Cost-Effectiveness of Vinorelbine Alone or Vinorelbine Plus Cisplatin for Stage IV NSCLC

March 1, 1998

Le Chevalier and colleagues have reported results of a randomized controlled clinical trial comparing vinorelbine alone, versus vinorelbine combined with cisplatin, versus standard treatment consisting of vindesine and cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Data on survival in the three study arms and estimates of the resources used to treat these patients were extracted from the publication and inserted into Statistics Canada’s POpulation HEalth Model (POHEM).

ABSTRACT: Le Chevalier and colleagues have reported results of a randomized controlled clinical trial comparing vinorelbine alone, versus vinorelbine combined with cisplatin, versus standard treatment consisting of vindesine and cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Data on survival in the three study arms and estimates of the resources used to treat these patients were extracted from the publication and inserted into Statistics Canada’s POpulation HEalth Model (POHEM). This model includes data on diagnostic methods, treatment, and outcomes appropriate for stage at presentation, health care utilization, and direct care costs ($ Canadian) for best supportive care and for several “standard” chemotherapy regimens used to treat advanced NSCLC. POHEM was then used to model the cost of care per patient and the total burden of cost on the Canadian health care system for each of the chemotherapy treatment strategies and for best supportive care. Based on the published survival curves for each of the vinorelbine regimens, it was possible to estimate the survival gain relative to the standard chemotherapy regimens and to best supportive care, and to estimate their cost-effectiveness as cost per life year gained. Based on this analysis, the most cost-effective standard regimen relative to best supportive care was vinblastine/cisplatin, as it increased average survival while reducing costs by $2,846 per case. Vinorelbine/cisplatin increased survival to a greater degree, but inpatient administration costs associated with the delivery of cisplatin increased treatment costs by $2,983 per case and resulted in a cost-effectiveness ratio of $6,386 per life year gained. As high-dose cisplatin is not routinely administered in the inpatient setting in Canadian institutions, estimates were made of the cost of outpatient administration. The cost of outpatient care was $55 less per case demonstrating that this is the most cost-effective way to administer the regimen. Relative to etoposide/cisplatin and vinblastine/cisplatin, outpatient vinorelbine/cisplatin proved to be cost-effective. Various chemotherapy regimens used in the management of advanced NSCLC all fall within the boundaries of cost-effectiveness generally accepted for health care interventions in Canada. Therefore, cost and cost-effectiveness should not be barriers to the utilization of vinorelbine/cisplatin in Canada.[ONCOLOGY(Suppl 4):18-26, 1998]

In 1996, the Health Protection Branch of Health, Canada, approved the use of vinorelbine (Navelbine, NVB) for the treatment of advanced non-small-cell lung cancer (NSCLC). Among the data that led to this approval was a large European clinical trial that demonstrated that treatment with vinorelbine (Navelbine) in combination with cisplatin (Platinol) (NVB-P) resulted in a higher response rate and longer survival than vindesine plus cisplatin (VDS-P) (P = .04), or vinorelbine (NVB) alone (P = .01).[1] The Ontario Practice Guideline Initiative Lung Disease Site Group (LDSG) reviewed the evidence on the efficacy of vinorelbine alone and in combination with cisplatin and concluded that this new semisynthetic vinca alkaloid was active against NSCLC and, in combination with cisplatin, was superior to standard chemotherapy (VDS-P).[2] Inferentially, it could also be concluded that NVB-P is superior to best supportive care (BSC), as VDS-P was superior to BSC in a National Cancer Institute of Canada (NCIC) randomized controlled clinical trial.[3] The practice guideline developed by the LDSG recommended that vinorelbine/cisplatin be offered to medically appropriate patients with advanced NSCLC after a full discussion with the patient of the potential harms and benefits of treatment. However, all new anticancer drugs are relatively expensive, and there were concerns that this new agent would significantly increase the costs of care of patients with incurable NSCLC. It was, therefore, felt that it would be useful to estimate the total burden of cost of vinorelbine assuming that all metastatic NSCLC patients in Canada were treated. Furthermore, it was felt that information on the relative cost-effectiveness of vinorelbine-based chemotherapy compared to other treatment options would be useful to clinicians who have to make decisions about which patients to treat and which chemotherapy agents to use.

