Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)

Comparison of predictions of baking volume using large deformation rheological properties

Three large deformation rheological tests, the Kieffer dough extensibility system, the D/R dough inflation system and the 2 g mixograph test, were carried out on doughs made from a large number of winter wheat lines and cultivars grown in Poland. These lines and cultivars represented a broad spread in baking performance in order to assess their suitability as predictors of baking volume. The parameters most closely associated with baking volume were strain hardening index, bubble failure strain, and mixograph bandwidth at 10min. Simple correlations with baking volume indicate that bubble failure strain and strain hardening index give the highest correlations, whilst the use of best subsets regression, which selects the best combination of parameters, gave increased correlations with R-2 = 0.865 for dough inflation parameters, R-2 = 0. 842 for Kieffer parameters and R-2 = 0.760 for mixograph parameters. (c) 2007 Elsevier Ltd. All rights reserved.

A novel haptic interface for navigation in large volume environments

Haptic interfaces can provide highly realistic interaction with objects within their workspace, but the task of interacting with objects over large areas or volumes is made difficult by the limits of interface travel. This paper details the development of a custom haptic interface - for navigating a large virtual environment (a simulated supermarket), and investigation into different control methods which allow for haptic interaction over extremely large workspaces.