Table 1.
Methodological challenges and recommendations when calculating the cost-effectiveness of DMTs.
| Methodological issue | Challenge | Recommendation |
|---|---|---|
| Technique of economic evaluation | Cost-minimization, cost-effectiveness, cost-utility or cost-benefit analysis | Apply cost-utility or cost-benefit analysis if difference in life expectancy and/or quality of life |
| Intervention and comparator | Majority of economic evaluations compare single DMT with supportive care | -Need to establish cost-effectiveness of DMT as compared with other active therapy; |
| -Account for treatment discontinuation and consider treatment sequences; | ||
| -Conduct multiple technology appraisal | ||
| Perspective | Significant cost impact of MS outside health care sector | Adopt societal perspective |
| Time horizon | Uncertainty about duration of treatment efficacy | Consider multiple time horizons in sensitivity analysis |
| Natural disease progression | -Evidence is dated and does not reflect actual clinical practice; | -Need for current, longitudinal studies of MS disease course; |
| -Disease progression is measured by change in EDSS score and relapse occurrence | -Use country-specific MS registry; | |
| -EDSS does not capture cognitive, psychological and other patient-relevant outcomes | ||
| Mortality | General or MS-specific mortality | Use general population data adjusted for MS mortality risk |
| Utility values | Cost-effectiveness is likely to be sensitive to utility values | Use jurisdiction-specific utility values |
| Relative effectiveness of DMTs | Evidence mainly relates to efficacy of DMT vs. supportive care | -Need for RCTs comparing different DMTs; |
| -Conduct network meta-analysis, simulated treatment comparison or matching-adjusted indirect comparison; | ||
| -Collect RWE in actual clinical practice and use MS registries | ||
| Outcome measure | Intermediate measure (e.g., number of relapses avoided) or final measure (e.g., QALY) | Use QALYs |
| Modeling approach | Heterogeneous disease and treatment | Apply Markov model or carry out discrete event simulation |
| Model validity | Conduct and report activities exploring different types of model validity | |
| Uncertainty | Cost-effectiveness is likely to be sensitive to changes in input parameter values | Conduct extensive deterministic and probabilistic sensitivity analyses |
Author's table based on Hernandez et al. (24), Thompson et al. (26), Guo et al. (27), Wiyani et al. (29), Yamamoto and Campbell (30), and Hawton et al. (31).
DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; QALY, quality-adjusted life year; RCT, randomized controlled trial; RWE, real-world evidence.