Joint longitudinal model-based meta-analysis of FEV1 and exacerbation rate in randomized COPD trials

Model-based meta-analysis (MBMA) is an approach that integrates relevant summary level data from heterogeneously designed randomized controlled trials (RCTs). This study not only evaluated the predictability of a published MBMA for forced expiratory volume in one second (FEV1) and its link to annual exacerbation rate in patients with chronic obstructive pulmonary disease (COPD) but also included data from new RCTs. A comparative effectiveness analysis across all drugs was also performed. Aggregated level data were collected from RCTs published between July 2013 and November 2020 (n = 132 references comprising 156 studies) and combined with data used in the legacy MBMA (published RCTs up to July 2013 - n = 142). The augmented data (n = 298) were used to evaluate the predictive performance of the published MBMA using goodness-of-fit plots for assessment. Furthermore, the model was extended including drugs that were not available before July 2013, estimating a new set of parameters. The legacy MBMA model predicted the post-2013 FEV1 data well, and new estimated parameters were similar to those of drugs in the same class. However, the exacerbation model overpredicted the post-2013 mean annual exacerbation rate data. Inclusion of year when the study started on the pre-treatment placebo rate improved the model predictive performance perhaps explaining potential improvements in the disease management over time. The addition of new data to the legacy COPD MBMA enabled a more robust model with increased predictability performance for both endpoints FEV1 and mean annual exacerbation rate.