Pharmacoeconomic issues in bisphosphonate treatment of metastatic bone disease.

Bisphosphonates provide a supportive benefit to patients with bone metastases from cancer by reducing skeletal complications, such as bone pain, pathologic fractures, and hypercalcemia. Although bisphosphonates have important therapeutic effects, such as significant improvements in the quality of remaining life, they do not, as yet, significantly improve the overall survival of affected patients. Furthermore, as with all new innovations, they exert a major impact on drug budgets dedicated for cancer care. Further research is warranted to identify clinical predictors of the optimum time in the course of the disease to start and stop therapy, to integrate use of bisphosphonates with other therapies, to identify their role in the adjuvant setting, and to determine their cost-benefit consequences. Current cost-effectiveness assessments have shown that the incremental costs per skeletal-related event are particularly sensitive to the unit price of the bisphosphonate modeled. Therefore, pharmacoeconomic evaluations should be combined with clinical trials to predict accurately the true costs (total resource usage) of this health care intervention and to ultimately assess the rational broad use of these agents.

Is cancer care best at high-volume providers?

For a variety of medical conditions and procedures, a higher volume-better outcome relationship has been hypothesized for over 25 years. An extensive, consistent body of literature supports a relationship between hospital volume and short-term outcomes for cancers treated with technologically complex surgical procedures. For cancer primarily treated by low-risk surgery, there are few studies. Recent studies found a modest (about 2%) difference in survival benefit between high-volume and low-volume providers associated with colon cancer surgery. Few evaluations in the last 15 years have addressed nonsurgical cancers, eg, lymphomas and testicular cancer. No reports have addressed recurrent or metastatic cancer. Care is better at high-volume providers for a select minority of cancers. Whether provider volume matters in the majority of cancers at the time of presentation has not been evaluated.

Ensuring quality cancer care by the use of clinical practice guidelines and critical pathways.

PURPOSE: We describe the impact of clinical practice guidelines (CPGs) on improvement in oncology treatment processes or outcomes. METHODS: We performed a comprehensive search of the literature from 1966 to the present and a directed review of the literature. RESULTS: Improvements have been demonstrated in compliance with evidence-based guidelines or evidence-based medicine, and in short-term length of stay, complication rates, and financial outcomes. The data suggest that patient satisfaction can be maintained despite a shorter length of stay. There has been one example of province-wide improvement in disease-free and overall survival of breast cancer patients coincident with the adoption of CPGS: The components of successful guidelines can be summarized as follows: (1) development is based on evidence, with the guideline formulated by key physicians in the group; (2) the guidelines are disseminated to all affected health care professionals for critique; (3) implementation includes direct feedback on performance to physicians or general feedback on system performance; and (4) there is accountability for performance according to the guidelines. This accountability can consist of voluntary peer pressure to conform to evidence-based medicine, and it does not require a financial reward or penalty. CONCLUSION: Some attempts to improve practice have been moderately successful in achievement of reduced health care costs, reduced hospital length of stay, and possibly improved outcomes. Other methods that are still in use have been demonstrated to have little effect. Programs that have not succeeded have relied on voluntary change in practice behavior without incentives to change or have had no accountability component. Further research is needed to assess how guidelines are enacted in organizations other than those demonstrably committed to improvement, ways to improve compliance of health care providers who are not committed to change, and methods to improve accountability.

Burden of illness associated with metastatic melanoma: an audit of 100 consecutive referral center cases.

