OBJECTIVES: Both comparative effectiveness and survival extrapolations are needed to assess survival benefits with novel therapies compared to standard-of-care. In HRNMA, PHA must hold and, for extrapolation purposes, should not be combined with non-PH models such as log-logistic and log-normal. If the PHA does not hold, then the use of PNMA is justified. Hence, in this application, we aimed to assess the impact of applying PNMA versus HRNMA on survival extrapolations in elderly patients with glioblastoma. Additional alternative methodologies such as mixture, mix-cure model (MCM), non-MCM, piecewise, spline, and fraction polynomial NMAs were also assessed.

METHODS: A previously published HRNMA in elderly patients with glioblastoma was identified. In the HRNMA were included five different studies and five different treatments: standard radiotherapy (SRT), hypofractionated radiotherapy (HRT), temozolomide (TMZ), SRT+TMZ and HRT+TMZ. Individual patient data (IPD) were constructed and validated from Kaplan-Meier curves for overall survival. If PHA was violated in at least one study, PNMA was applied. The extrapolations from the PNMA and the HRNMA based on Weibull distribution were compared.

RESULTS: PHA was violated in one study comparing SRT to HRT; therefore, it invalidated the HRNMA and justified the use of PNMA. In PNMA, the estimated overall mean survival was 0.64, 0.66, 0.70, 1.07, 0.91 years for SRT, HRT, TMZ, SRT+TMZ, HRT+TMZ, respectively. On the other hand, based on the published HRNMA, the estimated overall mean survival was 1.18, 1.24, 1.30, 1.52, 1.64 years for SRT, HRT, TMZ, SRT+TMZ, HRT+TMZ, respectively.

CONCLUSIONS: In this example, there are differences in both the overall mean survival and the order of efficacy, which may have an impact on subsequent reimbursement decisions. Furthermore, PNMA offered an additional advantage in addition to no need to follow proportionality assumptions: NMA results can directly be implemented into a health economic model.