OBJECTIVES: Highly Specialized Technology (HST) appraisals conducted by the National Institute for Health and Care Excellence (NICE) evaluate technologies, or orphan drugs, for very rare and severe diseases that have small numbers of patients and limited or no treatment options. Due to the challenges in evidence generation for rare diseases, clinical evidence requirements in HST appraisals are generally lower than standard appraisals and have higher willingness-to-pay thresholds.

This study reviewed all HST decisions made by NICE from the introduction of the HST process, including an assessment of clinical evidence submitted, cost-effectiveness estimates, and committee conclusions.

METHODS: HST guidance published by NICE between January 2015 and 25 June 2024 were identified from nice.org.uk. Information on the submitted evidence and the NICE committee decision was extracted, including the indication, clinical evidence submitted, application of quality-adjusted life year (QALY) weights, and use of commercial arrangements.

RESULTS: Twenty-eight technologies were appraised under the HST process, and all but one were recommended by NICE. All technologies were indicated for treatment of genetic conditions, and nine (32.1%) were recommended for use in infants, children, and young people. Eighteen (64.3%) technologies were stated by the evaluating committee to be innovative or potentially innovative.

Fifteen HSTs (53.6%) provided clinical evidence that included a randomized control trial (RCT), with population size ranging between 7 to 225 patients. Clinical evidence submitted in appraisals not including an RCT, were open-label single arm studies and extension studies, dose-comparison and dose-escalation studies, real world studies, and retrospective natural history studies. Fifteen technologies (53.6%) met the criteria for applying a QALY weighting, based on compelling evidence of significant health gains.

CONCLUSIONS: Technologies assessed through the NICE HST process have a high rate of positive recommendation. These findings provide insights into the appraisal strategies for HSTs and may inform future assessments and policy developments.