Background
Summary of DEVELOP-UK
Recipient Characteristic | EVLP N = 18 | STANDARD N = 184 | Total N = 202 | |
---|---|---|---|---|
Gender | Male n (%) | 13 (72.2) | 106 (57.6) | 119 (58.9) |
Female n (%) | 5 (27.8) | 78 (42.4) | 83 (41.1) | |
Age (Years) | n | 18 | 183 | 201 |
Missing | 0 | 1 | 1 | |
Median | 56 | 51 | 52 | |
IQR | 46–59 | 38–58 | 38–58 | |
Range | 20–64 | 18–70 | 18–70 | |
Diagnosis | COPD n (%) | 5 (27.8) | 40 (21.7) | 45 (22.3) |
Cystic Fibrosis n (%) | 4 (22.2) | 47 (25.5) | 51 (25.2) | |
Interstitial Lung Disease n (%) | 7 (38.9) | 47 (25.5) | 54 (26.7) | |
Emphysema n (%) | 0 (0) | 26 (14.1) | 26 (12.9) | |
Non-CF Bronchiectasis n (%) | 1 (5.6) | 8 (4.3) | 9 (4.5) | |
Obliterative Bronchiolitis n (%) | 0 (0) | 2 (1.1) | 2 (1.0) | |
Pulmonary Hypertension n (%) | 1 (5.6) | 3 (1.6) | 4 (2.0) | |
Other n (%) | 0 (0) | 9 (4.9) | 9 (4.5) | |
Missing n (%) | 0 (0) | 2 (1.1) | 2 (1.0) | |
Diabetes | Yes n (%) | 4 (22.2) | 33 (18.1) | 37 (18.3) |
No n (%) | 13 (72.2) | 142 (78.0) | 155 (76.7) | |
Missing n (%) | 1 (5.6) | 9 (3.9) | 10 (5.0) | |
BMI | n | 17 | 182 | 199 |
Missing | 1 | 2 | 3 | |
Median | 21.6 | 23.8 | 23.7 | |
IQR | 18.4–26.3 | 20.5–26.5 | 20.4–26.5 | |
Range | 17.6–32.5 | 15.4–34.2 | 15.4–34.2 | |
FEV1 (L) | n | 15 | 176 | 191 |
Missing | 3 | 8 | 11 | |
Median | 1.2 | 0.9 | 0.9 | |
IQR | 0.7–1.9 | 0.6–1.4 | 0.6–1.5 | |
Range | 0.5–2.5 | 0.3–3.6 | 0.3–3.6 | |
FEV1% | n | 15 | 171 | 186 |
Missing | 3 | 13 | 16 | |
Median | 29 | 26 | 27 | |
IQR | 22–50 | 20–45 | 20–45 | |
Range | 15–67 | 11–105 | 11–105 | |
Type of Transplant | Single n (%) | 2 (11.1)* | 24 (13.0)** | 26 (13) |
Bilateral n (%) | 16 (88.9) | 152 (82.6) | 168 (83) | |
Missing n (%) | 0 (0) * 1 left, 1 right | 8 (4.4) **9 left, 13 right, 2 NK | 8 (4) | |
Cardiopulmonary Bypass Use | No n (%) | 2 (11.1) | 46 (25.0) | 48 (24) |
Yes n (%) | 16 (88.9) | 116 (63.0) | 132 (65) | |
Not known n (%) | 0 (0) | 22 (12.0) | 22 (11) | |
Source[4] |
Aims
Methods
Analysis overview
Model structure
Model transitions
Model assumptions
-
The ‘Removed from waiting list’ state is an absorbing state, where a patient does not accrue costs or utilities (the probability attached to transitioning into this state is independent of transplant type). Patients transition to this state when they are too ill to receive a transplant, prognosis is extremely poor for these patients, with survival typically less than a month, Exploratory analysis was carried out to estimate the effects of this assumption, by including costs and QALYs for patients in this state and varying the survival between 1, 3 and 6 months.
-
NHSBT waiting list transitions were only available for three years post-registration. As only 5% of the cohort remained on the waiting list beyond three years, it was assumed that transitions remain constant from year three onwards.
-
It was assumed that utilities at 12 months post-transplant, derived from DEVELOP-UK data, were the same for 2 years post-transplant and onwards. This assumption is backed up by previous research where utilities post double-lung transplant were similar for 7–18 months (0.83), 19–36 months (0.81) and > 36 months (0.82) [14].
