Czytelnia Medyczna » Farmakoekonomika » 3/2003 » Cost-effectiveness of gemcitabine in combination with cisplatin versus vinorelbine in combination with cisplatin in the treatment of non-small cell lung cancer in Poland: a retrospective economic analysis of clinical trials

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Tilden D¹, Aristides M¹, Stynes G¹, Orlewska E², Krzakowski M³, Jassem J⁴, Załuski J⁵, Włodarczyk H⁵

Cost-effectiveness of gemcitabine in combination with cisplatin versus vinorelbine in combination with cisplatin in the treatment of non-small cell lung cancer in Poland: a retrospective economic analysis of clinical trials

¹M-TAG Hammersmith, United Kingdom
²Centre for Pharmacoeconomics, Warsaw, Poland
³Oncology Centre – M. Skłodowska-Curie Institute, Department of Lung and Thorax Cancer, Warsaw, Poland
⁴Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland
⁵Great Poland Center of Cancer, Department of Chemotherapy, Poznan, Poland

Summary
Objective: To evaluate the cost-effectiveness of gemcitabine/cisplatin (Gem/Cis) vs vinorelbine/cisplatin combinations (Vin/Cis) in the treatment of non small cell lung cancer (NSCLC) in Poland.
Methods: Costs and effectiveness of Gem/Cis and Vin/Cis were based on resource and outcome data from published head-to-head clinical trials and local data on health-care resource utilisation and unit cost. Only direct medical costs resulting from the chemotherapy (acquisition and administration), concomitant medication and treatment of adverse events were assessed. Information on current treatment practice was obtained from the Polish oncologist expert panel. The perspective of health-care payers and time horizon of 1 year was considered. The one-way sensitivity analyses were performed.
Results: The results of clinical trials show no statistically significant differences between Gem/Cis and Vin/Cis in terms of overall survival. The total direct medical cost was 17 132 PLN and 17 023 for Gem/Cis and Vin/Cis respectively. Chemo-therapy acquisition cost was the major cost factor and was accounted for 64% and 50% of total cost for Gem/Cis and Vin/Cis respectively. The higher acquisition costs of Gem/Cis are offset by lower drug administration costs and lower rates of hospitalisation for Gem/Cis patients. The results of sensitivity analyses show that, in most circumstances, the Gem/Cis combination is broadly similar in cost to Vin/Cis.
Conslusion: Given the proven equal efficacy in treatment, and the higher levels of toxicity associated with the vinorelbine regimen, the analysis supports a cost-effectiveness argument for the use of gemcitabine in the treatment of advanced NSCLC.

Key words: non-small cell lung cancer, gemcitabine, cost effectiveness analysis.

Polecane książki z księgarni medycznej BORGIS:

Zaburzenia gospodarki wodno elektrolitowej i kwasowo zasadowej

Podręcznik medycyny klinicznej opartej na zasadach EBM

Geneza gorączki

INTRODUCTION

The treatment of non-small cell lung cancer (NSCLC) remains a difficult and controversial area in oncology. It is particularly appropriate to address topics in lung cancer in that this malignancy continues to be a major international health problem, is the leading cause of cancer related death in many countries, and its incidence is rising in most countries. This study will consider issues in the treatment of patients with advanced lung cancer, a group that includes the majority of patients with this disease. As the use of palliative chemotherapy increases, the costs of cancer chemotherapy will escalate, and it is important to understand how these costs relate to benefits.

This paper presents an adaptation of the economic evaluation performed for the National Institute of Clinical Excellence (NICE) in England and Wales. The focus of the report is on the comparison between gemcitabine/cisplatin and vinorelbine/cisplatin in the Polish setting. These represent the new wave of therapies used in NSCLC. Until now, there has been little European evidence on the relative cost-effectiveness of these new regimens.