A study was therefore undertaken in collaboration with Statistics Canada using their POpulation HEalth Model (POHEM).[4-6] The economic analyses were possible because detailed information on drug and other resource utilization and raw survival data were available from the trial reported by Le Chevalier et al.[1] In addition, a cost analysis had been undertaken in the NCIC clinical trial (BR.5), which compared vindesine-cisplatin to BSC,[7] and this provided data on hospitalization and follow-up costs in the Canadian context.

Economic Analysis Based on Le Chevalier Results and Population Health Model

Materials and Methods
Statistics Canada is developing a POpulation HEalth Model to simulate the common illnesses of Canadians. In addition to lung and breast cancer, POHEM will eventually incorporate other malignancies, such as colon and prostate cancer, cardiovascular disease, arthritis and dementia. POHEM generates a synthetic cohort of people with the demographic characteristics, risk factor exposures, and health histories typical of Canadians.[4] POHEM assigns synthetic patients to diseases proportional to their incidence in the Canadian population and, for lung cancer cases, with the same distribution of histology and stage as found in Canadian lung cancer cases. The model then assigns data on diagnostic methods, treatment and its outcomes, health care utilization, and direct care costs based on information extracted from provincial health care data bases and individual institutions. The perspective of the costing model is that of the government as payor in a universal health care system.

Each simulated patient in the POHEM lung cancer submodule is assigned a standard set of diagnostic tests, procedures, and visits, including an initial medical contact with a family physician, specialist consultation and diagnostic work-up appropriate for disease stage. For patients presenting with stage IV NSCLC, the number of physician assessments and associated fees were determined from the number of chemotherapy treatments given and the expected number of physician encounters during these treatments. The frequency of visits for patients receiving best supportive care was extracted from the NCIC BR.5 study.[3] The costs of laboratory and imaging studies were estimated from their reported frequency in the methods section of the study protocols and the fees listed in the Ontario Schedule of Benefits. It was assumed that tests were not duplicated and that treatment was uncomplicated.

Chemotherapy-Specific Costs
The European randomized trial provided careful documentation on the dosage and administration schedules of NVB, NVB-P, and VDS-P. [1] From this it was possible to calculate the cost of chemotherapy and its administration. In the study, patients were randomly assigned to one of three regimens: (1) vinorelbine alone at a dosage of 30 mg/m² intravenously (IV) weekly (NVB); (2) vinorelbine, 30 mg/m² IV weekly plus cisplatin, 120 mg/m² on day 1 and day 29, then every 6 weeks (NVB-P); or (3) vindesine, 3 mg/m² weekly for 7 weeks, then every 2 weeks, plus cisplatin at the same dosage and schedule as for NVB-P (VDS-P).

The time spent by pharmacy and nursing personnel in the preparation and administration of the various chemotherapy regimens was determined using the Canadian Management Information System for pharmacy workload[8] and by measuring the time taken to administer NVB and NVB-P in the chemotherapy treatment unit at the Ottawa Regional Cancer Centre (ORCC). Nursing and pharmacy personnel costs were then determined by multiplying the amount of time expended by the hourly salary rate, including benefits, at the ORCC in 1993. Chemotherapy and antiemetic (ondansetron [Zofran]/dexamethasone) drug costs were based on their acquisition costs at the ORCC in 1993. The equipment and supplies necessary to prepare and deliver the chemotherapy were quantified and costed by the pharmacy and nursing staff of the ORCC.

Because etoposide (VePesid)/cisplatin (VP-16-P) and vinblastine (Velban)/cisplatin (VLB-P) have frequently been used by Canadian oncologists who treat non-small-cell lung cancer, it was felt that it would be important to determine the costs of these treatment strategies relative to the vinorelbine-based regimens. The costs associated with the administration of etoposide/cisplatin (etoposide, 100 mg/m² IV on days 1-3; cisplatin, 25 mg/m² on days 1-3 every 3 weeks) and vinblastine/cisplatin (vinblastine, 5 mg/m² IV on days 1 and 8, and cisplatin, 100 mg/m² IV on day 1 every 4 weeks) were estimated using the same approach as described above for NVB and NVB-P.

