scholarly journals Individual-level response adaptive crossover trial design for epilepsy: structure and simulation

2020 ◽  
Author(s):  
Wesley T. Kerr ◽  
Xingruo Zhang ◽  
John M. Stern
Keyword(s):  
Seizure Frequency ◽  
Statistical Power ◽  
Crossover Design ◽  
Controlled Clinical Trial ◽  
Duration Of Treatment ◽  
Individual Level ◽  
Group Assignment ◽  
Likelihood Approach ◽  
Adaptive Crossover ◽  
Static Group

Trials of antiseizure medications involve static group assignments for treatments with pre-specified durations. We propose a response-adaptive crossover design using basic statistical assumptions regarding both seizure count and duration of treatment to determine when a participant can change group assignment. We modelled seizure frequency as a Poisson process and estimated the likelihood that seizure frequency had decreased by 50% compares to baseline using both a Bayesian and maximum likelihood approach. We simulated trials to estimate the influence of this design on statistical power and observation duration with each treatment. For patients with 9 baseline seizures in 4 weeks who had no change in seizure frequency, the simulation identified non-response in a median of 16 days. The response-adaptive crossover design resulted in a modest increase in statistical power to identify an effective treatment while maximizing the time in a group producing a response. Only 8% of participants remained in the placebo group for all 90 days of the simulated trials. These example theoretical results can provide quantitative guidance regarding objective criteria to determine non-response in real-time during a controlled clinical trial without revealing the assigned treatment. Implementing a response-adaptive crossover design may both improve statistical power while minimizing participant risk.

The Limits of Ego Depletion

2019 ◽  
Vol 50 (5-6) ◽  
pp. 292-304 ◽  
Author(s):  
Mario Wenzel ◽  
Marina Lind ◽  
Zarah Rowland ◽  
Daniela Zahn ◽  
Thomas Kubiak
Keyword(s):  
Research Agenda ◽  
Statistical Power ◽  
Interindividual Variability ◽  
Ego Depletion ◽  
Crossover Design ◽  
Effect Sizes ◽  
Future Research ◽  
Future Research Agenda ◽  
Depletion Effect ◽  
Within Subjects

Abstract. Evidence on the existence of the ego depletion phenomena as well as the size of the effects and potential moderators and mediators are ambiguous. Building on a crossover design that enables superior statistical power within a single study, we investigated the robustness of the ego depletion effect between and within subjects and moderating and mediating influences of the ego depletion manipulation checks. Our results, based on a sample of 187 participants, demonstrated that (a) the between- and within-subject ego depletion effects only had negligible effect sizes and that there was (b) large interindividual variability that (c) could not be explained by differences in ego depletion manipulation checks. We discuss the implications of these results and outline a future research agenda.

scholarly journals Power analyses for moderator effects with (non)randomly varying slopes in cluster randomized trials

Methodology ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. 92-110
Author(s):  
Nianbo Dong ◽  
Jessaca Spybrook ◽  
Benjamin Kelcey ◽  
Metin Bulus
Keyword(s):  
Statistical Power ◽  
Randomized Trials ◽  
Future Research ◽  
Size Difference ◽  
Detectable Effect ◽  
Cluster Randomized Trials ◽  
Individual Level ◽  
Moderator Effects ◽  
Cluster Randomized ◽  
Power Analyses

Researchers often apply moderation analyses to examine whether the effects of an intervention differ conditional on individual or cluster moderator variables such as gender, pretest, or school size. This study develops formulas for power analyses to detect moderator effects in two-level cluster randomized trials (CRTs) using hierarchical linear models. We derive the formulas for estimating statistical power, minimum detectable effect size difference and 95% confidence intervals for cluster- and individual-level moderators. Our framework accommodates binary or continuous moderators, designs with or without covariates, and effects of individual-level moderators that vary randomly or nonrandomly across clusters. A small Monte Carlo simulation confirms the accuracy of our formulas. We also compare power between main effect analysis and moderation analysis, discuss the effects of mis-specification of the moderator slope (randomly vs. non-randomly varying), and conclude with directions for future research. We provide software for conducting a power analysis of moderator effects in CRTs.

Safety and Efficacy of Brivaracetam in Pediatric Refractory Epilepsy: A Single-Center Clinical Experience

2019 ◽  
Vol 35 (2) ◽  
pp. 102-105 ◽  
Author(s):  
Sara McGuire ◽  
Gustavo Silva ◽  
Darshan Lal ◽  
Divya S. Khurana ◽  
Agustin Legido ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Chart Review ◽  
Refractory Epilepsy ◽  
Focal Epilepsy ◽  
Retrospective Chart Review ◽  
Average Dose ◽  
Limited Data ◽  
Duration Of Treatment ◽  
Seizure Reduction ◽  
The Mean

Brivaracetam is a new antiepileptic drug with limited data in children. The objective of this study was to assess the efficacy/tolerability of brivaracetam. This is a retrospective chart review of children/adolescents with refractory epilepsy treated with brivaracetam from 2016 to 2018. The primary outcome was seizure reduction (decrease in seizure frequency >50%). Twenty-three patients were identified. Mean age at initiation was 12.5 years. Fourteen were females. Epilepsy was focal in 11, generalized in 6, and mixed in 3. Average dose was 3.9 mg/kg/d. The mean duration of treatment was 8.2 months. Eight had greater than 50% decrease in seizure frequency, of which 7 had focal epilepsy, and 1 had Lennox-Gastaut/mixed epilepsy. Two had drowsiness and 3 behavioral complaints. One experienced tingling and dizziness. Our retrospective review suggests that brivaracetam is an effective therapy for refractory focal epilepsy in children older than 4 years of age.

