OBJECTIVES:

The National Institute for Health and Care Excellence’s (NICE’s) Highly Specialised Technologies (HST) process assesses the clinical and cost-effectiveness of specialised therapies for rare chronic conditions. We reviewed published HST Evidence Review Group (ERG) reports to develop recommendations for future submissions.

METHODS:

ERG reports from the nine published HST appraisals were reviewed, and common methodological issues and evidence limitations were identified. Recommendations were developed based on the issues identified.

RESULTS:

Key issues in the reporting of systematic literature reviews (SLRs) included a lack of comprehensive search strategies and transparency in reporting, and inconsistencies in PRISMA flow diagrams. Small trial populations, endpoints lacking consensus and single-arm trials led to a lack of precision and uncertainty in the estimation of treatment effects. The use of a lower 1.5% discount rate and non-reference case health-related quality of life data were rejected by the ERG in several submissions.

CONCLUSIONS:

The issues identified reflect a combination of a lack of clarity in the guidance, lack of precedent, and the rare nature of the conditions being appraised. We recommend that in future submitting companies should: make SLR strategies comprehensive and report SLRs in a fully transparent manner, allowing the methods to be reproduced; use appropriate statistical methods when comparing single-arm trial data against historical control data; be prepared to fully justify novel endpoints and use well-established secondary endpoints; carefully justify the use of 1.5% discount rates; align de novo utility studies as closely as possible with NICE’s reference case if appropriate utility values are not available from trials or the literature; and be prepared to engage in commercial discussions – of published HST appraisals 6/9 have included a patient access scheme and 3/9 a managed access arrangement.