Network meta-interpolation: Effect modification adjustment in network meta-analysis using subgroup analyses

Abstract

Effect modification (EM) may cause bias in network meta-analysis (NMA). Existing population adjustment NMA methods use individual patient data to adjust for EM but disregard available subgroup information from aggregated data in the evidence network. Additionally, these methods often rely on the shared effect modification (SEM) assumption. In this paper, we propose Network Meta-Interpolation (NMI): a method using subgroup analyses to adjust for EM that does not assume SEM. NMI balances effect modifiers across studies by turning treatment effect (TE) estimates at the subgroup- and study level into TE and standard errors at EM values common to all studies. In an extensive simulation study, we simulate two evidence networks consisting of four treatments, and assess the impact of departure from the SEM assumption, variable EM correlation across trials, trial sample size and network size. NMI was compared to standard NMA, network meta-regression (NMR) and Multilevel NMR (ML-NMR) in terms of estimation accuracy and credible interval (CrI) coverage. In the base case non-SEM dataset, NMI achieved the highest estimation accuracy with root mean squared error (RMSE) of 0.228, followed by standard NMA (0.241), ML-NMR (0.447) and NMR (0.541). In the SEM dataset, NMI was again the most accurate method with RMSE of 0.222, followed by ML-NMR (0.255). CrI coverage followed a similar pattern. NMI's dominance in terms of estimation accuracy and CrI coverage appeared to be consistent across all scenarios. NMI represents an effective option for NMA in the presence of study imbalance and available subgroup data.