The analytic construction of D-optimal designs for the two-variable binary logistic regression model without interaction

Candidate locally D-optimal designs for the binary two-variable logistic model with no interaction, which comprise 3 and 4 support points lying in the first quadrant of the two-dimensional Euclidean space, were introduced by Haines et al. (D-optimal designs for logistic regression in two variables. In: Lopez-Fidalgo J, Rodrigez-Diaz JM, Torsney B, editors. MODA8 – advances in model-oriented designs and analysis. Heidelberg: Physica-Verlag; 2007. p. 91–98). The authors proved algebraically the global D-optimality of the 3-point design for the special case in which the intercept parameter is equal to?1.5434. However for other selected values of the intercept parameter, the global D-optimality of the proposed 3- and 4-point designs was only demonstrated numerically. In this paper, we provide analytical proofs of the D-optimality of these 3- and 4-point designs for all negative and zero intercept parameters of the binary two-variable logistic model with no interaction. The results are extended to the construction of D-optimal designs on a rectangular design space and illustrated by means of two examples of which one is a real example taken from the literature.     

Evaluation of program success for programs with multiple trials in binary outcomes

A late‐stage clinical development program typically contains multiple trials. Conventionally, the program's success or failure may not be known until the completion of all trials. Nowadays, interim analyses are often used to allow evaluation for early success and/or futility for each individual study by calculating conditional power, predictive power and other indexes. It presents a good opportunity for us to estimate the probability of program success (POPS) for the entire clinical development earlier. The sponsor may abandon the program early if the estimated POPS is very low and therefore permit resource savings and reallocation to other products. We provide a method to calculate probability of success (POS) at an individual study level and also POPS for clinical programs with multiple trials in binary outcomes. Methods for calculating variation and confidence measures of POS and POPS and timing for interim analysis will be discussed and evaluated through simulations. We also illustrate our approaches on historical data retrospectively from a completed clinical program for depression. Copyright © 2015 John Wiley & Sons, Ltd.     

To adjust or not to adjust for baseline when analyzing repeated binary responses? The case of complete data when treatment comparison at study end is of interest

The benefits of adjusting for baseline covariates are not as straightforward with repeated binary responses as with continuous response variables. Therefore, in this study, we compared different methods for analyzing repeated binary data through simulations when the outcome at the study endpoint is of interest. Methods compared included chi‐square, Fisher's exact test, covariate adjusted/unadjusted logistic regression (Adj.logit/Unadj.logit), covariate adjusted/unadjusted generalized estimating equations (Adj.GEE/Unadj.GEE), covariate adjusted/unadjusted generalized linear mixed model (Adj.GLMM/Unadj.GLMM). All these methods preserved the type I error close to the nominal level. Covariate adjusted methods improved power compared with the unadjusted methods because of the increased treatment effect estimates, especially when the correlation between the baseline and outcome was strong, even though there was an apparent increase in standard errors. Results of the Chi‐squared test were identical to those for the unadjusted logistic regression. Fisher's exact test was the most conservative test regarding the type I error rate and also with the lowest power. Without missing data, there was no gain in using a repeated measures approach over a simple logistic regression at the final time point. Analysis of results from five phase III diabetes trials of the same compound was consistent with the simulation findings. Therefore, covariate adjusted analysis is recommended for repeated binary data when the study endpoint is of interest. Copyright © 2015 John Wiley & Sons, Ltd.     

Ngā Mōwaho: an analysis of Māori responses to the Christchurch earthquakes

Since September 2010, a series of earthquakes have caused widespread social, financial and environmental devastation in Christchurch, New Zealand. Anecdotal evidence suggests that local Māori responded effectively to facilitate community recovery and resilience. However, the form, content and extent of that response has not been adequately recognised or documented. This qualitative research project, conducted in partnership with Te Rūnanga o Ngāi Tahu, has documented the way in which Māori cultural factors have facilitated disaster risk reduction and management in response to the earthquakes. This paper explores sets of understandings about marginalisation and inclusion within the narratives of 70 Māori community members who contributed to this research. Forms of marginalisation expressed in participants’ narratives include delayed linkages to the formal emergency management infrastructure, difficulties integrating Māori volunteers into the mainstream response as well as enduring barriers to Māori engagement within Civil Defence, illustrated in a lack of Māori representation as well as tikanga Māori within emergency planning. We argue that the knowledge, principles and practices embedded within Māori responses to the Christchurch earthquakes may be contextually relevant for national and regional policy development in the area of disaster risk management, response and recovery.     

