Table 1.
Model inputs: non-cost parameters such as general settings, efficacy inputs, probabilities of adverse events, and utilities used in the base-case model
| Parameter | Value (SE) | Distribution | Source |
|---|---|---|---|
| Average starting age | 38.7 (0.473) | Log-normal | CLARITY study [9] |
| Female/male ratio | 1.93 | N/A | CLARITY study [9] |
| Average patient weight | 70.67 (3.46) | Normal | NHS 2010 [19] |
| Annualized rate of relapse by EDSS state | |||
| EDSS 0 | 0.890 (0.267) | Log-normal | NICE [38] |
| EDSS 1 | 0.679 (0.204) | Log-normal | |
| EDSS 2 | 0.642 (0.193) | Log-normal | |
| EDSS 3 | 0.596 (0.179) | Log-normal | |
| EDSS 4 | 0.523 (0.157) | Log-normal | |
| EDSS 5 | 0.458 (0.137) | Log-normal | |
| EDSS 6 | 0.401 (0.120) | Log-normal | |
| EDSS 7 | 0.310 (0.093) | Log-normal | |
| EDSS 8 | 0.251 (0.075) | Log-normal | |
| EDSS 9 | 0.217 (0.065) | Log-normal | |
| Baseline EDSS distribution | |||
| EDSS 0 | 2.80% | Dirichlet | CLARITY study [9] |
| EDSS 1 | 2.80% | Dirichlet | |
| EDSS 2 | 32.50% | Dirichlet | |
| EDSS 3 | 21.50% | Dirichlet | |
| EDSS 4 | 23.50% | Dirichlet | |
| EDSS 5 | 11.10% | Dirichlet | |
| EDSS 6 | 5.80% | Dirichlet | |
| EDSS 7 | 0.00% | Dirichlet | |
| EDSS 8 | 0.00% | Dirichlet | |
| EDSS 9 | 0.00% | Dirichlet | |
| Mortality multiplier | |||
| EDSS 0 | 1.00 | Log-normal | Sadovnik et al. [39] |
| EDSS 1 | 1.43 | Log-normal | |
| EDSS 2–2.5 | 1.60 | Log-normal | |
| EDSS 3–3.5 | 1.64 | Log-normal | |
| EDSS 4–4.5 | 1.67 | Log-normal | |
| EDSS 5–5.5 | 1.84 | Log-normal | |
| EDSS 6–6.5 | 2.27 | Log-normal | |
| EDSS 7–7.5 | 3.10 | Log-normal | |
| EDSS 8–8.5 | 4.45 | Log-normal | |
| EDSS 9–9.5 | 6.45 | Log-normal | |
| Disability progression (hazard ratio versus placebo) | |||
| Cladribine | 0.180 (0.176) | Log-normal | NMA Merck [40] |
| Alemtuzumab | 0.360 (0.132) | Log-normal | |
| Natalizumab | 0.353 (0.139) | Log-normal | |
| Ocrelizumab | 0.180 (0.176) | Log-normal | |
| Acute relapse events (rate ratio versus placebo) | |||
| Cladribine | 0.350 (0.056) | Log-normal | NMA Merck [40] |
| Alemtuzumab | 0.353 (0.034) | Log-normal | |
| Natalizumab | 0.399 (0.031) | Log-normal | |
| Ocrelizumab | 0.366 (0.040) | Log-normal | |
| Recue therapy (only for cladribine) | 0.400 (0.076) | Log-normal | CLARITY study [9] |
| Treatment waning effect | |||
| 0–2 years | 1.000 | N/A | NICE assumption [12] |
| 2–4 years | 0.750 | N/A | |
| 4–10+ years | 0.500 | N/A | |
| Annual probability of treatment withdrawal | CLA1 | ALE1 | NAT2 | OCR3 | Dist | Source |
|---|---|---|---|---|---|---|
| Year 0–2 | 4.9% | 2.3% | 10.6% | 10.6% | N/A |
1Pooled trial data (CLARITY for cladribine tablets; CAMMS223, CARE-MS I, and CARE-MS II for alemtuzumab) 2NMA Merck 3Assumed to be equal to natalizumab Pooled trial data (CLARITY and Care-MS II for alemtuzumab) |
| Year 2–10 | 0% | 0% | 10.6% | 10.6% | N/A | |
| Year 10 to lifetime | 0% | 0% | 10.6% | 10.6% | N/A |
| Adverse event type | CLA | ALE | NAT | OCR | Dist | Source |
|---|---|---|---|---|---|---|
| Infusion-site reaction | 0.00% | 90.1% | 23.6% | 34.3% | Beta | NMA Merck [40] |
| PML | 0.00% | 0.00% | 0.21% | 0.00% | Beta | |
| Severe infection | 2.80% | 2.30% | 1.90% | 1.90% | Beta | |
| Gastrointestinal | 24.5% | 22.8% | 22.8% | 22.8% | Beta | |
| Thyroid-related events | 0.00% | 0.00% | 3.99% | 0.00% | Beta | |
| Flu symptoms | 1.30% | 1.10% | 0.10% | 1.20% | Beta | |
| Malignant tumor | 0.60% | 0.60% | 0.60% | 0.60% | Beta | |
| Idiopathic thrombocytopenic purpura | 0.00% | 1.80% | 0.00% | 0.00% | Beta |
| Utilities by EDSS state | Value (SE) | Distribution | Source (country/population/elicitation method) |
|---|---|---|---|
| EDSS 0 | 0.906 (0.026) | Log-normal |
CLARITY and CLARITY EXT study [9–11] (UK, US, Australia, Canada and Italy/ patients/ not informed by the company |
| EDSS 1 | 0.845 (0.046) | Log-normal | |
| EDSS 2 | 0.804 (0.012) | Log-normal | |
| EDSS 3 | 0.701 (0.012) | Log-normal | |
| EDSS 4 | 0.655 (0.013) | Log-normal | |
| EDSS 5 | 0.565 (0.026) | Log-normal | |
| EDSS 6 | 0.496 (0.012) | Log-normal |
Hawton and Green [35] (UK/ patients/ UK tariffs) |
| EDSS 7 | 0.392 (0.032) | Log-normal | |
| EDSS 8 | 0.025 (0.038) | Log-normal | |
| EDSS 9 | − 0.195 (0.087) | Normal |
Orme et al. [41] (UK/ patients/ UK tariffs) |
| Relapse | − 0.071 (0.013) | Normal |
| Utilities—adverse event type | Value (SE) | Distribution | Source |
|---|---|---|---|
| Infusion-site reaction | − 0.011 (0.002) | Normal | Alemtuzumab NICE submission [42] |
| PML | − 0.2 (0.04) | Normal | |
| Severe infection | − 0.19 (0.038) | Normal | Utilities for treatment-related adverse events in type 2 diabetes, Shingler et al. [43] |
| Gastrointestinal | − 0.04 (0.008) | Normal | |
| Thyroid-related events | − 0.11 (0.022) | Normal | Alemtuzumab NICE submission [42] |
| Influenza-like symptoms | − 0.21 (0.042) | Normal | Health state utilities associated with attributes of treatments for hepatitis C |
| Malignant tumor | − 0.116 (0.023) | Normal | Breast cancer in young women: health state utility impacts by race/ethnicity, Trogdon et al. [44] |
| Idiopathic thrombocytopenic purpura | − 0.09 (0.18) | Normal | Alemtuzumab NICE submission [42] |
ALE alemtuzumab, CLA cladribine, Dist distribution, N/A not applicable, NAT natalizumab, OCR ocrelizumab, PML progressive multifocal leukoencephalopathy, SE standard error