Lawrence M Paul1. 1. Bell Laboratories, Somerset, New Jersey, 08873, United States. lmpaul@sciencesupportconsulting.com.
Abstract
BACKGROUND: The use of meta-analysis to aggregate the results of multiple studies has increased dramatically over the last 40 years. For homogeneous meta-analysis, the Mantel-Haenszel technique has typically been utilized. In such meta-analyses, the effect size across the contributing studies of the meta-analysis differs only by statistical error. If homogeneity cannot be assumed or established, the most popular technique developed to date is the inverse-variance DerSimonian and Laird (DL) technique (DerSimonian and Laird, in Control Clin Trials 7(3):177-88, 1986). However, both of these techniques are based on large sample, asymptotic assumptions. At best, they are approximations especially when the number of cases observed in any cell of the corresponding contingency tables is small. RESULTS: This research develops an exact, non-parametric test for evaluating statistical significance and a related method for estimating effect size in the meta-analysis of k 2 × 2 tables for any level of heterogeneity as an alternative to the asymptotic techniques. Monte Carlo simulations show that even for large values of heterogeneity, the Enhanced Bernoulli Technique (EBT) is far superior at maintaining the pre-specified level of Type I Error than the DL technique. A fully tested implementation in the R statistical language is freely available from the author. In addition, a second related exact test for estimating the Effect Size was developed and is also freely available. CONCLUSIONS: This research has developed two exact tests for the meta-analysis of dichotomous, categorical data. The EBT technique was strongly superior to the DL technique in maintaining a pre-specified level of Type I Error even at extremely high levels of heterogeneity. As shown, the DL technique demonstrated many large violations of this level. Given the various biases towards finding statistical significance prevalent in epidemiology today, a strong focus on maintaining a pre-specified level of Type I Error would seem critical. In addition, a related exact method for estimating the Effect Size was developed.
BACKGROUND: The use of meta-analysis to aggregate the results of multiple studies has increased dramatically over the last 40 years. For homogeneous meta-analysis, the Mantel-Haenszel technique has typically been utilized. In such meta-analyses, the effect size across the contributing studies of the meta-analysis differs only by statistical error. If homogeneity cannot be assumed or established, the most popular technique developed to date is the inverse-variance DerSimonian and Laird (DL) technique (DerSimonian and Laird, in Control Clin Trials 7(3):177-88, 1986). However, both of these techniques are based on large sample, asymptotic assumptions. At best, they are approximations especially when the number of cases observed in any cell of the corresponding contingency tables is small. RESULTS: This research develops an exact, non-parametric test for evaluating statistical significance and a related method for estimating effect size in the meta-analysis of k 2 × 2 tables for any level of heterogeneity as an alternative to the asymptotic techniques. Monte Carlo simulations show that even for large values of heterogeneity, the Enhanced Bernoulli Technique (EBT) is far superior at maintaining the pre-specified level of Type I Error than the DL technique. A fully tested implementation in the R statistical language is freely available from the author. In addition, a second related exact test for estimating the Effect Size was developed and is also freely available. CONCLUSIONS: This research has developed two exact tests for the meta-analysis of dichotomous, categorical data. The EBT technique was strongly superior to the DL technique in maintaining a pre-specified level of Type I Error even at extremely high levels of heterogeneity. As shown, the DL technique demonstrated many large violations of this level. Given the various biases towards finding statistical significance prevalent in epidemiology today, a strong focus on maintaining a pre-specified level of Type I Error would seem critical. In addition, a related exact method for estimating the Effect Size was developed.