Using numerical modeling and simulation to assess the ethical burden in clinical trials and how it relates to the proportion of responders in a trial sample

In order to propose a more precise definition and explore how to reduce ethical losses in randomized controlled clinical trials (RCTs), we set out to identify trial participants who do not contribute to demonstrating that the treatment in the experimental arm is superior to that in the control arm. RCTs emerged mid-last century as the gold standard for assessing efficacy, becoming the cornerstone of the value of new therapies, yet their ethical grounds are a matter of debate. We introduce the concept of unnecessary participants in RCTs, the sum of non-informative participants and non-responders. The non-informative participants are considered not informative with respect to the efficacy measured in the trial in contrast to responders who carry all the information required to conclude on the treatment’s efficacy. The non-responders present the event whether or not they are treated with the experimental treatment. The unnecessary participants carry the burden of having to participate in a clinical trial without benefiting from it, which might include experiencing side effects. Thus, these unnecessary participants carry the ethical loss that is inherent to the RCT methodology. On the contrary, responders to the experimental treatment bear its entire efficacy in the RCT. Starting from the proportions observed in a real placebo-controlled trial from the literature, we carried out simulations of RCTs progressively increasing the proportion of responders up to 100%. We show that the number of unnecessary participants decreases steadily until the RCT’s ethical loss reaches a minimum. In parallel, the trial sample size decreases (presumably its cost as well), although the trial’s statistical power increases as shown by the increase of the chi-square comparing the event rates between the two arms. Thus, we expect that increasing the proportion of responders in RCTs would contribute to making them more ethically acceptable, with less false negative outcomes.

Flow of the Bingham-Papanastasiou Regularized Material in a Channel in the Presence of Obstacles: Correlation between Hydrodynamic Forces and Spacing of Obstacles

The numerical modeling and simulation for the stationary Bingham fluid flow around two confined circular cylinders with various gap ratios are studied. The singularity in the model’s apparent viscosity is dealt by Papanastasiou’s regularization. The model equations are discretized by adopting the methodology based on finite element method (FEM) by choosing a mixed higher order LBB-stable P 2 − P 1 finite element pair. The direct solver PARADISO has been utilized to solve the linearized system of equations. Hydrodynamic forces represented by drag and lift coefficients are computed, and a correlation coefficient is calculated for the gap ratios 0.1 ≤ G p ≤ 0.3 and for several values of the Bingham number 0 ≤ B n ≤ 50 . Line graphs for horizontal and vertical velocities are drawn. Moreover, velocity and pressure profiles are plotted for pertinent values of the parameters. Plug and shear zones are revealed via velocity snapshots in the domain. Pressure is nonlinear in the vicinity of the obstacles and becomes linear downstream in the cylinders as expected in channel flows.

Fast interaction of Cu2+ with S2O3 2− in aqueous solution

In this paper, a comparison between the experimental values for the kinetics of the fast redox reaction between Cu2+ and S2O3 2− and some possible variants of analogical modeling and numerical simulation for this pre-equilibrium reaction have been presented. One of them is based on a function with a periodical, strongly under-damped component. For a non-periodical fast damped evolution of reaction between Cu2+ and S2O3 2−, this paper proposes a variant of numerical modeling and simulation based on two exponential functions. For this complex reaction kinetics, the proposed approach based on application of neural networks is an efficient and accurate tool to solve modeling problems. The method ensures a good approximation of the experimental data, with a remarkable flexibility of analyses and synthesis as elaborated in the paper. The associated numerical simulation operates with an easy and flexible program, which allows the change in large limits of some structure parameters, for the adaptation of the numerical results with the experimental measurements.