Designing Studies for Dose Response

Wong, Weng Kee; Lachenbruch, Peter A.

doi:10.1002/(sici)1097-0258(19960229)15:4<343::aid-sim163>3.0.co;2-f

Cited by 35 publications

(7 citation statements)

References 11 publications

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“…The differences between the sham and the minimal treatment (100 pulses at 100 V) groups were studied by an independent samples t test. The dependency of the extent of BBBd in the number of pulses and treatment voltage was studied using a linear regression analysis [37] both for the MRI experiments and the EB experiments. Linearity, homoscedasticity and normality of the residuals were verified.…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration

et al. 2021

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The blood–brain barrier (BBB) is a major hurdle for the treatment of central nervous system disorders, limiting passage of both small and large therapeutic agents from the blood stream into the brain. Thus, means for inducing BBB disruption (BBBd) are urgently needed. Here, we studied the application of low pulsed electrical fields (PEFs) for inducing BBBd in mice. Mice were treated by low PEFs using electrodes pressed against both sides of the skull (100–400 square 50 µs pulses at 4 Hz with different voltages). BBBd as a function of treatment parameters was evaluated using MRI-based treatment response assessment maps (TRAMs) and Evans blue extravasation. A 3D numerical model of the mouse brain and electrodes was constructed using finite element software, simulating the electric fields distribution in the brain and ensuring no significant temperature elevation. BBBd was demonstrated immediately after treatment and significant linear regressions were found between treatment parameters and the extent of BBBd. The maximal induced electric field in the mice brains, calculated by the numerical model, ranged between 62.4 and 187.2 V/cm for the minimal and maximal applied voltages. These results demonstrate the feasibility of inducing significant BBBd using non-invasive low PEFs, well below the threshold for electroporation.

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Section: Discussionmentioning

confidence: 99%

Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration

et al. 2021

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“…Even when there is good rationale for a uniform design, the choice for the number of points can be problematic. (30) Note: The D-and τ -efficiencies of the design ξ u are given, along with the D-efficiencies of…”

Section: Locally Optimal Designs For the Hunt-bowman Modelmentioning

confidence: 99%

Optimal Experimental Design Strategies for Detecting Hormesis

Dette

Pepelyshev²,

Wong

2011

Risk Analysis

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Hormesis is a widely observed phenomenon in many branches of life sciences ranging from toxicology studies to agronomy with obvious public health and risk assessment implications. We address optimal experimental design strategies for determining the presence of hormesis in a controlled environment using the recently proposed Hunt-Bowman model. We propose alternative models that have an implicit hormetic threshold, discuss their advantages over current models, construct and study properties of optimal designs for (i) estimating model parameters, (ii) estimating the threshold dose, and (iii) testing for the presence of hormesis. We also determine maximin optimal designs that maximize the minimum of the design efficiencies when we have multiple design criteria or there is model uncertainty where we have a few plausible models of interest. We apply these optimal design strategies to a teratology study and show that the proposed designs outperform the implemented design by a wide margin for many situations.

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“…The recommended clinical dose should be chosen from both efficacy and safety points of view experimental design are given by Pukelsheim (1993) and Wong and Lachenbruch (1996) , who have reviewed the dose-response design and used optimal design criteria for linear and quadric regression with some simulations. Use of an active drug as a control may not be strictly needed to define the shape of the dose-response curve, and for novel indications there may be no drug with the relevant activity.…”

Section: Statistical Issues In the Drug Evaluation Processmentioning

confidence: 92%

2. Clinical and Medical Evaluation Process

Isomura

Hamasaki

Goto

2003

Journal of the Japanese Society of Computational Statistics

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The International Conference on Harmonization (ICH) has recently developed the ICH guidelines, which are the common guidelines for regulatory requirements in the ICH regions, i.e. Japan, and the United States (US) and Europe. The guidelines have been implemented in the three regions, and the people involved in drug evaluation in the pharmaceutical industry, such as statisticians and pharmaceutical scientists, have referred the guidelines to their daily work when they perform the drug evaluation process. This paper aims to discuss some statistical issues in the drug evaluation process that are commonly encountered when applying the ICH guidelines. It also provides a few practical ideas for the future drug evaluation process. In this paper the emphasis is placed on the following ICH guidelines: "Dose-Response Information to Support Drug Registration" (ICH-E4), "Ethnic Factors in the Acceptability of Foreign Clinical Data" (ICH-E5) and "Choice of Control Group in Clinical Trials" (ICH-E10).

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Designing Studies for Dose Response

Cited by 35 publications

References 11 publications

Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration

Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration

Optimal Experimental Design Strategies for Detecting Hormesis

2. Clinical and Medical Evaluation Process

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