Evidence
Same model and position · retrieved passages supplied · first output
Meta-analyses of randomized clinical trials with zero-inflated outcomes face particular challenges when the outcome distribution contains more zeros than the assumed Poisson model accommodates, and standard methods can yield distorted intervention effect estimates when such data are pooled across studies.
Passages supplied to the Evidence version
Card 1 · Random‐effects meta‐analysis of few studies involving rare events
Meta-analyses of clinical trials targeting rare events face particular challenges when the data lack adequate numbers of events for all treatment arms. Especially when the number of studies is low, standard random-effects meta-analysis methods can lead to serious distortions because of such data spa…
Read full passage excerpt
Meta-analyses of clinical trials targeting rare events face particular challenges when the data lack adequate numbers of events for all treatment arms. Especially when the number of studies is low, standard random-effects meta-analysis methods can lead to serious distortions because of such data sparsity. To overcome this, we suggest the use of weakly informative priors (WIPs) for the treatment effect parameter of a Bayesian meta-analysis model, which may also be seen as a form of penalization. As a data model, we use a binomial-normal hierarchical model (BNHM) that does not require continuity corrections in case of zero counts in one or both arms. We suggest a normal prior for the log-odds ratio with mean 0 and standard deviation 2.82, which is motivated (a) as a symmetric prior centered around unity and constraining the odds ratio within a range from 1/250 to 250 with 95% probability and (b) as consistent with empirically observed effect estimates from a set of 37 773 meta-analyses f …
Card 2 · Integrative High Dimensional Multiple Testing with Heterogeneity under Data Sharing Constraints
Identifying informative predictors in a high dimensional regression model is a critical step for association analysis and predictive modeling. Signal detection in the high dimensional setting often fails due to the limited sample size. One approach to improving power is through meta-analyzing multip…
Read full passage excerpt
Identifying informative predictors in a high dimensional regression model is a critical step for association analysis and predictive modeling. Signal detection in the high dimensional setting often fails due to the limited sample size. One approach to improving power is through meta-analyzing multiple studies which address the same scientific question. However, integrative analysis of high dimensional data from multiple studies is challenging in the presence of between-study heterogeneity. The challenge is even more pronounced with additional data sharing constraints under which only summary data can be shared across different sites. In this paper, we propose a novel data shielding integrative large-scale testing (DSILT) approach to signal detection allowing between-study heterogeneity and not requiring the sharing of individual level data. Assuming the underlying high dimensional regression models of the data differ across studies yet share similar support, the proposed method incorpo …
Card 3 · Empirical null and false discovery rate inference for exponential families
In large scale multiple testing, the use of an empirical null distribution rather than the theoretical null distribution can be critical for correct inference. This paper proposes a “mode matching” method for fitting an empirical null when the theoretical null belongs to any exponential family. Base…
Read full passage excerpt
In large scale multiple testing, the use of an empirical null distribution rather than the theoretical null distribution can be critical for correct inference. This paper proposes a “mode matching” method for fitting an empirical null when the theoretical null belongs to any exponential family. Based on the central matching method for z-scores, mode matching estimates the null density by fitting an appropriate exponential family to the histogram of the test statistics by Poisson regression in a region surrounding the mode. The empirical null estimate is then used to estimate local and tail false discovery rate (FDR) for inference. Delta-method covariance formulas and approximate asymptotic bias formulas are provided, as well as simulation studies of the effect of the tuning parameters of the procedure on the bias-variance trade-off. The standard FDR estimates are found to be biased down at the far tails. Correlation between test statistics is taken into account in the covariance estima …
Card 4 · Differential meta-analysis of RNA-seq data from multiple studies
BACKGROUND: High-throughput sequencing is now regularly used for studies of the transcriptome (RNA-seq), particularly for comparisons among experimental conditions. For the time being, a limited number of biological replicates are typically considered in such experiments, leading to low detection po…
Read full passage excerpt
BACKGROUND: High-throughput sequencing is now regularly used for studies of the transcriptome (RNA-seq), particularly for comparisons among experimental conditions. For the time being, a limited number of biological replicates are typically considered in such experiments, leading to low detection power for differential expression. As their cost continues to decrease, it is likely that additional follow-up studies will be conducted to re-address the same biological question. RESULTS: We demonstrate how p-value combination techniques previously used for microarray meta-analyses can be used for the differential analysis of RNA-seq data from multiple related studies. These techniques are compared to a negative binomial generalized linear model (GLM) including a fixed study effect on simulated data and real data on human melanoma cell lines. The GLM with fixed study effect performed well for low inter-study variation and small numbers of studies, but was outperformed by the meta-analysis me …
Model-reported card use
Card 1 · terminology
Affected output: face particular challenges when the outcome distribution contains more zeros than the assumed Poisson model accommodates
Model explanation: The row supplied the field-native framing of meta-analytic challenges arising from sparse or excess-zero event data, which shaped how the opening sentence characterizes the zero-inflation problem.
Card 1 · expression
Affected output: standard methods can yield distorted intervention effect estimates when such data are pooled across studies
Model explanation: The row provided the rhetorical pattern of attributing distortion to standard methods under data sparsity, which guided the expression of the consequence clause in the generated sentence.