Presentation (CTI)

OBJECTIVES: Introduced by NICE in February 2022, the cost-comparison route offers a streamlined health technology assessment pathway for treatments likely to deliver similar or greater health benefits at a similar or lower cost than their relevant comparator. In practice, however, companies and external assessment groups frequently disagree on the level of evidence required to demonstrate clinical similarity, creating uncertainty for manufacturers selecting this route. This research characterises the precedent for evidencing clinical similarity in NICE appraisals and translates these findings into practical recommendations for manufacturers preparing cost-comparison submissions.
METHODS: A targeted review was conducted of NICE technology appraisals published between February 2022 and May 2026. Appraisals were screened to identify evidence supporting claims of clinical similarity presented during scoping and within each company submission. Superseded and terminated appraisals were excluded.
RESULTS: The review identified 309 appraisals meeting the inclusion criteria: 48 cost-comparison appraisals and 261 single/multiple technology appraisals. Of the cost-comparison appraisals, 44 (91.7%) presented comparative efficacy estimates calculated using indirect treatment comparisons, either as primary or supportive evidence. Only four (8.3%) appraisals relied solely on head-to-head trial data.
In the appraisals presenting indirect evidence, 40 (90.9%) defined clinical similarity based on point estimates of hazard/odds ratios, or confidence/credible intervals crossing the line of equivalence. This was frequently met with criticism from external assessment groups who emphasised that this was not conclusive evidence of clinical similarity and requested additional evidence, including formal non-inferiority testing using validated minimal clinically important differences.
CONCLUSIONS: The evidence requirements for establishing clinical similarity under the NICE cost-comparison route remain highly variable and are inconsistently applied. While clinical expert opinion consistently appears impactful, interpretation of supporting evidence — including absence of a statistically significant difference and non-inferiority requirements — is more nuanced. Clearer NICE guidance on evidencing clinical similarity in cost-comparison appraisals would aid company planning and improve submission efficiency.