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Cost‐Effectiveness Analysis of Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukaemia in Portuguese Patients who are Unsuitable for Full-Dose Fludarabine-Based Therapy

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Abstract

Background

Chronic lymphocytic leukaemia (CLL) mostly affects patients with comorbidities and limited therapeutic options. Obinutuzumab in combination with chlorambucil (GClb) is a new therapeutic option for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy. This combination delays disease progression but incurs additional costs; thus, an assessment of its value for money is relevant.

Objective

To estimate the incremental cost-utility ratio of GClb in comparison with (i) rituximab in combination with chlorambucil (RClb), and (ii) chlorambucil alone (Clb) from the perspective of the Portuguese National Health Service (NHS).

Methods

A Markov model was used to predict disease progression. Pre‐progression clinical data were based on the latest CLL11 trial data, and post‐progression clinical data were obtained from CLL5 trial data. Utility values are from Kosmas et al. (Leuk Lymphoma 56:1320–1326, 14). Only direct medical costs were included. The resource consumption was estimated by a panel of Portuguese experts, and the unit costs were obtained from official sources. A discount rate of 5% was applied to costs and consequences.

Results

GClb and RClb were associated with an increase of 1.06 and 0.39 quality-adjusted life-years (QALY) at an additional cost of €21,720 and €9836 when compared to Clb, respectively. The cost-utility ratio of GClb versus Clb was €20,397/QALY, while RClb was extendedly dominated.

Conclusions

The use of GClb for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy incurs an incremental cost per QALY that is generally accepted in Portugal. Therefore, although there is some uncertainty, obinutuzumab is probably a cost-effective therapy in the Portuguese setting.

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Author information

Authors and Affiliations

  1. CISEP - Research Centre on the Portuguese Economy, ISEG, Universidade de Lisboa, Lisbon, Portugal

    Ana Teresa Paquete, Luís Silva Miguel & Carlos Gouveia Pinto

  2. F. Hoffmann-La Roche Ltd., Basel, Switzerland

    Ursula Becker

  3. Roche Farmacêutica Química, Lda., Lisbon, Portugal

    Catarina Pereira

  4. ISEG - Lisbon School of Economics and Management, Universidade de Lisboa, Lisbon, Portugal

    Carlos Gouveia Pinto

Authors
  1. Ana Teresa Paquete
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  2. Luís Silva Miguel
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  3. Ursula Becker
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  4. Catarina Pereira
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  5. Carlos Gouveia Pinto
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Corresponding author

Correspondence to Ana Teresa Paquete.

Ethics declarations

Roche Farmacêutica Química, Lda. funded CISEP for the contribution of its members to the adaptation of the economic model to the Portuguese setting and subsequent development of this manuscript. ATP and LSM worked at CISEP during the development of this project. They are currently working at the Center for Evidence-Based Medicine (CEMBE, Faculty of Medicine/ULisboa). UB is an employee of F. Hoffmann-La Roche Ltd. CP is an employee of Roche Farmacêutica Química, Lda. CGP works at CISEP.

Author Contributions

ATP and LSM wrote the initial version of the manuscript. All authors commented on the initial version and its revisions and approved the final manuscript.

Appendices

Appendix 1: Akaike Information Criteria (AIC) for PFS, with ranks in brackets

Parametric distribution

GClb

RClb

Clb

Exponential

780.1 (6)

808.8 (6)

285.8 (6)

Weibull

744.4 (1)

737.9 (4)

268.2 (3)

Log normal

773.4 (5)

715.3 (3)

270.3 (4)

Gamma

746.3 (3)

713.5 (2)

265.0 (2)

Log-logistic

744.5 (2)

697.5 (1)

259.4 (1)

Gompertz

755.9 (4)

782.9 (5)

283.2 (5)

  1. GClb obinutuzumab and chlorambucil, RClb rituximab and chlorambucil, Clb chlorambucil

Appendix 2: Expert panel results (resource consumption) and unit costs

2.1 Medicinal products and administration costs

Medicinal products

Unit cost (€)

Obinutuzumab (1000 mg vial)

3780.06a

Rituximab (500 mg vial; 10 mg/mL)

1023.88

Rituximab (100 mg vial; 10 mg/mL)

209.49

Chlorambucil (25 tablets package)

40.51

Administration

175.24b

  1. aIt should be acknowledged that the price of obinutuzumab is lower than the reported acquisition price currently used in the base case scenario, when charged to the Portuguese National Health Service. The financed price is confidential and could not be used in this study
  2. bAccording to Portaria 234/2015 [16], the price of a chemotherapy session is 496.30€. However, this price was estimated considering the cost due to drugs and the cost due to other resources. As the relevant cost for this economic evaluation is the latter, the price was multiplied by the proportion that is due to other resources—35.3% [17]

2.2 Health state costs per month

 

Progression free (values per month)

Post-progression (values per month)

Patients %

Number of times

Unit cost (€)

Weighed cost (€)

Patients %

Number of times

Unit cost (€)

Weighed cost (€)

