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4 authors, including:
Franciso Luis Pimentel
Luis Laranjeira
Eli Lilly
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Mariana Guerreiro
Eli Lilly
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available at www.sciencedirect.com
Hospital S
ao Sebasti
ao, Oncology Department, R. Dr. C
andido Pinho, 4520-211
Santa Maria da Feira, Portugal
b
Eli Lilly and Company, Lilly House, Priestly Road, Baskingstoke, Hampshire, RG24 9NL, UK
c
Lilly Portugal Produtos Farmac
euticos, Portugal, R. Dr. Ant
onio Loureiro Borges, Edifcio 1-Piso 1, Arquiparque-Miraores,
1499-016 Alg
es, Portugal
Received 23 January 2006 ; received in revised form 8 March 2006; accepted 10 March 2006
KEYWORDS
Cisplatin;
Cost-minimization;
Gemcitabine;
Non-small cell lung
cancer
Summary
Objectives: Economic evaluations of chemotherapy regimens for stage IIIB or IV non-small cell
lung cancer (NSCLC) have been conducted for many European countries, but not for Portugal.
This study evaluates the total health care costs of ve commonly used doublet regimens with
similar efcacy results.
Methods: Using the methodology reported by Schiller [Schiller JH, Tilden D, Aristides M, Lees
M, Kielhorn A, Maniadakis N, et al. Restropective cost analysis of gemcitabine in combination with cisplatin in non-small cell lung cancer compared to other combination therapies in
Europe. Lung Cancer 2004;43:10112], we conducted a cost-minimization analysis to compare vinorelbine-cisplatin (Vin/Cis), gemcitabine-cisplatin (Gem/Cis), paclitaxel-carboplatin
(Pac/Carb), docetaxel-cisplatin (Doc/Cis), and paclitaxel-cisplatin (Pac/Cis). The perspective
was that of the Portuguese National Health Service and included only direct medical costs
(reimbursed costs plus co-payments): chemotherapy acquisition, chemotherapy administration,
hospitalizations due to adverse events, and other medical resources. Unit costs were drawn
from ofcial sources (Diagnosis Related Groups and retail/hospital costs) (2003 value [Diagnosis
Related Groups (DRG) published at Di
ario da Rep
ublica; 2003]). Resource use was estimated
from two multicenter randomized phase III trials [Comella P, Frasci G, Panza N, Manzione L, De
Cataldis G, Ciof R, et al. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine
with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell
Corresponding author. Tel.: +351 256 379700; fax: +351 256 373867.
E-mail address: fpimentel@cs.ua.pt (F.L. Pimentel).
Associated Professor in SACS Aveiro University, Head of Oncology Department of Hospital S
ao Sebasti
ao.
0169-5002/$ see front matter 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.lungcan.2006.03.005
366
1. Introduction
Cancer is an important cause of morbidity and the second
leading cause of death in Portugal [1]. Worldwide, nonsmall cell lung cancer (NSCLC) is a leading cause of cancerrelated mortality. Over the past years, there has been slow
but steady progress in the treatment options of NSCLC.
Chemotherapy has achieved modest improvements in survival and quality of life. New diagnostic tools and the use
of novel drugs such as gemcitabine, vinorelbine, and the
taxanes have markedly changed the treatment options for
NSCLC over recent years.
Because of increases in health care costs, however, the
economic value of the various treatments has been under
considerable scrutiny. Rising health care costs, expensive
new health care technologies, and increasing patient expectations are placing huge pressures on health care systems.
As a result, decision makers need more information on the
relative cost of new therapies and treatments in addition to
their clinical benets. Portugal lacks robust data regarding
the economics of lung cancer. Pharmacoeconomics assumes
an ever increasing importance as changes in health care systems occur in response to market forces for improved cost
control, regulatory initiatives on cost and quality, and consumer demands for quality care and greater exibility in
provider choice.