EPIDEMIOLOGY

Lung cancer is in Poland the most prevalent malignant tumor among men (29.4%) and among women remains the second localisation (7%) (1-3). There are more than 20 000 new cases annually (4). Lung cancer remains the leading cause of cancer-related mortality in both sexes, accounting for every third and every tenth of cancer death in Polish men and women, respectively. Approximately 80% of lung cancers are of the non-small-cell (NSCLC) histology (4). At the time of diagnosis 50-55% of patients have advanced or metastatic disease (5). The long term prognosis is poor: the median survival of patients with untreated NSCLC is only four-five months, with survival rate at one year of only 10% (6).

THE ROLE OF CHEMOTHERAPY IN THE TREATMENT OF NSCLC

The evidence from randomized clinical trials showed conclusively that administration of chemotherapy offers a significant, but modest, survival advantage for all stages of NSCLC (6-9). In early-stage disease, postoperative cisplatin-based adjuvant chemotherapy is associated with a hazards ratio of 0.87, which is equivalent to an absolute survival benefit of 5% at 5 years. For patients with more advanced tumors, the hazards ratio for chemotherapy is 0.73, with 10% absolute improvement in survival at 1 year over supportive care alone.

In addition randomized studies comparing chemotherapy with the best supportive care have shown that chemotherapy reduces symptoms and improves the quality of life (10, 11).

A number of chemotherapy agents have been shown to be active in NSCLC (4, 12, 13). There is quite a widespread agreement about the inclusion of cisplatin in any first-line chemotherapy combination (8, 9). However, although cisplatin remains an important component of the most active regimens, paradoxically it may be this agent that limits the use of chemotherapy in NSCLC. In the last decade, the introduction into clinical practice of several new drugs with proven antitumor activity in NSCLC patients and reduced toxicity has renewed the interest of clinical oncologists in the treatment of this disease. Among newer active drugs, vinorelbine, gemcitabine and taxanes are the most promising, in view of their intrinsic cytotoxic activity and of their nonoverlapping toxicity and potential synergism when combined with cisplatin (13). The results obtained in phase II and III studies (14-42) showed that in advanced NSCLC:

1) the addition of a new agent to cisplatin improves both survival and quality of life when compared with cisplatin alone,

2) new agents in monotherapy demonstrate similar activity as standard cisplatin-based combination chemotherapy,

3) new agents in combinations with cisplatin (third generation regimens) provide at least significantly higher response rate and longer time to disease progression when compared with standard cisplatin-based combination chemotherapy,

4) there are no significant differences in survival among patients who received various third-generation regimens in head-to-head studies. However, there are differences in toxicity profile among treatment groups.

CLINICAL NEED AND PRACTICE

Most patients with NSCLC in Poland receive BSC and palliative radiotherapy. This may be due, in part, to a perception amongst health professionals and patients that chemotherapy is toxic and ineffective for the treatment of NSCLC. It is estimated that in Poland 4000-5000 patients diagnosed with NSCLC are potential candidates for chemotherapy (4). The most frequently used chemotherapy regimens are "standard” cisplatin-based regimens such as PE (etoposide/cisplatine), MIC (mitomycin, ifosfamide, cisplatin) and MVP (mitomycin, vindesine or vinblastine and cisplatin) (4).

According to clinical guidelines gemcitabine, vinorelbine and paclitaxel each all combined with a platinum analogue can be considered as part of first-line chemotherapy options for advanced (stage III and IV) NSCLC patients. Docetaxel monotherapy should be considered as a second line treatment in patients with locally advanced or metastatic NSCLC.

THE AIM OF THE STUDY

The aim of the study was to evaluate the cost-effectiveness of gemcitabine in combination with cisplatin (GemCis) versus vinorelbine with cisplatin (VinCis) in the treatment of patients with NSCLC stage IIIB and IV in the Polish setting. Vinorelbine/cisplatin regimen is in Poland the most commonly used novel cisplatin based doublet in NSCLC.

METHODS

The analysis builds on the foundations of the original analysis to NICE (National Institute of Clinical Excellence). The main modifications are adjustments for the costs of chemotherapy drug acquisition and administration costs, and inclusion of costs for a wider range of hospitalisations due to adverse events. There are also adjustments to the unit costs, and to resource use associated with radiotherapy and concomitant medications.

