Investigation of the Utility of Multivariate Meta-Analysis Methods in Estimating the Summary Dose Response Curve

Abstract

Background: Traditional meta-analyses often assess the effectiveness of different doses of the same intervention separately or examine the overall differences between intervention and placebo groups. The present study aimed to model the effect sizes obtained from different doses in multiple studies using a two-stage dose-response meta-analytic approach while taking dose variations into account. Methods: Different dose-response meta-analysis models using linear, quadratic, and restricted cubic spline (RCS) functions were fitted. A two-stage approach utilizing multivariate meta-analysis was performed and the obtained results were compared with those of the univariate meta-analysis. A random effect dose-response meta-analysis was performed using data from an existing systematic review on combination therapy with zonisamide and anti-Parkinson drugs for Parkinson’s disease. The effective or optimum dose for producing maximum response was also investigated. Moreover, a sensitivity analysis was performed by changing the knots of the RCS model. Results: Dose-response meta-analysis was performed using data from four double-blinded randomized controlled trials with 724 and 309 patients with Parkinson’s disease in dose and placebo arms, respectively. The quadratic model yielded the smallest Akaike information criterion (AIC), compared to the linear and RCS models, indicating it to be the best fit for the data. Conclusion: Compared to the traditional approach, the two-stage approach could model the dose-dependent effect of zonisamide on the Unified Parkinson’s Disease Rating Scale (UPRDS) part III score and predict the outcome for different doses through a single analysis.