Methods
Suppose that a meta-analysis includes a total of \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} independent studies. Let \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}$$\end{document} be the observed effect size in study \documentclass[12pt]{minimal}
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\begin{document}$$i$$\end{document} ( \documentclass[12pt]{minimal}
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\begin{document}$$i$$\end{document} = 1, 2, …, \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} ) and \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}$$\end{document} be its standard error. Meta-analysis models typically assume that each \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}$$\end{document} is approximately normally distributed with mean \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} and variance \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}^{2}$$\end{document} . Also, the observed standard errors \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}$$\end{document} ’s are conventionally treated as fixed variables, as if there is no error in their estimation. These assumptions are generally valid if the sample sizes in the studies are sufficiently large (e.g., due to the central limit theorem and law of large numbers), but extra cautions are needed for small sample sizes [ 10 , 29 ].
This article focuses on testing for the potential inconsistency between the \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} studies, so the distribution of the study-specific underlying true effect sizes \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} plays a critical role. The null hypothesis is that all studies are homogeneous, sharing a common effect size \documentclass[12pt]{minimal}
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\begin{document}$$\mu$$\end{document} ; that is, \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{1}={\mu }_{2}=\cdots ={\mu }_{k}=\mu$$\end{document} , and their distribution is a mass at \documentclass[12pt]{minimal}
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\begin{document}$$\mu$$\end{document} . In such cases, the common-effect model is used. If the homogeneity does not appear to hold, meta-analysts conventionally use the random-effects model to account for the between-study inconsistency. This model typically assumes that \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} ’s are random effects, following a normal distribution \documentclass[12pt]{minimal}
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\begin{document}$$N\left(\mu , {\tau }^{2}\right)$$\end{document} , where \documentclass[12pt]{minimal}
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\begin{document}$$\mu$$\end{document} represents the overall mean effect size in the random-effects framework and \documentclass[12pt]{minimal}
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\begin{document}$${\tau }^{2}$$\end{document} is the between-study variance [ 4 ]. Although alternative distributions are possible for the random effects [ 30 , 31 ], the between-study normality assumption has dominated the current literature of meta-analyses owing to its simplicity.
The \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test is the standard approach to examining inconsistency. Its statistic is defined as \documentclass[12pt]{minimal}
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\begin{document}$$Q={\sum }_{i=1}^{k}{\left({y}_{i}-{\widehat{\mu }}_{\text{CE}}\right)}^{2}/{s}_{i}^{2},$$\end{document}
Where the common-effect estimate is 1 \documentclass[12pt]{minimal}
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\begin{document}$${\widehat{\mu }}_{\text{CE}}=\frac{{\sum }_{i=1}^{k}{y}_{i}/{s}_{i}^{2}}{{\sum }_{i=1}^{k}1/{s}_{i}^{2}}.$$\end{document}
The \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic follows a \documentclass[12pt]{minimal}
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\begin{document}$${\chi }_{k-1}^{2}$$\end{document} distribution under the null hypothesis of homogeneity.
It is straightforward to rewrite the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic as \documentclass[12pt]{minimal}
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\begin{document}$$Q={\sum }_{i=1}^{k}{d}_{i}^{2}$$\end{document} , where \documentclass[12pt]{minimal}
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\begin{document}$${d}_{i}=\left({y}_{i}-{\widehat{\mu }}_{\text{CE}}\right)/{s}_{i}$$\end{document} may be interpreted as study-specific standardized deviates. As illustrated in the introduction section, this sum-of-squares structure is arguably suitable for the between-study normality assumption, but it may not work well for other between-study distributions. Consider the case that the meta-analysis contains an outlying study (denoting its index by \documentclass[12pt]{minimal}
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\begin{document}$$o$$\end{document} ) and all remaining studies are homogeneous. We would expect \documentclass[12pt]{minimal}
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\begin{document}$${d}_{o}$$\end{document} to take an extremely large value in absolute magnitude, while the other studies’ standardized deviates \documentclass[12pt]{minimal}
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\begin{document}$${d}_{j}$$\end{document} ( \documentclass[12pt]{minimal}
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\begin{document}$$j\ne o$$\end{document} ) are small. The between-study inconsistency can be mostly captured by \documentclass[12pt]{minimal}
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\begin{document}$${d}_{o}$$\end{document} , and the \documentclass[12pt]{minimal}
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\begin{document}$${d}_{j}$$\end{document} ’s ( \documentclass[12pt]{minimal}
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\begin{document}$$j\ne o$$\end{document} ) may add nuisance information to the sum of squares in \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} . Therefore, it is sensible to test for the inconsistency based solely on \documentclass[12pt]{minimal}
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\begin{document}$${d}_{o}$$\end{document} , i.e., the maximum value among the absolute values of all standardized deviates \documentclass[12pt]{minimal}
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\begin{document}$$\left|{d}_{i}\right|$$\end{document} ’s.
In addition, we may consider taking the sum of the \documentclass[12pt]{minimal}
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\begin{document}$$\left|{d}_{i}\right|$$\end{document} ’s with different mathematical powers \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} to reflect different weights contributed by individual studies. For example, when \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} = 1, the sum becomes \documentclass[12pt]{minimal}
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\begin{document}$${\sum }_{i=1}^{k}\left|{d}_{i}\right|$$\end{document} , which could reduce the impact of potential outliers and make the assessment of inconsistency more robust [ 9 ]. When \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} increases, the contributions of larger deviates to the sum become larger, while those of smaller deviates become smaller. If \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} approaches infinity, then only the largest deviate would dominate the sum, so the sum effectively plays a similar role to the maximum of all deviates. Different values of \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} could capture different patterns of the between-study distributions.
Formally, we propose the following alternative statistic for an integer value of the mathematical power \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} : 2 \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }={\sum }_{i=1}^{k}{\left(\left|{y}_{i}-{\widehat{\mu }}_{\text{CE}}\right|/{s}_{i}\right)}^{\gamma }$$\end{document}
If \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} = 2, the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} becomes the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic. For other values of \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} , the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistic could capture different patterns of between-study inconsistency and thus be more powerful than \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} . Also, because the largest deviate in absolute magnitude would dominate the sum as \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} approaches infinity, we define the statistic for \documentclass[12pt]{minimal}
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\begin{document}$$\gamma =\infty$$\end{document} as 3 \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }=\underset{i=1, \dots , k}{\text{max}}\left|{y}_{i}-{\widehat{\mu }}_{\text{CE}}\right|/{s}_{i}$$\end{document}
This article considers the values of 1, 2, …, 8, and \documentclass[12pt]{minimal}
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\begin{document}$$\infty$$\end{document} for \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} . Based on our empirical experiments, these values are sufficient to capture various patterns of between-study inconsistency. We denote the P -value of the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistic by \documentclass[12pt]{minimal}
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\begin{document}$${P}_{\gamma }$$\end{document} .