Data sources

Data on health outcome (expected survival), adverse event rates, specification for each regimen and the number of treatment cycles derived from the published head-to-head clinical trial (41). This trial randomised NSCLC patients to gemcitabine/cisplatin or vinorelbine/cisplatin and the interim analysis was carried out when 60 patients per arm were evaluable for survival. All patients had locally advanced or metastatic NSCLC (42% stage IIIB, 58% stage IV), were aged =70 years and had performance status =1 (41).

Where utilisation of particular health care resources was not available from the clinical trial report, values were derived from a search of the literature. The literature providing additional resource utilisation data included approved product information, Scagliotti et al. (42) (a clinical trial comparing gemcitabine/cisplatin, paclitaxel/carboplatin and vinorelbine/cisplatin), Schiller et al. (43) (a clinical trial comparing gemcitabine/cisplatin, paclitaxel/carboplatin, paclitaxel/cisplatin and docetaxel/cisplatin) and Rubio Terres et al. (44) (an unpublished modelled evaluation of gemcitabine/cisplatin compared with paclitaxel/carboplatin and vinorelbine/cisplatin).

Data on health-care utilization associated with country-specific treatment patterns were obtained from the panel of clinical experts through a survey performed in 3 Polish oncological centers (in Warsaw, Poznań and Gdańsk), which manage above 50% of patients in Poland under treatment for NSCLC. The questionnaire collected information on current treatment practices were ratified at the expert panel meeting.

Study design

The analysis was developed from payer´s perspective. Only direct health care costs are included in each analysis. Therefore, costs associated with lost time at paid work, at unpaid work, and lost leisure activities for patients and carers are excluded from the analyses. Costs associated with social services in support care are also excluded. Any potential for reducing such costs due to superior treatment of advanced NSCLC should be considered qualitatively, even if costs are not quantified.

An intention-to-treat approach to costing has been adopted, where resources used to treat eligible patients randomised to study therapy are valued. In this way, any potential inter-relationships between resource use and outcomes are accounted for. In each evaluation of gemcitabine/cisplatin, costs of chemotherapy drugs and administration are assumed to be incurred within an initial 12-month period and therefore remain undiscounted. All other costs also remain undiscounted, as it is difficult to ascertain which costs are incurred beyond the first year. The absence of discounting is unlikely to make a substantial difference, as the most significant cost components (chemotherapy, other drugs, hospitalisation) are all incurred in the initial 12 months. All costs were calculated in 2002 values.

Dosage regimens for the two therapies are shown in table 1.

Table 1. Chemotherapy regimens used in the reference clinical trial (41).

GEM/CIS combination	Gemcitabine	Cisplatin
Protocolled dose	1000 mg/m2	100 mg/m2
Dispensed dosea	1800 mg	180 mg
Doses per cycle	3	1
Cycles per patientb	2.6	2.6
Length of cycle	28 days	28 days
Day(s) of administration	1, 8, 15	2
VIN/CIS combination	Vinorelbine	Cisplatin
Protocolled dose	30 mg/m2	120 mg/m2
Dispensed dosea	54 mg	216 mg
Doses per cycle	5	1
Cycles per patientb	2.5	2.5
Length of cycle	35 days	35 days
Day(s) of administration	1, 8, 15, 22, 29	1, 29, then every subsequent 42 days

^a Dispensed doses assume a mean body surface area (BSA) of 1.8 m². This is consistent with the BSA of patients enrolled in the clinical trial
^b Average number of cycles per patient as reported in the clinical trial

RESULTS

Health outcomes

Health outcomes are summarised in Figure 1. Slightly greater values were observed with gemcitabine/cisplatin compared with vinorelbine/cisplatin in the median survival time (42 weeks versus 35 weeks) and response rates (30% versus 25%). Significance testing was not conducted on these interim data but it is noteworthy that the vinorelbin/cisplatin arm was stopped due to an early stopping rule for unfavourable survival. As statistical significance of the difference was not reported for efficacy end-points, the conservative assumption of equal efficacy across treatment arms was made. The economic evaluation based upon the Comella et al.trial (41) thus takes the form of a cost-minimisation analysis.

