A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK

Abstract

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.

How have Economic Evaluations in Relapsing Multiple Sclerosis Evolved Over Time? A Systematic Literature Review

“…Most models used the lifetime horizon ( n = 37), followed by 50-year ( n = 22) and 10-year ( n = 21) time horizons. DES models appear to be consistent, as three of four DES models used the lifetime horizon [ 110 , 112 , 113 ]. The most common cycle length used by the models was 1 year ( n = 63), followed by 3 months ( n = 12) and then 1 month ( n = 10) [ 42 , 43 , 50 , 64 , 68 , 71 , 73 , 76 , 137 , 138 ].…”

“…Our review suggests that models differ in several assumptions (e.g., long-term treatment effect and EDSS improvement over time) and in the approach in estimating mortality rates. At the same time, there are similarities in modeling aspects, such as the type of model, model The discrete event simulation model can better capture the individual disease journey of MS patients, such as switching between DMTs, long-term AEs, and outcomes as well as individual patient's attributes or comorbidities [112,113] Model health states…”

“…Most studies (n = 94) and HTA reports (n = 25) constructed Markov cohort models. The remaining studies used spreadsheet-based cohort models (n = 9) [38,39,69,[104][105][106][107][108][109], discrete event simulation (DES; n = 4) [110][111][112][113], a simulated decision tree (n = 1) [114], individual-level simulation models (n = 3) [37,40,57,115], and microsimulation (n = 1) [116]. A consistent approach was seen in most studies that constructed Markov cohort models, wherein models were structured per the Expanded Disability Status Scale (EDSS), a widely used scale to quantify disability in MS.…”

“…Considering the scarcity of data, it is recommended to conduct a sensitivity analysis with various sources of data inputs [190] b. [111][112][113]. Furthermore, it is important to highlight that only one model used in the HTA reports was a DES model and the rest were Markov cohort models, explaining the prominent use of Markov cohort model in economic evaluation studies in RMS.…”

Accounting for parameter uncertainty in the definition of parametric distributions used to describe individual patient variation in health economic models

“…The lack of specific guidance is illustrated by recently published modeling studies that do not fully utilize IPD while performing PSA, for example, by adjusting predicted values (stochastic uncertainty) with a random percentage [ 9 ], by excluding correlation between parametric distributions’ parameters [ 10 ], or altogether not reporting (including) parameter uncertainty in parametric distributions [ 11 ]. As a consequence of inadequately reflecting all types of uncertainty in the synthesized evidence used for analysis, suboptimal resource allocation and research prioritization decisions may be made due to biased outcomes of PSA, overestimated confidence in the corresponding expected values of the PSA, and ensuing biased estimation of the value of collecting additional evidence to better inform decision making [ 12 ].…”