Hospitalization and Other Costs
In both the NCIC and Le Chevalier studies, high-dose cisplatin was administered in hospital.[1,3] For the purposes of the cost estimates in this study, it was assumed that each hospitalization required 2 days. The daily costs of hospitalization for chemotherapy were based on the actual costs of giving inpatient chemotherapy at the Princess Margaret Hospital in Toronto, Canada, as determined during a previous costing study.[7] These were adjusted to 1993 costs by multiplying the 1984 costs by the increase in the average daily cost of operating tertiary health care facilities in Canada between 1984 and 1993 (a 12.4% increase). Because there are significant barriers to the admission of patients for inpatient chemotherapy, we estimated the costs of NVB-P administration using an outpatient schedule currently used in an NCIC clinical trial (vinorelbine, 30 mg/m² weekly, and cisplatin, 50 mg/m² on days 1 and 8 every 4 weeks).

The cost of radiotherapy in the management of metastatic NSCLC, as well as clinic overhead costs (hotel costs), were extracted from the study of the costs of chemotherapy and best supportive care determined during the BR.5 study[7] and adjusted to 1993 dollars by multiplying by the increase in the consumer price index (41.1%). The cost of best supportive care and the terminal care costs for stage IV chemotherapy-treated patients were extracted from the same study.[7] Importantly, patients who received chemotherapy required less palliative radiotherapy and fewer inpatient bed days. This information was inserted into the model, and we assumed, based on the clinical trial data, that chemotherapy-treated patients, including those receiving NVB and NVB-P, used 17.1 hospital bed days during terminal care, as opposed to 23.6 days for those receiving best supportive care.

Survival Data
In order to estimate the survival gain of various chemotherapy regimens over best supportive care, the survival data for all patients treated with NVB, NVB-P and VDS-P were obtained on computer diskette from the principal investigators of the European trial.[1] Based on these raw data, survival curves were modeled using a Weibull distribution. The survival data for stage IV patients treated in the NCIC BR.5 study were obtained from the NCIC clinical trials office and similarly modeled. Of interest was the fact that the survival curves for stage IV patients treated with VDS-P in the European and NCIC studies were superimposable. Based on other randomized trials in the literature, we assumed that the survival of patients treated with etoposide/cisplatin and vinblastine/cisplatin was the same as that of VDS-P-treated patients.[9,10]

Cost and Cost-Effectiveness
Assuming that all stage IV lung cancer patients in Canada would be treated with chemotherapy and knowing the total number of stage IV patients diagnosed in 1992, we estimated the cost of treating individual patients and the total burden of care for each of the chemotherapy treatment regimens and for best supportive care. The cost-effectiveness of these various approaches was then determined by dividing the total cost of care (including diagnostic work-up, follow-up, relapse and terminal care costs) by the estimated survival gain relative to BSC. We also undertook an analysis of cost-effectiveness relative to the “standard” regimens of vinblastine/cisplatin and etoposide/cisplatin.

This cost analysis was undertaken with financial support from Glaxo Wellcome Inc., Canada. No restraints were placed on the investigators in their conduct of the study and funding was provided to the Ottawa Regional Cancer Centre. The Centre in turn contracted with Statistics Canada for the use of the POHEM microsimulation software and the provision of analytical expertise for the economic analysis.

Results

The cost per case estimates are summarized in Table 1. Remembering that costs include diagnostic work-up, treatment, follow-up, relapse, and terminal care, it can be seen that best supportive care costs $28,617 per patient. Costs for vinorelbine alone, inpatient and outpatient NVB-P, VDS-P, etoposide/cisplatin, and vinblastine/cisplatin are also shown. It is clear from these data that the hospitalization required for high dose inpatient cisplatin substantially increases the cost per case for NVB-P and VDS-P. On the other hand, there is actually a reduction in the total cost per case for vinblastine/cisplatin, etoposide/cisplatin, NVB alone, and outpatient NVB-P. This smaller cost per case results from the decreased terminal care costs for patients treated with chemotherapy (17.1 hospital days) compared with those patients who received best supportive care (23.6 hospital days).