Figure 1. Treatment groups and health outcomes in the reference clinical trial (41).

Costs

A comprehensive set of direct health care costs was included in these evaluations. This was composed of:

l Acquisition of the chemotherapy

l Administration of the chemotherapy

l Hospitalisations associated with adverse events (febrile neutropenia, thrombocytopenia, anaemia, nausea and vomiting, neuropathy and events requiring IV antibiotics)

l Costs of other medical resources (visits to health care professionals, radiotherapy, transfusions of blood products and the use of concomitant medications)

Costing of chemotherapy drug acquisition

Acquisition of chemotherapy is based on the expected drug cost per cycle of chemotherapy multiplied by the average number of cycles administered as reported in the respective trial (tab. 2).

Table 2. Number and cost of chemotherapy vials used in the Comella et al. trial (41).

Regimen	Regimen cost per patienta (PLN)	Drug	Drug cost per patient (PLN)	Size of vial	Number of vials per patient	Unit cost per vial (PLN)
GEM/CIS	10975.77	Gemcitabine	10790.91	1000 mg 200 mg	7.8 31.2	756.85 156.65
GEM/CIS	10975.77	Cisplatin	184.86	50 mg 25 mg 10 mg	7.8 2.6 2.6	18.20 11.20 5.30
VIN/CIS	8558.50	Vinorelbine	8350.00	50 mg 10 mg	12.5 12.5	550.00 118.00
VIN/CIS	8558.50	Cisplatin	208.50	50 mg 10 mg	10 5	18.20 5.30

^a Regimen cost per patient = sum (type and size of vial x unit cost per vial)

Costing of chemotherapy administration

Cost of chemotherapy administration (tab. 3) was calculated by multiplying expected number of total doses administered by the unit cost per drug administration (the unit cost per drug administration is weighted by the expected number of inpatient and outpatient administrations).

Table 3. Number and cost of chemotherapy administrations in the Comella et al. trial (41).

Regimen	Admin. cost per patienta (PLN)	Admin. days per cycle	Cycles per patient	Admin. days per patient	IP admin. daysb	OP admin. daysc	OP admin. cost per day (PLN)
GEM/CIS	1287.00	3	2.6	7.8	0	7.8	165.00
VIN/CIS	2062.50	5	2.5	12.5	0	12.5	165.00

^a Admin. cost per patient = (inpatient admin. days x unit cost of inpatient admin days) + (outpatient admin. days x unit cost of outpatient admin days)
^b IP: Inpatient
^c OP: Outpatient

Costing of hospitalisation due to adverse events

The cost of hospitalization due to adverse events was calculated by multiplying the expected number of patients hospitalised with an adverse event as reported by the respective clinical trial (or other source as appropriate) by the expected cost per hospital episode (tab. 4.)

Table 4. Percentage of patients hospitalised for each adverse event and the cost of hospitalisations.

Adverse event	Unit cost (PLN)	Gemcitabine/Cisplatin		Vinorelbine/cisplatin
Adverse event	Unit cost (PLN)	Percentage	Cost (PLN)	Percentage	Cost (PLN)
Febrile neutropenia	4142.00	10.7%a	442.37	27.8%b	1151.48
Thrombocytopenia	1326.00	30.0%c	397.80	20.0%c	265.20
Nausea/vomiting	613.00	30.0%c	183.90	50.0%c	306.50
Neuropathy	2321.00	3.0%f	69.63	20.0%g	464.20
Anaemia	831.00	1.7%a	14.13	3.4%d	28.25
IV antibiotics	1454.00	25.0%a	363.65	26.5%e	385.93
Hospitalisation cost/patienth			1471.47		2601.56

