Supplementary Material 1. Delphi Questionnaire Content

Supplementary material 1. Delphi questionnaire content

The validation of model’s assumptions, parameters, and the clinical management of patients with FL were assessed performing an expert panel. To conduct the expert panel the Delphi methodology was applied.

The expert panel comprised two haematologists (Armando López-Guillermo and Antonio Salar) and an oncologist (Antonio Rueda) with expertise in the clinical management of patients with FL.

At first, a questionnaire was prepared and was sent to the three experts on June 12, 2013. After the experts completed the questionnaires, a meeting was planned on November 15, 2013 to discuss the discrepancies and to achieve a consensus.

The Delphi questionnaire contents were:

1. BACKGROUND

A brief introduction to the cost-effectiveness methodology

1. OBJECTIVE

The assessment of the cost-effectiveness of rituximab-bendamustine compared with R-CHOP as a first-line treatment for patients with FL in Spain.

1. MODEL STRUCTURE

The experts were asked about: the validity of the model structure, the validity of the sources of data used to estimate transition probabilities and the validity of the assumptions made.

1. MODEL PARAMETERS

The experts validated the source of data of the parameters initially proposed. When they were disagree with those parameters, they were encouraged to provide an alternative source of data. The parameters validated with the experts were:

1. Follicular lymphoma patient’s characteristics
2. Mean age
3. Mean weight
4. Mean body surface area (BSA)
5. First-line chemotherapy
6. Dosage
7. Premedication
8. Treatment pattern in first relapse
9. Treatment pattern in second relapse
10. Adverse events

Frequency

Clinical management

1. Follicular lymphoma management for each health state.
2. Utility values

Supplementary material 2.Probabilistic distributions parameters.

Parameter / Probabilitydistribution / Parameter α / Parameter β
EFFECTS / Choleskydecomposition*
COSTS
Prophylaxisrituximab-bendamustine / Gamma / 1 / 211.12 €
Prophylaxis R-CHOP / Gamma / 1 / 320.68 €
Adverse events management rituximab-bendamustine / Gamma / 1 / 85.46 €
Adverse events management R-CHOP / Gamma / 1 / 268.15 €
PF state (rituximab-bendamustine treatment) / Gamma / 1 / 242.18 €
PF state (R-CHOP treatment health state) / Gamma / 1 / 254.06 €
PF state (maintenance) / Gamma / 1 / 60.82 €
Progression state (first relapse, first cycle) / Gamma / 1 / 1,903 €
Progression state (first relapse, cycles) / Gamma / 1 / 1,760 €
Progression state (second relapse, first cycle) / Gamma / 1 / 2,206 €
Progression state (second relapse, cycles) / Gamma / 1 / 2,143 €
UTILITIES
PF state / Beta / 88 / 22
Progression state / Beta / 62 / 38
RELAPSES TREATMENT PATTERN
First relapse rituximab-bendamustine / Dirichlet / Π=(0.15,0.50,0.20,0.10,0.05)
First relapse R-CHOP / Dirichlet / Π=(0.15,0.00,0.15,0.10,0.60)
Second relapse rituximab-bendamustine / Dirichlet / Π=(0.15,0.05,0.10,0.05,0.15,
0.10,0.10,0.10,0.10,0.10)
Second relapse R-CHOP / Dirichlet / Π=(0.15,0.00,0.10,0.05,0.15,
0.10,0.10,0.15,0.10,0.10)

PF: progression free; R-CHOP: rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone

* Detailed parameters available on request

Supplementary material 3.One-way sensitivity analysis results.

