OBJECTIVES: Treatment effect waning (TEW) signifies the attenuation of treatment effects over time. Assumptions regarding the maintenance of treatment effects associated with immuno-oncology therapies (IOs) following treatment discontinuation have been a source of contention in health technology assessment (HTA). An investigation on how TEW is addressed in HTA was conducted, and evidence from the literature was explored.

METHODS: Oncology appraisals from the National Institute of Health and Care Excellence (NICE) and other English-language HTA agencies were reviewed to understand methods used to model TEW. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) database was searched for studies exploring TEW in HTA. Evidence on the long-term treatment effects of IOs beyond treatment discontinuation was assessed using a targeted literature review (TLR) of PubMed, to help inform future TEW analyses.

RESULTS: In HTA, TEW is modelled by equalizing event hazards between the treatments being compared. Inconsistencies were observed in the approaches taken to apply TEW across oncology appraisals. Two commonly utilized methods include immediate and gradual TEW. The ISPOR search indicated that gradual waning is more appropriate than immediate waning. The TLR identified evidence demonstrating the long-term survival benefits associated with IO treatments, however, no analyses explicitly comparing long-term hazards between IO-treated patients and comparator groups were found. An algorithm is proposed for assessing the necessity and appropriateness of presenting TEW scenario analyses in HTA.

CONCLUSIONS: These findings highlight an absence of external evidence to inform assumptions of a waning of effect for IO submissions to HTA agencies. In HTA, TEW is applied by modelling converging event hazards over time, but the TLR found no studies that directly provided evidence on this. There is a need for clear guidance on the consistent and appropriate implementation of TEW in HTA oncology appraisals, and for more informative analyses of long-term survival data.