Hospital services

Regular hospitalisation unit

2.5

1

2654.94

66.37

20.0

1

5195.86

1039.17

Palliative care unit

0.0

0

–

–

0.0

0

–

–

Outpatient services

Emergency episode

7.5

1

82.99

6.22

22.5

1

82.99

18.67

Haematology/oncology visits

30.0

1

31.00

9.30

100.0

1

31.00

31.00

General practice visits

10.0

1

31.00

3.10

7.5

1

31.00

2.33

Pain visits

2.5

1

51.60

1.29

2.5

1

51.60

1.29

Nutrition visits

0.5

1

16.00

0.08

0.5

1

16.00

0.08

Nursery visits

0.0

0

16.00

–

2.5

1

16.00

0.40

Psychiatry /psychology visits

2.5

1

24.50

0.61

10.0

1

24.50

2.45

Other specialist visits

50.0

1

–

–

50.0

1

–

–

Exams

Biochemistry examsa

30.0

1

8.00

2.40

100.0

1

8.00

8.00

Complete blood count

30.0

1

4.70

1.41

100.0

1

4.70

4.70

Glycaemia

30.0

1

4.00

1.20

100.0

1

4.00

4.00

Chest x-ray

10.0

1

9.00

0.90

30.0

1

9.00

2.70

CT scan

2.5

1

73.30

1.83

10.0

1

73.30

7.33

Anatomopathology

0.0

0

86.90

–

2.5

1

86.90

2.17

Myelogram

0.0

0

26.50

–

5.0

1

26.50

1.33

FISH test

0.0

0

287.50

–

8.3

1

287.50

23.86

Flow cytometry

0.0

0

110.88

–

8.3

1

110.88

9.20

Concomitant therapy and outpatient procedures

G-CSF

0.5

4

9.30

0.19

7.5

4

9.30

2.79

Immunoglobulins

5.0

1

20

1.01

10.0

1

20.20

2.02

Blood transfusion

0.5

1

125.10

0.63

5.0

1

125.10

6.26

Other therapies (ex. antibiotics, antidepressants, antihypertensives)

100

0

–

–

100.0

0

–

–

Domiciliary care

2.50

8696

33.10

7.20

2.5

8696

33.10

7.20

   

Total cost/month

103.74

  

Total cost/month

1176.94

  1. aCreatinine (€1.2), bilirubin (€1.4), ALT (€1.3), AST (€1.3), GGT (€1.5), alkaline phosphatase (€1.3)

2.3 Adverse event costs

  

Number

Patients %

Unit cost (€)

Weighed cost (€)

Anaemia: grade 3

Hospitalisation

 

1

5

1282.84

64.14

Emergency episode

 

2

95

82.99

157.69

Exams

Complete blood count

2

95

4.70

8.93

Therapy

Blood transfusion

1

95

125.10

118.85

Total cost per episode (€)

349.60

Neutropenia/leukopenia: grade 3/4

Hospitalisation

 

0

0

–

–

Emergency episode

 

1

100

82.99

82.99

Outpatient visits

Haematology/oncology

1

100

31.00

31.00

Exams

Complete blood count

1

100

4.70

4.70

 

Biochemistry

1

100

8.00

8.00

 

PCR

1

100

3.17

3.17

Therapy

G-CSF

4

65

9.30

24.18

Total cost per episode (€)

154.04

Thrombocytopenia: grade 3/4

Hospitalisation

 

1

2.5

2183.34

54.58

Emergency episode

 

1

98

82.99

80.92

Outpatient visits

Haematology/oncology

1

3

31.00

0.78

Exams

Complete blood count

2

98

4.70

9.17

 

Biochemistry

1

3

8.00

0.20

Therapy

Platelet transfusion

2

29

214.60

125.54

Total cost per episode (€)

271.18

Febrile neutropenia: grade 3/4

Hospitalisation

 

1

65

1282.84

833.85

Emergency episode

 

3

12

82.99

30.50

  

1

23

82.99

18.88

Exams

Complete blood count

2

30

4.70

1.73

 

Biochemistry

2

30

8.00

2.94

 

PCR

2

30

3.17

1.16

 

Blood culture

1

12

12.00

1.47

 

Urine culture

1

12

10.50

1.29

 

X-ray

1

12

9.00

1.10

 

CT scan

1

4

73.30

2.57

Therapy

Oral antibiotics

1

12

3.02

0.37

 

G-CSF

4

11

9.30

4.17

Total cost per episode (€)

903.63

Infection/pneumonia: grade 3

Hospitalisation

 

1

100

1110.88

1110.88

Total cost per episode (€)

1110.88

Other infections (urinary or respiratory): grade 3

Hospitalisation

 

1

90

1041.87

937.68

Total cost per episode (€)

937.68

Injection site reaction: grade 3

Hospitalisation

 

1

2.5

1541.65

38.54

Emergency episode

 

1

98

82.99

80.92

Exams

Biochemistry

1

98

8.00

7.80

 

Complete blood count

1

98

4.70

4.58

 

Arterial blood gas analysis

1

10

0.80

1.05

Therapy

Antihistamines; corticoids; IV fluid therapy; oxygen; antipyretic

1

98

11.24

10.96

Total cost per episode (€)

143.86

Maculopapular rash: grade 3

Hospitalisation

 

0

0

–

–

Emergency episode

 

1

100

82.99

82.99

Outpatient visits

Haematology/oncology

1

100

31.00

31.00

 

Dermatology

1

100

31.00

31.00

Therapy

Antihistamines and corticoids

1

100

2.28

2.28

Total cost per episode (€)

147.27

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Paquete, A.T., Miguel, L.S., Becker, U. et al. Cost‐Effectiveness Analysis of Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukaemia in Portuguese Patients who are Unsuitable for Full-Dose Fludarabine-Based Therapy. Appl Health Econ Health Policy 15, 501–512 (2017). https://doi.org/10.1007/s40258-017-0321-2

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