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INTRODUCTION: Estimating treatment effects as time savings in disease progression may be more easily interpretable than assessing the absolute difference or a percentage reduction. In this study, we investigate the statistical considerations of the existing method for estimating time savings and propose alternative complementary methods. METHODS: We propose five alternative methods to estimate the time savings from different perspectives. These methods are applied to simulated clinical trial data that mimic or modify the Clinical Dementia Rating Sum of Boxes progression trajectories observed in the Clarity AD lecanemab trial. RESULTS: Our study demonstrates that the proposed methods can generate more precise estimates by considering two crucial factors: (1) the absolute difference between treatment arms, and (2) the observed progression rate in the treatment arm. DISCUSSION: Quantifying treatment effects as time savings in disease progression offers distinct advantages. To provide comprehensive estimations, it is important to use various methods. Highlights: We explore the statistical considerations of the current method for estimating time savings.We proposed alternative methods that provide time savings estimations based on the observed absolute differences.By using various methods, a more comprehensive estimation of time savings can be achieved. [ABSTRACT FROM AUTHOR]

Asymptotic approaches are traditionally used to calculate confidence intervals for intraclass correlation coefficient in a clustered binary study. When sample size is small to medium, or correlation or response rate is near the boundary, asymptotic intervals often do not have satisfactory performance with regard to coverage. We propose using the importance sampling method to construct the profile confidence limits for the intraclass correlation coefficient. Importance sampling is a simulation based approach to reduce the variance of the estimated parameter. Four existing asymptotic limits are used as statistical quantities for sample space ordering in the importance sampling method. Simulation studies are performed to evaluate the performance of the proposed accurate intervals with regard to coverage and interval width. Simulation results indicate that the accurate intervals based on the asymptotic limits by Fleiss and Cuzick generally have shorter width than others in many cases, while the accurate intervals based on Zou and Donner asymptotic limits outperform others when correlation and response rate are close to their boundaries. [ABSTRACT FROM AUTHOR]

Background: Recently, several adaptive one-arm two-stage designs have been developed by fully using the information from previous stages to reduce the expected sample size in clinical trials with binary endpoints as primary outcome. It is important to compute exact confidence limits for these studies.Methods: In this article, we propose three new one-sided limits by ordering the sample space based on p-value, average response rate at each stage, and asymptotic lower limit, as compared to another three existing sample size ordering approaches based on average response rate. Among the three proposed approaches, the one based on the average response rate at each stage is not exact, and the remaining two approaches are exact with the coverage probability guaranteed.Results: We compare these exact intervals by using the two commonly used criteria: simple average length and expected length. The existing three approaches based on average response rate have similar performance, and they have shorter expected lengths than the two proposed exact approaches although the gain is small, while this trend is reversed under the simple average criterion.Conclusions: We would recommend the two exact proposed approaches based on p-value and asymptotic lower limit under the simple average length criterion, and the approach based on average response rate under the expected length criterion. [ABSTRACT FROM AUTHOR]

Background: Simon's two-stage design is the most widely implemented among multi-stage designs in phase II clinical trials to assess the activity of a new treatment in a single-arm study. In this two-stage design, the sample size from the second stage is fixed regardless of the number of responses observed in the first stage.Methods: We develop a new minimax adaptive design for phase II clinical trials, by using the branch-and-bound intelligent algorithm based on conditional error functions.Results: We compare the performance of the proposed design and competitors, including Simon's minimax design, and a modified Simon's design that allows early stopping for futility or efficacy. The maximum sample size of the proposed minimax adaptive design is guaranteed to be less than or equal to those from other existing designs. When the proposed design has the same maximum sample size as others, it always has the smallest expected sample size. In addition to the minimax adaptive design, we also introduce admissible adaptive designs determined from a Bayesian perspective.Conclusions: The proposed adaptive minimax design can save sample sizes for a clinical trial. The minimum required sample size is critical to reduce the cost of a project. [ABSTRACT FROM AUTHOR]

Introduction: Estimating treatment effects as time savings in disease progression may be more easily interpretable than assessing the absolute difference or a percentage reduction. In this study, we investigate the statistical considerations of the existing method for estimating time savings and propose alternative complementary methods., Methods: We propose five alternative methods to estimate the time savings from different perspectives. These methods are applied to simulated clinical trial data that mimic or modify the Clinical Dementia Rating Sum of Boxes progression trajectories observed in the Clarity AD lecanemab trial., Results: Our study demonstrates that the proposed methods can generate more precise estimates by considering two crucial factors: (1) the absolute difference between treatment arms, and (2) the observed progression rate in the treatment arm., Discussion: Quantifying treatment effects as time savings in disease progression offers distinct advantages. To provide comprehensive estimations, it is important to use various methods., Highlights: We explore the statistical considerations of the current method for estimating time savings. We proposed alternative methods that provide time savings estimations based on the observed absolute differences. By using various methods, a more comprehensive estimation of time savings can be achieved., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALK tSTIM ) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALK tSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALK tSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALK tSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALK tSTIM ; Placebo + WALK tSTIM ; and tAIH + WALK tSHAM . Participants receive daily tAIH (fifteen 90-sec episodes at 10% O 2 with 60-sec intervals at 21% O 2 ) or daily placebo (fifteen 90-sec episodes at 21% O 2 with 60-sec intervals at 21% O 2 ) before a 45-min session of WALK tSTIM or WALK tSHAM . Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI., Trial Registration: ClinicalTrials.gov, NCT05563103., Competing Interests: Drs. Gad and Edgerton are co-founders and hold shareholder interest in SpineX, Inc., (© William M. Muter et al., 2023; Published by Mary Ann Liebert, Inc.)

Objectives: In January 2014, Nevada became 1 of the 32 states that have expanded Medicaid under the Affordable Care Act. As a result of the expansion, 276,400 additional Nevada residents received Medicaid insurance. The objectives of this paper were to examine the impact of Nevada's Medicaid expansion on changes in rates of hospital admissions for ambulatory care-sensitive conditions (ACSCs), which are potentially preventable with good access to outpatient medical care, and to examine the racial/ethnic disparities in such rates., Study Design: We used complete inpatient discharge data (for the years 2012, 2013, and 2014, and the first 3 quarters of 2015) from all nonfederal acute care community hospitals in Nevada., Methods: We employed pooled cross-sectional design with a difference-in-differences approach to identify overall and race/ethnicity-specific changes in admissions for ACSCs, adjusted for secular trends unrelated to expansion. We examined admissions for ACSCs among adults aged 18 to 64 years (those most likely to have been affected by the reform) admitted for overall, acute, and chronic ACSC composites in the 24 months before and 21 months after the date on which expansion was implemented., Results: After adjusting for confounders, we found that Hispanic patients with Medicaid were more likely to be admitted for ACSCs after Nevada's Medicaid expansion (overall quality composite: odds ratio [OR], 1.20; P = .05; chronic quality composite: OR, 1.34; P = .02)., Conclusions: This analysis provides evidence that Medicaid expansion may have limited potential to reduce the disparities in rates of hospital admissions for ACSCs. In Nevada, additional efforts might be needed to improve access to outpatient care and reduce preventable admissions.