scholarly journals Effect of Keishibukuryogan on Endothelial Function in Patients with at Least One Component of the Diagnostic Criteria for Metabolic Syndrome: A Controlled Clinical Trial with Crossover Design

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yutaka Nagata ◽  
Hirozo Goto ◽  
Hiroaki Hikiami ◽  
Tatsuya Nogami ◽  
Makoto Fujimoto ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Trial ◽  
Endothelial Function ◽  
Reactive Hyperemia ◽  
Control Period ◽  
Crossover Design ◽  
Controlled Clinical Trial ◽  
Related Factors ◽  
Group A ◽  
Group B

We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan), a traditional Japanese (Kampo) formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000) in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval) or group B (first control, then KBG-treatment). In forty-nine (27, group A; 22, group B) patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI) increased and those of serum nonesterified fatty acid (NEFA), malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors.

scholarly journals Crossover design

2019 ◽  
Vol 7 (30) ◽  
pp. 63-66
Author(s):  
Shengpin Yang ◽  
Gilbert Berdine
Keyword(s):  
Clinical Trial ◽  
Study Design ◽  
Statistical Power ◽  
Crossover Design ◽  
Type Ii ◽  
Meaningful Difference ◽  
Total Budget ◽  
Sufficient Statistical Power

I am planning a clinical trial to compare two diets on reducing the risk of type II diabetes.Because there is a restriction on the total budget, I would prefer to enroll a small number ofparticipants. Meanwhile, it is important that there is sufficient statistical power to detect aclinically meaningful difference. Is there any study design that can be utilized?

Robustness of Statistical Power in Group-Randomized Studies of Mediation Under an Optimal Sampling Framework

Methodology ◽  
2019 ◽  
Vol 15 (3) ◽  
pp. 106-118
Author(s):  
Kyle Cox ◽  
Benjamin Kelcey
Keyword(s):  
Statistical Power ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Design Stage ◽  
Optimal Sampling ◽  
True Parameter ◽  
Individual Level ◽  
Randomized Studies ◽  
Sample Allocation ◽  
Parameter Values

Abstract. When planning group-randomized studies probing mediation, effective and efficient sample allocation is governed by several parameters including treatment-mediator and mediator-outcome path coefficients and the mediator and outcome intraclass correlation coefficients. In the design stage, these parameters are typically approximated using information from prior research and these approximations are likely to deviate from the true values eventually realized in the study. This study investigates the robustness of statistical power under an optimal sampling framework to misspecified parameter values in group-randomized designs with group- or individual-level mediators. The results suggest that estimates of statistical power are robust to misspecified parameter values across a variety of conditions and tests. Relative power remained above 90% in most conditions when the incorrect parameter value ranged between 50% and 150% of the true parameter.

scholarly journals A pooling-based approach to mapping genetic variants associated with DNA methylation

2015 ◽  
Author(s):  
Irene Miriam Kaplow ◽  
Julia L MacIsaac ◽  
Sarah M Mah ◽  
Lisa M McEwen ◽  
Michael S Kobor ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Variants ◽  
Statistical Power ◽  
Epigenetic Modification ◽  
Chromatin Accessibility ◽  
Ctcf Binding ◽  
Sequencing Data ◽  
Individual Level ◽  
Novel Approach ◽  
Genome Wide

DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover less than 2% of the genome and cannot account for allele-specific methylation (ASM). Other studies have performed whole-genome bisulfite sequencing on a few individuals, but these lack statistical power to identify variants associated with DNA methylation. We present a novel approach in which bisulfite-treated DNA from many individuals is sequenced together in a single pool, resulting in a truly genome-wide map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified over 2,000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.

scholarly journals Oxcabazepine (®Trileptal) in Anti-Epileptic Polytherapy

1990 ◽  
Vol 3 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Peder Klosterskov Jensen
Keyword(s):  
Seizure Frequency ◽  
Active Metabolite ◽  
Epileptic Activity ◽  
Double Blind Study ◽  
Duration Of Treatment ◽  
Double Blind ◽  
Significant Difference ◽  
Daily Dose ◽  
Adults And Children ◽  
Clonic Seizures

The anti-epileptic activity of oxcarbazepine (OXC) was compared with that of carbamazepine (CBZ) and the primary active metabolite of OXC, a monohydroxy derivative (MHD). Altogether 255 patients receiving either OXC or MHD (192 and 63 patients respectively) were included in the analysis of efficacy. Out of these 255 patients a total of 40 were children. The duration of treatment varied between 8 and 24weeks. The daily dose of OXC or MHD varied between 600 and 5400 mg (in children 600–2400 mg). Out of five studies two were double-blind controlled studies (including a total of 105 patients) whereas the remaining three were open studies. The results of these studies indicate that, in adults with epilepsy, there is no statistically significant difference in overall seizure frequency between CBZ and OXC. In one double-blind study the number of generalized tonic-clonic seizures was significantly less frequent during treatment with OXC than with CBZ. No statistically significant difference with regard to side-effects was observed between OXC and CBZ. The results in children with epilepsy show a statistically significant difference in seizure frequency in favour of OXC, in comparison with CBZ. Overall, the polytherapy studies in adults and children support the effectiveness and safety of oxcarbazepine.

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