BACKGROUND: Although long-term survival in patients with metastatic melanoma (MM) is infrequent, response to a variety of cytotoxic and immunotherapies occurs and survival varies based on the site of metastases. Because different patterns of care of MM are likely to vary substantially in their intensity and resource use, the authors audited care at a regional referral center. METHODS: The records of 100 consecutive new patients with MM who presented at the University of Pittsburgh Cancer Institute (UPCI) after January 1997 were audited. Demographics, disease sites, and treatment prior to presentation at UPCI as well as the diagnostic and therapeutic methods undertaken at UPCI were tracked monthly with regard to inpatient and outpatient activity. RESULTS: The median age of the patient cohort was 51 years was a median 2.2 years after the time of initial diagnosis. Eighty-two percent of the patients had died and only 8% had been lost to long-term follow-up. Eighty-seven percent of patients had been referred to UPCI and 28% had received some treatment prior to presenting at UPCI. The median survival was 9.0 months. The lung was the most common symptomatic site and 38% of patients developed central nervous system (CNS) metastases. Eighty-four percent of patients initially were treated on a research protocol 30% of whom were part of a Phase III study. Twenty-nine percent of the patients were never hospitalized. The most common reason for hospitalization was elective treatment with high-dose interleukin-2. Lifetime hospital days averaged only 7.3 days. Therapeutic actions (if ever given) by category type were surgery in 23% of patients, radiation therapy in 44%, immunotherapy in 75%, and chemotherapy in 51%. Using assigned values for the identified resources used, the approximate cost per patient averaged $59,400. CONCLUSIONS: The current audit of MM patients demonstrated that lung and CNS metastases dominate a broad variety of complications, that clinical trial participation was the norm, that hospitalizations occurred relatively infrequently, and that the direct health care costs of current treatment patterns are among the highest for all malignancies. Medical auditing of contemporary American cancer care provides meaningful insights into its patterns of care.

Cost-effectiveness analysis of exemestane compared with megestrol in patients with advanced breast carcinoma.

BACKGROUND: The objective of this study was to determine the potential economic implications resulting from using exemestane (EXE), a new steroidal, irreversible aromatase inactivator, compared with megestrol acetate (MA) in patients with advanced breast carcinoma. METHODS: The model used the clinical results from the manufacturer-sponsored, international, randomized, controlled, double-blind trial of patients with postmenopausal, tamoxifen-refractory advanced breast carcinoma. Seven hundred sixty-nine women were randomized to EXE 25 mg per day or MA 40 mg four times daily EXE was well tolerated, significantly delayed tumor progression (relative risk [RR], 0.82; 95% confidence interval [95% CI], 0.70-0.97), and prolonged survival (RR, 0.77; 95% CI, 0.59-0.99). Lifetime effectiveness projections were made using the trial efficacy results to the U.S. market using a 1000-day ( approximately 3-year) time frame. Because the median survival of patients who received EXE was not reached, it was projected from the Cox model. There were no differences in the rate of hospitalization. The average wholesale prices for EXE and MA were used. RESULTS: Patients who received EXE were projected to have a mean survival benefit of 53.5 days (estimated 95% CI, 2-100 days) and to incur at an additional cost of $1559 per patient (estimated 95% CI, 880-2075 dollars). The incremental cost effectiveness (CE) ratio using EXE was 10,600 dollars per life year gained (estimated 95% CI, 6200-209,000 dollars). If MA had no costs, then the CE ratio increased to 12,200 dollars per life year. Using a 5-year projection, the CE ratio for EXE was 5900 dollars per life year. The projected survival at 1000 days was 53.9% in the EXE cohort compared with 44.8% in the MA cohort. CONCLUSIONS: EXE, compared with MA, is projected to increase survival at a modest added cost. If treatment with EXE delays or defers initiating more costly therapies, then it may even be cost saving.

The role of bisphosphonates in metastatic breast cancer.

The American Society of Clinical Oncology has recently developed guidelines for the use of bisphosphonates in breast cancer. Highlights of these guidelines are reviewed. Specific issues addressed included when in the course of disease should treatment be started, the duration of therapy, the role of bisphosphonates in pain control, their safety, and current estimates of their cost effectiveness. Although intravenous bisphosphonates, primarily pamidronate, have been shown to reduce the frequency of skeletal-related complications in women with known lytic bone metastases from breast cancer, numerous major areas of clinical importance related to their use have not been studied and are highlighted.

Hospital and physician volume or specialization and outcomes in cancer treatment: importance in quality of cancer care.

