When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of confidential PAS discount.

The DES model shows that only a modest discount to the UK fingolimod list-price is required to make fingolimod a more cost-effective option than natalizumab in RES RRMS.

In conclusion, fingolimod remains cost-effective in HA RRMS following the introduction of DMF to the UK market, and this paper supports the evidence that has led fingolimod to be the only oral DMT reimbursed for HA RRMS in England. This model supports the restriction imposed by National Institute for Health and Care Excellence (NICE) on DMF in HA RRMS and highlights the importance of considering different sub-groups of multiple sclerosis when performing health economic analyses.

Despite convergence over time to a similar Markov structure, there are still significant discrepancies between health economic models of RRMS in the United Kingdom. Differing methods, assumptions, and data sources render the comparison of model implementation and results problematic. The commonly used Markov structure leads to problems such as incapability to deal with heterogeneous populations and multiplying complexity with the addition of treatment sequences; these would best be solved by using alternative models such as discrete event simulations.

Children are not mini-adults, and thus require studies to be conducted in the population of interest to inform decisions about their care. The paucity of such studies for clinical efficacy lead them to be termed 'therapeutic orphans'. Following the introduction of the 'fourth hurdle' of reimbursement approval on the basis of cost-utility analysis, utility data is now a key requirement for patients to access treatments in England and many other countries. This special report considers whether a paucity of utility valuation studies in children may have made them 'economic orphans' as well and presents results of a review of NICE appraisals as a window on this problem over time.