OBJECTIVES : Despite the significant unmet need in ultra-orphan indications (prevalence: <1:50,000), therapies can have difficulties meeting Health Technology Assessment (HTA) clinical- and cost-effectiveness criteria following European Marketing Authorisation (MA) due to low patient numbers limiting the supporting clinical evidence generated and resulting in high per-patient prices. Since 2013, NICE appraise Highly Specialised Technologies (HST) (“for use in the provision of services for rare and very rare conditions”) using a distinct appraisal framework. This research compares NICE HST appraisal outcomes with corresponding guidance by other European HTA bodies, stratified by archetype: cost-effectiveness versus clinical-effectiveness.

METHODS : All NICE HST guidance was screened (1/1/13–3/6/19) alongside corresponding guidance by HAS, G-BA, NCPE, SMC, TLV, and ZIN.

RESULTS : NICE have published nine HST guidance, all with positive recommendations, a median of 20 months (range 7–38) after European MA. An additional 11 HST guidance are in development with MAs for a median of 14 months (range: 0–53) with six having draft guidance issued, all being “not recommended”. Of the 20 HSTs with NICE guidance published/in-development, 16, 14, 8, 6, 2, and 6 were assessed by HAS, G-BA, NCPE, SMC, TLV, and ZIN, respectively. Of these, 22/30 (73%) and 7/22 (32%) of assessments made by clinical-effectiveness and cost-effectiveness HTA bodies received positive outcomes, respectively, with median delays between European MA and positive appraisal outcomes of 7 and 37 months, respectively.

CONCLUSIONS : Although NICE HST appraisals have more positive recommendations and have faster time to recommendations following European MA than other cost-effectiveness HTA bodies, time to positive recommendation is still substantially delayed compared to clinical-effectiveness HTA bodies. In 2018, a new SMC appraisal framework was introduced, whereby ultra-orphan therapies would be made available for ≥3-years while additional evidence is collected pending a final SMC appraisal. This could potentially prove a more suitable best-practice model.