Table 3.
Model parameters
| Parameter | Value | Lower 95% CI | Upper 95% CI | Distribution | Source or justification |
|---|---|---|---|---|---|
| Discount rate, costs | 3.50% | NA | NA | Varied in scenario analysis | NICE reference case [59] |
| Discount rate, QALYs | 3.50% | NA | NA | Varied in scenario analysis | |
| Discount rate, LYs | 0.00% | NA | NA | Varied in scenario analysis | |
| Model cycle length | 1 week | NA | NA | Not varied | Structural assumption |
| Model time horizon | 40 years | NA | NA | Not varied | NICE reference case [59] |
| HR: improvement in OS for avelumab (TN vs. TE) | 0.800 | 0.655 | 0.968 | Log-normal | Assumptions validated by clinical expert opinion |
| HR: improvement in PFS for avelumab (TN vs. TE) | 1.000 | 0.818 | 1.210 | Log-normal | |
| RDI: avelumab | 95.43% | 93.59% | 97.27% | Normal | JAVELIN Merkel 200 [7] |
| RDI: chemotherapy | 66.67% | 53.60% | 79.73% | Normal | Clinical validation |
| Utility, progression-free, (-5L) | 0.827 | 0.783 | 0.867 | Beta | Kaufman et al. [39] |
| Utility, post-progression (-5L) | 0.742 | 0.690 | 0.790 | Beta | |
| Utility, > 100 days to death (-3L) | 0.774 | 0.734 | 0.813 | Beta | NICE TA517 [55] |
| Utility, 30–100 days to death (-3L) | − 0.020 | 0.000 | − 0.108 | Beta | |
| Utility, < 30 days to death (-3L) | − 0.066 | − 0.020 | − 0.138 | Beta | |
| Administration cost, IV drugs | £199.00 | £198.81 | £199.19 | Normal | NHS reference costs 15–16 [50], PSSRU 2016 [51] |
| Cost, GP visit | £36.00 | £28.94 | £43.06 | Normal | |
| Cost, CT scan | £120.99 | £120.95 | £121.03 | Normal | |
| Cost, FBC | £3.00 | £3.00 | £3.00 | Normal | |
| Cost, LFT | £1.00 | £0.80 | £1.20 | Normal | |
| Cost, RFT | £1.00 | £0.80 | £1.20 | Normal | |
| Cost, TFT | £1.00 | £0.80 | £1.20 | Normal | |
| Cost, radiotherapy | £126.60 | £126.58 | £126.62 | Normal | |
| Cost, EoL, health care | £4867.53 | £3913.51 | £5821.55 | Normal | Round et al. [54] |
| Cost, EoL, social care | £2151.59 | £1729.89 | £2573.29 | Normal | |
| MRU frequency, GP visit, avelumab, PF | 0.250 | 0.201 | 0.299 | Normal | Assumptions validated by clinical expert opinion |
| MRU frequency, CT scan, avelumab, PF | 0.077 | 0.062 | 0.092 | Normal | |
| MRU frequency, FBC, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
| MRU frequency, LFT, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
| MRU frequency, RFT, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
| MRU frequency, TFT, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
| MRU frequency, radiotherapy, avelumab, PF | 0.000 | 0.000 | 0.000 | Normal | |
| MRU frequency, GP visit, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
| MRU frequency, CT scan, chemotherapy, PF | 0.115 | 0.093 | 0.138 | Normal | |
| MRU frequency, FBC, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
| MRU frequency, LFT, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
| MRU frequency, RFT, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
| MRU frequency, TFT, chemotherapy, PF | 0.000 | 0.000 | 0.000 | Normal | |
| MRU frequency, radiotherapy, chemotherapy, PF | 0.000 | 0.000 | 0.000 | Normal | |
| Drug cost, avelumab | £768.00 | NA | NA | Not varied | BNF online [46] |
| Drug cost, carboplatin | £25.25 | £25.18 | £25.32 | Normal | eMIT [60] |
| Drug cost, etoposide IV | £24.96 | £22.16 | £27.76 | Normal | eMIT [60] |
| Drug cost, etoposide oral | £87.23 | NA | NA | Not varied | BNF online [46] |
| Drug cost, cisplatin | £10.56 | £10.49 | £10.63 | Normal | eMIT [60] |
| AE probability, lymphopenia, avelumab | 2.27% | Beta | JAVELIN Merkel 200 [7] | ||
| AE probability, anaemia, carboplatin + etoposide | 7.38% | Beta | Socinski et al. [36] | ||
| AE probability, fatigue, carboplatin + etoposide | 3.13% | Beta | |||
| AE probability, febrile neutropenia, carboplatin + etoposide | 4.47% | Beta | |||
| AE probability, hyponatraemia, carboplatin + etoposide | 1.12% | Beta | |||
| AE probability, leukopenia, carboplatin + etoposide | 8.28% | Beta | |||