The consequences of unobserved heterogeneity in a sequential logit model

Cameron and Heckman (1998) established that a sequential logit model is more sensitive than many other models to the possible biasing influence of unobserved heterogeneity. This article proposes a method which allows researchers to find out how large this potential problem is for their data, their model, and their hypothesis of interest. This is done by proposing a set of scenarios for this unobserved heterogeneity, and showing how to estimate the effects of interest given these scenarios. The set of results from these scenarios give an indication of how sensitive the results are to assumptions regarding unobserved heterogeneity. This sensitivity analysis has been applied to a study of educational attainment in the Netherlands, and it showed that that the finding that the effect of father's education declined over transitions is quite sensitive to the assumptions made about unobserved heterogeneity, but that the finding that the effect of father's education declined over birth cohorts is more robust than is often feared.     

Evaluating Item Discrimination Power of WHOQOL-BREF from an Item Response Model Perspectives

Quality of life (QOL) has become an important component of health. By using the methodology of psychometric theory, we examine the item properties of the WHOQOL-BRIEF. Samejima’s graded response model with natural metrics of the logistic response function was fitted. The results showed items with negative natures were less discriminating. Items written in a specific way were more suitable to assess certain subgroups. The national items showed variation in discriminatory power. Questions measuring objective and specific issues performed worse than items assessing general aspects of the QOL.     

An EWMA chart for monitoring process mean

In the statistical process control literature, there exists several improved quality control charts based on cost-effective sampling schemes, including the ranked set sampling (RSS) and median RSS (MRSS). A generalized cost-effective RSS scheme has been recently introduced for efficiently estimating the population mean, namely varied L RSS (VLRSS). In this article, we propose a new exponentially weighted moving average (EWMA) control chart for monitoring the process mean using VLRSS, named the EWMA-VLRSS chart, under both perfect and imperfect rankings. The EWMA-VLRSS chart encompasses the existing EWMA charts based on RSS and MRSS (named the EWMA-RSS and EWMA-MRSS charts). We use extensive Monte Carlo simulations to compute the run length characteristics of the EWMA-VLRSS chart. The proposed chart is then compared with the existing EWMA charts. It is found that, with either perfect or imperfect rankings, the EWMA-VLRSS chart is more sensitive than the EWMA-RSS and EWMA-MRSS charts in detecting small to large shifts in the process mean. A real dataset is also used to explain the working of the EWMA-VLRSS chart.     

A new estimator of proportion with a linear function using data from two-decks randomized response model

A new estimator for estimating the proportion of a potentially sensitive attribute in survey sampling has been introduced by solving a linear equation. The proposed estimator has been compared with the estimator proposed by Odumade and Singh (2009) with equal protection to all of the respondents. The asymptotic properties of the proposed estimator are investigated through exact numerical illustrations for different choices of parameters. A non randomized response approach has been suggested. A scope for further research has also been pointed out.     

Response‐adaptive designs for binary responses: How to offer patient benefit while being robust to time trends?

Response‐adaptive randomisation (RAR) can considerably improve the chances of a successful treatment outcome for patients in a clinical trial by skewing the allocation probability towards better performing treatments as data accumulates. There is considerable interest in using RAR designs in drug development for rare diseases, where traditional designs are not either feasible or ethically questionable. In this paper, we discuss and address a major criticism levelled at RAR: namely, type I error inflation due to an unknown time trend over the course of the trial. The most common cause of this phenomenon is changes in the characteristics of recruited patients—referred to as patient drift. This is a realistic concern for clinical trials in rare diseases due to their lengthly accrual rate. We compute the type I error inflation as a function of the time trend magnitude to determine in which contexts the problem is most exacerbated. We then assess the ability of different correction methods to preserve type I error in these contexts and their performance in terms of other operating characteristics, including patient benefit and power. We make recommendations as to which correction methods are most suitable in the rare disease context for several RAR rules, differentiating between the 2‐armed and the multi‐armed case. We further propose a RAR design for multi‐armed clinical trials, which is computationally efficient and robust to several time trends considered.