PURPOSE: To conduct a comprehensive review of the health services literature to search for evidence that hospital or physician volume or specialty affects the outcome of cancer care. METHODS: We reviewed the 1988 to 1999 MEDLINE literature that considered the hypothesis that higher volume or specialization equals better outcome in processes or outcomes of cancer treatments. RESULTS: An extensive, consistent literature that supported a volume-outcome relationship was found for cancers treated with technologically complex surgical procedures, eg, most intra-abdominal and lung cancers. These studies predominantly measured in-hospital or 30-day mortality and used the hospital as the unit of analysis. For cancer primarily treated with low-risk surgery, there were fewer studies. An association with hospital and surgeon volume in colon cancer varied with the volume threshold. For breast cancer, British studies found that physician specialty and volume were associated with improved long-term outcomes, and the single American report showed an association between hospital volume of initial surgery and better 5-year survival. Studies of nonsurgical cancers, principally lymphomas and testicular cancer, were few but consistently showed better long-term outcomes associated with larger hospital volume or specialty focus. Studies in recurrent or metastatic cancer were absent. Across studies, the absolute benefit from care at high-volume centers exceeds the benefit from break-through treatments. CONCLUSION: Although these reports are all retrospective, rely on registries with dated data, rarely have predefined hypotheses, and may have publication and self-interest biases, most support a positive volume-outcome relationship in initial cancer treatment. Given the public fear of cancer, its well-defined first identification, and the tumor-node-metastasis taxonomy, actual cancer care should and can be prospectively measured, assessed, and benchmarked. The literature suggests that, for all forms of cancer, efforts to concentrate its initial care would be appropriate.

Post hoc economic analysis of temozolomide versus dacarbazine in the treatment of advanced metastatic melanoma.

PURPOSE: To determine the potential economic implications resulting from oral temozolomide (TEM) compared with intravenous (IV) dacarbazine (DTIC) for metastatic melanoma. PATIENTS AND METHODS: We performed a cost-effectiveness (CE) analysis using hazard ratios (HRs) from the phase III (Schering I95-018) trial comparing TEM 200 mg/m(2)/d orally for 5 days every 28 days with DTIC 250 mg/m(2)/d IV for 5 days every 21 days. Sensitivity analyses assessed a range of TEM's efficacy and costs, direct nonmedical costs, and the DTIC schedule. RESULTS: The trial found an overall survival trend favoring TEM; median survival times of patients treated with DTIC and TEM were 6.4 and 7.7 months, respectively (HR = 1.18; 95% confidence interval [CI], 0.92 to 1.52; intention to treat, P =.20). The mean increase in survival of TEM over DTIC was 1.1 months. The projected average costs per patient were greater with TEM than DTIC ($6,902 v $3,697, respectively). The incremental CE ratio using TEM was $36,990 per life-year or $101 per day of life gained. The CE ratio's 95% CI ranged from -$65,180 (DTIC is more effective) to $18, 670 per year of life gained. The CE ratios decreased 50% if direct nonmedical costs were included and increased 50% if DTIC's efficacy was unchanged if given as a single daily dosage. Sixty percent of simulations found TEM with a CE threshold of less than $50,000 per life-year gained. CONCLUSION: Although the base-case efficacy of TEM compared with DTIC was not statistically significant, its associated incremental CE would be comparable with many interventions. TEM for metastatic melanoma illustrates the tension confronting providers choosing between similar agents that markedly differ in convenience and costs.

American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonates Expert Panel.

PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of bone metastases in breast cancer and their role relative to other therapies for this condition. METHODS: An expert multidisciplinary panel reviewed pertinent information from the published literature and meeting abstracts through May 1999. Additional data collected as part of randomized trials and submitted to the United States Food and Drug Administration were also reviewed, and investigators were contacted for more recent information. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the panel. Expert consensus was used if there were insufficient published data. The panel addressed which patients to treat and when in their course of disease, specific drug delivery issues, duration of therapy, management of bony metastases with other therapies, and the public policy implications. The guideline underwent external review by selected physicians, members of the American Society of Clinical Oncology (ASCO) Health Services Research Committee, and the ASCO Board of Directors. RESULTS: Bisphosphonates have not had an impact on the most reliable cancer end point: overall survival. The benefits have been reductions in skeletal complications, ie, pathologic fractures, surgery for fracture or impending fracture, radiation, spinal cord compression, and hypercalcemia. Intravenous (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. For women with only an abnormal bone scan but without bony destruction by imaging studies or localized pain, there is insufficient evidence to suggest starting bisphosphonates. Starting bisphosphonates in patients without evidence of bony metastasis, even in the presence of other extraskeletal metastases, is not recommended. Studies of bisphosphonates in the adjuvant setting have yielded inconsistent results. Starting bisphosphonates in patients at any stage of their nonosseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended. Oral bisphosphonates are one of several options which can be used for preservation of bone density in premenopausal patients with treatment-induced menopause. The panel suggests that, once initiated, IV bisphosphonates be continued until evidence of substantial decline in a patient's general performance status. The panel stresses that clinical judgment must guide what is a substantial decline. There is no evidence addressing the consequences of stopping bisphosphonates after one or more adverse skeletal events. Symptoms in the spine, pelvis, or femur require careful evaluation for spinal cord compression and pathologic fracture before bisphosphonate use and if symptoms recur, persist, or worsen during therapy. The panel recommends that current standards of care for cancer pain, analgesics and local radiation therapy, not be displaced by bisphosphonates. IV pamidronate is recommended in women with pain caused by osteolytic metastasis to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, since it was associated with a modest pain control benefit in controlled trials. CONCLUSION: Bisphosphonates provide a meaningful supportive but not life-prolonging benefit to many patients with bone metastases from cancer. Further research is warranted to identify clinical predictors of when to start and stop therapy, to integrate their use with other treatments for bone metastases, to identify their role in the adjuvant setting in preventing bone metastases, and to better determine their cost-benefit consequences.

