Table 1.
Model input parameters and values
| Variable | Value | Measurement of uncertainty in DSA and PSA | Distribution used in PSA | Source |
|---|---|---|---|---|
| Model settings | ||||
| Discount rate (costs) | 4.00% | NA | NA | Dutch EE guideline 12 |
| Discount rate (benefits) | 1.5% | NA | NA | |
| Time horizon | 88 y | NA | NA | NA |
| Patient characteristics | ||||
| Starting age (years) | 12 | 95% CI: 1; 25 | Normal | Pooled data |
| Percent female | 46.63% | SE: 0.04 | Beta | |
| Mean body surface area (BSA) | 1.3 | SE: 0.03 | Normal | |
| Mean weight (kg) | 41.7 | SE: 1.52 | Normal | |
| Efficacy | ||||
| OS distribution | Log normal | Different distributions selected in DSA | Bootstrapped | Assumption validated by clinical expert |
| EFS distribution | Gompertz | |||
| Duration of benefit in months | 60 | NA | NA | |
| EFS vs OS ratio for all comparators | 0.69 | SE: 25% of mean | Beta | Van den Berg et al, 2011 |
| Drug and procedure acquisition cost | ||||
| Pretreatment cost for lymphodepleting regimen | €521 | SE: 25% of mean | Gamma | ELIANA trial (resource use); Dutch Z‐index (unit cost) |
| Tisagenlecleucel | €320 000 | Dutch Z‐index public list price | ||
| Clofarabine monotherapy | €71 020 | Jeha et al 2006 (dosing schedule); Dutch Z‐index (unit cost) | ||
| Clofarabine combination therapy | €35 453 | Hijiya et al 2011 (dosing schedule); Dutch Z‐index (unit cost) | ||
| Blinatumomab | €117 934 | von Stackelberg 2016 (dosing schedule); Dutch Z‐index (unit cost) | ||
| Inpatient and outpatient administration cost | ||||
| Pretreatment cost for lymphodepleting regimen | €6301 | SE: 25% of mean | Gamma | ELIANA (resource use); Dutch EE guideline and Franken et al, (unit cost inpatient and daycare respectively) |
| Tisagenlecleucel | €15 932 | |||
| Clofarabine monotherapy | €2437 | Clinical expert opinion (resource use); Franken et al, 2018 (unit cost) | ||
| Clofarabine combination therapy | €4292 | Clinical expert opinion (resource use); Dutch EE guideline (unit cost) | ||
| Blinatumomab | €1997 | Clinical expert opinion (resource use); Franken et al, 2018 (unit cost); von Stackelberg et al 2016 (distribution of patients over treatment cycles) | ||
| Subsequent HSCT | ||||
| Rates for tisagenlecleucel | 16.58% | SE: 25% of mean | Beta | pooled data, (duration and percentage) |
| Rate for clofarabine monotherapy | 16.39% | SE: 0.07 | Evoltra product label (duration and percentage) | |
| Rate for clofarabine combination therapy | 40.00% | SE: 0.05 | Hijiya et al 2011 (duration and percentage) | |
| Rate for blinatumomab | 34.29% | SE: 0.10 | von Stackelberg et al 2016 (duration and percentage) | |
| Disutility (treatment) | ‐0.21 | SE: 25% of mean | Beta | Forsythe et al, 2018 |
| Disutility (6‐12 mo after treatment) | ‐0.02 | |||
| Costs: stem cell harvesting a | €66 581 | SE: 25% of mean | Gamma | Blommestein et al, 2012 |
| Costs: initial HSCT procedure a | €44 391 | |||
| Follow‐up costs after HSCT (up to 1 y) a | €106 618 | |||
| Health‐state utilities and disutilities | ||||
| Utility for EFS | 0.83 | SE: 0.03 | Beta | ELIANA trial |
| Utility for PD | 0.68 | SE 0.05 | ||
| Disutility for tisagenlecleucel (duration in days) | ‐0.20 (26) | SE: 25% of mean | Kwon et al 2018 (utility value) 33 ; Gaynon et al 2006 (duration Clo‐M) 47 ; Hijiya et al 2011 (duration (Clo‐C) 26 ; von Stackelberg et al 2016 (duration Blina) 3 | |
| Disutility for Clo‐M (duration in days) | ‐0.20 (66) | |||
| Disutility for Clo‐C therapy (duration in days) | ‐0.20 (47) | |||
| Disutility for Blina (duration in days) | ‐0.20 (61) | |||
| Age‐related utilities |
Age < 25:0.95 Age 25‐74:0.93 ‐ 0.89 Age 75+: 0.83 |
NA | Janssen et al 2014 34 | |
| Future costs | ||||
| Future medical costs | Various costs per treatment and age group | NA | NA | Van Baal et al, 2011 19 |
| Future non‐medical (consumption) costs | Various costs per treatment and age group | NA | NA | |
| Patient and family costs | ||||
| Distance to hospital | 79 kilometers | NA | NA | Own calculation |
| Travel costs b | €3.09 parking costs per visit, €0.19 per kilometer for travelling by car | NA | NA | Dutch EE guideline 12 |
| Average number of caregivers/ parents accompanying patient | 1.5 | NA | NA | Expert opinion |
| Parents stay at a charity hotel during treatment | €60 | NA | NA | Charity hotel website (Ronald McDonald) |
| Informal care c | € 14.52 per hour, 8 h per outpatient visit, daycare treatment, or inpatient hospital day | NA | NA | Dutch EE guideline 12 |
| Productivity losses | ||||
| Total productivity losses females | € 12 499 | SE: 25% of mean b | Gamma d | Dutch EE guideline 12 (wage per hour) |
| Total productivity losses males | € 8993 | |||
| Rate of females with productivity losses | 60% | Hovén et al, 2013 48 (proportion of parents going back to work) Statistics Netherlands (proportion of parents contributing to the labor force) | ||
| Rate of males with productivity losses | 85% | |||
Abbreviations: Allo‐SCT, allogeneic stem cell transplantation; CI, confidence interval; MUD, matched unrelated donor; NA, not applicable; SE, standard error; sib, sibling donor; UCB, umbilical cord blood.
a
Based on proportions for different HSCT type (see Appendix S1)
b
The amount of travel trips is dependent on the assumed treatment regimen and respective number of visits during treatment and follow‐up visits (see Appendix S1 for treatment schedules and follow‐up visit frequencies).
c
Informal care was assumed for patients aged < 18 y.
d
Only total costs of the productivity losses were varied in both DSA and PSA (ie, a combination of the rate and the costs).