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 focussed 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 focusses 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-term and long-term endpoints

Operational loads on a tidal turbine due to environmental conditions

Accurate assessment of the fatigue life of tidal stream turbines and components requires prediction of the unsteady loading of turbine components over a wide range of frequencies. This study focuses on the influence of ambient turbulence, velocity shear and the approach taken to model wave kinematics, on the variation of thrust load imposed on the rotor shaft and supporting tower. Load cycles are assessed based on sea-state occurrence data taken over a five month period for a case study site. The influence of each environmental parameter on component loading is evaluated and the impact on material design parameters assessed. Alternative approaches are considered for modelling turbulent loading and wave loading. The frequency variation of loads due to turbulence are scaled from experimental data from trials of a three-bladed horizontal axis turbine of 1.2 m diameter on a bed-mounted supporting structure. Frequency dependent wave loading is estimated by a relative form of the drag term of the widely used equation of Morison et al. (1950), with the depth decay of kinematics modelled by linear wave theory. Over the five month interval considered a ten year design life can be obtained with a lower design load by accounting for variation of turbulence intensity that occurs during each tidal cycle. This is expected to vary further with the approach taken to model the onset turbulence. A component can also be designed for lower loads over the same time period if irregular waves are modelled instead of regular

Adaptive clinical trials incorporating treatment selection and evaluation: methodology and application in progressive multiple sclerosis

In progressive multiple sclerosis (MS) irreversible disability often takes many years to accumulate as a result prolonged trials are required to assess the benefits of therapies. There is a need to understand the relationship between short-term outcome measures such as MRI endpoints and long-term clinical outcomes in progression to determine the evolution of the disease early on. Thus, the common phase I-II-III paradigm for clinical trial design with separate trials for each phase may not be appropriate

Variation of loads on a three-bladed horizontal axis tidal turbine with frequency and blade position

Sustainable and cost effective design for tidal current turbines requires knowledge of the complex nature of unsteady loads on turbine components including blades, rotor and support structure. This study investigates experimentally the variation with frequency of rotor thrust and torque loads, of streamwise root bending moment on individual blades and of loads on foundation at the bed. Comparisons between these different load spectra are also established. The impact of absolute rotor angular position on blade and rotor thrust loads is also examined. The study is based on measurements from a 1/15 scale, three-bladed, horizontal axis machine tested in a recirculating flume, in onset flows of 3% and 12% turbulence intensity. It is found that for frequencies below the rotational frequency, load spectra are correlated to spectral density of the onset flow velocity. Above the rotational frequency, loads are mainly affected by turbine operation phenomena. The tower shadowing effect is clearly identified through frequency and angular analysis. Finally, thrust loads as experienced by the rotor alone are for the first time compared with streamwise and transverse foundation loads. Higher frequency loads experienced by the tower are shown to be affected by different vortex shedding regimes associated with different regions of the wake. All the experimental measurements presented in this article can be accessed from http://dx.doi.org/10.7488/ds/2423