^a Schiller et al. (42)
^b Product information
^c Comella et al. (41)
^d Scagliotti et al. (43)
^e Average of other novel regimens
^f Average of Comella et al. (41), Rubio Terres et al. (44), Schiller et al. (42) results
^g Average of Rubio Terres et al. (44), Schiller et al. (42) results
^h Hospitalisation cost per patient = sum (probability of suffering each adverse event x unit cost of each adverse event)

Cost of other medical resources

Cost of other medical resources includes visits to health care professionals (tab. 5), radiotherapy (tab. 6), transfusions of blood and blood products (tab. 7) and the use of concomitant medications (tab. 8).

Table 5. Cost of GP visits for patients receiving chemotherapy for advanced NSCLC in the Comella et al. (41).

	Gemcitabine/Cisplatin	Vinorelbine/cisplatin
Time to progression	4.5 months	4.0 months
Overall survival	8.1 months	8.1 months
Number of GP visits	11.7	12.2
Cost per visit	PLN 35.00	PLN 35.00
Cost of GP visitsa	PLN 409.50	PLN 427.00

^a Cost of GP visits per patient = assumed number of visits x unit cost per visit

Table 6. Cost of patients requiring radiotherapy.

	Gemcitabine/cisplatin	Vinorelbine/Cisplatin
Percentage of patients requiring radiotherapy	23.3%b	23.3%b
Administration cost of radiotherapy	PLN 7717.00	PLN 7717.00
Cost of radiotherapya	PLN 1800.63	PLN 1800.63

^a Cost of radiotherapy per patient = probability of requiring radiotherapy x administration cost of radiotherapy
^b Comella et al. (41)

Table 7. Cost of blood product transfusions over the course of therapy (41). Unit costs of blood products can be found in the table in the appendix.

	Gemcitabine/cisplatin	Vinorelbine/Cisplatin
Packed red blood cells	16%a	21%a
Cost per patientb	PLN 212.00	PLN 212.00
Platelets	8%a	8%a
Cost per patientc	PLN 372.00	PLN 372.00
Expected cost per patientd	PLN 63.68	PLN 74.28

^a Scagliotti et al. (43)
^b A cost of PLN 212.00 is based on a 600 ml transfusion (PLN 100.00 per 300 ml) and a cost to perform the transfusion of PLN 12.00
^c A cost of PLN 372.00 is based on a 300 ml transfusion (PLN 60.00 per 50 ml) and a cost to perform the transfusion of PLN 12.00
^d Cost of blood transfusions per patient = (probability of requiring packed red blood cells x cost of cells per patient) + (probability of requiring platelets x cost of platelets per patient)

Table 8. Units and costs of concomitant medications in patients receiving novel chemotherapy for NSCLC in the Comella et al. (41). Unit costs of concomitant medications can be found in the table in the appendix.

Medication	Gemcitabine/Cisplatin	Vinorelbine/cisplatin
Tropisetron (5 mg infusion followed by 5 mg daily for 5 days)
5 mg vials	3	4
5 mg tablets	15	20
Cost (tropisetron)	PLN 1045.32	PLN 1393.76
Saline (units)	12351	17563
Cost (saline)	PLN 53.36	PLN 75.87
Chlorpromazine HCl (10 mg, 6 daily, 5 days)
Units per patient	90	120
Cost (chlorpromazine)	PLN 9.00	PLN 12.00
Laxatives
Units per patient	30	30
Cost (laxatives)	PLN 16.50	PLN 16.50
Total pre/post medsa	PLN 1124.18	PLN 1498.13

^a Cost of concomitant medication per patient = sum (expected unit requirement of each medication x unit cost of each medication)

In the comparisons of gemcitabine/cisplatin with vinorelbine/cisplatin the visits to medical professionals were not reported. It was assumed the costs for visits to nurses and other professionals (excluding GPs) were identical between the treatment groups. On the basis of opinion of Polish oncology experts it is assumed that patients will visit a GP once monthly during treatment (in addition to all the chemotherapy and associated visits to oncologists), and twice monthly for palliative therapy – symptomatic control and palliation – after disease progression.