Outcomes
Costs
Assessment of cost-effectiveness
Uncertainty
Parameters | Mean | Alpha/Beta | Distribution | Source |
---|---|---|---|---|
Model transitions | ||||
From ‘Waiting list’ to ‘Removed from waiting list’ (Standard and EVLP service) | ||||
Year 1 | 0.020 | 5.02, 245.98 | Beta | NHSBT [11] |
Year 2 | 0.030 | 2.51, 80.32 | Beta | NHSBT [11] |
Year 3 onwards | 0.077 | 2.51, 30.12 | Beta | NHSBT [11] |
From ‘Waiting list’ to Transition to ‘Death’ (Standard and EVLP service) | ||||
Year 1 | 0.150 | 37.65, 213.35 | Beta | NHSBT [11] |
Year 2 | 0.212 | 17.57, 65.26 | Beta | NHSBT [11] |
Year 3 onwards | 0.077 | 2.51, 30.12 | Beta | NHSBT [11] |
From ‘Waiting list’ to ‘Receiving a standard lung transplant’ | ||||
Year 1 | 0.510 | 128, 122.99 | Beta | NHSBT [11] |
Year 2 | 0.364 | 30.1, 52.71 | Beta | NHSBT [11] |
Year 3 onwards | 0.462 | 15.1, 17.57 | Beta | NHSBT [11] |
Increase in lung transplant activity due to EVLP procedure (Applied in addition to standard LTx transition in EVLP service arm) | 10% | 18, 184 | Beta | DEVELOP-UK data [4] |
Post lung transplant survival | ||||
One-year survival for standard and EVLP | 0.77 | 257.91, 77.04 | Beta | UK cardio audit [27] |
Area under the curve | ||||
1-year survival | 0.77 | 257.91, 77.04 | Beta | UK cardio audit [27] |
3-year survival | 0.7 | 225.19, 96.51, | Beta | UK cardio audit [27] |
5-year survival | 0.53 | 167.15, 148.23 | Beta | UK cardio audit [27] |
10-year survival | 0.34 | 116.90, 226.93 | Beta | UK cardio audit [27] |
Utilities | ||||
Waiting list | 0.563 | 2292.2, 1782.4 | Beta | DEVELOP-UK data [4] |
1-year post standard lung transplant | 0.702 | 465.8, 197.3 | Beta | DEVELOP-UK data [4] |
2 years onwards post standard lung transplant | 0.734 | 439.7, 159.4 | Beta | DEVELOP-UK data [4] |
1-year post EVLP lung transplant | 0.702 | 465.8, 197.3 | Beta | DEVELOP-UK data [4] |
2 years onwards post EVLP transplant | 0.734 | 439.7, 159.4 | Beta | DEVELOP-UK data [4] |
Costs | ||||
Waiting list cost per year | £23,829 | 103.1, 239.3 | Gamma | Anyanwu [14] |
Standard lung transplant | £51,778 | 304.2, 175.5 | Gamma | DEVELOP-UK data [4] |
EVLP lung transplant | £137,527 | 98.4, 1441.1 | Gamma | DEVELOP-UK data [4] |
Post lung transplant costs – standard LTx (outpatient and concomitant medication Table 38 HTA report[4]) | ||||
Year 1 | £9700 | 93.5, 107.1 | Gamma | DEVELOP-UK data [4] |
Year 2 | £3812 | 93.4, 42.1 | Gamma | DEVELOP-UK data [4] |
Year 3 onwards | £3506 | 93.4, 38.7 | Gamma | DEVELOP-UK data [4] |
Post lung transplant costs – EVLP LTx | ||||
Year 1 | £5919 | 20.2, 302.7 | Gamma | DEVELOP-UK data [4] |
Year 2 | £2326 | 20.2, 118.9 | Gamma | DEVELOP-UK data [4] |
Year 3 onwards | £2140 | 20.2, 109.4 | Gamma | DEVELOP-UK data [4] |
Parameters | Mean | Alpha/Beta | Distribution | Source |
---|---|---|---|---|
Scenario 1: Pre-trial model transitions | ||||
From ‘Waiting list’ to ‘Removed from waiting list’ (Standard and EVLP service) | ||||
Year 1 | 0.08 | 16, 180 | Beta | NHSBT [24] |
Year 2 | 0.03 | 2, 67 | Beta | NHSBT [24] |
Year 3 onwards | 0.11 | 3, 32 | Beta | NHSBT [24] |
From ‘Waiting list’ to Transition to ‘Death’ (Standard and EVLP service) | ||||
Year 1 | 0.17 | 33,163 | Beta | NHSBT [24] |
Year 2 | 0.09 | 6, 63 | Beta | NHSBT [24] |
Year 3 onwards | 0.17 | 6, 29 | Beta | NHSBT [24] |
From ‘Waiting list’ to ‘Receiving a standard lung transplant’ | ||||