Chemotherapy is supported by the national health care
service in Portugal for the treatment of cancer, so it is
important to evaluate the impact of different regimens with
respect to health care expenditures. Such information could
better equip health care decision makers not only to choose
the most cost-efcient regimen, but also to improve health
care policies and decisions.
Two recent multicenter randomized phase III trials
(Comella et al. [2]; Schiller et al. [3]) demonstrated
that ve platinum-based doublets with novel agents were
comparable in terms of efcacy in the treatment of
advanced NSCLC. A retrospective cost analysis of these
two studies provided an economic rationale for the use of
gemcitabine-cisplatin (Gem/Cis) as a rst-line treatment
option in ve European countries for patients with NSCLC,
as compared to vinorelbine-cisplatin (Vin/Cis), paclitaxelcarboplatin (Pac/Carb), docetaxel-cisplatin (Doc/Cis), and
paclitaxel-cisplatin (Pac/Cis) [4].
Economic evaluations of chemotherapy regimens for
advanced NSCLC have been conducted for many European
2. Methods
2.1. Economic evaluation
Our economic analysis was conducted from the perspective
of the Portuguese National Health Service and performed
using the time frame of a complete course of chemotherapy. A cost-minimization approach was chosen based on the
clinical data extracted from two comparative randomized
phase III trials [2,3]. These two studies present an economic evaluation in European countries, using the therapeutic regimens more frequently used in Portugal for the
treatment of NSCLC. In these two studies, patients were
randomized to receive one of ve doublet treatments for
stage IIIB or IV NSCLC (Table 1). Regimens used in the
Comella study included Gem/Cis and Vin/Cis. Regimens used
in the Schiller study were Pac/Cis, Gem/Cis, Doc/Cis, and
Pac/Carb. Except for the longer time to progressive disease observed for Gem/Cis compared with that of Pac/Cis
(4.2 months versus 3.4 months) in the Schiller study, there
were no signicant differences found among the efcacy
outcomes in either study.
On the basis of these clinical results, we performed a
cost-minimization analysis to identify which of the abovementioned treatments is the most cost-efcient (i.e., offers
the lowest cost and thus the greatest monetary value) in
Portugal.
367
Resources utilized
Comella et al. [2]
Gem/Cis
(n = 70)
Vin/Cis
(n = 68)
Gem/Cis
(n = 288)
Pac/Carb
(n = 290)
Doc/Cis
(n = 290)
Pac/Cis
(n = 288)
Dose (mg/m2 )
No. of doses by cycle
Cycle length (weeks)
No. of cycles per patient
Outpatients (%)
No. of drug administrations
1000/100
3/1
4
2.6
100
7.8
30/120
5/1
5
2.5
100
12.5
1000/100
3/1
4
3.4
100
10.3
225/AUC 6
1/1
3
3.6
100
3.6
75/75
1/1
3
3.5
100
3.5
135/75
1/1
3
4.0
0
4.0
10.7
30.0
30.0
3.0
1.7
25.0
27.8
20.0
50.0
20.0
3.4
26.5
10.7
30.0
33.0
8.6
1.7
25.0
7.7
2.0
9.0
24.8
1.0
18.3
17.8
1.0
21.0
5.0
2.0
29.0
24.7
2.0
24.0
5.0
1.0
33.8
23.3
16.0
8.0
11.7
23.3
21.0
8.0
12.2
22.2
16.0
8.0
12.0
23.4
6.0
2.0
13.1
23.4
14.3
6.0
11.1
23.4
14.3
6.0
12.2
[6,7]), and discounting rates were not applied since the time
horizon did not exceed 1 year. Costs (at year 2003) are presented in euros (D ), and related only to branded drugs. Labs,
diagnostic, or monitoring tests were assumed to be equal
across the doublets, and were not included in the cost comparison.