In practice, however, it is infeasible to justify the optimal \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} for a specific meta-analysis because identifying the between-study distribution is challenging. Borrowing the idea of adaptive testing [ 27 , 28 , 32 ], we propose a hybrid test for the between-study inconsistency. Specifically, we first consider a set of candidate tests for inconsistency, say \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} with \documentclass[12pt]{minimal}
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\begin{document}$$\gamma \in\Gamma =\left\{1, 2, \dots , 8, \infty \right\}$$\end{document} . Then, the hybrid test statistic is defined as the minimum P -value of all candidate tests; that is, 4 \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}=\underset{\gamma \in\Gamma }{\text{min}}{P}_{\gamma }$$\end{document}
As the minimum among the P -values of a pool of tests, the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} is no longer a valid P -value because it cannot control the type I error rate. Indeed, we treat \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} as a test statistic rather than a P -value. The following subsection proposes a resampling method to derive the null distribution of the hybrid test statistic and thus calculate its P -value \documentclass[12pt]{minimal}
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\begin{document}$${P}_{\text{hyb}}$$\end{document} . Because it is also difficult to derive the theoretical null distribution of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} (except for \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} = 2, which leads to the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test statistic), the resampling method is used to derive the P -values of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} ’s as well.
The resampling method for calculating the P -values of the proposed tests is as follows. First, under the null hypothesis of homogeneity, the common effect size \documentclass[12pt]{minimal}
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\begin{document}$${\widehat{\mu }}_{\text{CE}}$$\end{document} is estimated as in Eq. ( 1 ), the test statistic \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} for each \documentclass[12pt]{minimal}
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\begin{document}$$\gamma \in\Gamma$$\end{document} is obtained using Eqs. ( 2 ) or ( 3 ), and the hybrid test statistic \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} is obtained using Eq. ( 4 ). Second, we generate resampled replicates of the meta-analysis for \documentclass[12pt]{minimal}
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\begin{document}$$B$$\end{document} times (say, \documentclass[12pt]{minimal}
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\begin{document}$$B$$\end{document} = 1,000). Ideally, \documentclass[12pt]{minimal}
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\begin{document}$$B$$\end{document} should be as large as computational resources allow to minimize Monte Carlo error. For each resampling iteration \documentclass[12pt]{minimal}
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\begin{document}$$b$$\end{document} ( \documentclass[12pt]{minimal}
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\begin{document}$$b$$\end{document} = 1, 2, …, \documentclass[12pt]{minimal}
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\begin{document}$$B$$\end{document} ), we draw study-specific standard errors \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}^{\left(b\right)}$$\end{document} with replacement from the original standard errors \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}$$\end{document} ( \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} ), and the effect size estimates are obtained as \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}^{\left(b\right)}\sim N\left({\widehat{\mu }}_{\text{CE}}, {\left({s}_{i}^{\left(b\right)}\right)}^{2}\right)$$\end{document} . For the \documentclass[12pt]{minimal}
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\begin{document}$$b$$\end{document} th resampled meta-analysis, we calculate \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }^{\left(b\right)}$$\end{document} for each \documentclass[12pt]{minimal}
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\begin{document}$$\gamma \in\Gamma$$\end{document} using \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}^{\left(b\right)}$$\end{document} and \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}^{\left(b\right)}$$\end{document} . These resampled test statistics form null distributions for each \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} ; thus, the P -value of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} can be calculated as 5 \documentclass[12pt]{minimal}
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\begin{document}$${P}_{\gamma }=\frac{{\sum }_{b=1}^{B}I\left({Q}_{\gamma }^{\left(b\right)}\ge {Q}_{\gamma }\right)+1}{B+1}$$\end{document}
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\begin{document}$$I\left(\cdot \right)$$\end{document} is the indicator function. A constant 1 is added to both the denominator and the numerator to avoid the P -value being calculated as 0.
Of note, the P -values of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} based on Eq. ( 5 ) are obtained for the original meta-analyses. To obtain the P -value of the hybrid test, we need to calculate the hybrid test statistic for each resampled meta-analysis, which depends on the P -values of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} for the resampled meta-analysis. For the \documentclass[12pt]{minimal}
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\begin{document}$$b$$\end{document} th resampled meta-analysis with the test statistic \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }^{\left(b\right)}$$\end{document} , the statistics \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }^{\left(c\right)}$$\end{document} in other resampled meta-analyses ( \documentclass[12pt]{minimal}
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\begin{document}$$c$$\end{document} = 1, 2, …, \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} but \documentclass[12pt]{minimal}
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\begin{document}$$c\ne b$$\end{document} ) can serve as an empirical distribution for \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }^{\left(b\right)}$$\end{document} . Thus, the P -value of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }^{\left(b\right)}$$\end{document} can be calculated as \documentclass[12pt]{minimal}
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\begin{document}$${P}_{\gamma }^{\left(b\right)}=\frac{{\sum }_{c\ne b}I\left({Q}_{\gamma }^{\left(c\right)}\ge {Q}_{\gamma }^{\left(b\right)}\right)+1}{B}$$\end{document}
With these P -values, for the \documentclass[12pt]{minimal}
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\begin{document}$$b$$\end{document} th resampled meta-analysis, its hybrid test statistic is \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}^{\left(b\right)}=\underset{\gamma \in\Gamma }{\text{min}}{P}_{\gamma }^{\left(b\right)}$$\end{document}
Finally, based on the hybrid test statistics of the resampled meta-analyses under the null hypothesis, the P -value of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} is \documentclass[12pt]{minimal}
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\begin{document}$${P}_{\text{hyb}}=\frac{{\sum }_{b=1}^{B}I\left({Q}_{\text{hyb}}^{\left(b\right)}\le {Q}_{\text{hyb}}\right)+1}{B+1}$$\end{document}
In addition to testing for inconsistency, it is also of great interest to quantify it [ 33 ]. Like the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic, the magnitudes of the proposed \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} , so \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} cannot be directly used as measures of between-study inconsistency in different meta-analyses. Motivated by the popular \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} statistic [ 20 , 34 ], we extend the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistics to derive alternative inconsistency measures.
Specifically, the \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}=\text{max}\left\{\frac{Q-\left(k-1\right)}{Q}, 0\right\}\times 100\%$$\end{document}
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\begin{document}$$Q$$\end{document} is the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic. It is interpreted as the percentage of the total variation in study estimates due to the between-study inconsistency rather than the sampling error. Thus, conceptually, the \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} statistic can be considered as a form of 7 \documentclass[12pt]{minimal}
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\begin{document}$$\frac{{\tau }^{2}}{{\tau }^{2}+{\sigma }^{2}}$$\end{document}
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\begin{document}$${\tau }^{2}$$\end{document} represents the between-study variance and \documentclass[12pt]{minimal}
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\begin{document}$${\sigma }^{2}$$\end{document} is a summary of all sample variances from individual studies [ 34 ]. The Cochrane Handbook gives a rough guide for interpreting the \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} statistic as unimportant, moderate, or substantial inconsistency [ 2 ].
In the framework of this article, however, we do not pursue new measures with a similar interpretation as in Eq. ( 7 ) The marginal variance \documentclass[12pt]{minimal}
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\begin{document}$${\tau }^{2}+{\sigma }^{2}$$\end{document} may be intuitive under the between-study normality assumption, but it may not be meaningful in general settings of inconsistency, e.g., the existence of outlying studies. Instead, we are motivated to construct new inconsistency measures by taking another look at the formula of \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} in Eq. ( 6 ). Because \documentclass[12pt]{minimal}
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\begin{document}$$k-1$$\end{document} in the numerator is the expectation of the \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic under the hypothesis, \documentclass[12pt]{minimal}
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\begin{document}$$Q-\left(k-1\right)$$\end{document} describes the excess of the observed \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic compared with its null expectation, and thus \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} can also be viewed as the percentage of excess inconsistency. This interpretation shares a similar idea with the concept of excess statistical significance used for assessing publication bias [ 35 , 36 ].
