Assessment of type I error rate associated with dose-group switching in a longitudinal Alzheimer trial

In clinical trials, there always is the possibility to use data-driven adaptation at the end of a study. There prevails, however, concern on whether the type I error rate of the trial could be inflated with such design, thus, necessitating multiplicity adjustment. In this project, a simulation experiment was set up to assess type I error rate inflation associated with switching dose group as a function of dropout rate at the end of the study, where the primary analysis is in terms of a longitudinal outcome. This simulation is inspired by a clinical trial in Alzheimer's disease. The type I error rate was assessed under a number of scenarios, in terms of differing correlations between efficacy and tolerance, different missingness mechanisms, and different probabilities of switching. A collection of parameter values was used to assess sensitivity of the analysis. Results from ignorable likelihood analysis show that the type I error rate with and without switching was approximately the posited error rate for the various scenarios. Under last observation carried forward (LOCF), the type I error rate blew up both with and without switching. The type I error inflation is clearly connected to the criterion used for switching. While in general switching, in a way related to the primary endpoint, may impact the type I error, this was not the case for most scenarios in the longitudinal Alzheimer trial setting under consideration, where patients are expected to worsen over time.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=lbps20status: publishe

Development and formative evaluation of an innovative mHealth intervention for improving coverage of community-based maternal, newborn and child health services in rural areas of India. Glob Health Action 2015; 8:26769

Background: A new cadre of village-based frontline health workers, called Accredited Social Health Activists (ASHAs), was created in India. However, coverage of selected community-based maternal, newborn and child health (MNCH) services remains low. Objective: This article describes the process of development and formative evaluation of a complex mHealth intervention (ImTeCHO) to increase the coverage of proven MNCH services in rural India by improving the performance of ASHAs. Design: The Medical Research Council (MRC) framework for developing complex interventions was used. Gaps were identified in the usual care provided by ASHAs, based on a literature search, and SEWA Rural'

Development and formative evaluation of an innovative mHealth intervention for improving coverage of community-based maternal, newborn and child health services in rural areas of India

Background: A new cadre of village-based frontline health workers, called Accredited Social Health Activists (ASHAs), was created in India. However, coverage of selected community-based maternal, newborn and child health (MNCH) services remains low. Objective: This article describes the process of development and formative evaluation of a complex mHealth intervention (ImTeCHO) to increase the coverage of proven MNCH services in rural India by improving the performance of ASHAs. Design: The Medical Research Council (MRC) framework for developing complex interventions was used. Gaps were identified in the usual care provided by ASHAs, based on a literature search, and SEWA Rural's1 three decades of grassroots experience. The components of the intervention (mHealth strategies) were designed to overcome the gaps in care. The intervention, in the form of the ImTeCHO mobile phone and web application, along with the delivery model, was developed to incorporate these mHealth strategies. The intervention was piloted through 45 ASHAs among 45 villages in Gujarat (population: 45,000) over 7 months in 2013 to assess the acceptability, feasibility, and usefulness of the intervention and to identify barriers to its delivery. Results: Inadequate supervision and support to ASHAs were noted as a gap in usual care, resulting in low coverage of selected MNCH services and care received by complicated cases. Therefore, the ImTeCHO application was developed to integrate mHealth strategies in the form of job aid to ASHAs to assist with scheduling, behavior change communication, diagnosis, and patient management, along with supervision and support of ASHAs. During the pilot, the intervention and its delivery were found to be largely acceptable, feasible, and useful. A few changes were made to the intervention and its delivery, including 1) a new helpline for ASHAs, 2) further simplification of processes within the ImTeCHO incentive management system and 3) additional web-based features for enhancing value and supervision of Primary Health Center (PHC) staff. Conclusions: The effectiveness of the improved ImTeCHO intervention will be now tested through a cluster randomized trial