As no data were collected regarding concomitant medications in relevant trials or other publications, only medications used prior to chemotherapy administration and those used after chemotherapy to ameliorate the effects of the chemotherapy are included.

TOTAL COSTS BY TREATMENT GROUP

Patients treated with gemcitabine/cisplatin were associated with approximately equal total treatment costs compared to those treated with vinorelbine/cisplatin. The average additional cost associated with gemcitabine/cisplatin was PLN 110 per patient. A summary of results from the economic evaluation based on the Comella et al.trial (41) are presented in table 9.

Table 9. Costs associated with novel chemotherapy regimens for NSCLC.

Resource component	GEM/CIS	VIN/CIS	Incremental
Chemotherapy	PLN 10976	PLN 8559	+ PLN 2417
Drug administration	PLN 1287	PLN 2063	- PLN 776
Hospitalisations	PLN 1471	PLN 2602	- PLN 1130
Other medical resources	PLN 3398	PLN 3800	- PLN 402
Total	PLN 17132	PLN 17023	+ PLN 110

The gemcitabine/cisplatin regimen is associated with approximately similar total costs over the course of therapy to the vinorelbine/cisplatin regimen. The higher costs of chemotherapy associated with the gemcitabine/cisplatin regimen are offset by lower costs of drug administration and fewer hospitalisation costs. Acquisition of gemcitabine is more expensive, but the drug requires less time and physical resources to administer. In addition, vinorelbine is linked with higher levels of toxicity and, hence, greater expenditure on subsequent medical attention. This is demonstrated in Figure 2, which shows the relative contribution of each resource category to the total cost of each treatment group.

Figure 2. Contribution of each resource category to total cost of therapy.

SENSITIVITY ANALYSIS

A range of sensitivity analyses was performed, to test the effect of changes in the value of key variables and assumptions on the overall results. As this economic analysis has been primarily a costing exercise, most variation occurs in the cost variables and assumptions. The main drivers of cost differences between the regimens are the costs of chemotherapy drugs, chemotherapy administration, hospitalisations due to adverse events and concomitant medication use. Resource use and unit costs in each of these categories are varied to test the impact on overall results.

Table 10 presents the incremental cost of gemcitabine/cisplatin when the magnitude of each major cost component is varied. The cost of chemotherapy medications has the biggest impact on the cost disparity between the regimens.

Table 10. Sensitivity analysis: Impact of the costs of major health care resource on the incremental cost of Gem/CIS relative to VIN/CIS.

Change from baseline	GEM/CIS	VIN/CIS	Incremental Cost of GEM/CIS relative to VIN/CIS
Baseline	PLN 17132	PLN 17023	+ PLN 110
Chemotherapy costs: + 10% - 10%	PLN 18230 PLN 16035	PLN 17878 PLN 16167	+ PLN 35 - PLN 132
Drug administration: + 10% - 10%	PLN 17261 PLN 17004	PLN 17229 PLN 16816	- PLN 32 + PLN 187
Hospitalisations: + 10% - 10%	PLN 17279 PLN 16985	PLN 17283 PLN 16762	- PLN 3 + PLN 223
Other medical resources: + 10% - 10%	PLN 17472 PLN 16792	PLN 17403 PLN 16643	+ PLN 69 + PLN 150

Table 11 presents a sensitivity analysis of various assumptions and parameters in the cost analysis.

Table 11. Sensitivity analysis of various model parameters and assumptions.

