Combining Optimization and Randomization Approaches for the Design of Clinical Trials

t Intentional sampling methods are non-randomized procedures that select a group of individuals for a sample with the purpose of meeting specific prescribed criteria. In this paper we extend previous works related to intentional sampling, and address the problem of sequential allocation for clinical trials with few patients. Roughly speaking, patients are enrolled sequentially, according to the order in which they start the treatment at the clinic or hospital. The allocation problem consists in assigning each new patient to one, and only one, of the alternative treatment arms. The main requisite is that the profiles in the alternative arms remain similar with respect to some relevant patients’ attributes (age, gender, disease, symptom severity and others). We perform numerical experiments based on a real case study and discuss how to conveniently set up perturbation parameters, in order to yield a suitable balance between optimality – the similarity among the relative frequencies of patients in the several categories for both arms, and decoupling – the absence of a tendency to allocate each pair of patients consistently to the same arm

A fast preamplifier concept for SiPM-based time-of-flight PET detectors

Silicon photomultipliers (SiPMs) offer high gain and fast response to light, making them interesting for fast timing applications such as time-of-flight (TOF) PET. To fully exploit the potential of these photosensors, dedicated preamplifiers that do not deteriorate the rise time and signal-to-noise ratio are crucial. Challenges include the high sensor capacitance, typically > 300 pF for a 3 mm x 3 mm SiPM sensor, as well as oscillation issues. Here we present a preamplifier concept based on low noise, high speed transistors, designed for optimum timing performance. The input stage consists of a transimpedance common-base amplifier with a very low input impedance even at high frequencies, which assures a good linearity and avoids that the high detector capacitance affects the amplifier bandwidth. The amplifier has a fast timing output as well as a 'slow' energy output optimized for determining the total charge content of the pulse. The rise time of the amplifier is about 300 ps. The measured coincidence resolving time (CRT) for 511 keV photon pairs using the amplifiers in combination with 3 mm x 3 mm SiPMs (Hamamatsu MPPC-S10362-33-050C) coupled to 3 mm x 3 mm x 5 mm LaBr3:Ce and LYSO:Ce crystals equals 95 ps FWHM and 138 ps FWHM, respectively. (C) 2011 Elsevier B.V. All rights reserved