Chemotherapy acquisition cost was estimated as the drug
cost per cycle multiplied by the average number of cycles
received per patient based on trial data. Total chemotherapy dose and cost were based on an average body surface
area of 1.8 m2 per patient and used the following formula:
sum of all cost components = cost of chemotherapy acquisition + cost of chemotherapy administration + cost of hospitalization + cost of other medical resources. The cost of
chemotherapy administration was calculated by multiplying the number of doses used per cycle by the unit cost
of inpatient or outpatient administration, depending on the
regimen. DRG data was used to estimate the cost of administering platelet transfusions. Cost of hospitalization per
patient was calculated by summing the products obtained
from the percentage of patients hospitalized times the cost
per hospital episode for each type of adverse event. The
costs for other medical resources were estimated by multiplying the expected cost per patient by the number of
patients requiring the intervention. The hospital visit cost
was computed as the average cost of one central hospital
visit and one oncology hospital visit.
368
3. Results
Fig. 1
Table 2
Component
Vin/Cis
(n = 68)
Pac/Carb
(n = 290)
Doc/Cis
(n = 290)
Pac/Cis
(n = 288)
2330
362
2004
2155
580
3071
3065
476
2219
6919
166
1478
4288
163
1541
4642
882
1830
1351
295
695
19
342
1442
308
695
22
417
1323
303
660
18
342
1444
330
697
6
412
1418
280
696
16
426
1445
307
697
16
426
Total cost
Incremental cost vs. Gem/Cis
6046
7247
+1201
7083
10008
+2925
7409
+326
8800
+1717
a Hospitalization costs separated by adverse event was not available. GREAT software only provides the aggregated cost for
hospitalizations.
369
Pac/Carbb (n = 290)
Doc/Cisb (n = 290)
Pac/Cisb (n = 288)
Cost of GEM/CIS
10%
+10%
1425
976
3231
2618
625
26
2015
1418
No. of cycles
20%
+20%
1172
1231
2325
3646
171
497
1336
2085
988
1414
3073
2777
462
190
1795
1639
1157
1245
2987
2863
389
263
1636
1798
Administration of chemotherapy
100% inpatient
2014
100% outpatient
1201
1769
2925
+842
326
+59
1021
a
b
Table 4
Country
Gem/Cis (n = 70)
Vin/Cis (n = 68)
Gem/Cis (n = 288)
Pac/Carb (n = 290)
Doc/Cis (n = 290)
Pac/Cis (n = 288)
France
Germany
Italy
Spain
5640
6999
5310
4072
7472
8143
6500
4899
6551
8250
5972
5082
11893
12265
8640
9750
7135
8329
8121
6512
8694
11052
8082
6746
UKa
7904
[4968]
9959
[6260]
9642
[6061]
13504
[8488]
10053
[6319]
11259
[7077]
Portugal
6046
7247
7083
10008
7409
8800
1 Sterling = D 1.5909 per annual average Bank of England exchange rate for 2002.
370
Fig. 3
Cost distribution for each regimen by country (data from Schiller et al.) [3,4].
4. Discussion
Our study, conducted from the perspective of the National
Health Service of Portugal, identied Gem/Cis as a costsaving alternative when compared with other currently used
combination regimens in Portugal, like Vin/Cis, Pac/Carb,
Pac/Cis, and Doc/Cis, with Pac/Carb being the least costefcient regimen.
According to our results, per patient savings due to adopting the Gem/Cis regimen as a rst-line treatment for NSCLC
would range from D 326 (compared to Doc/Cis) to D 2925
(compared to Pac/Carb). These results were submitted to
sensitivity analyses, which conrmed that Gem/Cis offers
the greatest value for money under almost all of the
hypothesized scenarios.
Despite the similarity in efcacy results for the platinumbased doublet regimens in the Comella and Schiller studies,
we hypothesized that variable toxicity proles may lead to
possible differences among the regimens in hospitalization
costs. Our evaluation showed that Gem/Cis was associated
371
Acknowledgement
The study and this publication were funded by Lilly Portugal
Produtos Farmac
euticos, Portugal.
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