Total Cost and Cost-Effectiveness
If one assumes that all 4,986 new cases of stage IV NSCLC diagnosed in Canada in 1992 are actually treated with chemotherapy, estimates can be made of the total direct care costs to the Canadian health care system. These numbers are summarized in Table 2. It is of interest to point out that the POHEM model projects a significant net reduction in health care costs with the use of vinblastine/cisplatin, etoposide/cisplatin, and NVB alone relative to BSC; the magnitude of these savings ranges from $14.3 million for vinblastine/cisplatin, to $7.1 million for etoposide/cisplatin, to $5.1 million for NVB alone. On the other hand, the model estimates that NVB-P and VDS-P with inpatient cisplatin would result in a net increase in health care expenditure of $14.5 and $18.1 million, respectively. Alternatively, if outpatient NVB-P therapy were to become the regimen of choice, there would be no significant increase in Canadian health care expenditures, but there would be a slight survival gain. Based on these estimates of total cost and the survival of patients in the Canadian and European trials, the cost-effectiveness of the various regimens relative to BSC and standard chemotherapy was calculated. Table 3 shows cost-effectiveness relative to BSC expressed as the cost per life year gained, or as the cost saving per case. Vinblastine/cisplatin and etoposide/cisplatin were the most cost-effective regimens. Both increased average survival by 0.27 years while decreasing the cost per case by $2,865 and $1,418, respectively. Vinorelbine alone increased survival relative to BSC, while saving $1,014 per case. Vinorelbine/cisplatin (either in- or outpatient) increased survival by an average of 0.45 years, but outpatient NVB-P was far less costly than inpatient chemotherapy administration. Vindesine/cisplatin and inpatient NVB-P were the least cost-effective treatment approaches at $13,568 and $6,386 per life year gained, respectively.

When cost-effectiveness analyses were performed with etoposide/cisplatin as standard treatment (Table 4), outpatient NVB-P was cost-effective at $7,450 per life year gained, whereas inpatient NVB-P was much less cost-effective at $23,053. When vinblastine/cisplatin was used as the standard, NVB-P in an outpatient regimen was in the cost-effective range, at $15,171 per life year gained. If all patients with stage IV NSCLC in Canada were to be treated with outpatient NVB-P in lieu of vinblastine/cisplatin as first-line therapy, the increase to the total health care expenditures in Canada could be as much as $14.2 million.

Sensitivity Analysis for Survival
Randomized controlled clinical trials can demonstrate the efficacy of a treatment approach, but patients are usually highly selected and may have better performance status and other more favorable prognostic factors than patients seen in the community. Therefore, we undertook sensitivity analyses, reducing the survival gain of the NVB-P patients by 25% and 50%. We also undertook sensitivity analyses to increase the number of hospital bed days from 17.1 to 23 in the chemotherapy-treated patients. Even with these analyses, outpatient NVB-P remained cost effective, as demonstrated in Tables 5 and 6.

Discussion

For several decades the treatment of metastatic NSCLC has been controversial, and a large segment of the medical profession has felt that chemotherapy is not worthwhile, because of lack of evidence of significant improvement in survival, symptom improvement, and quality of life, and because of concerns about the cost of therapy. The weight of evidence has shifted. Results from multiple randomized controlled clinical trials and three meta-analyses have demonstrated that there is a small, but definite, survival advantage for patients receiving systemic chemotherapy.[11-13] Furthermore, evidence is accumulating of substantial symptom improvement, even though the objective response rate to the current best chemotherapy regimens remains low. A recent randomized controlled clinical trial reported by Cullen et al using mitomycin/ifosfamide (Ifex)/cisplatin chemotherapy in patients with advanced NSCLC demonstrates not only a survival advantage,[14] but improvement in quality of life in the chemotherapy-treated group.[15] Despite all of this evidence, many practitioners are still reluctant to refer patients with advanced NSCLC for treatment, and there remains some hesitancy to treat these patients even among Canadian medical oncologists.[16] Part of this reluctance relates to the perceived high cost of treatment.

