Table 1.
Variables of the model
| Dimension | Base case value | Sensitivity analysis values (range) | References |
|---|---|---|---|
| Characteristics of the patients | |||
| Age | 71.7 | – | 7 |
| Body weight | 72.2 kg | – | 16 |
| Height | 162.4 cm | – | 16 |
| Body surface area | 1.80 m2 | – | Calculateda |
| Distribution for PFS | Weibull | Exponential | 15 |
| Log-logistic | |||
| Log-normal | |||
| Gamma | |||
| Gompertz | |||
| Postprogression survival | CLL5 | CLL8 | 19,20 |
| Health state utilitiesb | |||
| PFS on initial therapy oral treatment | 0.71 | 0.67–0.75 | 21 |
| PFS on initial therapy IV treatment | 0.67 | 0.63–0.71 | 21 |
| PFS on initial therapy with increased hospital visits | 0.55 | 0.50–0.61 | 21 |
| PFS without treatment | 0.82 | 0.78–0.85 | 21 |
| Progression after first-line therapy | 0.66 | 0.62–0.71 | 21 |
| PFS on second-line therapy | 0.55 | 0.50–0.60 | 21 |
| PFS without second-line therapy | 0.71 | 0.66–0.75 | 21 |
| Further progression | 0.59 | 0.55–0.64 | 21 |
| Relapsed lines of treatment | 0.42 | 0.37–0.47 | 21 |
| Drug costs (reported EFP) | |||
| Obinutuzumab (1,000 mg vial) | €3,970.00 | €3,048.96–3,430.08c | Roche Farma SA |
| Rituximab (100 mg vial) | €247.59 | €210.45d | 37 |
| Rituximab (500 mg vial) | €1,234.53 | €1,049.35d | 37 |
| Chlorambucil (2 mg; 25 tablets) | €50.00 | – | Experts panel |
| Dose and duration of treatmente | CLL11 | SmPC | 7 |
| Costs of adverse events | |||
| Anemia | €334,52 | €267.62–401.43 | 22 |
| Febrile neutropenia | €5,772.20 | €4,617.76–6,926.64 | 22 |
| Infection | €2,733.07 | €2,186.45–3,279.68 | 22 |
| Infusion-related reactionf | €592.52 | €474.02–711.03 | 23 |
| Neutropenia | €573.89 | €459.11–688.66 | 22 |
| Pneumonia | €2,099.34 | €1,679.47–2,519.21 | 22 |
| Thrombocytopenia | €929.01 | €743.21–1,114.81 | 22 |
| Weekly supportive care costsg | |||
| GClb treatment | €15.35 | €12.28–18.43 | 22 |
| RClb treatment | €13.44 | €10.75–16.12 | 22 |
| Cost of IV administration | €218.94 | €175.15–262.73 | 25 |
| Time horizon | 20 years | 10 and 15 years | 25 |
| Annual discount rate (costs and benefits) | 3% | 0% and 5% | 28 |
Notes: All costs are expressed in euros corresponding to February 2016. Panel, panel of clinical experts.
Based on the Mosteller formula: body surface (m2) = [(height (cm) × body weight (kg)/3,600)]½.
Base case: mean utility values; sensitivity analysis: 95% confidence interval.
10% and 20% lower than base case and 4% discount due to RD.
15% discount due to RD.
Base case: real doses of the drugs used in the CLL11 trial with maximum vial sharing; sensitivity analysis: the theoretical rituximab dose was considered according to the SmPC, the mean body surface of the patients in the CLL11 trial, and with maximum vial sharing.
Bronchospasm, chills, dyspnea, hypertension, hypotension, pyrexia, vomiting.
Weekly costs were calculated considering the cost of one hematology visit (€93.36).22
Abbreviations: CLL, chronic lymphocytic leukemia; EFP, ex-factory price; GClb, obinutuzumab + chlorambucil; IV, intravenous; PFS, progression-free survival; RClb, rituximab + chlorambucil; RD, Spanish Royal Decree-Law; SmPC, Summaries of Product Characteristics.