Assessing the impact of case-mix heterogeneity in individual participant data meta-analysis: Novel use of I2 statistic and prediction interval

Case mix differences between trials form an important factor that contributes to the statistical heterogeneity observed in a meta-analysis. In this paper, we propose two methods to assess whether important heterogeneity would remain if the different trials in the meta-analysis were conducted in one common population defined by a given case-mix. To achieve this goal, we first standardize results of different trials over the case-mix of a target population. We then quantify the amount of heterogeneity arising from case-mix and beyond case-mix reasons by using corresponding I2 statistics and prediction intervals. These new approaches enable a better understanding of the overall heterogeneity between trial results, and can be used to support standard heterogeneity assessments in individual participant data meta-analysis practice.