NM1 A Comparison on Different Network-Meta Analysis (NMA) Models Using Randomized Clinical Trials (RCTS) in Transplant-Ineligible (TIE) NEWLY Diagnosed Multiple Myeloma (NDMM)

Abstract

An NMA survival extrapolation decision-framework based on clinical plausibility is proposed. It suggests mixture-cure models in case cure is clinically realistic. In case of no cure, parametric mixture (PM) models are proposed for subgroups with long-term survival, and piecewise (PW), splines (S) and fractional polynomial (FP) models are suggested for subsets with fluctuating hazards. Otherwise, standard parametric approaches are proposed. Following the framework, a parametric NMA (PNMA) would be most clinically plausible in TIE NDMM since cure, and subgroups with long-term survival and fluctuating hazards are not anticipated. It was aimed to compare estimated survival using different NMA methods. The network of evidence included n=5 RCTs on n=3 treatments (MP, MPT-T, MPR-R) in TIE NDMM. Published Kaplan-Meiers were used to extract individual-patient data. The proportional-hazard assumption was violated, and thus a PNMA was conducted. The PNMA has been compared to PW, S, PM, and FP models. Mixture- and non-mixture cure models were excluded since cure was not clinically realistic. Only the Weibull distribution was used to extrapolate survival. The overall model fit was assessed using the leave-one-out-information-criteria (LOOIC). The PNMA demonstrated lowest LOOIC [6588.62], compared to the other models (second-lowest: FP [6588.89]). PNMA and FP models predicted survival of respectively 4.47 and 4.67 years for MP, 5.50 and 5.50 years for MPT-T, and 4.70 and 4.45 years for MPR-R. Incremental survival of MP against MPT-T and MPR-R was 1.04 and 0.23 years for PNMA and 0.83 and 0.22 years for FP. Incremental survival between PNMA and FP was 0.20 and 0.45 years for MP versus MPT-T and MPR-R, respectively. The framework demonstrates to work. Estimated survival varied per model, which impacts health economic outcomes such as the incremental cost-effectiveness ratio (ICER), relevant for medical decision-making. Conducting NMA methods should be tailored to the data and take clinical plausibility into account.