OBJECTIVES

NMAs on hazard ratios (HRs) are frequently applied in cost-effectiveness analyses for HTA purposes; however, this method requires the proportional hazard (PH) assumption to be held. When the PH assumption is violated, NMA methods allowing non-proportional hazards may be applied. This study quantifies the advanced methods applied in NMAs submitted for HTA assessment, determines the rationale for their application and critique by HTA committees.

METHODS

An HTA review of oncology submissions was conducted via the National Institute for Health and Care Excellence (NICE) database on single technology assessment (STA) appraisals published between 2001-2019. The methodologies applied, rationale and critiques were extracted and evaluated.

RESULTS

The review covered 155 NICE STA oncology submissions. 39 STAs reported NMAs, which were implemented in the economic model. 25 NMAs applied an HR NMA. The remainder applied more advanced techniques, of which 2 were parametric NMAs, 9 were fractional polynomial (FP) NMAs and 3 were unanchored FP NMAs based on population adjusted data from a simulated treatment comparison. The most common rationale for applying advanced NMA techniques was the violation of the PH assumption.

According to the NICE committee, the advanced methodology of 3 submissions was appropriate for decision-making (all FP NMAs). In 6 submissions, the advanced methods were considered appropriate for decision-making, but uncertainty remained mainly due to the heterogeneity across the studies in the network (5 of 6) or the poor application of the methodology which was later amended (1 of 6). In 5 submissions, the results were treated with caution due to heterogeneity, as well as the lack of crossover adjustment (2 of 5) and limitations of unanchored NMA (3 of 5).

CONCLUSIONS

This review provides insight into the trends in NMA methodologies and other advanced techniques. More complex techniques for dealing with proportional hazard violations have been applied and accepted by HTA reviewers.