Presentation (CTI)

OBJECTIVES: Economic models often require health state utility values (HSUVs) for health states defined by more than one condition simultaneously, yet direct estimates are rarely available. Combining single-condition values using additive, multiplicative, or minimum methods is common practice, yet each generates materially different estimates with direct consequences for the incremental cost-effectiveness ratio (ICER) and reimbursement decisions. Despite an interim NICE recommendation favouring the multiplicative method, no consensus exists. This study characterises HSUV combination in NICE technology appraisals (TAs) for rare diseases.
METHODS: The sample frame comprised 22 NICE TA and highly specialised technology (HST) reports identified by Meregaglia et al. (2022) for non-cancer European Medicines Agency (EMA) orphan-designated products, re-examined with a focus on utility combination, defined as any instance where HSUVs were combined to reflect co-occurring conditions, adverse events or disease sequelae. Combination approach, context, and methodological justification were extracted from manufacturer submissions, Evidence Review Group (ERG) reports, and committee papers.
RESULTS: Of 22 appraisals, one (HST9) was excluded as NICE guidance was withdrawn. Six further appraisals contained no utility combination; 15 were analysed. Combinations reflected adverse events (AE) or disease sequelae applied on top of base health state utilities. Additive combination was most common (14/15; 93%). Multiplicative combination was identified in one appraisal (HST12) for disease sequelae, with additive used concurrently for AE. In TA606, the ERG recommended multiplicative combination; the company submitted both as scenarios, with minimal impact on net monetary benefit. Methodological justification was not reported in any appraisal.
CONCLUSIONS: Additive combination was more common across NICE rare disease appraisals, with no methodological justification or ERG critique observed, despite interim guidance recommending the multiplicative method. This lack of consistency and transparency raises concerns for ICER comparability. With the post-2022 QALY severity modifier further amplifying the consequences of method choice, future research establishing standardised guidance on HSUV combination is recommended.