It was for these reasons that we used Statistics Canada’s lung cancer model as the framework to determine the costs of managing stage IV NSCLC. Best supportive care was used as the base case and the potential cost impact of offering various systemic chemotherapy regimens was then determined in lieu of a BSC strategy. The randomized trial reported by Le Chevalier et al compared NVB, NVB-P, and VDS-P and demonstrated the superiority of NVB-P to the other interventions.[1] As NVB is viewed as relatively expensive and the inpatient administration of cisplatin is virtually impossible in a fiscally-constrained health care environment, we were interested to know how these interventions would compare in a cost-effectiveness analysis against best supportive care.

Our analysis using the POHEM lung cancer model has clearly shown that inpatient NVB-P is associated with substantially greater costs relative to best supportive care, but it is still relatively cost-effective at $6,386 per life year gained. If all 4,986 patients with stage IV NSCLC diagnosed in 1992 were treated with inpatient NVB-P, the total health care costs in Canada could increase by as much as $14.5 million. This incremental cost argues against the use of inpatient NVB-P, but it must also be realized that only a fraction of all stage IV NSCLC patients ever become candidates for chemotherapy. Many of these individuals are elderly and have important comorbid conditions that preclude the use of systemic therapy. A more realistic estimate of the proportion of patients who might be candidates for systemic therapy would be one third this number.

NVB-P has essentially the same per case outpatient costs as BSC but results in 0.45 years saved. If all 4,986 patients were treated with outpatient NVB-P, there would be the potential for a net saving of $110,000 to the Canadian health care system. Although NVB alone does not prolong survival relative to VDS-P, it is also an option to be considered when compared to best supportive care as it has few toxicities and is less costly, saving $1,014 per case. This approach may be particularly useful in the elderly, medically frail patient who wants treatment but is not a candidate for a cisplatin-based regimen.

Although chemotherapy has not been used routinely in Canada in the management of stage IV NSCLC patients, those who do treat such patients have tended to use regimens such as etoposide/cisplatin or vinblastine/cisplatin. In fact, randomized studies have demonstrated equivalency between these regimens and VDS-P.[9,10] If these trial results are true and all three regimens produce equivalent survival, then vinblastine/cisplatin and etoposide/cisplatin are the most cost-effective of all treatment regimens studied compared to BSC. Because of the observation that chemotherapy reduces the number of hospital bed days, chemotherapy-treated patients in the model are assigned fewer bed days for terminal care than those receiving BSC. On this basis, either of these regimens could potentially result in a reduction in overall health care costs. This would amount to a saving of up to $2,865 per case or a net saving of up to $14.3 million, if vinblastine/cisplatin were the chemotherapy regimen of preference. For etoposide/cisplatin, the saving per case would be $1,418 for a maximum potential saving of $7.1 million. It is clear that in all comparisons, VDS-P is the most costly regimen, with an incremental cost per case of $3,623 relative to BSC. Despite its previously demonstrated superiority in a randomized controlled clinical trial in Canada, its toxicities and the difficulty of accessing hospital beds for the administration of high-dose cisplatin have curtailed the use of VDS-P in Canada.

When cost-effectiveness analyses were performed with etoposide/cisplatin as standard treatment (Table 4), outpatient NVB-P was cost-effective at $7,450 per life year gained, whereas inpatient NVB-P was much less cost- effective at $23,053. When VLB-P was used as the standard, NVB-P in an outpatient regimen was in the cost-effective range, at $15,171 per life year gained. If all patients with stage IV NSCLC in Canada were to be treated with outpatient NVB-P in lieu of VLB-P as first-line therapy, there would be the potential to increase the total health care expenditures in Canada by $14.2 million. Again, recognizing that only a minority of metastatic NSCLC patients will be candidates for systemic chemotherapy, the actual incremental cost is more likely to be in the range of $3 to $4 million. This should be possible to absorb within a national health care budget estimated to be $71.7 billion in direct care costs.[17]

