Ultra-orphan therapies (prevalence: <1:50,000) can have trouble meeting Health Technology Assessment (HTA) clinical- and cost-effectiveness criteria, set by HTA bodies to inform reimbursement decision-making, due to low patient numbers limiting the supporting clinical evidence generated and high per-patient prices. Since 2013, National Institute of Health and Care Excellence (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 HTA bodies.

All NICE HST technology guidance was screened (1 January 2013–6 November 2018) alongside corresponding guidance by Gemeinsamer Bundesausschuss (G-BA), Haute Autorité de Santé (HAS), Scottish Medicines Consortium (SMC), and National Centre for Pharmacoeconomics (NCPE).

NICE have published eight HST guidances all with positive recommendations after a median of 21 months (range: 7–38) after European Marketing Authorization (MA). An additional eight HST have guidance in-development despite having European MA for a median of 12 months (range: 2–46) with 5/8 having draft guidance issued, all being “not recommended”. Of the 18 HSTs with NICE guidance published/in-development, 29 percent (2/7), and 33 percent (2/6) have been assessed with positive outcomes (definition: “recommended”/”accepted”/“conditional”/”restricted”) by SMC, and NCPE, respectively vs. 100 percent (9/9) by G-BA (definition: any additional benefit), and 50 percent (5/10) by HAS (definition: ASMR I-III). Median delays between European MA and positive appraisal outcomes were seven (G-BA), nine (HAS), 12 (NCPE), and 19.5 months (SMC).

Although all NICE HST final guidances to date have been positive, few technologies have completed this process after substantial delays from MA. Other cost/QALY HTA bodies (i.e. excluding the G-BA and HAS clinical-assessment HTAs) have shown low appraisal and recommendation rates for these technologies; therefore, ultra-orphan technologies may require a distinct appraisal process/framework but the HST may not (yet) represent best-practice.