Change from baseline	GEM/CIS	VIN/CIS	Incremental Cost of GEM/CIS relative to VIN/CIS
Baseline	PLN 17132	PLN 17023	+ PLN 110
Chemotherapy drug costs only	PLN 10,976	PLN 8,559	+ PLN 2,417
No. of chemotherapy cycles per patient - by 20% + by 20%	PLN 14679 PLN 19585	PLN 14897 PLN 19148	- PLN 218 + PLN 437
Unit costs of hospitalisations - by 20% + by 20%	PLN 16838 PLN 17427	PLN 16502 PLN 17543	+ PLN 336 - PLN 116
Unit cost of chemotherapy administration - by 20% + by 20%	PLN 16875 PLN 17390	PLN 16610 PLN 17435	+ PLN 265 - PLN 45
Administration of chemotherapy 100% inpatient 100% outpatient	PLN 18965 PLN 17132	PLN 19960 PLN 17023	- PLN 995 + PLN 110

It is clear that some changes will have more impact on overall costs than others. The more noticeable changes in overall cost occur if non-chemotherapy related costs are excluded from the analysis and when the mode of chemotherapy administration is varied.

The incremental results show that, in most circumstances, the vinorelbine/cisplatin combination is broadly similar in cost to gemcitabine/cisplatin. Also, it may be that incomplete comparative evidence on adverse events has resulted in a slight underestimate of the cost associated with vinorelbine/cisplatin adverse events. A comparison of the gemcitabine/cisplatin and vinorelbine/cisplatin adverse event profiles suggests that the latter is associated with a higher frequency of treatment-related adverse events and therefore the potential for greater costs in the management of adverse events. This will further increase the cost of vinorelbine/cisplatin relative to gemcitabine/cisplatin.

These sensitivity analyses demonstrate the robustness of the original results. Overall, gemcitabine/cisplatin is approximately cost-neutral with respect to the vinorelbine/cisplatin regimen in nearly all sensitivity analyses. Given the trend to improved overall survival and improved progression-free survival, gemcitabine/cisplatin is potentially a dominant alternative to vinorelbine/cisplatin for the treatment of advanced NSCLC.

DISCUSSION

The economic evaluation based on the Comella et al.clinical trial (41) show that in most circumstances the vinorelbine/cisplatin combination is broadly similar in cost to gemcitabine/cisplatin. The higher acquisition costs of gemcitabine are offset by lower drug administration costs and lower rates of hospitalisation for gemcitabine/cisplatin patients. Given the proven equal efficacy in treatment, and the higher levels of toxicity associated with the vinorelbine regimen, the analysis supports a cost-effectiveness argument for the use of gemcitabine in the treatment of advanced NSCLC.

The results of the presented economic evaluation should be interpreted within the limitation of the methods used and data on which they are based. Outcome and resource utilization data for the analysis were based on published head-to-head clinical trial, as best evidence for comparative clinical performance, and to minimise other potential measurement bias. There are two main problems linked with this approach: the transferability of data from country to country and the transferability of results from clinical trial setting to clinical practice and.

Polish patients were not enrolled in head-to-head trials which are used in the economic evaluation. As no Polish direct clinical and economic data were available, we decided to use data from international clinical trial and to supplement information on the use of resources obtained from abroad with Polish data to adjust and adapt the analysis to Polish conditions. Data on health outcome and toxicity can be extrapolated to the Polish health care setting, because clinical data in most diseases can be considered not to be country specific (45-47). External clinical opinion leaders agreed with this assumption for NSCLC. Specification for each regimen and the number of treatment cycles is associated with the health outcome and toxicity, so should remain as in the relevant clinical trials. In contrast to clinical data, economic data must be country specific. In the presented evaluations data on adverse events treatment costs correspond with Polish conditions, as they were collected in a survey performed in representative Polish oncology departments and reflect those achieved in actual practice. Costing information consisted of actual costs and prices or tariffs and was obtained from official price and tariff lists in Poland.

Although there is the possibility of protocol-driven costs being included in the analysis, the authors take the view that resource use reported in each trial, including hospitalization and visits to healthcare professionals, represents the satisfaction on a health need rather than trial protocol. In the disease area under consideration, this is especially true for hospitalizations and hospital visits (two main cost drivers), which are due primarily to dealing with treatment-related adverse events.