Year 1 | 0.4 | 78, 118 | Beta | NHSBT [24] |
Year 2 | 0.38 | 26, 43 | Beta | NHSBT [24] |
Year 3 onwards | 0.28 | 10, 25 | Beta | NHSBT [24] |
Scenario 2: 20% increase in lung transplant activity due to EVLP procedure | ||||
Increase in LTx activity due to EVLP procedure (Applied in addition to standard LTx transition in ‘EVLP service’ arm) | 0.2 | 36, 184 | Beta | DEVELOP-UK data [4] |
Scenario 3: 45% Conversion rate | ||||
EVLP lung transplant | £119,672 | 75.1, 1644.4 | Gamma | DEVELOP-UK data [4] |
Scenario 4: 1:1 conversion rate | ||||
EVLP lung transplant | £89,455 | 42.4, 2174.3 | Gamma | DEVELOP-UK data [4] |
Scenario 5: Utilities from literature | ||||
Waiting list | 0.31 | 59.72, 132.93 | Beta | Anyanwu et al. [25] |
1-year post standard lung transplant | 0.83 | 1099.12, 257.82 | Beta | Anyanwu et al. [25] |
2 years onwards post standard lung transplant | 0.82 | 854.12, 187.49 | Beta | Anyanwu et al. [25] |
1-year post EVLP lung transplant | 0.83 | 1099.12, 257.82 | Beta | Anyanwu et al. [25] |
2 years onwards post EVLP transplant | 0.82 | 854.12, 187.49 | Beta | Anyanwu et al. [25] |
Scenario 6: Increase in LTx activity (Excluding EVLP) | ||||
Pre-trial
| ||||
From ‘Waiting list’ to ‘Removed from waiting list’ | ||||
Year 1 | 0.08 | 16, 180 | Beta | NHSBT [11] |
Year 2 | 0.03 | 2, 67 | Beta | NHSBT [11] |
Year 3 onwards | 0.11 | 3, 32 | Beta | NHSBT [11] |
From ‘Waiting list’ to Transition to ‘Death’ | ||||
Year 1 | 0.17 | 33,163 | Beta | NHSBT [11] |
Year 2 | 0.09 | 6, 63 | Beta | NHSBT [11] |
Year 3 onwards | 0.17 | 6, 29 | Beta | NHSBT [11] |
From ‘Waiting list’ to ‘Receiving a standard lung transplant’ | ||||
Year 1 | 0.40 | 78, 118 | Beta | NHSBT [11] |
Year 2 | 0.38 | 26, 43 | Beta | NHSBT [11] |
Year 3 onwards | 0.28 | 10, 25 | Beta | NHSBT [11] |
Within trial
| ||||
From ‘Waiting list’ to ‘Removed from waiting list’ | ||||
Year 1 | 0.020 | 5.02, 245.98 | Beta | NHSBT [24] |
Year 2 | 0.030 | 2.51, 80.32 | Beta | NHSBT [24] |
Year 3 onwards | 0.077 | 2.51, 30.12 | Beta | NHSBT [24] |
From ‘Waiting list’ to Transition to ‘Death’ | ||||
Year 1 | 0.150 | 37.65, 213.35 | Beta | NHSBT [24] |
Year 2 | 0.212 | 17.57, 65.26 | Beta | NHSBT [24] |
Year 3 onwards | 0.077 | 2.51, 30.12 | Beta | NHSBT [24] |
From ‘Waiting list’ to ‘Receiving a standard lung transplant’ | ||||
Year 1 | 0.510 | 128, 122.99 | Beta | NHSBT [24] |
Year 2 | 0.364 | 30.1, 52.71 | Beta | NHSBT [24] |
Year 3 onwards | 0.462 | 15.1, 17.57 | Beta | NHSBT [24] |
Scenario 7: DEVELOP-UK one-year survival post-transplant | ||||
Standard service | 0.80 | 161.8, 40.4 | Beta | DEVELOP-UK [4] |
EVLP service | 0.67 | 11.64, 5.73 | Beta | DEVELOP-UK [4] |
Scenario 8: Same costs of post-transplant inpatient care in both arms (EVLP service = standard service costs plus costs of EVLP procedure) | ||||
Standard service transplant | £51,778 | 304.2, 175.5 | Gamma | DEVELOP-UK data [4] |
EVLP service transplant | £95,750 | 344.74, 269.29 | Gamma | DEVELOP-UK data [4] |
Scenario 9: Increase in waiting list costs by 120% | ||||
Increase waiting list cost | £50,830 | 96.04, 529.26 | Gamma | 120% increase |
Ethics approval and consent to participate to DEVELOP-UK
Results
Base-case results
‘Standard Service’ | ‘EVLP service’ | ||
---|---|---|---|
Discounted | Mean costs | £69,954 | £73,964 |
Mean life-years gained | 5.62 | 5.66 | |
