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Graphical augmentations to sample-size-based funnel plot in meta-analysis.

ABSTRACT: Assessing publication bias is a critical procedure in meta-analyses for rating the synthesized overall evidence. Because statistical tests for publication bias are usually not powerful and only give P values that inform either the presence or absence of the bias, examining the asymmetry of funnel plots has been popular to investigate potentially missing studies and the direction of the bias. Most funnel plots present treatment effects against their standard errors, and the contours depicting studies' significance levels have been used in the plots to distinguish publication bias from other factors (such as heterogeneity and subgroup effects) that may cause the plots' asymmetry. However, treatment effects and their standard errors are frequently associated even if no publication bias exists (eg, both variables depend on the four data cells in a 2 × 2 table for the odds ratio), so standard-error-based funnel plots may lead to false positive conclusions when such association may not be negligible. In addition, the missingness of studies may relate to their sample sizes besides P values (which are partly determined by standard errors); studies with more samples are more likely published. Therefore, funnel plots based on sample sizes can be an alternative tool. However, the contours for standard-error-based funnel plots cannot be directly applied to sample-size-based ones. This article introduces contours for sample-size-based funnel plots of various effect sizes, which may help meta-analysts properly interpret such plots' asymmetry. We provide five examples to illustrate the use of the proposed contours.

SUBMITTER: Lin L

PROVIDER: S-EPMC6642847 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Graphical augmentations to sample-size-based funnel plot in meta-analysis.

Lin Lifeng L

Research synthesis methods 20190207 3

Assessing publication bias is a critical procedure in meta-analyses for rating the synthesized overall evidence. Because statistical tests for publication bias are usually not powerful and only give P values that inform either the presence or absence of the bias, examining the asymmetry of funnel plots has been popular to investigate potentially missing studies and the direction of the bias. Most funnel plots present treatment effects against their standard errors, and the contours depicting stu ...[more]

PMID: 30664834

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Project description:BackgroundA common task in analyzing microarray data is to determine which genes are differentially expressed across two (or more) kind of tissue samples or samples submitted under experimental conditions. Several statistical methods have been proposed to accomplish this goal, generally based on measures of distance between classes. It is well known that biological samples are heterogeneous because of factors such as molecular subtypes or genetic background that are often unknown to the experimenter. For instance, in experiments which involve molecular classification of tumors it is important to identify significant subtypes of cancer. Bimodal or multimodal distributions often reflect the presence of subsamples mixtures. Consequently, there can be genes differentially expressed on sample subgroups which are missed if usual statistical approaches are used. In this paper we propose a new graphical tool which not only identifies genes with up and down regulations, but also genes with differential expression in different subclasses, that are usually missed if current statistical methods are used. This tool is based on two measures of distance between samples, namely the overlapping coefficient (OVL) between two densities and the area under the receiver operating characteristic (ROC) curve. The methodology proposed here was implemented in the open-source R software.ResultsThis method was applied to a publicly available dataset, as well as to a simulated dataset. We compared our results with the ones obtained using some of the standard methods for detecting differentially expressed genes, namely Welch t-statistic, fold change (FC), rank products (RP), average difference (AD), weighted average difference (WAD), moderated t-statistic (modT), intensity-based moderated t-statistic (ibmT), significance analysis of microarrays (samT) and area under the ROC curve (AUC). On both datasets all differentially expressed genes with bimodal or multimodal distributions were not selected by all standard selection procedures. We also compared our results with (i) area between ROC curve and rising area (ABCR) and (ii) the test for not proper ROC curves (TNRC). We found our methodology more comprehensive, because it detects both bimodal and multimodal distributions and different variances can be considered on both samples. Another advantage of our method is that we can analyze graphically the behavior of different kinds of differentially expressed genes.ConclusionOur results indicate that the arrow plot represents a new flexible and useful tool for the analysis of gene expression profiles from microarrays.

Dataset Information

Graphical augmentations to sample-size-based funnel plot in meta-analysis.

Publications

Graphical augmentations to sample-size-based funnel plot in meta-analysis.

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