As with any model, POHEM has some limitations. First, it does not completely account for the complications of treatment and their costs. When the lung cancer model was being developed, we found a general lack of information on the frequency of complications of therapy and the resources used in managing surgical and radiation complications or chemotherapy-related side effects, such as nausea and vomiting or febrile neutropenia. However, the length of stay for chemotherapy-treated patients was obtained from the BR.5 study data and this included chemotherapy- and non-chemotherapy-related admissions. The report by Le Chevalier et al documents the frequency and severity of chemotherapy toxicities experienced during the trial but lacks detail concerning the amount of hospitalization required to manage these toxicities or the resources consumed in treating them.[1] It was impossible, therefore, to measure these costs. In a recent study by Smith et al, who estimated the cost-effectiveness of the Le Chevalier trial in the American health care environment, the cost of toxicities was estimated to be about 5% of the total health care costs.[18] Therefore, the degree to which we may have underestimated the true cost of care is likely to be small.

A second area of expenditure that is not well accounted for are costs incurred by patients outside of institutions. These costs would include home care visits, family physician involvement in palliative care, terminal care costs outside of acute care hospitals, and indirect costs incurred by patients in travelling to treatment centers for care. The failure to capture these costs in the model will tend to underestimate the total economic burden of lung cancer.

We made the assumption in this analysis that the number of terminal care hospital days for chemotherapy-treated patients would be reduced from 23 days for best supportive care to 17.1 days, based on observations made during an NCIC clinical trial in 1984. It might be argued that pressures to optimize bed utilization may have narrowed this gap in bed utilization. To determine if such a change had occurred, we obtained the data from the Manitoba Cancer Registry, which confirmed that the average number of bed days used by stage IV NSCLC patients during the last 3 months of life continues to be 23 days, if no chemotherapy is administered.[personal communication, J. M. Berthelot, 1997] The registry data also confirmed that chemo- therapy-treated patients use approximately 6 fewer hospital bed days than BSC patients, as was observed in the clinical trial setting. Even when one assumes that the length of hospitalization for terminal care has shortened, sensitivity analyses show that combination chemotherapy, although less cost-effective, is still well within the range regarded as cost-effective for a health care intervention in Canada[19] or the United States.[20,21]

Until recently, those who treated advanced NSCLC in Canada most commonly used either etoposide/cisplatin or vinblastine/cisplatin. Therefore, it was felt that estimates of cost-effectiveness should be made for the newer regimens against these two regimens as the base case. When the analyses were performed with etoposide/cisplatin as standard treatment (Table 6), outpatient NVB-P was cost-effective, whereas inpatient NVB-P was much less so, at $23,053 per life year gained. With vinblastine/cisplatin as the base case, outpatient NVB-P was in the cost-effective range, at $15,171 per life year gained. If it is assumed that vindesine/cisplatin, vinblastine/cisplatin, and etoposide/cisplatin produce similar survival outcomes, based on available randomized controlled trials, and that NVB-P is superior in terms of survival, based on the Le Chevalier data, then the treatment of choice is NVB-P (outpatient), as it is cost-effective when compared to all of the older “standard” treatment options.

We originally reported on the cost and cost-effectiveness of vinorelbine-based chemotherapy in the European Journal of Cancer in 1996.[22] The actual costs of care and cost-effectiveness are different in this publication compared with the original article. This highlights one of the issues associated with the conduct of economic analyses. Such analyses are time-specific, as the costs of care are constantly changing.

The earlier analysis was based on the number of stage IV lung cancer patients in Canada in 1988, rather than 1992 case numbers. In addition, there were two other changes. One was a minor refinement of the model, which added the time (1/2 hour) and associated cost of nursing care to each follow-up visit in the first year. More importantly, the number of bed days during initial hospitalization for diagnosis and initial non-surgical treatment was determined to be 12 days, based on the most recent Ontario hospital discharge abstract data. This increased the cost of hospitalization by 2 ´ $818.50, or $1,637, plus additional physician hospital visit charges. In the previous report, the number of hospital days had been estimated to be 10 days. The actual cost of chemotherapy remained the same, as there has been no change in the costs of the drugs or in their administration costs over the interval since the model was last updated. Overall, the total cost of care has increased approximately $1,000 to $1,500 since the last analysis. This, however, does alter the basic results of the earlier analysis, which also concluded that outpatient NVB-P was a cost-effective treatment for patients with advanced NSCLC.