Mean QALYs | 3.67 | 3.71 | |
Incremental | Costs | £4010 | |
Life-years gained | 0.040 | ||
QALYs | 0.045 | ||
ICER | Life-years gained | £100,000 | |
QALYs | £90,000 | ||
Number of | Standard lung transplants | 721 | 675 |
EVLP transplants | 67 |
Scenario analysis results
Scenario number | Without EVLP | With EVLP | ICER | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Cost | LYG | QALYs | Standard LTx | Cost | LYG | QALYs | Standard LTx | EVLP LTx | Cost per LYG | Cost per QALY gained | |
Base-case | £69,954 | 5.620 | 3.669 | 721 | £73,964 | 5.660 | 3.714 | 675 | 67 | £100,000 | £90,000 |
1) Pre-trial transitions & 10% | £ 65,778 | 5.153 | 3.304 | 620 | £69,265 | 5.199 | 3.354 | 586 | 59 | £75,000 | £71,000 |
2) EVLP rate 20% | £69,990 | 5.613 | 3.663 | 721 | £77,128 | 5.691 | 3.747 | 635 | 127 | £91,000 | £85,000 |
3) Conversion rate 45% | £70,014 | 5.631 | 3.679 | 721 | £73,014 | 5.673 | 3.725 | 675 | 67 | £71,000 | £65,000 |
4) 1:1 conversion rate | £70,136 | 5.634 | 3.675 | 721 | £71,300 | 5.675 | 3.720 | 675 | 67 | £28,000 | £26,000 |
5) Utilities from literature | £69,851 | 5.606 | 3.937 | 721 | £73,941 | 5.647 | 4.020 | 675 | 67 | £98,000 | £49,000 |
6) Increase in standard LTx in trial | £65,439 | 5.010 | 3.200 | 620 | £73,377 | 5.500 | 3.590 | 721 | 0 | £16,000 | £20,000 |
7) DEVELOP-UK one-year survival post-transplant | £72,050 | 5.630 | 3.670 | 721 | £76,128 | 5.620 | 3.680 | 675 | 67 | Standard dominant | £408,000 |
8) Same post-transplant costs plus EVLP process costs in EVLP arm | £69,970 | 5.631 | 3.673 | 721 | £71,569 | 5.674 | 3.720 | 675 | 67 | £37,000 | £34,000 |
9) Increased waiting list costs (120%) | £82,531 | 5.628 | 3.674 | 721 | £83,742 | 5.671 | 3.721 | 675 | 67 | £28,124 | £25,855 |
Exploratory analysis
Results of exploratory analysis | |||||||
---|---|---|---|---|---|---|---|
Without EVLP | With EVLP | ||||||
Survival after removal from waiting list | Cost | QALYs | Cost | QALYs | ICER | Cost source | QALY source |
One month | £69,955 | 3.67 | £73,964 | 3.71 | £90,000 | Dzingina [28] | DEVELOP-UK [4] |
£69,955 | 3.67 | £73,964 | 3.71 | £90,000 | Dzingina [28] | Anyanwu [14] | |
£69,956 | 3.67 | £73,964 | 3.71 | £90,000 | Georghiou [29] | DEVELOP-UK [4] | |
£69,956 | 3.67 | £73,964 | 3.71 | £90,000 | Georghiou [29] | Anyanwu [14] | |
Three months | £69,958 | 3.67 | £73,964 | 3.71 | £90,000 | Dzingina [28] | DEVELOP-UK [4] |
£69,958 | 3.67 | £73,964 | 3.71 | £90,000 | Dzingina [28] | Anyanwu [14] | |
£69,959 | 3.67 | £73,964 | 3.71 | £90,000 | Georghiou [29] | DEVELOP-UK [4] | |
£69,959 | 3.67 | £73,964 | 3.71 | £90,000 | Georghiou [29] | Anyanwu [14] | |
Six months | £69,961 | 3.67 | £73,964 | 3.71 | £90,000 | Dzingina [28] | DEVELOP-UK [4] |
£69,961 | 3.67 | £73,964 | 3.71 | £90,000 | Dzingina [28] | Anyanwu [14] | |
£69,964 | 3.67 | £73,964 | 3.71 | £90,000 | Georghiou [29] | DEVELOP-UK [4] | |
£69,964 | 3.67 | £73,964 | 3.71 | £90,000 | Georghiou [29] | Anyanwu [14] | |
Parameters | |||||||
Source | Disease area | Parameter type | Parameter value | ||||
Dzingina 2017 | Advanced chronic disease | Palliative care cost per month | £1173 | ||||
Georghiou 2014 | Any palliative care | Palliative care cost per month | £1644 | ||||
DEVELOP-UK | Lung transplant | Quality adjusted life-years | 0.563 | ||||
Anyanwu | Lung transplant | Quality adjusted life-years | 0.31 |