It is acknowledged that there are limitations to the generalisability of analyses which are based on clinical trials. However, any limitations with this approach must be considered in the light of limitations of alternative approaches where analysts make systematic adjustments to the data or pursue predominantly modeled analyses. These analytical "trade-offs” are recognized in the Australian pharmacoeconomic guidelines for reimbursement (48). In these guidelines, analyses based on head-to-head trials are seen as a pivotal step in value-for-money assessment which can later be complemented by modeled analyses.

Acknowledgements

This study was carried out with a research grant from Eli Lilly Company.

Appendix: UNIT COSTS

All Polish unit costs (tabs. A.1, A.2, A.3) were provided in Polish Zloty (1 EURO = 4 PLN).

Table A.1. Unit costs of chemotherapy medications derived from hospital pharmacy price list (2002).

Medication	Cost (PLN)	Reference
Gemcitabine 1000 mg vial	756.85	Hospital pharmacy price list (2002)
Gemcitabine 200 mg vial	156.65	Hospital pharmacy price list (2002)
Vinorelbine 50 mg vial	550.00	Hospital pharmacy price list (2002)
Vinorelbine 10 mg vial	118.00	Hospital pharmacy price list (2002)
Cisplatin 50 mg vial	18.20	Hospital pharmacy price list (2002)
Cisplatin 25 mg vial	11.20	Hospital pharmacy price list (2002)
Cisplatin 10 mg vial	5.30	Hospital pharmacy price list (2002)

Table A.2. Unit costs of other medical resources.

Medical resource	Cost (PLN)	Reference
Drug administration
Chemotherapy admin.: inpatient	324-500/day mean: 400	Medical Services Schedule, 2002 (from oncology hospitals)
Chemotherapy admin.: outpatient	70-260 mean: 165	Medical Services Schedule, 2002 (from oncology hospitals)
Hospitalisation episodes
Febrile neutropenia	4142.00	Data from 3 oncology centers, collected using a questionnaire and discussed during a consensus meeting
Thrombocytopenia	1326.00	Data from 3 oncology centers, collected using a questionnaire and discussed during a consensus meeting
Nausea and vomiting	613.00	Data from 3 oncology centers, collected using a questionnaire and discussed during a consensus meeting
Neuropathy	2321.00	Data from 3 oncology centers, collected using a questionnaire and discussed during a consensus meeting
Anaemia	831.00	Data from 3 oncology centers, collected using a questionnaire and discussed during a consensus meeting
IV antibiotics	1454.00	Data from 3 oncology centers, collected using a questionnaire and discussed during a consensus meeting
Other medical resources
Consultation with GP	35.00	Medical Services Schedule, 2002 (from oncology hospitals)
Unit of packed red blood cells (300 ml)	100.00	Local Blood Donation Station price, September 2002
Unit of platelets (50 ml)	60.00	Local Blood Donation Station price, September 2002
Administration of blood products	12.00	Expert opinion
Radiotherapy	7717.00	Medical Services Schedule, 2002 (from oncology hospitals)

Table A.3. Unit costs of other medications derived from hospital pharmacy price list (2002).

Medication	Cost (PLN)	Reference
Tropisetron (5 mg vials)	58.44	Hospital pharmacy price list (2002)
Tropisetron (5 mg tablets)	58.00	Hospital pharmacy price list (2002)
Saline (1 ml)	0.00432	Hospital pharmacy price list (2002)
Chlorpromazine HCl (10 mg tablets)	0.10	Hospital pharmacy price list (2002)
Perphenazine (2 mg tablets)	0.24	Hospital pharmacy price list (2002)
Laxatives (100 mg capsules)	0.55	Hospital pharmacy price list (2002)
Dexamethasone (500 mcg tablets)	0.06	Hospital pharmacy price list (2002)
Chlorpheniramine (4 mg tablets)	1.80	Hospital pharmacy price list (2002)
Cimetidine (200 mg tablets)	1.50	Hospital pharmacy price list (2002)

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Wielka interna Pulmonologia część 2

Piśmiennictwo

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