Nanosheet-Assembled NiO Microstructures for High-Performance Supercapacitors

Nanosheet-assembled NiO microstructures have been synthesized via a hydrothermal method. The presence of anionic surfactant in the fabrication process initiates the formation of lamellar micelles and a self-assembling process. This leads to the formation of NiO nanosheets and organizes it into microstructures. The effect of preparation temperature on the morphological, structural, and electrochemical properties and stability upon continuous charge/discharge cycles has been examined for supercapacitor applications. Electrochemical analysis demonstrated that NiO nanosheets prepared at 160 °C are capable of delivering a specific capacitance of 989 F g^–1 at a scan rate of 3 mV s^–1 for the potential window of 0–0.6 V. The nanosheets exhibit excellent capacity retention, 97% retention after 1000 continuous charge/discharge cycles, and an energy density of 49.45 W h kg^–1

Representativeness of European clinical trial populations in mild Alzheimer’s disease dementia: a comparison of 18-month outcomes with real-world data from the GERAS observational study

Abstract Background Comparison of disease progression between placebo-group patients from randomised controlled trials (RCTs) and real-world patients can aid in assessing the generalisability of RCT outcomes. This analysis compared outcomes between community-dwelling patients with mild Alzheimer’s disease (AD) dementia from two RCTs (pooled European (EU) data from EXPEDITION and EXPEDITION 2) and similar patients from the EU GERAS observational study. Methods Data from placebo-group patients with mild AD dementia from the RCTs (EU countries only) were compared with data from GERAS patients with mild AD dementia. Between-group differences for changes over 18 months were analysed for cognition, functioning, neuropsychiatric symptoms, health-related quality of life (HRQoL) and caregiver time using propensity score-adjusted models. A sensitivity analysis compared EU/North American (EU/NA) EXPEDITION patients with GERAS patients. Results EU EXPEDITION patients (n = 168) were younger than GERAS patients (n = 566) (mean (standard deviation, SD) age 71.9 (7.4) versus 77.3 (6.9) years; p < 0.001) and were more likely to use AD treatment (95% versus 84%; p < 0.001). Cognitive performance was similar at baseline in both populations, although GERAS patients showed greater functional impairment (p = 0.005) and lower HRQoL (p < 0.05). At 18 months, no statistically significant differences between EXPEDITION (n = 133) and GERAS (n = 417) patients were observed for changes in cognitive, functional, neuropsychiatric and HRQoL outcomes. Least squares mean (95% confidence interval) change in caregiver time (hours/month) spent on instrumental activities of daily living (iADL; 29.22 (19.16, 39.27) versus 3.20 (−11.89, 18.28), p = 0.001) and supervision (66.59 (47.49, 85.69) versus 3.04 (−25.39, 31.48), p < 0.001) showed greater increases in GERAS than EXPEDITION. In the sensitivity analysis, changes in neuropsychiatric and HRQoL scores and caregiver time spent on basic ADL were also significantly greater in GERAS than in EU/NA EXPEDITION patients. Conclusions Patients with mild AD dementia participating in the EU EXPEDITION RCTs and the GERAS observational study showed a similar decline in cognitive, functional and neuropsychiatric symptoms over 18 months, whereas changes in caregiver time measures were significantly greater in GERAS. Results indicate the importance of using similar regions when comparing real-world and RCT data. Trial registration ClinicalTrials.gov NCT00905372 EXPEDITION. Registered 18 May 2009. ClinicalTrials.gov NCT00904683 EXPEDITION 2. Registered 18 May 2009

Minimally informative prior distributions for non-parametric Bayesian analysis

We address the problem of how to conduct a minimally informative, non-parametric Bayesian analysis. The central question is how to devise a model so that the posterior distribution satisfies a few basic properties. The concept of 'local mass' provides the key to the development of the limiting Dirichlet process model. This model is then used to provide an engine for inference in the compound decision problem and for multiple-comparisons inference in a one-way analysis-of-variance setting. Our analysis in this setting may be viewed as a limit of the analyses that were developed by Escobar and by Gopalan and Berry. Computations for the analysis are described, and the predictive performance of the model is compared with that of mixture of Dirichlet processes models. Copyright (c) 2010 Royal Statistical Society.