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\begin{document}$${Q}_{\gamma }$$\end{document} , we propose to quantify inconsistency by \documentclass[12pt]{minimal}
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\begin{document}$$E_\gamma=\text{max}\left\{\frac{Q_\gamma-E\left[Q_\gamma\vert H_0\right]}{Q_\gamma},0\right\}\times100\%$$\end{document}
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\begin{document}$$E\left[{Q}_{\gamma }|{H}_{0}\right]$$\end{document} is the expectation of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} under the null hypothesis. The \documentclass[12pt]{minimal}
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\begin{document}$${E}_{\gamma }$$\end{document} measure is interpreted as the percentage excess inconsistency based on the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistic. When \documentclass[12pt]{minimal}
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\begin{document}$${E}_{2}$$\end{document} is identical to the \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} statistic. In addition, like \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} [ 34 ], the \documentclass[12pt]{minimal}
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\begin{document}$${E}_{\gamma }$$\end{document} measure is scale-invariant because \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} is unit-free.
We can derive the theoretical null expectations of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} for \documentclass[12pt]{minimal}
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\begin{document}$$\gamma <\infty$$\end{document} . Recall that \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }={\sum }_{i=1}^{k}{\left(\left|{y}_{i}-{\widehat{\mu }}_{\text{CE}}\right|/{s}_{i}\right)}^{\gamma }$$\end{document} , where \documentclass[12pt]{minimal}
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\begin{document}$${\widehat{\mu }}_{\text{CE}}=\left[{\sum }_{i=1}^{k}{y}_{i}/{s}_{i}^{2}\right]/\left[{\sum }_{i=1}^{k}1/{s}_{i}^{2}\right]$$\end{document} . Because \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}$$\end{document} follows normal distribution, so \documentclass[12pt]{minimal}
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\begin{document}$$\left|{y}_{i}-{\widehat{\mu }}_{\text{CE}}\right|/{s}_{i}$$\end{document} follows a folded normal distribution with mean 0 if \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}$$\end{document} ’s are treated as fixed values. By this property, we can derive the following formula of \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\gamma }|{H}_{0}\right]$$\end{document} using the \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\gamma }|{H}_{0}\right]=\frac{{2}^{\gamma /2}}{\sqrt{\pi }}\Gamma \left(\frac{\gamma +1}{2}\right){\sum }_{i=1}^{k}{\sigma }_{i}^{\gamma }$$\end{document}
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\begin{document}$$\Gamma \left(\cdot \right)$$\end{document} denotes the Gamma function and \documentclass[12pt]{minimal}
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\begin{document}$${\sigma }_{i}=\sqrt{1-1/\left[{s}_{i}^{2}{\sum }_{j=1}^{k}1/{s}_{j}^{2}\right]}$$\end{document} . The detailed proof is given in Additional File 1. Here, we list the equations of \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\gamma }|{H}_{0}\right]$$\end{document} with \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{6}|{H}_{0}\right]=15{\sum }_{i=1}^{k}{\sigma }_{i}^{6}$$\end{document} ; \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{7}|{H}_{0}\right]=48\sqrt{\frac{2}{\pi }}{\sum }_{i=1}^{k}{\sigma }_{i}^{7}$$\end{document} ; and \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{8}|{H}_{0}\right]=105{\sum }_{i=1}^{k}{\sigma }_{i}^{8}$$\end{document} .
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\begin{document}$$E\left[{Q}_{1}|{H}_{0}\right]=\sqrt{\frac{2}{\pi }}{\sum }_{i=1}^{k}{\sigma }_{i}$$\end{document} ;
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\begin{document}$$E\left[{Q}_{2}|{H}_{0}\right]={\sum }_{i=1}^{k}{\sigma }_{i}^{2}=k-1$$\end{document} ;
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\begin{document}$$E\left[{Q}_{3}|{H}_{0}\right]=2\sqrt{\frac{2}{\pi }}{\sum }_{i=1}^{k}{\sigma }_{i}^{3}$$\end{document} ;
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\begin{document}$$E\left[{Q}_{4}|{H}_{0}\right]=3{\sum }_{i=1}^{k}{\sigma }_{i}^{4}$$\end{document} ;
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\begin{document}$$E\left[{Q}_{5}|{H}_{0}\right]=8\sqrt{\frac{2}{\pi }}{\sum }_{i=1}^{k}{\sigma }_{i}^{5}$$\end{document} ;
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\begin{document}$$E\left[{Q}_{6}|{H}_{0}\right]=15{\sum }_{i=1}^{k}{\sigma }_{i}^{6}$$\end{document} ;
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\begin{document}$$E\left[{Q}_{7}|{H}_{0}\right]=48\sqrt{\frac{2}{\pi }}{\sum }_{i=1}^{k}{\sigma }_{i}^{7}$$\end{document} ; and
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\begin{document}$$E\left[{Q}_{8}|{H}_{0}\right]=105{\sum }_{i=1}^{k}{\sigma }_{i}^{8}$$\end{document} .
It is infeasible to obtain the explicit equations of \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\infty }|{H}_{0}\right]$$\end{document} and \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\text{hyb}}|{H}_{0}\right]$$\end{document} . Nevertheless, the resampling method introduced in the previous subsection can also be used to calculate the null expectation based on the resampled meta-analyses; that is, \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\gamma }|{H}_{0}\right]\approx \frac{1}{B}{\sum }_{b=1}^{B}{Q}_{\gamma }^{\left(b\right)}$$\end{document}
This approximation can be readily used for obtaining \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\infty }|{H}_{0}\right]$$\end{document} with \documentclass[12pt]{minimal}
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\begin{document}$$\gamma =\infty$$\end{document} .
For the hybrid test statistic, it is not straightforward to derive \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{Q}_{\text{hyb}}|{H}_{0}\right]$$\end{document} in a similar way for two reasons. First, a large value of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} implies a large inconsistency between studies. On the contrary, a large value of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} implies a small inconsistency between studies. Second, \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} only ranges from 0 to 1; therefore, it is difficult to compare its magnitudes across meta-analyses when \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} becomes small, say, \documentclass[12pt]{minimal}
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\begin{document}$${10}^{-3}$$\end{document} and \documentclass[12pt]{minimal}
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\begin{document}$${10}^{-4}$$\end{document} . To solve these problems, we apply a log transformation with base 10 to \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} and impose a negative sign; the transformed statistic is \documentclass[12pt]{minimal}
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\begin{document}$${L}_{\text{hyb}}=-{\text{log}}_{10}\left({Q}_{\text{hyb}}\right)$$\end{document} . After this transformation, we can use the foregoing resampling method for \documentclass[12pt]{minimal}
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\begin{document}$${L}_{\text{hyb}}$$\end{document} to approximate the \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{L}_{\text{hyb}}|{H}_{0}\right]$$\end{document} : \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{L}_{\text{hyb}}|{H}_{0}\right]\approx -\frac{1}{B}{\sum }_{b=1}^{B}{\text{log}}_{10}\left({Q}_{\text{hyb}}^{\left(b\right)}\right)$$\end{document}
Thus, the measure of inconsistency based on the hybrid statistic is calculated as \documentclass[12pt]{minimal}
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\begin{document}$$E_{\mathrm{hyb}}=\text{max}\left\{\frac{L_{\mathrm{hyb}}-E\left[L_{\mathrm{hyb}}\vert H_0\right]}{L_{\mathrm{hyb}}},0\right\}\times100\%$$\end{document}
Similar to the interpretation of \documentclass[12pt]{minimal}
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\begin{document}$${E}_{\gamma }$$\end{document} , \documentclass[12pt]{minimal}
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\begin{document}$$E_{hyb}$$\end{document} represents the percentage of excess inconsistency, but it is derived from the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} (or equivalently, \documentclass[12pt]{minimal}
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\begin{document}$${L}_{\text{hyb}}$$\end{document} ) statistic. For example, if \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} = 0.001, corresponding to \documentclass[12pt]{minimal}
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\begin{document}$${L}_{\text{hyb}}$$\end{document} = 3, and the expected value under the null hypothesis is \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{L}_{\text{hyb}}|{H}_{0}\right]$$\end{document} = 1, then \documentclass[12pt]{minimal}
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\begin{document}$${E}_{\text{hyb}}$$\end{document} = (3–1)/3 = 66.7%.
