UK multiple sclerosis risk-sharing scheme: a new natural history dataset and an improved Markov model

Abstract

ObjectivesIn 2002, the UK's National Institute for Health and Care Excellence concluded that the multiple sclerosis (MS) disease modifying therapies; interferon-β and glatiramer acetate, were not cost effective over the short term but recognised that reducing disability over the longer term might dramatically improve the cost effectiveness. The UK Risk-sharing Scheme (RSS) was established to ensure cost-effective provision by prospectively collecting disability-related data from UK-treated patients with MS and comparing findings to a natural history (untreated) cohort. However, deficiencies were found in the originally selected untreated cohort and the resulting analytical approach. This study aims to identify a more suitable natural history cohort and to develop a robust analytical approach using the new cohort.DesignThe Scientific Advisory Group, recommended the British Columbia Multiple Sclerosis (BCMS) database, Canada, as providing a more suitable natural history comparator cohort. Transition probabilities were derived and different Markov models (discrete and continuous) with and without baseline covariates were applied.SettingMS clinics in Canada and the UK.ParticipantsFrom the BCMS database, 898 ‘untreated’ patients with MS considered eligible for drug treatment based on the UK's Association of British Neurologists criteria.Outcome measureThe predicted Expanded Disability Status Scale (EDSS) score was collected and assessed for goodness of fit when compared with actual outcome.ResultsThe BCMS untreated cohort contributed 7335 EDSS scores over a median 6.4 years (6357 EDSS ‘transitions’ recorded at consecutive visits) during the period 1980–1995. A continuous Markov model with ‘onset age’ as a binary covariate was deemed the most suitable model for future RSS analysis.ConclusionsA new untreated MS cohort from British Columbia has been selected and will be modelled using a continuous Markov model with onset age as a baseline covariate. This approach will now be applied to the treated UK RSS MS cohort for future price adjustment calculations.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

“…Details of the BCMS cohort have been published elsewhere. 153 In brief, the BCMS database is a population-based database established in the 1980s that captures about 80% of people with MS in British Columbia, Canada.…”

“…153 Table 34 shows the annual transition probabilities between RRMS health states used in the natural history arm. In sensitivity analysis, the manufacturer derived other transition probabilities, using information from the ADVANCE trial 213 extrapolated with information from the BCMS data set 153 or the London Ontario data set. 80 The transition probabilities for RRMS to SPMS were based on information from the London Ontario data set.…”

“…Transition probabilities for people progressing within SPMS health states were estimated from the BCMS cohort. 153 These annual probabilities were derived using a multistate model. Table 36 shows the transitions between SPMS states.…”

“…The 6-year interim analyses used the British Columbia cohort, which was initiated in 1980, before DMTs were made routinely available in Canada. This cohort has prospectively recorded EDSS scores and covers about 80% of the relevant MS population in that area, providing a rich source of data about the natural history of MS. 152,153 Patients from the British Columbia cohort who would have met the criteria for prescribing IFN-β or GA were selected for comparison with those in the UK RSS. [153][154][155] Analysis of the 6-year data of the UK clinical cohort, comparing disease progression against the historical comparator cohort, suggested that, on the whole, the DMTs included in the RSS reduced disability progression and did so to the agreed level of cost-effectiveness.…”

“…Utilities for RRMS by EDSS level were based on pooling data from the MS Trust survey and Orme et al, 101 following the RSS. 153 Utilities for SPMS by EDSS level were assumed to be the same as for RRMS. Carers' disutilities were based on information obtained from the manufacturer's submission to NICE for TA127.…”