A comparison of methods for constructing confidence intervals after phase II/III clinical trials

Recently, in order to accelerate drug development, trials that use adaptive seamless designs such as phase II/III clinical trials have been proposed. Phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages. Using stage 1 data, an interim analysis is performed to answer phase II objectives and after collection of stage 2 data, a final confirmatory analysis is performed to answer phase III objectives. In this paper we consider phase II/III clinical trials in which, at stage 1, several experimental treatments are compared to a control and the apparently most effective experimental treatment is selected to continue to stage 2. Although these trials are attractive because the confirmatory analysis includes phase II data from stage 1, the inference methods used for trials that compare a single experimental treatment to a control and do not have an interim analysis are no longer appropriate. Several methods for analysing phase II/III clinical trials have been developed. These methods are recent and so there is little literature on extensive comparisons of their characteristics. In this paper we review and compare the various methods available for constructing confidence intervals after phase II/III clinical trials.

Sea surface temperature datasets for climate applications from Phase 1 of the European Space Agency Climate Change Initiative (SST CCI)

Sea surface temperature (SST) datasets have been generated from satellite observations for the period 1991–2010, intended for use in climate science applications. Attributes of the datasets specifically relevant to climate applications are: first, independence from in situ observations; second, effort to ensure homogeneity and stability through the time-series; third, context-specific uncertainty estimates attached to each SST value; and, fourth, provision of estimates of both skin SST (the fundamental measure- ment, relevant to air-sea fluxes) and SST at standard depth and local time (partly model mediated, enabling comparison with his- torical in situ datasets). These attributes in part reflect requirements solicited from climate data users prior to and during the project. Datasets consisting of SSTs on satellite swaths are derived from the Along-Track Scanning Radiometers (ATSRs) and Advanced Very High Resolution Radiometers (AVHRRs). These are then used as sole SST inputs to a daily, spatially complete, analysis SST product, with a latitude-longitude resolution of 0.05°C and good discrimination of ocean surface thermal features. A product user guide is available, linking to reports describing the datasets’ algorithmic basis, validation results, format, uncer- tainty information and experimental use in trial climate applications. Future versions of the datasets will span at least 1982–2015, better addressing the need in many climate applications for stable records of global SST that are at least 30 years in length.

A comparison of methods for treatment selection in seamless phase II/III clinical trials incorporating information on short-term endpoints

In an adaptive seamless phase II/III clinical trial interim analysis, data are used for treatment selection, enabling resources to be focused on comparison of more effective treatment(s) with a control. In this paper, we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focuses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short- and long-term endpoints.

Energy consistent discontinuous Galerkin methods for a quasi-incompressible diffuse two phase flow model

We design consistent discontinuous Galerkin finite element schemes for the approximation of a quasi-incompressible two phase flow model of Allen–Cahn/Cahn–Hilliard/Navier–Stokes–Korteweg type which allows for phase transitions. We show that the scheme is mass conservative and monotonically energy dissipative. In this case the dissipation is isolated to discrete equivalents of those effects already causing dissipation on the continuous level, that is, there is no artificial numerical dissipation added into the scheme. In this sense the methods are consistent with the energy dissipation of the continuous PDE system.

Sparse space-time boundary element methods for the heat equation

The goal of this work is the efficient solution of the heat equation with Dirichlet or Neumann boundary conditions using the Boundary Elements Method (BEM). Efficiently solving the heat equation is useful, as it is a simple model problem for other types of parabolic problems. In complicated spatial domains as often found in engineering, BEM can be beneficial since only the boundary of the domain has to be discretised. This makes BEM easier than domain methods such as finite elements and finite differences, conventionally combined with time-stepping schemes to solve this problem. The contribution of this work is to further decrease the complexity of solving the heat equation, leading both to speed gains (in CPU time) as well as requiring smaller amounts of memory to solve the same problem. To do this we will combine the complexity gains of boundary reduction by integral equation formulations with a discretisation using wavelet bases. This reduces the total work to O(h

Phase 1

Exhibition investigating the role of different methods of drawing in the visualization of architectural space