We validated the performance of various tests for between-study inconsistency via simulation studies. We considered the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test, the proposed \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests with \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} = 1, 2, …, 8, and \documentclass[12pt]{minimal}
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\begin{document}$$\infty$$\end{document} , as well as the hybrid test. The tests’ performance was assessed in terms of their type I error rates and statistical power.
To derive type I error rates, we generated meta-analyses with observed effect sizes as \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}\sim N\left({\mu }_{\text{CE}}, {s}_{i}^{2}\right)$$\end{document} under the null hypothesis of homogeneity (Case 0). Without loss of generality, we set \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{\text{CE}}$$\end{document} = 0. In addition, the within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}$$\end{document} were sampled from a uniform distribution, \documentclass[12pt]{minimal}
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\begin{document}$$U\left(1, 2\right)$$\end{document} or \documentclass[12pt]{minimal}
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\begin{document}$$U\left(2, 3\right)$$\end{document} .
To derive statistical power, we considered various settings of the alternative hypothesis of between-study inconsistency. Specifically, the study-specific effect sizes \documentclass[12pt]{minimal}
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\begin{document}$${y}_{i}$$\end{document} were generated from \documentclass[12pt]{minimal}
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\begin{document}$$N\left({\mu }_{i}, {s}_{i}^{2}\right)$$\end{document} , where \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} was the true effect size of study \documentclass[12pt]{minimal}
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\begin{document}$$i$$\end{document} and followed various distributions as follows to reflect different patterns of between-study inconsistency. Case 1: \documentclass[12pt]{minimal}
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\begin{document}$$N\left(0, 2\right)$$\end{document} ; Case 2: the mixture normal distribution, \documentclass[12pt]{minimal}
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\begin{document}$$0.85N\left(0, 0.2\right)+0.15N\left(0, 20\right)$$\end{document} , consisting of two normal distributions with the same mean 0 and different variances; Case 3: the gamma distribution with shape parameter 0.05 and rate parameter 0.1, \documentclass[12pt]{minimal}
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\begin{document}$$\text{Gamma}\left(0.05, 0.1\right)$$\end{document} ; Case 4: the \documentclass[12pt]{minimal}
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\begin{document}$$F$$\end{document} distribution with degrees of freedom 3 and 8, \documentclass[12pt]{minimal}
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\begin{document}$${F}_{\text{3,8}}$$\end{document} . Case 5: the mixture normal distribution, \documentclass[12pt]{minimal}
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\begin{document}$$0.70N\left(0, 1\right)+0.30N\left(1.5, 1\right)$$\end{document} , consisting of two normal distributions with different means but the same variance;
Case 1: \documentclass[12pt]{minimal}
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\begin{document}$$N\left(0, 2\right)$$\end{document} ;
Case 2: the mixture normal distribution, \documentclass[12pt]{minimal}
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\begin{document}$$0.85N\left(0, 0.2\right)+0.15N\left(0, 20\right)$$\end{document} , consisting of two normal distributions with the same mean 0 and different variances;
Case 3: the gamma distribution with shape parameter 0.05 and rate parameter 0.1, \documentclass[12pt]{minimal}
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\begin{document}$$\text{Gamma}\left(0.05, 0.1\right)$$\end{document} ;
Case 4: the \documentclass[12pt]{minimal}
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\begin{document}$$F$$\end{document} distribution with degrees of freedom 3 and 8, \documentclass[12pt]{minimal}
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\begin{document}$${F}_{\text{3,8}}$$\end{document} .
Case 5: the mixture normal distribution, \documentclass[12pt]{minimal}
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\begin{document}$$0.70N\left(0, 1\right)+0.30N\left(1.5, 1\right)$$\end{document} , consisting of two normal distributions with different means but the same variance;
The normality assumption in Case 1 is conventional for most meta-analysis methods. The distribution in Case 2 had heavier tails than a single normal distribution, which could generate extreme values. The distributions in Cases 3 and 4 were skewed, arguably reflecting the potential influence of publication bias or small-study effects. In Case 5, the distribution conceptually represents scenarios in which a meta-analysis includes two subgroups, each centered at a different overall effect size. The distributions in Cases 3 to 5 have non-zero mean; to make fair comparisons, we centralized these distributions at 0 so that \documentclass[12pt]{minimal}
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\begin{document}$$E\left[{\mu }_{i}\right]$$\end{document} = 0.
We additionally considered two cases of contamination: Case 6: all \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} = \documentclass[12pt]{minimal}
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\begin{document}$$-$$\end{document} 0.2 expect that \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{11}=0.2\left(k-1\right)$$\end{document} ; Case 7: all \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} = 0 but \documentclass[12pt]{minimal}
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\begin{document}$${y}_{6}$$\end{document} was artificially added by a discrepancy value of \documentclass[12pt]{minimal}
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\begin{document}$$\epsilon$$\end{document} = 3.
Case 6: all \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} = \documentclass[12pt]{minimal}
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\begin{document}$$-$$\end{document} 0.2 expect that \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{11}=0.2\left(k-1\right)$$\end{document} ;
Case 7: all \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} = 0 but \documentclass[12pt]{minimal}
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\begin{document}$${y}_{6}$$\end{document} was artificially added by a discrepancy value of \documentclass[12pt]{minimal}
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\begin{document}$$\epsilon$$\end{document} = 3.
The cases occur when most studies in a meta-analysis are homogeneous, but one study based on a dramatically different population is inappropriately included in the meta-analysis.
Each simulated meta-analysis consisted of \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15 or 30 studies. We generated 1,000 replicates for each simulation setting. Because the resampling algorithm is computationally intensive, and considering that it needed to be repeated for 1,000 Monte Carlo replications in the simulations, we used \documentclass[12pt]{minimal}
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\begin{document}$$B$$\end{document} = 500 resampling iterations instead of a much larger number. The significance level for inconsistency was set to 0.10 because inconsistency tests typically have low power in many cases, as indicated by existing simulation studies [ 37 ].
To illustrate the practical utility of the proposed methods, we applied the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests and the hybrid tests to three real-world meta-analyses. For each meta-analysis, we calculated the P -values of the various tests and the corresponding inconsistency measures. The resampling method was used for calculating the P -values, and the number of resampling iterations was 10,000. Of note, we used a much larger \documentclass[12pt]{minimal}
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\begin{document}$$B$$\end{document} in these case studies than in the simulations because only three meta-analyses were analyzed, making the larger number of resampling iterations computationally feasible and allowing for smaller Monte Carlo resampling error.
