arXiv subjects

Hisashi Noma

Publications and source records attributed to Hisashi Noma.

23 records · Page 2Linked to original sources

arXiv2019

Bayesian influence diagnostics and outlier detection for meta-analysis of diagnostic test accuracy

Meta-analyses of diagnostic test accuracy (DTA) studies have been gaining prominence in research in clinical epidemiology and health technology development. In these DTA meta-analyses, some studies may have markedly different characteristics from the others, and potentially be inappropriate to include. The inclusion of these "outlying" studies might lead to biases, yielding misleading results. In addition, there might be influential studies that have notable impacts on the results. In this article, we propose Bayesian methods for detecting outlying studies and their influence diagnostics in DTA meta-analyses. Synthetic influence measures based on the bivariate hierarchical Bayesian random effects models are developed because the overall influences of individual studies should be simultaneously assessed by the two outcome variables and their correlation information. We propose four synthetic measures for influence analyses: (1) relative distance, (2) standardized residual, (3) Bayesian p-value, and (4) influence statistic on the area under the summary receiver operating characteristic curve. We also show conventional univariate Bayesian influential measures can be applied to the bivariate random effects models, which can be used as marginal influential measures. We illustrate the effectiveness of the proposed methods by applying them to a DTA meta-analysis of ultrasound in screening for vesicoureteral reflux among children with urinary tract infections.

stat.ME↗

arXiv2019

Permutation inference methods for multivariate meta-analysis

Multivariate meta-analysis is gaining prominence in evidence synthesis research because it enables simultaneous synthesis of multiple correlated outcome data, and random-effects models have generally been used for addressing between-studies heterogeneities. However, coverage probabilities of confidence regions or intervals for standard inference methods for random-effects models (e.g., restricted maximum likelihood estimation) cannot retain their nominal confidence levels in general, especially when the number of synthesized studies is small because their validities depend on large sample approximations. In this article, we provide permutation-based inference methods that enable exact joint inferences for average outcome measures without large sample approximations. We also provide accurate marginal inference methods under general settings of multivariate meta-analyses. We propose effective approaches for permutation inferences using optimal weighting based on the efficient score statistic. The effectiveness of the proposed methods is illustrated via applications to bivariate meta-analyses of diagnostic accuracy studies for airway eosinophilia in asthma and a network meta-analysis for antihypertensive drugs on incident diabetes, as well as through simulation experiments. In numerical evaluations performed via simulations, our methods generally provided accurate confidence regions or intervals under a broad range of settings, whereas the current standard inference methods exhibited serious undercoverage properties.

stat.ME↗

arXiv2019

Frequentist performances of Bayesian prediction intervals for random-effects meta-analysis

The prediction interval has been increasingly used in meta-analyses as a useful measure for assessing the magnitude of treatment effect and between-studies heterogeneity. In calculations of the prediction interval, although the Higgins-Thompson-Spiegelhalter method is used most often in practice, it might not have adequate coverage probability for the true treatment effect of a future study under realistic situations. An effective alternative candidate is the Bayesian prediction interval, which has also been widely used in general prediction problems. However, these prediction intervals are constructed based on the Bayesian philosophy, and their frequentist validities are only justified by large-sample approximations even if non-informative priors are adopted. There has been no certain evidence that evaluated their frequentist performances under realistic situations of meta-analyses. In this study, we conducted extensive simulation studies to assess the frequentist coverage performances of Bayesian prediction intervals with 11 non-informative prior distributions under general meta-analysis settings. Through these simulation studies, we found that frequentist coverage performances strongly depended on what prior distributions were adopted. In addition, when the number of studies was smaller than 10, there were no prior distributions that retained accurate frequentist coverage properties. We also illustrated these methods via applications to eight real meta-analysis datasets. The resultant prediction intervals also differed according to the adopted prior distributions. Inaccurate prediction intervals may provide invalid evidence and misleading conclusions. Thus, if frequentist accuracy is required, Bayesian prediction intervals should be used cautiously in practice.

stat.ME↗

arXiv2019

A Unified Method for Improved Inference in Random-effects Meta-analysis

Random-effects meta-analyses have been widely applied in evidence synthesis for various types of medical studies. However, standard inference methods (e.g. restricted maximum likelihood estimation) usually underestimate statistical errors and possibly provide highly overconfident results under realistic situations; for instance, coverage probabilities of confidence intervals can be substantially below the nominal level. The main reason is that these inference methods rely on large sample approximations even though the number of synthesized studies is usually small or moderate in practice. In this article we solve this problem using a unified inference method based on Monte Carlo conditioning for broad application to random-effects meta-analysis. The developed method provides improved confidence intervals with coverage probabilities that are closer to the nominal level than standard methods. As specific applications, we provide new inference procedures for three types of meta-analysis: conventional univariate meta-analysis for pairwise treatment comparisons, meta-analysis of diagnostic test accuracy, and multiple treatment comparisons via network meta-analysis. We also illustrate the practical effectiveness of these methods via real data applications and simulation studies.

stat.ME↗

arXiv2018

An efficient and robust method for analyzing population pharmacokinetic data in genome-wide pharmacogenomic studies: a generalized estimating equation approach

Powerful array-based single-nucleotide polymorphism--typing platforms have recently heralded a new era in which genome-wide studies are conducted with increasing frequency. A genetic polymorphism associated with population pharmacokinetics (PK) is typically analyzed using nonlinear mixed-effect models (NLMM). Applying NLMM to large-scale data, such as those generated by genome-wide studies, raises several issues related to the assumption of random effects, as follows: (i) Computation time: it takes a long time to compute the marginal likelihood. (ii) Convergence of iterative calculation: an adaptive Gauss-Hermite quadrature is generally used to estimate NLMM; however, iterative calculations may not converge in complex models. (iii) Random-effects misspecification leads to slightly inflated type-I error rates. As an alternative effective approach to resolving these issues, in this article we propose a generalized estimating equation (GEE) approach for analyzing population PK data. In general, GEE analysis does not account for inter-individual variability in PK parameters; therefore, the usual GEE estimators cannot be interpreted straightforwardly, and their validities have not been justified. Here, we propose valid inference methods for using GEE even under conditions of inter-individual variability, and provide theoretical justifications of the proposed GEE estimators for population PK data. In numerical evaluations by simulations, the proposed GEE approach exhibited high computational speed and stability relative to the NLMM approach. Furthermore, the NLMM analysis was sensitive to the misspecification of the random-effects distribution, and the proposed GEE inference is valid for any distributional form. An illustration is provided using data from a genome-wide pharmacogenomic study of an anticancer drug.

stat.ME↗