Undue reliance on I2 in assessing heterogeneity may mislead

Abstract

Background: The heterogeneity statistic I2, interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error, depends on precision, that is, the size of the studies included. Methods: Based on a real meta-analysis, we simulate artificially 'inflating' the sample size under the random effects model. For a given inflation factor M = 1, 2, 3,. and for each trial i, we create a M-inflated trial by drawing a treatment effect estimate from the random effects model, using s i2 IM as within-trial sampling variance. Results: As precision increases, while estimates of the heterogeneity variance τ2 remain unchanged on average, estimates of I2 increase rapidly to nearly 100%. A similar phenomenon is apparent in a sample of 157 meta-analyses. Conclusion: When deciding whether or not to pool treatment estimates in a meta-analysis, the yard-stick should be the clinical relevance of any heterogeneity present. τ2, rather than I2, is the appropriate measure for this purpose.