Coherence principles in interval‐based dose finding

This paper studies the notion of coherence in interval‐based dose‐finding methods. An incoherent decision is either (a) a recommendation to escalate the dose following an observed dose‐limiting toxicity or (b) a recommendation to deescalate the dose following a non–dose‐limiting toxicity. In a simulated example, we illustrate that the Bayesian optimal interval method and the Keyboard method are not coherent. We generated dose‐limiting toxicity outcomes under an assumed set of true probabilities for a trial of n=36 patients in cohorts of size 1, and we counted the number of incoherent dosing decisions that were made throughout this simulated trial. Each of the methods studied resulted in 13/36 (36%) incoherent decisions in the simulated trial. Additionally, for two different target dose‐limiting toxicity rates, 20% and 30%, and a sample size of n=30 patients, we randomly generated 100 dose‐toxicity curves and tabulated the number of incoherent decisions made by each method in 1000 simulated trials under each curve. For each method studied, the probability of incurring at least one incoherent decision during the conduct of a single trial is greater than 75%. Coherency is an important principle in the conduct of dose‐finding trials. Interval‐based methods violate this principle for cohorts of size 1 and require additional modifications to overcome this shortcoming. Researchers need to take a closer look at the dose assignment behavior of interval‐based methods when using them to plan dose‐finding studies.     

Using Panel Data to Understand the Dynamics of Human Behavior in Response to Flooding

Insights into the dynamics of human behavior in response to flooding are urgently needed for the development of effective integrated flood risk management strategies, and for integrating human behavior in flood risk modeling. However, our understanding of the dynamics of risk perceptions, attitudes, individual recovery processes, as well as adaptive (i.e., risk reducing) intention and behavior are currently limited because of the predominant use of cross-sectional surveys in the flood risk domain. Here, we present the results from one of the first panel surveys in the flood risk domain covering a relatively long period of time (i.e., four years after a damaging event), three survey waves, and a wide range of topics relevant to the role of citizens in integrated flood risk management. The panel data, consisting of 227 individuals affected by the 2013 flood in Germany, were analyzed using repeated-measures ANOVA and latent class growth analysis (LCGA) to utilize the unique temporal dimension of the data set. Results show that attitudes, such as the respondents’ perceived responsibility within flood risk management, remain fairly stable over time. Changes are observed partly for risk perceptions and mainly for individual recovery and intentions to undertake risk-reducing measures. LCGA reveal heterogeneous recovery and adaptation trajectories that need to be taken into account in policies supporting individual recovery and stimulating societal preparedness. More panel studies in the flood risk domain are needed to gain better insights into the dynamics of individual recovery, risk-reducing behavior, and associated risk and protective factors.     

Cox regression with missing covariate data using a modified partial likelihood method

Missing covariate values is a common problem in survival analysis. In this paper we propose a novel method for the Cox regression model that is close to maximum likelihood but avoids the use of the EM-algorithm. It exploits that the observed hazard function is multiplicative in the baseline hazard function with the idea being to profile out this function before carrying out the estimation of the parameter of interest. In this step one uses a Breslow type estimator to estimate the cumulative baseline hazard function. We focus on the situation where the observed covariates are categorical which allows us to calculate estimators without having to assume anything about the distribution of the covariates. We show that the proposed estimator is consistent and asymptotically normal, and derive a consistent estimator of the variance–covariance matrix that does not involve any choice of a perturbation parameter. Moderate sample size performance of the estimators is investigated via simulation and by application to a real data example.     

Throughput and delay analysis of an opportunistic tree algorithm

Tree algorithms are a well-known class of random access algorithms with a provable maximum stable throughput under the infinite population model (as opposed to ALOHA or the binary exponential backoff algorithm). In this article, we propose a tree algorithm for opportunistic spectrum usage in cognitive radio networks. A channel in such a network is shared among so-called primary and secondary users, where the secondary users are allowed to use the channel only if there is no primary user activity. The tree algorithm designed in this article can be used by the secondary users to share the channel capacity left by the primary users.

We analyze the maximum stable throughput and mean packet delay of the secondary users by developing a tree structured Quasi-Birth Death Markov chain under the assumption that the primary user activity can be modeled by means of a finite state Markov chain and that packets lengths follow a discrete phase-type distribution.

Numerical experiments provide insight on the effect of various system parameters and indicate that the proposed algorithm is able to make good use of the bandwidth left by the primary users.     

Linear Increments with Non‐monotone Missing Data and Measurement Error

Linear increments (LI) are used to analyse repeated outcome data with missing values. Previously, two LI methods have been proposed, one allowing non‐monotone missingness but not independent measurement error and one allowing independent measurement error but only monotone missingness. In both, it was suggested that the expected increment could depend on current outcome. We show that LI can allow non‐monotone missingness and either independent measurement error of unknown variance or dependence of expected increment on current outcome but not both. A popular alternative to LI is a multivariate normal model ignoring the missingness pattern. This gives consistent estimation when data are normally distributed and missing at random (MAR). We clarify the relation between MAR and the assumptions of LI and show that for continuous outcomes multivariate normal estimators are also consistent under (non‐MAR and non‐normal) assumptions not much stronger than those of LI. Moreover, when missingness is non‐monotone, they are typically more efficient.     

Evaluating the Use of Spatial Covariance Structures in the Analysis of Cardiovascular Imaging Data

This article investigates the choice of working covariance structures in the analysis of spatially correlated observations motivated by cardiac imaging data. Through Monte Carlo simulations, we found that the choice of covariance structure affects the efficiency of the estimator and power of the test. Choosing the popular unstructured working covariance structure results in an over-inflated Type I error possibly due to a sample size not large enough relative to the number of parameters being estimated. With regard to model fit indices, Bayesian Information Criterion outperforms Akaike Information Criterion in choosing the correct covariance structure used to generate data.     

Comparative Study of Generalized Estimating Equations and Logistic Regressions on Different Sample Sizes and Correlation Levels

In this study, it was aimed to determine accuracy of generalized estimating equations versus logistic regressions on different correlation levels and sample sizes. For this aim, two methods were compared with different sample sizes 10, 25, 50 and 100 and correlation levels 0.0, 0.3, 0.5 and 0.8. Result of this study showed that using generalized estimating equations could be preferred versus logistic regression when the sample size is over than 25 and correlation level is higher than 0.3 on data taken from studies with repeated measurements, but logistic regression could be better when the autocorrelations do not exist.     

On the robustness of the generalized fused lasso to prior specifications

Using networks as prior knowledge to guide model selection is a way to reach structured sparsity. In particular, the fused lasso that was originally designed to penalize differences of coefficients corresponding to successive features has been generalized to handle features whose effects are structured according to a given network. As any prior information, the network provided in the penalty may contain misleading edges that connect coefficients whose difference is not zero, and the extent to which the performance of the method depend on the suitability of the graph has never been clearly assessed. In this work we investigate the theoretical and empirical properties of the adaptive generalized fused lasso in the context of generalized linear models. In the fixed \(p\) setting, we show that, asymptotically, adding misleading edges in the graph does not prevent the adaptive generalized fused lasso from enjoying asymptotic oracle properties, while forgetting suitable edges can be more problematic. These theoretical results are complemented by an extensive simulation study that assesses the robustness of the adaptive generalized fused lasso against misspecification of the network as well as its applicability when theoretical coefficients are not exactly equal. Our contribution is also to evaluate the applicability of the generalized fused lasso for the joint modeling of multiple sparse regression functions. Illustrations are provided on two real data examples.