Background: NICE has encountered various evidential, clinical and methodological challenges during its Health Technology Assessments (HTAs) of disease-modifying therapies (DMTs) for the treatment of relapsing–remitting multiple sclerosis (RRMS).

Risk Sharing Scheme (RSS): NICE guidance published in 2002 did not recommend the use of beta interferons and glatiramer acetate in the NHS because there was insufficient evidence to show their cost effectiveness over a 20-year time horizon. The NHS and the manufacturers of the DMTs agreed to create the RRMS RSS to make these treatments available. The use of data from this scheme to inform a subsequent review of NICE guidance is examined.

Changing clinical landscape: Substantial advances in the treatment of RRMS have led to the approval of a range of new DMTs and the identification of several subgroups of patients with RRMS who may benefit from certain DMTs. The definitions of these subgroups often come from clinical trials, which are subject to change as clinical understanding of the role of DMTs improves. The definition of clinically relevant groups can vary between trials, creating challenges with generalising evidence when assessing DMTs. Efforts from NICE to ensure its guidance reflects this changing landscape and provides clinicians with clear and relevant recommendations are discussed.

Common uncertainties in HTAs of DMTs for RRMS: NICE has identified several areas of uncertainty, which may drive cost-effectiveness results in HTAs of DMTs for RRMS. These include the costs associated with different health states, the long-term effectiveness of DMTs and different approaches to modelling the mortality rates of people with RRMS. The HTA appraisal committee’s judgements about these uncertainties is discussed, along with recommendations for future research.