Results
Tables 1 , 2 , 3 , and 4 present the simulation results under a range of data-generating settings that varied the distribution of the true effects \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} , the within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} or \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} , and the number of studies \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15 or 30. Monte Carlo standard errors were mostly around 2%, ensuring reliable comparisons of type I error rates or statistical power across settings. The settings covered symmetric, skewed, heavy-tailed, and contaminated distributions, offering a comprehensive assessment of test performance under diverse conditions.
Table 1 Type I error rates (Case 0) and statistical power (Cases 1–7), expressed as percentages, for various tests under the setting with within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15. Monte Carlo standard errors are shown in parentheses. The significance level was set at 10% Setting
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\begin{document}$${Q}_{1}$$\end{document}
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\begin{document}$${Q}_{\infty }$$\end{document}
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Case 0 8.6 (0.9) 8.8 (0.9) 9.1 (0.9) 8.9 (0.9) 9.0 (0.9) 9.2 (0.9) 9.3 (0.9) 9.4 (0.9) 9.3 (0.9) 9.1 (0.9) Case 1 68.2 (1.5) 71.3 (1.4) 69.9 (1.5) 67.0 (1.5) 65.3 (1.5) 64.0 (1.5) 62.9 (1.6) 62.0 (1.6) 56.2 (1.6) 69.0 (1.5) Case 2 58.7 (1.6) 65.4 (1.5) 66.8 (1.5) 66.6 (1.5) 66.2 (1.5) 65.9 (1.5) 65.5 (1.5) 65.6 (1.5) 65.2 (1.5) 66.4 (1.5) Case 3 42.2 (1.6) 47.3 (1.6) 49.1 (1.6) 48.6 (1.6) 48.6 (1.6) 48.8 (1.6) 48.5 (1.6) 48.7 (1.6) 48.7 (1.6) 47.9 (1.6) Case 4 55.5 (1.6) 61.0 (1.6) 60.1 (1.6) 58.7 (1.6) 58.0 (1.6) 57.4 (1.6) 56.7 (1.6) 56.2 (1.6) 53.8 (1.6) 59.9 (1.6) Case 5 55.9 (1.6) 60.0 (1.5) 58.2 (1.6) 56.5 (1.6) 55.2 (1.6) 53.8 (1.6) 52.4 (1.6) 51.9 (1.6) 47.1 (1.6) 56.6 (1.6) Case 6 24.9 (1.3) 29.7 (1.4) 33.2 (1.5) 34.2 (1.5) 34.5 (1.5) 34.6 (1.5) 34.7 (1.5) 35.0 (1.5) 34.7 (1.5) 33.0 (1.5) Case 7 23.0 (1.3) 29.2 (1.4) 32.8 (1.5) 33.1 (1.5) 33.2 (1.5) 33.3 (1.5) 32.7 (1.5) 32.3 (1.5) 32.2 (1.5) 31.4 (1.5)
Type I error rates (Case 0) and statistical power (Cases 1–7), expressed as percentages, for various tests under the setting with within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15. Monte Carlo standard errors are shown in parentheses. The significance level was set at 10%
Under the null hypothesis (Case 0: \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}$$\end{document} = 0), all tests controlled the type I error rates well at the nominal 10% level. For example, in Table 1 with \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, the type I error rates ranged from 8.6% to 9.4%; in Table 2 with \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, the rates had similar ranges (e.g., 8.5% for \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} , 9.4% for \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} ). With \documentclass[12pt]{minimal}
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Table 2 Type I error rates (Case 0) and statistical power (Cases 1–7), expressed as percentages, for various tests under the setting with within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15. Monte Carlo standard errors are shown in parentheses. The significance level was set at 10% Setting
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Case 0 8.5 (0.9) 8.6 (0.9) 9.1 (0.9) 8.8 (0.9) 9.1 (0.9) 9.1 (0.9) 9.4 (0.9) 9.2 (0.9) 9.4 (0.9) 9.1 (0.9 Case 1 32.8 (1.5) 35.4 (1.5) 34.3 (1.5) 33.1 (1.5) 32.4 (1.5) 31.0 (1.5) 30.7 (1.5) 30.3 (1.5) 28.2 (1.4) 34.8 (1.5) Case 2 36.2 (1.5) 43.5 (1.6) 43.8 (1.6) 43.3 (1.6) 43.5 (1.6) 43.5 (1.6) 43.4 (1.6) 43.0 (1.6) 41.4 (1.6) 43.2 (1.6) Case 3 30.7 (1.5) 35.2 (1.5) 36.5 (1.6) 36.0 (1.5) 36.1 (1.5) 35.9 (1.5) 36.0 (1.5) 35.7 (1.5) 35.3 (1.5) 35.6 (1.5) Case 4 30.0 (1.4) 35.9 (1.5) 35.9 (1.5) 35.8 (1.5) 34.4 (1.5) 34.1 (1.5) 33.7 (1.5) 33.7 (1.5) 31.9 (1.5) 35.9 (1.5) Case 5 22.7 (1.3) 23.9 (1.3) 24.2 (1.4) 23.3 (1.3) 22.9 (1.3) 22.4 (1.3) 21.7 (1.3) 21.6 (1.3) 20.2 (1.3) 23.6 (1.3) Case 6 14.4 (1.1) 17.2 (1.2) 17.8 (1.2) 17.8 (1.2) 18.1 (1.2) 17.8 (1.2) 17.4 (1.2) 17.4 (1.2) 17.2 (1.2) 16.6 (1.2) Case 7 13.7 (1.0) 14.9 (1.1) 15.5 (1.1) 15.0 (1.1) 14.9 (1.1) 15.3 (1.1) 15.3 (1.1) 15.5 (1.1) 15.4 (1.1) 14.7 (1.1)
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Table 3 Type I error rates (Case 0) and statistical power (Cases 1–7), expressed as percentages, for various tests under the setting with within-study standard errors \documentclass[12pt]{minimal}
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Case 0 11.0 (1.0) 10.6 (1.0) 10.5 (1.0) 9.8 (0.9) 9.3 (0.9) 9.5 (0.9) 8.8 (0.9) 9.0 (0.9) 9.3 (0.9) 9.9 (0.9) Case 1 86.8 (1.1) 89.4 (1.0) 88.4 (1.0) 86.6 (1.1) 84.3 (1.2) 81.4 (1.2) 79.8 (1.3) 77.7 (1.3) 68.8 (1.5) 87.4 (1.0) Case 2 75.9 (1.3) 82.8 (1.2) 84.0 (1.2) 84.1 (1.2) 84.1 (1.2) 83.9 (1.2) 83.8 (1.2) 83.9 (1.2) 82.7 (1.2) 84.6 (1.2) Case 3 57.5 (1.6) 65.6 (1.5) 67.6 (1.5) 67.9 (1.5) 67.8 (1.5) 67.8 (1.5) 67.7 (1.5) 67.7 (1.5) 68.0 (1.5) 67.2 (1.5) Case 4 73.3 (1.4) 78.8 (1.3) 78.3 (1.3) 77.3 (1.3) 75.9 (1.3) 75.0 (1.3) 74.7 (1.3) 73.4 (1.4) 69.5 (1.5) 77.3 (1.3) Case 5 75.5 (1.4) 79.4 (1.3) 77.8 (1.3) 73.8 (1.4) 70.5 (1.4) 67.3 (1.5) 65.4 (1.5) 63.3 (1.5) 54.6 (1.6) 75.5 (1.4) Case 6 40.8 (1.6) 68.5 (1.5) 78.7 (1.3) 81.8 (1.2) 83.3 (1.2) 83.7 (1.2) 84.1 (1.1) 84.3 (1.1) 84.6 (1.1) 81.9 (1.2) Case 7 17.9 (1.2) 22.9 (1.3) 26.6 (1.4) 27.5 (1.4) 29.2 (1.4) 28.8 (1.4) 28.8 (1.4) 28.7 (1.4) 28.4 (1.4) 27.0 (1.4)
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Table 4 Type I error rates (Case 0) and statistical power (Cases 1–7), expressed as percentages, for various tests under the setting with within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30. Monte Carlo standard errors are shown in parentheses. The significance level was set at 10% Setting
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\begin{document}$${Q}_{6}$$\end{document}
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\begin{document}$${Q}_{7}$$\end{document}
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\begin{document}$${Q}_{\infty }$$\end{document}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document}
