Sample Size Requirements and Study Duration for Testing Main Effects and Interactions in Completely Randomized Factorial Designs When Time to Event is the Outcome

In this paper, we develop the methodology for designing clinical trials with any factorial arrangement when the primary outcome is time to event. We provide a matrix formulation for calculating the sample size and study duration necessary to test any effect with a prespecified type I error rate and power. Assuming that a time to event follows an exponential distribution, we describe the relationships between the effect size, the power, and the sample size. We present examples for illustration purposes. We provide a simulation study to verify the numerical calculations of the expected number of events and the duration of the trial. The change in the power produced by a reduced number of observations or by accruing no patients to certain factorial combinations is also described.     

Markov chain models for multivariate repeated binary data analysis

Repeated categorical outcomes frequently occur in clinical trials. Muenz and Rubinstein (1985) presented Markov chain models to analyze binary repeated data in a breast cancer study. We extend their method to the setting when more than one repeated outcome variable is of interest. In a randomized clinical trial of breast cancer, we investigate the dependency of toxicities on predictor variables and the relationship among multiple toxic effects.     

Choice of Baselines in Clinical Trials: A Simulation Study from Statistical Power Perspective

Multiple assessments of an efficacy variable are often conducted prior to the initiation of randomized treatments in clinical trials as baseline information. Two goals are investigated in this article, where the first goal is to investigate the choice of these baselines in the analysis of covariance (ANCOVA) to increase the statistical power, and the second to investigate the magnitude of power loss when a continuous efficacy variable is dichotomized to categorical variable as commonly reported the biomedical literature. A statistical power analysis is developed with extensive simulations based on data from clinical trials in study participants with end stage renal disease (ESRD). It is found that the baseline choices primarily depend on the correlations among the baselines and the efficacy variable, with substantial gains for correlations greater than 0.6 and negligible for less than 0.2. Continuous efficacy variables always give higher statistical power in the ANCOVA modeling and dichotomizing the efficacy variable generally decreases the statistical power by 25%, which is an important practicum in designing clinical trials for study sample size and realistically budget. These findings can be easily applied in and extended to other clinical trials with similar design.     

Permutation Methods for Comparing the Accuracy of Nested Prediction Models in Survival Analysis

When making patient-specific prediction, it is important to compare prediction models to evaluate the gain in prediction accuracy for including additional covariates. We propose two statistical testing methods, the complete data permutation (CDP) and the permutation cross-validation (PCV) for comparing prediction models. We simulate clinical trial settings extensively and show that both methods are robust and achieve almost correct test sizes; the methods have comparable power in moderate to large sample situations, while the CDP is more efficient in computation. The methods are also applied to ovarian cancer clinical trial data.     

Grappling with Realities: Policy and Practice in HIV Social Work

In 2012 the NSW HIV Strategy 2012–2015: A New Era was released, with a goal of eradicating Human Immunodeficiency Virus (HIV) by 2020. This new policy, prioritising biomedical treatment, has raised challenges for social work practitioners working in the HIV field. We undertook a research project exploring the implications of the Strategy on social work clients and practice. A questionnaire was sent to 57 HIV social workers and 32 (56.1%) responses were received. Thematic analysis identified five main themes affecting social workers and their clients. These were a new stigma, treatment benefits, the complexity of people's lives, the psychosocial voice, and ethical and professional tensions. We propose that a more holistic HIV strategy including the psychosocial realities that inform HIV transmission, testing and treatment options, and adherence be adopted.     

Incorporating Multicultural Learning in Clinically-Based Education in the United States

This study attempted to explore and clarify the ambiguity surrounding cultural concepts, broaden and deepen the current understanding of cultural competency, and operationalize its core components in multicultural education in the United States. The research findings presented in this study were organized into three overarching themes: Level I: knowledge development; Level II: integrative processes; and Level III: practice evaluation. The findings contributed to the formulation of levels in multicultural learning and to the specification of core cultural components in clinical practice.     

Developing a clinical trial governance framework for pharmaceutical industry-funded clinical trials

ABSTRACT

Rising concerns relating to pharmaceutical sponsor bias in the conduct of clinical trials have compelled the need to develop a clinical trial governance framework. This article describes the development of the Conflict of Interest in Research (COIR), a clinical trial governance framework. The COIR, consisting of three process phases (initiation, concurrent, and ongoing), developed following a needs assessment, using a four-stage methodology, and evaluated against the International Conference on Harmonization--Good Clinical Practice (ICH-GCP) guidelines. The Conflict of Interest Resolution algorithm, the backbone of COIR, enables constant surveillance to detect/resolve conflicts at all stages of the clinical trial life-cycle. COIR promotes interaction between the regulatory system and the sponsors, independent of individuals. COIR enables rapid detection of scientific and financial conflicts, to prevent subject harm and, to assure optimal funds utilization, the latter feature helped to reduce a significant burden for the ethics committee, as it lacks financial expertise. COIR is a semi-automated Oracle system, requires manpower, and is affected by human expertise and subjectivity. Complete automation to overcome this limitation will still need human expertise to scale changing trial regulations. Nevertheless, the COIR has won the distinction of the “most favored site” from pharmaceutical sponsors and is anticipated to be adopted by other clinical trial sites.     

Randomized trial of Promoting First Relationships: Effects on maltreated toddlers' separation distress and sleep regulation after reunification

This study investigates the impact of an attachment focused intervention, Promoting First Relationships (PFR), on sleep problems among toddlers in child welfare recently reunified with their birth parent. Recently reunified parent–toddler dyads (n = 43) were drawn from a larger random control trial. Toddlers (11–36 months) and their parents were assessed in two-hour research home visits at enrollment (baseline), and a 6-month post-intervention follow-up. Measures included parental report of sleep problems and research visitor observation of separation distress (using the Toddler Attachment Sort-45). The PFR intervention predicted fewer sleep problems, adjusting for a baseline measure of sleep problems and other covariates. A path model showed evidence of an indirect effect of PFR on sleep problems through declines in separation distress. An attachment focused intervention like PFR that reduces infant separation distress can lead to reductions in sleep problems.     

Improving Outcomes for Unemployed and Homeless Young People: Findings of the YP4 Clinical Controlled Trial of Joined Up Case Management

Abstract

The YP⁴ study was a clinical controlled trial (CCT) of joined up services for young people experiencing both homelessness and unemployment in Victoria, Australia. The joined up service delivery (J group, n = 222) participants were offered intensive client-centred case management, involving direct provision of a range of services as well as the brokering of additional services. The standard services (S group, n = 174) participants remained eligible for standard services. Access to the Australian Government income support agency's (Centrelink) administrative data provided a retention rate close to 90% over the three annual data collection points of the study (baseline, 12 months and 24 months). Both groups improved their circumstances over the two years of the trial. The results showed no statistically significant treatment effects. The effect for employment earnings was approaching significance (p = .06) with J group increasing their employment earnings to a greater extent than S group. The findings and their implications for the implementation of joined up case management, future policy and practice, and future homelessness research is discussed.