, as well as harmony between different roles, may be important constituents of health promotion/rehabilitation programmes.     

Report on the 14th Annual Meeting of the German Society for Geriatric Research

Members of the German Society for Geriatric Research (Deutsche Gesellschaft für Alternsforschung) and various invited speakers met in Karlsruhe, Germany, in November 2004 to discuss new findings and exchange views on intriguing problems in the broad field of aging research. This report summarizes some of the diverse topics that arose at the meeting, including diapause in insects, mitochondrial morphology in fungi, the production of reactive oxygen species, neurogenesis, and age-dependent changes of the cardiac system in mammals.     

Estimation in the Positive Stable Shared Frailty Cox Proportional Hazards Model

Shared frailty models are of interest when one has clustered survival data and when focus is on comparing the lifetimes within clusters and further on estimating the correlation between lifetimes from the same cluster. It is well known that the positive stable model should be preferred to the gamma model in situations where the correlated survival data show a decreasing association with time. In this paper, we devise a likelihood based estimation procedure for the positive stable shared frailty Cox model, which is expected to obtain high efficiency. The proposed estimator is provided with large sample properties and also a consistent estimator of standard errors is given. Simulation studies show that the estimation procedure is appropriate for practical use, and that it is much more efficient than a recently suggested procedure. The suggested methodology is applied to a dataset concerning time to blindness for patients with diabetic retinopathy.     

Liberalism,Postmaterialism, and the Growth of Freedom

An influential analysis by Przeworski and Limongi (1997 Przeworski A Limongi F (1997) ‘Modernization: Theories and facts’ World Politics vol. 49 pp. 155–183  [Google Scholar]) argued that a pro-democratic culture may help existing democracies survive, but political culture does not contribute to the process of democratization, which is entirely done by elites. We challenge this conclusion, arguing that it neglects the very nature of democratization. For (as Human Development theory argues), democratization is a liberating process that maximizes human freedom by establishing civil and political rights. Consequently, the aspect of political culture that is most relevant to democratization is mass aspirations for freedom – and if a given public emphasizes these values relatively strongly, democratization is likely to occur. To test this thesis, we use data from the Values Surveys, demonstrating that a specific component of postmaterialism (‘liberty aspirations’) had a major impact on the extent to which societies gained or lost freedom during the Third Wave of democratization. This effect holds up in tests of Granger causality, remaining strong when we control for prior levels of freedom. No other indicator, including GDP/capita and social capital, can explain away the impact of liberty aspirations on democratization. Mass liberty aspirations play a role in democratization that has been greatly underestimated.