Case 0 11.1 (1.0) 10.5 (1.0) 10.3 (1.0) 9.6 (0.9) 9.0 (0.9) 9.5 (0.9) 8.9 (0.9) 9.0 (0.9) 9.1 (0.9) 9.8 (0.9) Case 1 40.7 (1.6) 44.0 (1.6) 42.6 (1.6) 40.3 (1.6) 37.8 (1.6) 35.0 (1.5) 33.9 (1.5) 32.6 (1.5) 29.9 (1.4) 40.5 (1.6) Case 2 44.8 (1.6) 55.6 (1.6) 57.0 (1.6) 57.5 (1.6) 56.9 (1.6) 56.2 (1.6) 55.5 (1.6) 55.2 (1.6) 52.8 (1.6) 57.0 (1.6) Case 3 37.7 (1.6) 48.4 (1.6) 50.3 (1.6) 50.4 (1.6) 50.5 (1.6) 50.7 (1.6) 50.7 (1.6) 50.6 (1.6) 49.8 (1.6) 50.0 (1.6) Case 4 39.5 (1.6) 44.9 (1.6) 46.1 (1.6) 45.5 (1.6) 44.9 (1.6) 43.7 (1.6) 43.1 (1.6) 42.6 (1.6) 38.6 (1.6) 44.9 (1.6) Case 5 33.8 (1.5) 35.5 (1.5) 34.2 (1.5) 33.2 (1.5) 30.3 (1.5) 28.7 (1.4) 27.7 (1.4) 27.2 (1.4) 24.8 (1.4) 34.0 (1.5) Case 6 22.2 (1.3) 30.4 (1.5) 36.3 (1.6) 38.7 (1.6) 39.7 (1.6) 40.0 (1.6) 39.8 (1.6) 40.2 (1.6) 39.6 (1.6) 38.1 (1.6) Case 7 11.3 (1.0) 13.1 (1.0) 13.1 (1.0) 12.5 (1.0) 13.0 (1.0) 13.2 (1.0) 13.3 (1.0) 13.2 (1.0) 13.2 (1.0) 12.8 (1.0)
Type I error rates (Case 0) and statistical power (Cases 1–7), expressed as percentages, for various tests under the setting with within-study standard errors \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} and the number of studies \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30. Monte Carlo standard errors are shown in parentheses. The significance level was set at 10%
Under the conventional normality assumption for between-study inconsistency, with \documentclass[12pt]{minimal}
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\begin{document}$${\mu }_{i}\sim N\left(0, 2\right)$$\end{document} , the statistical power of all tests increased substantially with the number of studies. For example, in the setting \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} (Tables 1 and 3 ), the hybrid test \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} achieved a power of 69.0% when \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, which increased to 87.4% when \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30. Notably, the \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} test demonstrated the highest power among all \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests in this scenario, reaching 71.3% for \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15 and 89.4% for \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30. It also slightly outperformed the hybrid test. When the within-study standard errors followed a wider distribution with \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} in Tables 2 and 4 , the power of all tests declined due to increased within-study uncertainties. Nevertheless, \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} remained one of the best-performing methods, with power values of 35.4% ( \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15) and 44.0% ( \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30), consistently outperforming most other tests.
Across all settings, the hybrid test \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\text{hyb}}$$\end{document} demonstrated strong robustness and consistently competitive power. For \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} and \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, the hybrid test achieved a power of 66.4%, which was slightly lower than the best-performing \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests, such as 66.8% for \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{3}$$\end{document} , 66.6% for \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{4}$$\end{document} , and 66.2% for \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{5}$$\end{document} . Nevertheless, it remained among the top-performing methods, and its power was notably higher than \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} (with power of 58.7%) and comparable to \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (65.4%), as shown in Table 1 . When within-study standard errors were larger, power declined for all methods. The hybrid test maintained solid performance with power of 43.2%, outperforming \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} (36.2%), and having similar power to \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (43.5%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{5}$$\end{document} (43.5%), as shown in Table 2 . With more studies ( \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30) in meta-analyses, the hybrid test showed clearer advantages. In Table 3 with \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} , its power reached 84.6%, outperforming \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} (75.9%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (82.8%), and closely matching \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{5}$$\end{document} (84.1%). In Table 4 with \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} , it again led with 57.0% power, exceeding the power of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} (44.8%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (55.6%).
For the gamma (Case 3) and \documentclass[12pt]{minimal}
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\begin{document}$$F$$\end{document} -distributed (Case 4) inconsistency, the hybrid test continued to perform well. For instance, in Table 3 ’s Case 4, the hybrid test’s power was 77.3%, outperforming \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} (73.3%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{8}$$\end{document} (73.4%). In Table 4 ’s Case 3, the hybrid test reached the power of 50.0%, on par with \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{8}$$\end{document} (50.6%) and superior to \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (48.4%). These demonstrated the hybrid test’s adaptability to skewed distributions.
With \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, the hybrid test demonstrated stable and competitive performance. In Table 1 , the hybrid test attained a power of 56.6%, closely matching \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (60.0%) and outperforming both \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{5}$$\end{document} (55.2%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (47.1%). Under the scenario with larger within-study variances, the hybrid test still achieved 23.6% power, comparable to the best-performing test \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{3}$$\end{document} (24.2%) and exceeding \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (20.2%) (Table 2 ). These results suggested that the hybrid test maintained reasonable sensitivity in detecting inconsistency even when the underlying effect sizes may be from different subgroups.
In scenarios involving structural or data-driven contamination, test robustness is essential. Recall that Case 6 simulated effect reversal in one study, while Case 7 introduced a single extreme value. In Case 6, with \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, the hybrid test achieved 33.0% power under the setting of \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} in Table 1 , higher than \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (29.7%) and slightly below \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (34.7%). Under the setting of \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} in Table 2 , all three tests performed similarly (with power in the range of 16.6–17.2%). With \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30, the hybrid test’s advantage became more evident. Under the setting of \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} , its power reached 81.9%, notably higher than \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (68.5%) and close to \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{8}$$\end{document} (84.3%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (84.6%), as shown in Table 3 . Under the setting of \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} , the hybrid test’s power achieved 38.1%, ranking between \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (30.4%) and \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (39.6%), as shown in Table 4 . In Case 7, under \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 15, the hybrid test had power of 31.4% under the setting of \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(1, 2\right)$$\end{document} , outperforming \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (29.2%) and slightly below \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (32.2%) (Table 1 ). Under the setting of \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} , its power achieved 14.7%, modestly below \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (17.2%) (Table 2 ). With \documentclass[12pt]{minimal}
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\begin{document}$$k$$\end{document} = 30, Table 3 shows the hybrid test with power at 27.0% for \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(\text{1,2}\right)$$\end{document} , above \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} (22.9%) and slightly below \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\infty }$$\end{document} (28.4%). For \documentclass[12pt]{minimal}
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\begin{document}$${s}_{i}\sim U\left(2, 3\right)$$\end{document} , the hybrid test’s power was 12.8%, slightly behind \documentclass[12pt]{minimal}
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Overall, \documentclass[12pt]{minimal}
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Figure 1 displays the forest plots of the three real-world meta-analyses used as our case studies. Table 5 presents their results after applying the various inconsistency tests and measures; it also gives the inconsistency measures \documentclass[12pt]{minimal}
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Fig. 1 The forest plots of three real-world meta-analyses
The forest plots of three real-world meta-analyses
Table 5 P -values of the various \documentclass[12pt]{minimal}
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Hughes et al. [ 38 ] P -value 0.593 0.221 0.094 0.060 0.047 0.042 0.040 0.038 0.034 0.065
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0 0.237 0.490 0.640 0.725 0.774 0.801 0.813 0.357 0.599 Gafter-Gvili et al. [ 39 ] P -value 0.041 0.136 0.243 0.321 0.371 0.407 0.428 0.446 0.556 0.082
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0.279 0.308 0.245 0.104 0 0 0 0 0 0.568 Saha et al. [ 40 ] P -value 0.139 0.109 0.144 0.184 0.216 0.240 0.256 0.269 0.293 0.187
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0.196 0.348 0.393 0.367 0.277 0.111 0 0 0.112 0.396
P -values of the various \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} and hybrid tests for between-study inconsistency and their corresponding inconsistency measures \documentclass[12pt]{minimal}
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\begin{document}$${E}_{\gamma }$$\end{document} for the three real-world meta-analyses
Specifically, the first meta-analysis was from Hughes et al. [ 38 ]; it assessed the effectiveness of ovulation suppression agents in the treatment of endometriosis-associated subfertility in improving pregnancy outcomes, including live birth. The number of studies in this meta-analysis was 11. The P -value of the traditional \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} test was 0.221, while the P -value of \documentclass[12pt]{minimal}
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\begin{document}$$\gamma \ge$$\end{document} 3. The hybrid test yielded a P -value of 0.065, suggesting statistical significance at the 10% level (Fig. 1 A and Table 5 ). This example highlights the hybrid test’s improved sensitivity in detecting inconsistency, making it a valuable tool for enhancing the detection of inconsistency in meta-analyses.
The second meta-analysis was from Gafter-Gvili et al. [ 39 ]; it evaluated the effectiveness of antibiotic prophylaxis for preventing bacterial infections in afebrile neutropenic patients following chemotherapy. The number of studies was 14. The P -value of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{1}$$\end{document} test was relatively small (0.041); the P -value of the hybrid test was also lower than 0.1, indicating statistical significance (Fig. 1 B and Table 5 ). The \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} values had P -values greater than 0.1, failing to detect significant inconsistency.
The third meta-analysis was from Saha et al. [ 40 ], and it investigated the effects of chlorpromazine with atypical or second-generation antipsychotic drugs for the treatment of people with schizophrenia. It consisted of 12 studies. As shown in Table 5 , most of the P -values across all tests were above the conventional significance threshold of 0.1. Specifically, the P -values of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{2}$$\end{document} were 0.139 and 0.109, respectively. Overall, the results indicate weak evidence of inconsistency across studies in this meta-analysis (Fig. 1 C).
As a final remark, the hybrid test evaluates whether any deviation pattern among the family of candidate \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistics is convincingly present. Through resampling, it accounts for the correlations among the individual \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests and thus provides a conservative overall assessment when no evidence of inconsistency is detected, while being more sensitive when a particular \documentclass[12pt]{minimal}
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\begin{document}$$\gamma$$\end{document} value captures a pattern that others miss. In contrast, the individual \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests may not be interpreted collectively as formal hypothesis tests for overall inconsistency, because they do not adjust for multiple testing. A single significant \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} result does not necessarily indicate significant overall inconsistency; rather, these tests are intended to help explore and understand potential patterns of between-study inconsistency.
Background
Meta-analysis is widely used to combine results from multiple studies on the same research topic in a wide range of fields [ 1 , 2 ]. A critical step for validating a meta-analysis is to assess the differences between studies. Because the multiple studies recruited participants with potentially different characteristics and were conducted by different research teams with different methods, their results are usually expected to have a certain extent of heterogeneity [ 3 ]. If the studies are considered mostly homogeneous, such that they share a common true effect size, a common-effect model is employed for the meta-analysis. On the other hand, if the studies are heterogeneous, such that their underlying true effect sizes differ, a random-effects model is typically used to account for the heterogeneity [ 4 , 5 ]. As such, the assessment of the differences between studies offers valuable information for model selection and appraising the interpretability of meta-analysis conclusions.
The \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test is traditionally used to measure the between-study heterogeneity in a meta-analysis. Under the null hypothesis of homogeneity, the \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic follows a chi-squared distribution. This statistic takes the sum of squared standardized deviates from individual studies. Conceptually, it shares a similar idea with the classical least-squares regression that minimizes the sum of squared errors. The structure of the sum of squares may be suitable for the conventional assumption made by the random-effects meta-analysis models; that is, the underlying true effect sizes of all individual studies follow a normal distribution with a certain heterogeneity variance. The theoretical properties of the \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic have been mostly investigated under such between-study normality [ 6 – 8 ]. Nevertheless, this is not always the case of discrepancies between studies’ results, and the normality assumption could be questionable in many applications [ 9 – 12 ]. For example, a meta-analysis may include a few outlying studies whose results take extreme values compared with the majority of studies [ 13 ]. It may also inappropriately pool multiple subgroups in the same analysis; the subgroups could be distinguished based on certain study-level summaries of population characteristics, such as average ages [ 14 ]. The studies in different subgroups could have dramatically different effect sizes, while those in the same group may share more homogeneous effect sizes. In such cases, the underlying effect sizes from the whole studies may have a distribution with multiple modes. Moreover, publication bias or small-study effects can distort the observed distribution of studies. For example, if studies reporting effects in one direction (say, positive effects of an intervention) are more likely to be published, the between-study distribution may become skewed, often with a longer tail on the side favored by the bias. It is well documented in the meta-analysis literature that publication bias can interact with heterogeneity assessments, potentially exaggerating between-study variability or even masking true inconsistency [ 15 ]. Indeed, ignoring the coexistence of publication bias and heterogeneity may lead to misleading conclusions about both [ 16 , 17 ]. In summary, the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test may not be suitable for the foregoing non-normal cases, as it may suffer from low statistical power, especially when the number of studies in a meta-analysis is relatively small [ 18 , 19 ].
Considering the diversity of factors that may cause the discrepancies between studies on the same research topic, this article refers to such discrepancies as inconsistency in general instead of heterogeneity in particular. The term “inconsistency” was also used by Higgins et al. [ 20 ] when they introduced the famous \documentclass[12pt]{minimal}
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\begin{document}$${I}^{2}$$\end{document} statistic to the medical community for quantifying the discrepancies between studies. Moreover, this terminology is adopted in the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework for assessing the certainty of evidence [ 21 ]. In the literature of meta-analysis methodology, on the other hand, the term “heterogeneity” seems to be more widely used for the same purpose. It is frequently paired with the random-effects model, which assumes between-study normality; that is, the discrepancies permeate the entire meta-analysis, rather than being limited to certain subgroups or a few outlying studies. This article uses the term “inconsistency” to inclusively cover all types of discrepancies, including subgroup effects and potential outliers. It is important to note that this usage differs from evidence inconsistency in network meta-analysis, which refers to disagreement between direct and indirect comparisons of multiple interventions [ 22 , 23 ].
Beyond the traditional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test, several likelihood-based approaches, including the score test, likelihood-ratio test, and Wald test, have been proposed for assessing between-study heterogeneity [ 24 , 25 ]. Similar to the \documentclass[12pt]{minimal}
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Motivated by these limitations, this article presents alternative test statistics to examine the between-study inconsistency. These statistics are designed based on the sum of absolute values of standardized deviates with different mathematical powers (e.g., square, cubic, maximum, and so on). They attempt to serve as suitable candidates under various scenarios of between-study distributions. For example, consider a meta-analysis with an extremely outlying study; except for the outliers, all remaining studies are mostly homogeneous. If the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} statistic is used to test for the inconsistency, the sum of squares of standardized deviates would include too much noise, given that most studies are actually homogeneous. Indeed, in such a case, the maximum of the standardized deviates would efficiently capture the inconsistency with the minimal contamination by noises from homogeneous studies, as the outlying study is expected to create the largest deviate.
By their designs, the various alternative tests for inconsistency have different statistical power under different settings that cause discrepancies between individual studies’ results, so there is no universally best test. In practice, it is infeasible to justify an optimal test that fits a specific meta-analysis dataset. As such, using the idea of adaptive testing [ 27 , 28 ], we derive a hybrid test based on the various tests for inconsistency. The hybrid test statistic takes the minimum P -values from various tests for inconsistency so that it can achieve relatively high power across a wide range of settings. To properly control the type I error rate of the hybrid test, we propose a parametric resampling procedure to derive the null distribution and thus calculate the empirical P -value of the hybrid test.
This article is organized as follows. We start with presenting the setup of the inconsistency problem in a meta-analysis, reviewing the existing popular \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test for inconsistency, proposing the alternative test statistics and hybrid test, and providing the algorithm of the resampling method for deriving the tests’ P -values. Then, we present simulation studies to compare the statistical power of the various tests and use three case studies to illustrate the real-world performance of the tests. Finally, we conclude this article with discussions about the proposed methods’ limitations and potential future directions.
Discussion
This article introduces several alternative \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} , for assessing between-study inconsistency in meta-analyses, along with a hybrid test that combines the strengths of these \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} tests. Our simulation studies and real-world case applications demonstrate that the hybrid test consistently achieves strong performance across a wide range of between-study inconsistency scenarios, particularly when the distribution of true effects deviates from normality.
A major strength of the proposed methods is their ability to address the challenge posed by non-normal between-study distributions. Although the assumption of normality has been a longstanding foundation in meta-analysis methodology and remains widely used in practice, its validity in any given analysis is often uncertain. Even if the assumption is approximately reasonable in many cases, it is difficult to verify whether it holds in a specific meta-analysis or whether its violation materially affects the assessment of inconsistency. This uncertainty largely stems from the fact that testing for between-study normality is inherently limited in power due to the typically small number of studies in meta-analyses.
The hybrid test is particularly well-suited to this dilemma. Without requiring knowledge of the precise form of the between-study distribution, it adaptively integrates information from a family of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistics, each tailored to different patterns of inconsistency. As a result, it maintains relatively high power across diverse conditions, making it a robust tool for evidence synthesis.
Another strength of the hybrid test is its potential adaptability to meta-analyses affected by publication bias or small-study effects. In such cases, the between-study distribution may become skewed due to selective reporting, making the normality assumption unrealistic. Some of our simulation settings included skewed between-study distributions, which mimic scenarios involving publication bias. As discussed in the Introduction, the assessments of publication bias and between-study inconsistency are often interrelated and may influence each other. The proposed approach offers a promising tool to improve inconsistency assessment in the presence of publication bias, although further research is warranted to evaluate its performance under various bias-generating mechanisms. In practice, researchers may first use conventional methods for detecting publication bias, such as funnel plots or Egger’s regression test [ 41 , 42 ]. If evidence of bias is detected, the traditional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test may be suboptimal, and our proposed methods could serve as more robust alternatives.
Despite its strengths, the hybrid test has several limitations. First, like traditional meta-analysis models, it assumes that the within-study variances are known. This assumption may be questionable in certain contexts, such as studies with small sample sizes or rare event probabilities. More precise modeling approaches, such as generalized linear mixed models, can address this limitation [ 43 , 44 ]. While our proposed test statistics and measures could be extended to these models, doing so would require replacing the sample-based within-study variances with the underlying variance parameters. Achieving this may necessitate additional methodological development, such as incorporating Bayesian hierarchical models [ 45 ], which represents a promising avenue for future research.
Second, although the methods are designed to relax the assumption of between-study normality, they still rely on the assumption of within-study normality. This can be justified by asymptotic arguments when studies have large sample sizes, but it may not hold when sample sizes are small.
Third, the choice of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} values and consider expanding the candidate set if the observed patterns suggest the need for additional sensitivity. Such adjustments may involve a trade-off between potential gains in power and computational burden, as including more \documentclass[12pt]{minimal}
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In addition, our simulation studies for validating the proposed methods included only meta-analyses with 15 or 30 studies. In practice, many meta-analyses contain fewer studies [ 46 , 47 ], and the statistical power of all tests, including the proposed ones, would be expected to decrease substantially in such cases. When the number of studies is very small, relying solely on statistical testing to assess heterogeneity may not be valid or reliable because of the limited power [ 48 ]. We recommend that researchers also consider the potential sources and implications of heterogeneity from clinical perspectives, such as the presence of effect modifiers or study-level characteristics that may influence effect sizes [ 49 , 50 ]. Despite our simulations being restricted to 15 and 30 studies, we believe that the results adequately demonstrate how the proposed hybrid approach integrates the strengths of various component tests and achieves competitive performance across diverse scenarios.
Conclusions
We proposed a family of alternative \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} -like tests and a hybrid test to assess between-study inconsistency in meta-analyses, offering flexible and powerful tools beyond the conventional \documentclass[12pt]{minimal}
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\begin{document}$$Q$$\end{document} test. Through simulations and real-world applications, we demonstrated that the hybrid test maintains robust performance across a wide range of inconsistency scenarios, particularly when the between-study distribution deviates from normality. These methods provide practical solutions for improving the detection and quantification of inconsistency in meta-analysis, especially when traditional assumptions are questionable. Future work may extend these approaches to accommodate more complex models and further refine the choice of test statistics.
Supplementary Material
Additional file 1: Derivation of the expectations of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistics under the null hypothesis.
Additional file 1: Derivation of the expectations of \documentclass[12pt]{minimal}
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\begin{document}$${Q}_{\gamma }$$\end{document} statistics under the null hypothesis.
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