Model scenario / Rituximab-bendamustine / R-CHOP / Difference / Cost-effectiveness ratios
Costs / LYG / QALYs / Costs / LYG / QALYs / Costs / LYG / QALYs / ICER (€/LYG) / ICER (€/QALYs)
Base Case / €68,357 / 12.86 / 9.63 / 69,528 € / 12.62 / 9.23 / -€1.171 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Sensitivity analysis
Time horizon
Temporal horizon (15 years) / €62,621 / 10.05 / 7.55 / €62,428 / 9.93 / 7.32 / € 193.29 / 0.12 / 0.23 / € 1,598 / € 854.82
Temporal horizon (30 years) / €69,636 / 13.50 / 10.10 / € 71,115 / 13.23 / 9.67 / -€ 1,479 / 0.27 / 0.43 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Cohort average age (63 years) / €68,357 / 12.86 / 9.63 / 69,528 € / 12.62 / 9.23 / -€1.171 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Discount rate
Discount rate (0%) / €68,973 / 13.12 / 9.82 / € 70,273 / 12.87 / 9.41 / -€ 1,300 / 0.25 / 0.40 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Discount rate (5%) / €67,956 / 12.70 / 9.50 / € 69,043 / 12.46 / 9.12 / -€ 1,087 / 0.24 / 0.38 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Costs
Rituximab-bendamustine treatment costs (-20%) / €65,075 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 4,453 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Rituximab-bendamustine treatment costs(+20%) / € 71,639 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / € 2,112 / 0.24 / 0.39 / € 8,696 / € 5,383
R-CHOP treatment costs (-20%) / € 68,357 / 12.86 / 9.63 / € 67,414 / 12.62 / 9.23 / € 943.40 / 0.24 / 0.39 / € 3,885 / € 2,405
R-CHOP treatment costs(+20%) / € 68,357 / 12.86 / 9.63 / € 71,642 / 12.62 / 9.23 / -€ 3,285 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Rituximab maintenance cost(-20%) / € 65,435 / 12.86 / 9.63 / € 66,572 / 12.62 / 9.23 / -€ 1,137 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Rituximabmaintenaincecost(+20%) / € 71,280 / 12.86 / 9.63 / € 72,484 / 12.62 / 9.23 / -€ 1,204 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Prophylaxis Rituximab-bendamustine (-20%) / € 68,105 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 1,423 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Prophylaxis Rituximab-bendamustine (+20%) / € 68,609 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 918.83 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Prophylaxis R-CHOP (-20%) / € 68,357 / 12.86 / 9.63 / € 69,272 / 12.62 / 9.23 / -€ 914.93 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Prophylaxis R-CHOP (+20%) / € 68,357 / 12.86 / 9.63 / € 69,784 / 12.62 / 9.23 / -€ 1,427 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st Relapse in Rituximab-bendamustine arm (-20%) / € 67,083 / 12.86 / 9.63 / € 67,886 / 12.62 / 9.23 / -€ 803.49 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st Relapse in Rituximab-bendamustine arm (+20%) / € 69,631 / 12.86 / 9.63 / € 71,169 / 12.62 / 9.23 / -€ 1,538 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st Relapse in R-CHOP arm (-20%) / € 68,357 / 12.86 / 9.63 / € 68,568 / 12.62 / 9.23 / -€ 211.03 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st Relapse in R-CHOP arm (+20%) / € 68,357 / 12.86 / 9.63 / € 72,185 / 12.62 / 9.23 / -€ 3,828 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
2nd Relapse in Rituximab-bendamustine arm (-20%) / € 67,431 / 12.86 / 9.63 / € 68,333 / 12.62 / 9.23 / -€ 901.57 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
2nd Relapse in Rituximab-bendamustine arm (+20%) / € 69,283 / 12.86 / 9.63 / € 70,723 / 12.62 / 9.23 / -€ 1,440 / 0.24 / 0.39 / Rituximab-bendamustineDominant / Rituximab-bendamustineDominant
2nd Relapse in R-CHOP arm (-20%) / € 68,357 / 12.86 / 9.63 / €68,345 / 12.62 / 9.23 / €12.48 / 0.24 / 0.39 / €51.41 / €31.83
2nd Relapse in R-CHOP arm (+20%) / € 68,357 / 12.86 / 9.63 / € 70,740 / 12.62 / 9.23 / --€ 2,383 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Adverse events Rituximab-bendamustine arm costs (-20%) / € 68,255 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 1,273 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Adverse events Rituximab-bendamustine costs (+20%) / € 68,459 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 1,069 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Adverse events R-CHOP costs (-20%) / € 68,357 / 12.86 / 9.63 / € 69,314 / 12.62 / 9.23 / -€ 956.84 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Adverse events R-CHOP costs (+20%) / € 68,357 / 12.86 / 9.63 / € 69,742 / 12.62 / 9.23 / -€ 1,385 / 0.24 / 0.39 / Rituximab-bendamustineDominant / Rituximab-bendamustineDominant
