Statistical Methods in Medical Research This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

A literature-based approach to evaluate the predictive capacity of a marker using time-dependent summary receiver operating characteristics
Meta-analyses are popular tools to summarize the results of publications. Prognostic performances of a marker are usually summarized by meta-analyses of survival curves or hazard ratios. These approaches may detect a difference in survival according to the marker but do not allow evaluation of its prognostic capacity. Time-dependent receiver operating characteristic curves evaluate the ability of a marker to predict time-to-event. In this article, we describe an adaptation of time-dependent summary receiver operating characteristic curves from published survival curves. To achieve this goal, we modeled the marker and the t...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Combescure, C., Daures, J., Foucher, Y. Tags: Articles Source Type: research

A Phase I/II trial design when response is unobserved in subjects with dose-limiting toxicity
We propose a Phase I/II trial design in which subjects with dose-limiting toxicity are not followed for response, leading to three possible outcomes for each subject: dose-limiting toxicity, absence of therapeutic response without dose-limiting toxicity, and presence of therapeutic response without dose-limiting toxicity. We define the latter outcome as a ‘success,’ and the goal of the trial is to identify the dose with the largest probability of success. This dose is commonly referred to as the most successful dose. We propose a design that accumulates information on subjects with regard to both dose-limiting ...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Braun, T. M., Kang, S., Taylor, J. M. Tags: Articles Source Type: research

A Bayesian semiparametric approach with change points for spatial ordinal data
The change-point model has drawn much attention over the past few decades. It can accommodate the jump process, which allows for changes of the effects before and after the change point. Intellectual disability is a long-term disability that impacts performance in cognitive aspects of life and usually has its onset prior to birth. Among many potential causes, soil chemical exposures are associated with the risk of intellectual disability in children. Motivated by a study for soil metal effects on intellectual disability, we propose a Bayesian hierarchical spatial model with change points for spatial ordinal data to detect ...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Cai, B., Lawson, A. B., McDermott, S., Aelion, C. M. Tags: Articles Source Type: research

Misspecification of the covariance structure in generalized linear mixed models
When fitting marginal models to correlated outcomes, the so-called sandwich variance is commonly used. However, this is not the case when fitting mixed models. Using two data sets, we illustrate the problems that can be encountered. We show that the differences or the ratios between the naive and sandwich standard deviations of the fixed effects estimators provide convenient means of assessing the fit of the model, as both are consistent when the covariance structure is correctly specified, but only the latter is when that structure is misspecified. When the number of statistical units is not too small, the sandwich formul...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Chavance, M., Escolano, S. Tags: Articles Source Type: research

Comparison of two drug safety signals in a pharmacovigilance data mining framework
Since adverse drug reactions are a major public health concern, early detection of drug safety signals has become a top priority for regulatory agencies and the pharmaceutical industry. Quantitative methods for analyzing spontaneous reporting material recorded in pharmacovigilance databases through data mining have been proposed in the last decades and are increasingly used to flag potential safety problems. While automated data mining is motivated by the usually huge size of pharmacovigilance databases, it does not systematically produce relevant alerts. Moreover, each detected signal requires appropriate assessment that ...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Tubert-Bitter, P., Begaud, B., Ahmed, I. Tags: Articles Source Type: research

Iterated combination-based paired permutation tests to determine shape effects of chemotherapy in patients with esophageal cancer
The nonparametric combination of dependent permutation tests method is a useful general tool when a testing problem can be broken down into a set of different k > 1 partial tests. These partial tests, after adjustment of p-values to control for multiplicity, can be marginally analyzed, but jointly considered they can provide information on an overall hypothesis, which might represent the true goal of the testing problem. On the one hand, independence among the partial tests is usually an unrealistic assumption; on the other, even when the underlying dependence relations are known quite often they are difficult to cope w...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Alfieri, R., Bonnini, S., Brombin, C., Castoro, C., Salmaso, L. Tags: Articles Source Type: research

Statistical analysis of life history calendar data
The life history calendar is a data-collection tool for obtaining reliable retrospective data about life events. To illustrate the analysis of such data, we compare the model-based probabilistic event history analysis and the model-free data mining method, sequence analysis. In event history analysis, we estimate instead of transition hazards the cumulative prediction probabilities of life events in the entire trajectory. In sequence analysis, we compare several dissimilarity metrics and contrast data-driven and user-defined substitution costs. As an example, we study young adults' transition to adulthood as a sequence of ...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Eerola, M., Helske, S. Tags: Articles Source Type: research

Estimating controlled direct effects in the presence of intermediate confounding of the mediator-outcome relationship: Comparison of five different methods
In mediation analysis between an exposure X and an outcome Y, estimation of the direct effect of X on Y by usual regression after adjustment for the mediator M may be biased if Z is a confounder between M and Y, and is also affected by X. Alternative methods have been described to avoid such a bias: inverse probability of treatment weighting with and without weight truncation, the sequential g-estimator and g-computation. Our aim was to compare the usual linear regression adjusted for M to these methods when estimating the controlled direct effect between X and Y in the causal structure and to explore the size of the poten...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Lepage, B., Dedieu, D., Savy, N., Lang, T. Tags: Articles Source Type: research