Laupacis and associates have reported that new medical technologies that cost between $20,000 and $40,000 per quality adjusted life year saved are acceptable to the Canadian public.[19] The cost-utility of several of these regimens was recently estimated based on physician perceptions of the utilities of these various regimens. The average utility assigned by 22 oncologists for NVB-P was 0.6.[23] The quality adjusted life year gained for NVB-P would still place this regimen well within the range of cost-effectiveness suggested as being acceptable by Laupacis et al in the Canadian health care environment, as it improves survival while reducing the cost per treated case.

The decision to treat a patient with stage IV NSCLC is a complex one that must consider not only the patient’s overall medical condition and performance status, effectiveness of the available therapies, and the quality of life of the patient on treatment but also the patient’s own values and preferences. Cost and cost-effectiveness are factors of increasing importance to physicians and patients alike. This analysis suggests that NVB-P is very cost-effective relative to health care interventions generally considered acceptable to the Canadian population. Thus, cost in and of itself should not be a barrier to access to care for patients with stage IV NSCLC in Canada.

Discussion

Question: The model you used is very complicated. Why not use a more classic modeling methodology like Markov or decision analysis?

Dr. Evans: We used this model because at Statistics Canada we have a health analysis modeling group that is in the process of creating models that integrate risk factors with actual treatments and the data from various cancer registries, etc.

We are also using the POHEM model to assess the interplay between the cost of smoking prevention strategies and reduction in smoking in the Canadian population, and then to determine how that interacts with the costs of delivering care for lung cancer.

Dr. Weeks: In the United States recently, a regimen of carboplatin/paclitaxel is emerging as a standard of care for patients with non-small-cell lung cancer. This is surprising to me because there are no randomized trial data to support that as the optimal regimen. Nevertheless, the carboplatin/paclitaxel regimen is becoming the natural comparator for us. Have you examined the costs for platinum/vinorelbine versus those for carboplatin/paclitaxel?

Dr. Evans: I agree that in the absence of clinical trial data, one wonders why this has become one of the standards of care. We have not yet analyzed paclitaxel/platinum or paclitaxel/carboplatin in the model. We have assessed paclitaxel alone, and we recently received the survival data from the Eastern Cooperative Oncology Group study of paclitaxel/cisplatin versus etoposide/cisplatin. We will be conducting a cost and cost-effectiveness analysis based on that trial in the near future. We have been waiting for the trial results to mature so that the survival data would be clear. There has been some discussion at various meetings as to whether survival with paclitaxel/cisplatin is significantly superior to that achieved with etoposide/cisplatin. Results presented at the recent Dublin meeting suggest that it is somewhat superior but borderline in terms of statistical significance. Once those data are mature enough, we will conduct the cost study and then have a league table for non-small-cell lung cancer chemotherapy regimens.

Although I am not comfortable with league tables that compare, for example, cost-effectiveness of screening for breast cancer versus hemodialysis, a league table that deals with one disease entity in a common model and shows all of the various regimens is useful to policy-makers and to clinicians. If all other factors are equal in terms of toxicity and survival, etc, then having a league table that shows the most effective regimens can contribute to the clinician’s decision-making process. We hope to have that available approximately in the next year.

References:

1. Le Chevalier T, Brisgand D, Douillard JY, et al: A randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell carcinoma: Results of a European multicenter trial including 612 patients. J Clin Oncol 12:360-367, 1994.

2. Goss GD, Logan DL, Newman TE, et al: Use of vinorelbine in non-small cell lung cancer. Cancer Prevention and Control 1:28-38, 1997.

3. Rapp E, Pater JL, Willan A, et al: Chemotherapy can prolong survival in patients with advanced non-small cell lung cancer—report of a Canadian multicentre randomized trial. J Clin Oncol 6:633-641, 1988.