PF treatment with Rituximab-bendamustine health state management cost (-20%) / € 68,068 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 1,460 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
PF treatment with Rituximab-bendamustine health state management cost (+20%) / € 68,646 / 12.86 / 9.63 / € 69,528 / 12.62 / 9.23 / -€ 881.78 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
PF treatment with R-CHOP health state management cost (-20%) / € 68,357 / 12.86 / 9.63 / € 69,325 / 12.62 / 9.23 / -€ 968.08 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
PF treatment with R- CHOP health state management cost (+20%) / € 68,357 / 12.86 / 9.63 / € 69,730 / 12.62 / 9.23 / -€ 1,373 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
PF maintenance with rituximab health state management cost (-20%) / € 67,007 / 12.86 / 9.63 / € 68,359 / 12.62 / 9.23 / -€ 1,352 / 0.24 / 0.39 / Rituximab-bendamustineDominant / Rituximab-bendamustineDominant
PF maintenance with rituximab health state management cost (+20%) / € 69,707 / 12.86 / 9.63 / € 70,696 / 12.62 / 9.23 / -€ 989.36 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st relapse, 1stcycle management (-20%) / €68,323 / 12.86 / 9.63 / € 69,485 / 12.62 / 9.23 / -€1,161 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st relapse, 1st cycle management (+20%) / € 68,391 / 12.86 / 9.63 / €69,571 / 12.62 / 9.23 / -€1,180 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st relapse, 2nd and following cycle management (-20%) / € 68,237 / 12.86 / 9.63 / € 69,380 / 12.62 / 9.23 / -€ 1,143 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
1st relapse, 2nd and following cycle management (+20%) / € 68,477 / 12.86 / 9.63 / € 69,676 / 12.62 / 9.23 / -€ 1,199 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
2nd relapse, 1st cycle management (-20%) / € 68,328 / 12.86 / 9.63 / €69,490 / 12.62 / 9.23 / -€1,162 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
2nd relapse, 1st cycle management (+20%) / €68,386 / 12.86 / 9.63 / €69,565 / 12.62 / 9.23 / -€1,179 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
2nd relapse, 2nd and following cycle management (-20%) / € 65,203 / 12.86 / 9.63 / € 65,517 / 12.62 / 9.23 / -€ 314.83 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
2nd relapse, 2nd and following cycle management (+20%) / € 71,511 / 12.86 / 9.63 / € 73,538 / 12.62 / 9.23 / -€ 2,027 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Utilities
PF on treatment (0.640) / € 68,357 / 12.86 / 9.58 / € 69,528 / 12.62 / 9.20 / -€ 1,171 / 0.24 / 0.38 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
PF on treatment (0.966) / € 68,357 / 12.86 / 9.67 / € 69,528 / 12.62 / 9.26 / -€ 1,171 / 0.24 / 0.41 / Rituximab-bendamustineDominant / Rituximab-bendamustineDominant
PF on maintenance (0.640) / € 68,357 / 12.86 / 8.73 / € 69,528 / 12.62 / 8.46 / -€ 1,171 / 0.24 / 0.27 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
PF on maintenance (0.966) / € 68,357 / 12.86 / 10.43 / € 69,528 / 12.62 / 9.93 / -€ 1,171 / 0.24 / 0.50 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Progression disease, 1st relapse (0.494) / € 68,357 / 12.86 / 9.59 / € 69,528 / 12.62 / 9.19 / -€ 1,171 / 0.24 / 0.40 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Progression disease, 1st relapse (0.742) / € 68,357 / 12.86 / 9.64 / € 69,528 / 12.62 / 9.25 / -€ 1,171 / 0.24 / 0.39 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Progression disease, 2nd relapse (0.494) / € 68,357 / 12.86 / 8.81 / € 69,528 / 12.62 / 8.20 / -€ 1,171 / 0.24 / 0.61 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Progression disease, 2ndrelapse (0.742) / € 68,357 / 12.86 / 9.93 / € 69,528 / 12.62 / 9.62 / -€ 1,171 / 0.24 / 0.31 / Rituximab-bendamustine Dominant / Rituximab-bendamustine Dominant
Survival parametric curves
Weibull for rituximab-bendamustinePFS, rituximab maintenance and relapses
Exponential for R-CHOP PFS / €58,037 / 13.01 / 9.95 / €55,867 / 12.78 / 9.63 / €2,170 / 0.23 / 0.32 / €9,239.07 / €6,823.90

ICER: incremental cost-effectiveness ratio; ICUR: incremental cost-utility ratio; LYG: life year gained; QALY: quality adjusted life year;PF: progression free; PFS: progression free survival ; R-CHOP: rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone