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There is sometimes a clear evidence of a strong secular trend in the treatment effect of studies included in a meta‐analysis. In such cases, estimating the present‐day treatment effect by meta‐regression is both reasonable and straightforward. We however consider the more common situation where a secular trend is suspected, but is not strongly statistically significant. Typically, this lack of significance is due to the small number of studies included in the analysis, so that a meta‐regression could give wild point estimates. We introduce an empirical Bayes meta‐analysis methodology, which shrinks the secular trend toward zero. This has the effect that treatment effects are adjusted for trend, but where the evidence from data is weak, wild results are not obtained. We explore several frequentist approaches and a fully Bayesian method is also implemented. A measure of trend analogous to I2 is described, and exact significance tests for trend are given. Our preferred method is one based on penalized or h‐likelihood, which is computationally simple, and allows invariance of predictions to the (arbitrary) choice of time origin. We suggest that a trendless standard random effects meta‐analysis should routinely be supplemented with an h‐likelihood analysis as a sensitivity analysis. 相似文献
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A common goal of microarray and related high-throughput genomic experiments is to identify genes that vary across biological condition. Most often this is accomplished by identifying genes with changes in mean expression level, so called differentially expressed (DE) genes, and a number of effective methods for identifying DE genes have been developed. Although useful, these approaches do not accommodate other types of differential regulation. An important example concerns differential coexpression (DC). Investigations of this class of genes are hampered by the large cardinality of the space to be interrogated as well as by influential outliers. As a result, existing DC approaches are often underpowered, exceedingly prone to false discoveries, and/or computationally intractable for even a moderately large number of pairs. To address this, an empirical Bayesian approach for identifying DC gene pairs is developed. The approach provides a false discovery rate controlled list of significant DC gene pairs without sacrificing power. It is applicable within a single study as well as across multiple studies. Computations are greatly facilitated by a modification to the expectation-maximization algorithm and a procedural heuristic. Simulations suggest that the proposed approach outperforms existing methods in far less computational time; and case study results suggest that the approach will likely prove to be a useful complement to current DE methods in high-throughput genomic studies. 相似文献
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Nonparametric and parametric approaches have been proposed to estimate false discovery rate under the independent hypothesis testing assumption. The parametric approach has been shown to have better performance than the nonparametric approaches. In this article, we study the nonparametric approaches and quantify the underlying relations between parametric and nonparametric approaches. Our study reveals the conservative nature of the nonparametric approaches, and establishes the connections between the empirical Bayes method and p-value-based nonparametric methods. Based on our results, we advocate using the parametric approach, or directly modeling the test statistics using the empirical Bayes method. 相似文献
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Evidence synthesis, both qualitatively and quantitatively through meta-analysis, is central to the development of evidence-based medicine. Unfortunately, meta-analysis is often complicated by the suspicion that the available studies represent a biased subset of the evidence, possibly due to publication bias or other systematically different effects in small studies. A number of statistical methods have been proposed to address this, among which the trim-and-fill method and the Copas selection model are two of the most widely discussed. However, both methods have drawbacks: the trim-and-fill method is based on strong assumptions about the symmetry of the funnel plot; the Copas selection model is less accessible to systematic reviewers, and sometimes encounters estimation problems. In this article, we adopt a logistic selection model, and show how treatment effects can be rapidly estimated via multiple imputation. Specifically, we impute studies under a missing at random assumption, and then reweight to obtain estimates under nonrandom selection. Our proposal is computationally straightforward. It allows users to increase selection while monitoring the extent of remaining funnel plot asymmetry, and also visualize the results using the funnel plot. We illustrate our approach using a small meta-analysis of benign prostatic hyperplasia. 相似文献
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Josemar Rodrigues Luis A. Milan Jos G. Leite 《Biometrical journal. Biometrische Zeitschrift》2001,43(6):737-746
This paper is concerned with the estimation of the number of species in a population through a fully hierarchical Bayesian model using the Metropolis algorithm. The proposed Bayesian estimator is based on Poisson random variables with means that are distributed according to some prior distributions with unknown hyperparameters. An empirical Bayes approach is considered and compared with the fully Bayesian approach based on biological data. 相似文献
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Approximations to Bayesian clustering rules 总被引：1，自引：0，他引：1
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Lawrence J 《Biometrical journal. Biometrische Zeitschrift》2005,47(5):616-622
In an active-controlled trial, the experimental treatment can be declared to be non-inferior to the control if the confidence interval for the difference excludes a fixed pre-specified margin. Recently, some articles have discussed an alternative method where the data from the current study and placebo-controlled studies for the active control are combined together into a single test statistic to test whether a fixed fraction of the effect of the active control is preserved. It has been shown that, conditional on nuisance parameters from the active-controlled study, a fixed margin can be defined that will be operationally equivalent to this latter method. In this article, we will discuss statistical properties associated with these approaches. Specifically, the interim monitoring boundaries and level of evidence will be considered. 相似文献