Current practice of temporary vena cava filter insertion: a multicenter registry.

PURPOSE: To evaluate the current practice of temporary vena cava filter placement and its complications. MATERIALS AND METHODS: A multicenter registry was conducted from May 1995 until May 1997 using a standardized questionnaire. One hundred eighty-eight patients were evaluated. Patient characteristics, filter indications, filter characteristics, and complications were registered. RESULTS: Deep vein thrombosis was proven in 95.2% of the patients. Main filter indication was thrombolysis therapy (53.1%). Average filter time was 5.4 days. An Antheor filter was inserted in 56.4%, a Guenther filter in 26.6%, and a Prolyser filter in 17.%. Transfemoral filter implantation was slightly preferred (54.8%). Four patients died of pulmonary embolism (PE) during filter protection. Major filter problems were filter thrombosis (16%) and filter dislocation (4.8%). When thrombus was found in or at the filter before explantation, additional thrombolysis was performed in 16.7%, additional filter implantation in 10%, and thrombus aspiration in 6.7%; 4.8% of filters were replaced with permanent filters. DISCUSSION: Temporary vena cava filters are placed to prevent PE in a defined patient population. Despite their presence, PEs still occur in a small percentage. Problems of filter thrombosis and dislocation have to be solved. CONCLUSION: The results of this multicenter registry support the need for innovative filter design, as well as a randomized, prospective study.

Pamidronate in prevention of bone complications in metastatic breast cancer: a cost-effectiveness analysis.

PURPOSE: Pamidronate is effective in reducing bony complications in patients with metastatic breast cancer who have known osteolytic lesions. However, pamidronate does not increase survival and is associated with additional financial costs and inconvenience. We conducted a post-hoc evaluation of the cost-effectiveness of pamidronate using the results of two randomized trials that evaluated pamidronate 90 mg administered intravenously every month versus placebo. PATIENTS AND METHODS: The trials differed only in the initial systemic therapy administered (hormonal or chemotherapy). Total skeletal related events (SREs), including surgery for pathologic fracture, radiation for fracture or pain control, conservatively treated pathologic fracture, spinal cord compression, or hypercalcemia, were taken directly from the trials. Using a societal perspective, direct health care costs were assigned to each SRE. Each group's monthly survival was equal and was projected to decline using observed median survivals. The cost of pamidronate reflected the average wholesale price of the drug plus infusion. The value or disutility of an adverse event per month was evaluated using a zero value (events avoided) or an assigned one (range, 0.2 to 0.8). RESULTS: The cost of pamidronate therapy exceeded the cost savings from prevented adverse events. The difference between the treated and placebo groups was larger with hormonal systemic therapy than with chemotherapy (additional $7,685 compared with $3,968 per woman). The projected net cost per SRE avoided was $3,940 with chemotherapy and $9,390 with hormonal therapy. The cost-effectiveness ratios were $108,200 with chemotherapy and $305, 300 with hormonal therapy per quality-adjusted year. CONCLUSION: Although pamidronate is effective in preventing a feared, common adverse outcome in metastatic breast cancer, its use is associated with high incremental costs per adverse event avoided. The analysis is most sensitive to the costs of pamidronate and pathologic fractures that were asymptomatic or treated conservatively.

Tamoxifen should be cost-effective in reducing breast cancer risk in high-risk women.

