The failure to contain health care costs and curtail their growth is a problem common to all nations and a continuing focus of public policy debate. Attempts to control costs cannot be left to administrators and public health officials. As Eisenberg has stated, to suggest that medical decision making can be divorced from consideration of cost denigrates the complexity of patient care. The application of economic principles to medicine does not necessarily mean that less money should or will be spent in total or for a specific condition, but rather, that these resources will be used more efficiently. Oncology services have been a particular focus of attention regarding medical costs. Oncologic costs of care for Medicare patients grew by approximately 17% annually in the late 1980s. Current estimates are that costs for oncologic care account for about 15% to 20% of the health care dollar in the United States. The several reasons for this growth include:
- Demographic changes
- A common reluctance to stop active therapy
- Increasing attention to quality-of-life concerns
- Innovations in biotechnology (ie, potentially effective new therapies)
- There is rarely one optimal treatment for an individuals cancer.
The use of chemotherapy for metastatic non-small-cell lung cancer (NSCLC) is controversial. A common perception has been that chemotherapy has little impact on long-term survival. Two meta-analyses of published clinical trials, however, found a 27% to 34% reduction in risk of early death with treatment at 6 months.[2,3] In addition, recent practice guidelines from the American Society of Clinical Oncology state that chemotherapy, ideally a platinum-based regimen, is appropriate for selected patients who have a good performance status with both unresectable, locally advanced, and metastatic NSCLC. Whether the use of chemotherapy has a beneficial effect on disease costs and is cost-effective is uncertain. A common perception is that chemotherapy is a poor use of societal resources.
For these reasons, we performed a post-hoc analysis using financial data from the Medical College of Virginia/Virginia Commonwealth University, representative of large American academic centers of the three arm vinorelbine (Navelbine) trial led by Dr. Le Chevalier.[5,6] We sought to estimate the cost and cost-effectiveness of vinorelbine alone and vinorelbine plus cisplatin (Platinol) against a regimen commonly used in Europe of vindesine plus cisplatin, using results from the largest randomized trial of vinorelbine. The intent of this analysis was to assess the incremental efficacy (the difference in survival between regimens), incremental costs (the difference in treatment toxicity, monitoring, and drug costs), and incremental cost-effectiveness (the societal resources necessary to gain an additional year of life with each regimen).
Mean survival, preferred to median survival as a measure of benefit for use in cost-effectiveness calculations, was estimated from a clinical trial in which 612 patients were randomly assigned to one of three arms: (1) vinorelbine alone, 30 mg/m² intravenously (IV) weekly; (2) vinorelbine, 30 mg/m² IV weekly, plus cisplatin, 120 mg/m² IV on days 1 and 29, then every 6 weeks; or (3) vindesine, 3 mg/m² IV weekly for 7 weeks, then every 2 weeks, plus cisplatin at the same dose and schedule. Table 1 summarizes clinical results for patients in all three study arms.
The clinical trial did not prospectively collect economic or quality-of-life data. We were given access to the primary data. The cost-effectiveness analysis was performed using the final data set that included any additional 12 months of patient follow-up. The analysis assumed that all patients were treated until disease progression, unaccept- able toxicity, or patient refusal, or had stable disease for 18 months post-treatment. The post-hoc analysis included all direct treatment costs including toxicities and monitoring. The analysis was performed as if all patients were treated at the Medical College of Virginia. The analysis assumed that all patients received identical supportive care. The efficacy and costs of second-line chemotherapy or other palliative care were not assessed. Costs were estimated from specific institutional cost-to-charge ratios that varied with the type of service, such as drug acquisition, radiology, hospital hotel costs, etc. The costs of vinorelbine were based on the projected wholesale price. Patients treated with cisplatin were assumed to receive it as outpatients, reflecting the current US pattern of care.
The findings of the economic analysis are summarized in Table 2 above. The vinorelbine used as monotherapy arm had the lowest costs due to fewer required antiemetic drugs and laboratory monitoring tests. Vinorelbine plus cisplatin had the highest total treatment costs; 64% to 81% of total treatment costs were for chemotherapy, supportive drugs, and laboratory tests, and 41% to 46% of costs were for chemotherapy only.
The incremental costs per patient for these regimens ranged from $1,150 to $2,700, or about $42 to $60 per day of life gained. When multiplied by 365 days to convert these findings to the benchmark of comparison, cost per year of life saved, the incremental costs ranged from $15,500 to $22,100 per life year gained.
Quality of life with each of the treatment strategies was not formally prospectively collected during the clinical trial. Our analysis allowed us to speculate about the effect of relative differences in quality of life between the single-drug arm (vinorelbine) and the cisplatin-containing arms. A sensitivity analysis of the importance of patient utilities for cisplatin-associated toxicity found that if vinorelbine compared with cisplatin treatment was associated with a 0.12 (absolute) greater utility or quality of life, then the vinorelbine alone strategy was the preferred one.
Concerns about the costs of established and new medical therapies will be increasingly scrutinized. Long-term efficacy of chemotherapy for non-small-cell lung cancer is less than desired, but the efficacy and cost effectiveness of new treatment combinations using vinorelbine are comparable to those of other commonly accepted medical therapies. A common assumption that oncology treatments for advanced disease are not effective or cost effective may not be justified if efficacy from clinical trials can be translated to community settings. In addition, once results are available from ongoing head-to-head randomized comparisons of multi-drug regimens, eg, vinorelbine plus cisplatin compared with carboplatin (Paraplatin) plus a taxane, clinical economists will be able to make more direct inferences about the incremental cost effectiveness of these newer interventions.
1. Eisenberg JM: Clinical economics. A guide to the economic analysis of clinical practices. JAMA 262:2879-2886, 1989.
2. Grilli R, Oxman AD, Julian JA: Chemotherapy for advanced non-small-lung cancer: How much benefit is enough? J Clin Oncol 11:1866-1872, 1993.
3. Souquet PJ, Chauvin F, Boissel JP, et al: Polychemotherapy in advanced non-small-cell lung cancer: A meta-analysis. Lancet 342:19-21, 1993.
4. Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer. Adopted on May 16, 1997 by the American Society of Clinical Oncology. J Clin Oncol 15:2996-3018, 1997
5. Smith TJ, Hillner BE, Neighbors 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.
6. Le Chevalier T, Brisgand D, Douillard JY, et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: Results of a European multicenter trial including 612 patients. J Clin Oncol 12:360-367, 1994.