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Steinschneider et al. (2017) investigate model choices made in the hierarchical climate reconstruction approach of Schofield et al. (2016). We identify two flaws in their approach. The first is the use of an unusual approximation to Bayesian inference that unnecessarily discards important information. The second is that they mischaracterize the robustness of their reconstructions due to overlooking important features of the out-of-sample predictions. We demonstrate how full Bayesian inference can be conducted with no additional effort, providing R/JAGS code. We also show how graphical visualization of the out-of-sample predictions can lead to better understanding and comparison of the models fitted. 相似文献
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A Bayesian perspective on the Bonferroni adjustment 总被引：1，自引：0，他引：1
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肠道菌群代谢作用与人体健康关系的研究进展 总被引：1，自引：0，他引：1
人体肠道内寄居的大量共生微生物可以通过多方面作用影响人体健康,特别是肠道内菌群的代谢作用,及与人体自身代谢的交互作用在人类的健康促进与疾病的发生、发展中起着重要作用。本文从正反两面讨论了肠道菌群代谢作用对人体健康的影响,并进一步探讨了肠道菌群代谢在健康监测、疾病的预防与治疗,以及个体化医疗方面的运用。 相似文献
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SUMMARY: We consider the problem of testing for partial conjunction of hypothesis, which argues that at least u out of n tested hypotheses are false. It offers an in-between approach to the testing of the conjunction of null hypotheses against the alternative that at least one is not, and the testing of the disjunction of null hypotheses against the alternative that all hypotheses are not null. We suggest powerful test statistics for testing such a partial conjunction hypothesis that are valid under dependence between the test statistics as well as under independence. We then address the problem of testing many partial conjunction hypotheses simultaneously using the false discovery rate (FDR) approach. We prove that if the FDR controlling procedure in Benjamini and Hochberg (1995, Journal of the Royal Statistical Society, Series B 57, 289-300) is used for this purpose the FDR is controlled under various dependency structures. Moreover, we can screen at all levels simultaneously in order to display the findings on a superimposed map and still control an appropriate FDR measure. We apply the method to examples from microarray analysis and functional magnetic resonance imaging (fMRI), two application areas where the need for partial conjunction analysis has been identified. 相似文献
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Recent work on Bayesian inference of disease mapping models discusses the advantages of the fully Bayesian (FB) approach over its empirical Bayes (EB) counterpart, suggesting that FB posterior standard deviations of small-area relative risks are more reflective of the uncertainty associated with the relative risk estimation than counterparts based on EB inference, since the latter fail to account for the variability in the estimation of the hyperparameters. In this article, an EB bootstrap methodology for relative risk inference with accurate parametric EB confidence intervals is developed, illustrated, and contrasted with the hyperprior Bayes. We elucidate the close connection between the EB bootstrap methodology and hyperprior Bayes, present a comparison between FB inference via hybrid Markov chain Monte Carlo and EB inference via penalized quasi-likelihood, and illustrate the ability of parametric bootstrap procedures to adjust for the undercoverage in the \"naive\" EB interval estimates. We discuss the important roles that FB and EB methods play in risk inference, map interpretation, and real-life applications. The work is motivated by a recent analysis of small-area infant mortality rates in the province of British Columbia in Canada. 相似文献
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Summary Temporal boundary misalignment occurs when area boundaries shift across time (e.g., census tract boundaries change at each census year), complicating the modeling of temporal trends across space. Large area-level datasets with temporal boundary misalignment are becoming increasingly common in practice. The few existing approaches for temporally misaligned data do not account for correlation in spatial random effects over time. To overcome issues associated with temporal misalignment, we construct a geostatistical model for aggregate count data by assuming that an underlying continuous risk surface induces spatial correlation between areas. We implement the model within the framework of a generalized linear mixed model using radial basis splines. Using this approach, boundary misalignment becomes a nonissue. Additionally, this disease-mapping framework facilitates fast, easy model fitting by using a penalized quasilikelihood approximation to maximum likelihood estimation. We anticipate that the method will also be useful for large disease-mapping datasets for which fully Bayesian approaches are infeasible. We apply our method to assess socioeconomic trends in breast cancer incidence in Los Angeles between the periods 1988-1992 and 1998-2002. 相似文献
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Edwards JW Page GP Gadbury G Heo M Kayo T Weindruch R Allison DB 《Functional & integrative genomics》2005,5(1):32-39
Micro-array technology allows investigators the opportunity to measure expression levels of thousands of genes simultaneously. However, investigators are also faced with the challenge of simultaneous estimation of gene expression differences for thousands of genes with very small sample sizes. Traditional estimators of differences between treatment means (ordinary least squares estimators or OLS) are not the best estimators if interest is in estimation of gene expression differences for an ensemble of genes. In the case that gene expression differences are regarded as exchangeable samples from a common population, estimators are available that result in much smaller average mean-square error across the population of gene expression difference estimates. We have simulated the application of such an estimator, namely an empirical Bayes (EB) estimator of random effects in a hierarchical linear model (normal-normal). Simulation results revealed mean-square error as low as 0.05 times the mean-square error of OLS estimators (i.e., the difference between treatment means). We applied the analysis to an example dataset as a demonstration of the shrinkage of EB estimators and of the reduction in mean-square error, i.e., increase in precision, associated with EB estimators in this analysis. The method described here is available in software that is available at . 相似文献