| AE probability, nausea/vomiting, carboplatin + etoposide | 0.90% | Beta | |||
| AE probability, neutropenia, carboplatin + etoposide | 46.98% | Beta | |||
| AE probability, thrombocytopenia, carboplatin + etoposide | 10.29% | Beta | |||
| AE probability, hair loss, carboplatin + etoposide | 34.00% | Beta | |||
| AE probability, anaemia, cisplatin + etoposide | 6.67% | Beta | Sun et al. [37] | ||
| AE probability, low haemoglobin, cisplatin + etoposide | 5.33% | Beta | |||
| AE probability, leukopenia, cisplatin + etoposide | 19.33% | Beta | |||
| AE probability, nausea/vomiting, cisplatin + etoposide | 6.70% | Beta | |||
| AE probability, neutropenia, cisplatin + etoposide | 44.00% | Beta | |||
| AE probability, thrombocytopenia, cisplatin + etoposide | 7.33% | Beta | |||
| AE probability, hair loss, cisplatin + etoposide | 13.33% | Beta | |||
| AE cost, anaemia | £799.39 | £657.09 | £977.46 | Normal | Vouk et al. [52] and Wehler et al. [53] |
| AE cost, fatigue | £66.45 | £53.43 | £79.47 | Normal | |
| AE cost, febrile neutropenia | £4543.44 | £3652.94 | £5433.93 | Normal | |
| AE cost, low haemoglobin | £66.45 | £53.43 | £79.47 | Normal | |
| AE cost, hyponatraemia | £66.45 | £53.43 | £79.47 | Normal | |
| AE cost, leukopenia | £281.67 | £226.46 | £336.88 | Normal | |
| AE cost, lymphopenia | £281.67 | £226.46 | £336.88 | Normal | |
| AE cost, nausea/vomiting | £218.27 | £181.41 | £269.86 | Normal | |
| AE cost, neutropenia | £281.67 | £226.46 | £336.88 | Normal | |
| AE cost, thrombocytopenia | £286.12 | £230.05 | £342.20 | Normal | |
| AE cost, hair loss | £0.00 | £0.00 | £0.00 | Normal | |
| AE disutility, anaemia | − 0.090 | − 0.055 | − 0.133 | Beta | Nafees et al. [43], Ossa et al. [45], Tolley et al. [44] and assumptions validated by clinical expert opinion |
| AE disutility, fatigue | − 0.073 | − 0.041 | − 0.114 | Beta | |
| AE disutility, febrile neutropenia | − 0.090 | − 0.061 | − 0.124 | Beta | |
| AE disutility, low haemoglobin | − 0.080 | − 0.052 | − 0.114 | Beta | |
| AE disutility, hyponatraemia | − 0.090 | − 0.062 | − 0.122 | Beta | |
| AE disutility, leukopenia | − 0.090 | − 0.062 | − 0.122 | Beta | |
| AE disutility, lymphopenia | − 0.090 | − 0.062 | − 0.122 | Beta | |
| AE disutility, nausea/vomiting | − 0.048 | − 0.022 | − 0.084 | Beta | |
| AE disutility, neutropenia | − 0.090 | − 0.062 | − 0.122 | Beta | |
| AE disutility, thrombocytopenia | − 0.108 | − 0.089 | − 0.128 | Beta | |
| AE disutility, hair loss | − 0.045 | − 0.021 | − 0.078 | Beta | |
| AE duration, anaemia | 21 days | 17 days | 25 days | Normal | Assumptions validated by clinical expert opinion |
| AE duration, fatigue | 21 days | 17 days | 25 days | Normal | |
| AE duration, febrile neutropenia | 4 days | 3 days | 5 days | Normal | |
| AE duration, low haemoglobin | 21 days | 17 days | 25 days | Normal | |
| AE duration, hyponatraemia | 2 days | 2 days | 2 days | Normal | |
| AE duration, leukopenia | 2 days | 2 days | 2 days | Normal | |
| AE duration, lymphopenia | 2 days | 2 days | 2 days | Normal | |
| AE duration, nausea/vomiting | 3 days | 2 days | 4 days | Normal | |
| AE duration, neutropenia | 2 days | 2 days | 2 days | Normal | |
| AE duration, thrombocytopenia | 24 days | 19 days | 28 days | Normal | |
| AE duration, hair loss | 21 days | 17 days | 25 days | Normal |
3L 3-level, 5L 5-level, AE adverse event, BNF British National Formulary, CI confidence interval, CT computed tomography, eMIT electronic market information tool, EoL end of life, FBC full blood count, GP general practitioner, HR hazard ratio, IV intravenous, LFT liver function test, LYs life-years, MRU medical resource use, NA not applicable, NHS National Health Service, NICE National Institute for Health and Care Excellence, OS overall survival, PF progression-free, PFS progression-free survival, PSSRU Personal Social Services Research Unit, QALYs quality-adjusted life-years, RDI relative dose intensity, RFT renal function test, TA technology appraisal, TE treatment-experienced, TFT thyroid function test, TN treatment-naïve