ONLINE RESOURCE 1: SUPPLEMENTARY MATERIAL
Cost Effectiveness of Romiplostim for the Treatment of Chronic Immune
Thrombocytopenia in Ireland
Authors: Dawn Lee1, Patrick Thornton, Alexander Hirst, Lucie Kutikova, Robert Deuson, Nic
Brereton
1
BresMed, Sheffield, UK
Email: dlee@bresmed.co.uk
Table 1A. Adjusted overall response ratesa for romiplostim versus eltrombopag based on
indirect comparison1
Reported response rate,
proportion of patients (%)
Indirect comparison OR
(95% CI)
Adjusted probability of
responding to eltrombopag
Eltrombopag vs Placebo
Eltrombopag
Placebo/ SoC
Romiplostim vs Placebo
Romiplostim Placebo/SoC
77/135 = 57%
69/83 = 83%
7/62 = 11%
3/42 = 7%
0.11 (0.02, 0.66)
PR x (OR/ (1 - PR+PR x OR)
= 83% * (0.11/(1-83% + 83%*0.11) = 35%
a
Overall response rate (durable plus transient response) from randomized clinical trials (romiplostim) or derived in post-hoc
analysis (eltrombopag). Durable response: weekly platelet counts ≥ 50 x 109/L during ≥6 weeks (consecutive for eltrombopag)
of the last 8 weeks of treatment, excluding patients with rescue medication at any time during study. Transient response: ≥4
weekly (consecutive for eltrombopag) platelet responses ≥ 50 x 109/L (50-400 x 109/L for eltrombopag) without a durable
platelet response from week 2-25.
PR romiplostim probability of response, OR Odds Ratio (eltrombopag versus romiplostim)
Table 2A. Survival analysis curve fits for romiplostim and eltrombopag
Curve
Akaike Information Criterion
Romiplostim
Eltrombopag
Log-normal
516.85
717.42
Log-logistic
524.33
740.51
Gompertz
526.04
742.46
Exponential
527.86
730.88
Weibull
529.85
737.82
Table 3A. Parameters for probabilistic sensitivity analyses
Parameter
Deterministic estimate
Measure of uncertainty
Distribution
Population age
52 years2
SE 1.39
Normal
Patient height
1.68m3
SE 0.0065
Normal
Patient weight
79.73kg3
SE 0.36
Normal
Treatment pathways (UK)
1. TPOra 100%; 2. Rituximab 80%; 3. Azathioprine
SE 20% of the mean
Beta
0.406,7
α = 49.781; β = 74.219
Beta
0.086,7
α = 10.255; β = 113.745
Beta
Probability of bleed if platelets ≥50x109/L
Outpatient 12.64%6,7
α = 15.674; β = 108.326
Beta
Probability of bleed if platelets <50x109/L
Outpatient 40.77%; Inpatient 3.69%6,7
Outpatient α = 50.557; β = 73.443;
Beta
59%; 4. MMF 37%; 5. Cyclosporine
IVIg usage per cycle for patients with platelets
4%4,5
<50x109/L
Steroid usage per cycle for patients with platelets
<50x109/L
Inpatient α = 4.578; β = 119.422
Mortality associated with bleed-related hospitalization
(death rate per cycle)
GI bleed 0.046; Intracranial haemorrhage 0.132;
Other bleed
0.0178
Other bleed α = 501.789; β = 29015.211;
Beta
GI bleed α = 1357.782; β = 28159.218;
Intracranial hemorrhage α = 3896.244; β
= 25620.756
Cost of minor (outpatient) bleed
€1499
SE 10% of the mean
Normal
Cost of GI or other inpatient bleed
€2,9139
SE 10% of the mean
Normal
Cost of intracranial haemorrhage
€6,8549
SE 10% of the mean
Normal
Blood tests cost
€11.6010
SE 10% of the mean
Normal
Hepatic, bone marrow or blood film testing cost
€3.87
SE 10% of the mean
Normal
Physician appointment cost
€1499
SE 10% of the mean