4. Wolfson MC: POHEM—a framework for understanding and modelling the health of human populations. Presented at Bureau of Census 1992 Annual Research Conference, Arlington, Virginia. Proc Ann Res Conf, pp 261-282, 1992.

5. Evans WK, Will BP, Berthelot J-M, et al: Diagnostic and therapeutic approaches to lung cancer in Canada and their costs. Br J Cancer 72:1270-1277, 1995.

6. Evans WK, Will BP, Berthelot J-M, et al: Estimating the cost of lung cancer diagnosis and treatment in Canada: The POHEM model. Can J Oncol 5:408-419, 1995.

7. Jaakkimainen L, Goodwin PJ, Pater J, et al: Counting the cost of chemotherapy in a National Cancer Institute of Canada randomized trial in non-small cell lung cancer. J Clin Oncol 8:1301-1309, 1990.

8. Wodinsky HB, DeAngelis C, Rusthoven JJ, et al: Re-evaluating the cost of outpatient cancer chemotherapy. Can Med Assoc J 137:903-906, 1987.

9. Dhingra HM, Valdivieso M, Carr DT, et al: Randomized trial of three combinations of cisplatin with vindesine and/or VP-16 in the treatment of advanced non-small-cell lung cancer. J Clin Oncol 3:176-183, 1985.

10. Ruckdeschel JC, Finkelstein DM, Ettinger DS, et al: A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol 4:14-22, 1996.

11. Grilli R, Oxman, AD, Julian JA: Chemotherapy for advanced non-small-cell lung cancer: How much benefit is enough? J Clin Oncol 11:1866-1872, 1993.

12. Souquet PJ, Chauvin F, Boissel JP, et al: Polychemotherapy in non-small-cell lung cancer: A meta-analysis using updated individual patient data from 52 randomized clinical trials. Lancet 342:19-21 1993.

13. Non-Small-Cell Lung Cancer Collaborative Group. Chemotherapy in non-small-cell lung cancer: A meta-analysis using updated individual patient data from 52 clinic trials. Br Med J 311:899-909, 1995.

14. Cullen MH, Woodroffe CM, Billingham AD, et al: Mitomycin, ifosfamide and cisplatin (MIC) in non-small cell lung cancer (NSCLC): Results of a randomized trial in patients with extensive disease (abstract 11). Lung Cancer 18(suppl 1):4, 1997.

15. Billingham LJ, Cullen MH, Woods J et al: Mitomycin, ifosfamide and cisplatin (MIC) in non-small-cell lung cancer (NSCLC). Results of a randomized trial evaluating palliation and quality of life (abstract 26). Lung Cancer 18(suppl 1):9, 1997.

16. Raby B, Pater J, MacKillop WJ: Does knowledge guide practice? Another look at the management of non-small-cell lung cancer. J Clin Oncol 13:1904-1911, 1995.

17. Moore R, Mao Y, Zhang J, et al: Economic burden of illness in Canada 1993. Catalogue no. H 21-136/1993 E. Public Works and Government Services, Canada, 1997.

18. Smith TJ, Hillner BE, Neighbours DM, et al: Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small cell lung cancer. J Clin Oncol 13:2166-2173, 1995.

19. Laupacis A, Feeney D, Detsky AS, et al: How attractive does new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. Can Med Assoc J 146:473-481, 1992.

20. Shulman KA, Lynn LA, Glick HA, et al: Cost-effectiveness of low-dose zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV). Ann Intern Med 114:798-802, 1991.

21. Tangs TO, Adams ME, Pliskin JS, et al: 500 life-saving interventions and their cost-effectiveness. Risk Analysis 15:369-390, 1995.

22. Evans WK, Le Chevalier T: The cost-effectiveness of Navelbine alone or in combination with cisplatin in comparison to other chemotherapy regimens and best supportive care in stage IV non-small cell lung cancer. Eur J Cancer 32: 2249-2255, 1996.

23. Earle C, Evans WK, Berthelot J-M, et al: Comparison of the costs, toxicities and inconvenience of the different chemotherapy regimens for advanced non-small-cell lung cancer (abstract 90). Lung Cancer 18(suppl 1):26, 1997.