Background A quality-adjusted life year (QALY) is a measure that combines the size of the clinical benefit of a treatment, measured as health-related quality of life, with the time over which the patient benefits from it, i.e., the time horizon. The National Institute for Health and Care Excellence (NICE) in England use QALYs to assess the cost-effectiveness of treatments and to formulate recommendations for their funding in the National Health Service (NHS) of England and Wales. Treatments evaluated under the Highly Specialised Technologies (HST) programme for very rare diseases at NICE benefit from a QALY modifier which increases the odds of patient access in case ≥10 QALYs are gained. Our investigation takes a closer look at the consistency of how QALYs of treatments assessed under the HST programme are determined.

Method The time horizon is one of the factors that determines how many total QALYs are gained. For our analysis, we therefore extracted the length of the time horizons used for the calculation of the QALY gains from publicly available documents of evaluations conducted under the HST programme. These evaluations include two innovative treatments for the porphyrias: afamelanotide for treating erythropoietic protoporphyria (HST27) and givosiran for treating acute hepatic porphyria (HST16).

Results In the initial assessment of afamelanotide in 2018, a time horizon of 35 years was used to calculate the QALY gain. Afamelanotide is approved for use from age 18 and is a lifelong treatment. For givosiran, during the evaluation at NICE clinical experts estimated a treatment duration of 13 years for most patients, i.e., a starting age of treatment of 37 years and a stopping age of 50 years. However, for the calculation of the QALY gain, a 60-year time horizon was accepted by the NICE committee. When analyzing all completed evaluations conducted under the HST programme (n=29), we found a time horizon of median 97.5 years (range: 35 to 125 years).

Discussion Our analysis shows that most time horizons accepted for calculating the QALY gains of treatments evaluated under the HST programme are longer than either the expected treatment duration or the estimated general life expectancy of 81 years. In contrast, for afamelanotide, the only treatment with a negative funding decision, a time horizon shorter than the expected treatment duration was applied. In 2023, after presenting preliminary results of our analysis, the NICE committee adjusted the time horizon to 60 years. While more realistic, a 60-year time horizon also does not cover the entire treatment duration with afamelanotide.

Conclusion The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE is not ensured and should be reviewed. However, access to treatments for patients with very rare diseases with an already positive recommendation by NICE must not be compromised.