Normal
Nurse appointment cost for romiplostim
€8.8811
SE 10% of the mean
Normal
€30013
SE 30% of the mean
Normal
11,12
administration
Administration cost of rituximab, IVIg or IV steroids
Parameter
Deterministic estimate
Cost eltrombopag, 28 x 50mg
€2,043.5814
IVIg cost per g
Real-life cost used in base case
(€455)
Measure of uncertainty
Distribution
SE 10% of the mean
Normal
SE 10% of the mean
Normal
List price (€70.01)15 not used
Romiplostim dosing
1 vial per week2
SE 10% of the mean
Gamma
Utility, platelets ≥50x109/L and no bleed
0.86316
α = 3.672; β = 0.583
Beta
0.73416
α = 3.236; β = 1.173
Beta
16
α = 2.274; β = 0.430
Beta
and outpatient bleed
0.73216
α = 3.246; β = 1.188
Beta
and IC bleed
0.03816
SE 0.46
Normal
and GI bleed
0.54017
α = 19.095; β = 16.266
Beta
and other bleed
0.54017
α = 19.095; β = 16.266
Beta
IVIg response rate
80.53%18-29
α = 6.282; β = 1.519
Beta
IV steroids response rate
45.96%21,30
α = 22.609; β = 26.588
Beta
Romiplostim response rate
83%2
α = 22.672; β = 4.578
Beta
Eltrombopag response rate
35%1
α = 118.418; β = 217.376
Beta
Rituximab response rate
58%31,32
α = 17.479; β = 12.814
Beta
Azathioprine response rate
56%33-35
α = 161.886; β = 125.050
Beta
MMF response rate
50%36-38
α = 7.039; β = 6.966
Beta
Cyclosporine response rate
57%34,39-41
α = 4.485; β = 3.442
Beta
Constant: 0.02176101
Multivariate normal
Utility, platelets
≥50x109/L
and outpatient bleed
9
Utility, platelets <50x10 /L and no bleed
Utility, platelets
<50x109/L
Utility, platelets
<50x109/L
Utility, platelets
<50x109/L
Utility, platelets
<50x109/L
Romiplostim treatment duration
0.841
140.86
cycles42
ln(p): 0.00822917
Eltrombopag treatment duration
89.66
cycles43
Constant: 0.00931
Multivariate normal
ln(p):
0.00292988
Rituximab treatment duration
Azathioprine treatment duration
18.87
cycles44-46
λ = 0.053, SE = 0.006, n=2
Normal (exponential distribution)
20.34
cycles47
λ = 0.049, SE = 0.011, n=2
Normal (exponential distribution)
Parameter
MMF treatment duration
Cyclosporine treatment duration
Deterministic estimate
5.68
cycles37
14.54
cycles41
Measure of uncertainty
Distribution
SE 0.87
Normal
SE 10% of the mean
Normal
GI gastrointestinal, IVIg intravenous immunoglobulin, IC intracranial, MMF mycophenolate mofetil, SE standard error, TPOra thrombopoietin receptor agonist
Figure 1A. Treatment duration curves for romiplostim and eltrombopag fitted to
observed data
Proportion of patients on treatment
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0
10
20
30
40
50
Number of 4-week Cycles
60
70
Eltrombopag Survival
Eltrombopag Fitted Curve
Romiplostim Survival
Romiplostim Fitted Curve
80
Figure 2A. Cost-effectiveness acceptability curve for romiplostim compared to
eltrombopag and standard of care (SoC)
Probability of romiplostim cost effectiveness
QALY quality-adjusted life-year
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
€0
€10,000 €20,000 €30,000 €40,000 €50,000 €60,000 €70,000 €80,000 €90,000 €100,000
Willingness-to-pay threshold (per QALY gained)
Romiplostim vs SoC
Romiplostim vs Eltrombopag
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