Obtaining evidence by a single well-powered trial or several modestly powered trials
There is debate whether clinical trials with suboptimal power are justified and whether results from large studies are more reliable than the (combined) results of smaller trials. We quantified the error rates for evaluations based on single conventionally powered trials (80% or 90% power) versus evaluations based on the random-effects meta-analysis of a series of smaller trials. When a treatment was assumed to have no effect but heterogeneity was present, the error rates for a single trial were increased more than 10-fold above the nominal rate, even for low heterogeneity. Conversely, for meta-analyses on a series of tria...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: IntHout, J., Ioannidis, J. P., Borm, G. F. Tags: Articles Source Type: research

Modeling clinical outcome using multiple correlated functional biomarkers: A Bayesian approach
In some biomedical studies, biomarkers are measured repeatedly along some spatial structure or over time and are subject to measurement error. In these studies, it is often of interest to evaluate associations between a clinical endpoint and these biomarkers (also known as functional biomarkers). There are potentially two levels of correlation in such data, namely, between repeated measurements of a biomarker from the same subject and between multiple biomarkers from the same subject; none of the existing methods accounts for correlation between multiple functional biomarkers. We propose a Bayesian approach to model a clin...
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Long, Q., Zhang, X., Zhao, Y., Johnson, B. A., Bostick, R. M. Tags: Articles Source Type: research

Design effects for sample size computation in three-level designs
Experiments with multiple nested levels where randomization can take place at any level bring challenges to the computation of sample sizes. Formulas derived under simple single-level experiments must be adjusted using multiplicative factors or design effects. In this work, we take a unified approach to finding the design effects in terms of intracluster correlations and present formulas to compute sample sizes of different levels. Equal cluster sample sizes and homogeneous within cluster variances are assumed. (Source: Statistical Methods in Medical Research)
Source: Statistical Methods in Medical Research - April 21, 2016 Category: Statistics Authors: Cunningham, T. D., Johnson, R. E. Tags: Articles Source Type: research

Tree-based identification of subgroups for time-varying covariate survival data
Classification and regression tree analyses identify subsets of a sample that differ on an outcome. Discrimination of subsets is performed using recursive binary splitting on a set of covariates, allowing for interactions of variable subgroups not easily captured in standard model building techniques. Using classification and regression tree with epidemiological data can be problematic as there is often a need to adjust for potential confounders and to account for time-varying covariates in the context of right-censored survival data. While classification and regression tree variations exist individually for survival analy...
Source: Statistical Methods in Medical Research - February 16, 2016 Category: Statistics Authors: Bertolet, M., Brooks, M. M., Bittner, V. Tags: Articles Source Type: research

The limitations of simple gene set enrichment analysis assuming gene independence
Since its first publication in 2003, the Gene Set Enrichment Analysis method, based on the Kolmogorov-Smirnov statistic, has been heavily used, modified, and also questioned. Recently a simplified approach using a one-sample t-test score to assess enrichment and ignoring gene-gene correlations was proposed by Irizarry et al. 2009 as a serious contender. The argument criticizes Gene Set Enrichment Analysis’s nonparametric nature and its use of an empirical null distribution as unnecessary and hard to compute. We refute these claims by careful consideration of the assumptions of the simplified method and its resul...
Source: Statistical Methods in Medical Research - February 16, 2016 Category: Statistics Authors: Tamayo, P., Steinhardt, G., Liberzon, A., Mesirov, J. P. Tags: Articles Source Type: research

Classification using longitudinal trajectory of biomarker in the presence of detection limits
Discriminant analysis is commonly used to evaluate the ability of candidate biomarkers to separate patients into pre-defined groups. Recent extension of discriminant analysis to longitudinal data enables us to improve the classification accuracy based on biomarker profiles rather than on a single biomarker measurement. However, the biomarker measurement is often limited by the sensitivity of the given assay, resulting in data that are censored at either the lower or the upper limit of detection. Inappropriate handling of censored data may affect the classification accuracy of biomarker and hinder the evaluation of its pote...
Source: Statistical Methods in Medical Research - February 16, 2016 Category: Statistics Authors: Kim, Y., Kong, L. Tags: Articles Source Type: research

Comparing paired biomarkers in predicting quantitative health outcome subject to random censoring
This paper uses a non-parametric test, based on consistently estimated discrimination accuracy defined as concordance probability between quantitative predictor and outcome, to compare paired biomarkers in predicting a health outcome, possibly subject to random censoring. Comparing with the Wilcoxon test for paired predictors based on Harrell’s C-index, we found that the proposed test is better in presence of random censoring, although the two unbiased tests are equivalent for outcome either uncensored or censored by a constant. A simulation study also demonstrates that the bias in estimated difference in concordance...
Source: Statistical Methods in Medical Research - February 16, 2016 Category: Statistics Authors: Liu, X., Jin, Z., Graziano, J. H. Tags: Articles Source Type: research