PURPOSE: To estimate the cost-effectiveness of tamoxifen in the prevention of breast cancer. PATIENTS AND METHODS: Clinical trial results of National Surgical Adjuvant Breast Program P-1 compared tamoxifen versus placebo in the prevention of breast cancer, and direct medical care costs were estimated from the Agency for Health Care Policy and Research and local sources. The base estimate of effectiveness included all women on the trial. RESULTS: For every 100 women treated for 5 years, 1.665 expected cancers would not be detected. If breast cancer death is fully prevented by this strategy, then the cost-effectiveness of tamoxifen compared with no intervention is $8,479 per additional year of life gained. If lifetime prevention of the risk of death from breast cancer exceeded 17%, then the cost-effectiveness ratio would be less than $50,000 per year of life gained (a common benchmark). CONCLUSIONS: Tamoxifen for breast cancer prevention should be cost-effective under nearly all circumstances. Its use will require additional resources because it is not cost saving, but it fits within accepted guidelines.

Cost-effectiveness of adding an electron-beam boost to tangential radiation therapy in patients with negative margins after conservative surgery for early-stage breast cancer.

PURPOSE: Electron-beam boosts (EBB) are routinely added after conservative surgery and tangential radiation therapy (TRT) for early-stage breast cancer. We performed an incremental cost-utility analysis to evaluate their cost-effectiveness. METHODS: A Markov model examined the impact of adding an EBB to TRT from a societal perspective. Outcomes were measured in quality-adjusted life years (QALYs). On the basis of the Lyon trial, the EBB was assumed to reduce local recurrences by approximately 2% at 10 years but to have no impact on survival. Patients' utilities were used to adjust for quality of life. Given the small absolute benefit of the EBB, baseline utilities were assumed to be the same with or without it, an assumption evaluated by Monte Carlo simulation. Direct medical, time, and travel costs were considered. RESULTS: Adding the EBB led to an additional cost of $2,008, an increase of 0.0065 QALYs and, therefore, an incremental cost-effectiveness ratio of over $300,000/QALY. In a sensitivity analysis, the ratio was moderately sensitive to the efficacy and cost of the EBB and highly sensitive to patients' utilities for treatment without it. Even if patients do value a small risk reduction, the mean cost-effectiveness ratio estimated by the Monte Carlo simulation remains high, at $70,859/QALY (95% confidence interval, $53,141 to $105,182/QALY). CONCLUSION: On the basis of currently available data, the cost-effectiveness ratio for the EBB is well above the commonly cited threshold for cost-effective care ($50,000/QALY). The EBB becomes cost-effective only if patients place an unexpectedly high value on the small absolute reduction in local recurrences achievable with it.

Is the use of radiation therapy after mastectomy cost-effective?

With the publication of two randomized trials showing an improvement in overall survival after the use of postmastectomy radiation therapy, interest in the use of radiation therapy in this setting has been rekindled. These results are in contrast to those reported in the most recent meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, in which a statistically significant survival benefit was not detected. Although evidence of a survival benefit was sufficient in the past for an intervention to gain acceptance, payers are increasingly interested in knowing whether its use is also cost-effective. This article briefly reviews the methods used in performing cost-effectiveness analyses, summarizes the results of one published and a second preliminary cost-effectiveness analysis of postmastectomy radiation therapy, and highlights several areas for future research.

A sociodemographic and economic comparison of breast reconstruction, mastectomy, and conservative surgery.

BACKGROUND: There are a variety of surgical choices for women with early-stage breast cancer, including breast-conserving surgery, mastectomy, or mastectomy plus reconstructive surgery. This report examines some of the factors that affect these choices and the costs of the various treatment options. METHODS: Data from the Virginia Cancer Registry were linked to insurance claims from the Trigon Blue Cross and Blue Shield Company for women with local and regional staged breast cancer from 1989 to 1991 in Virginia. Multivariate analyses and cost studies were performed. RESULTS: There were 592 women who underwent breast-conserving surgery (BCS, 26%), mastectomy (58%), or mastectomy plus reconstruction (16%). Increasing age reduced the use of reconstruction. The choice of reconstruction was not affected by tumor size, nodal status, or race. Sixty percent of women had immediate breast reconstruction at the time of mastectomy; the majority had the implant procedure. The cost of BCS ($21,582) was higher than that of mastectomy ($16,122, P < .01). The costs for BCS and mastectomy were significantly lower than for mastectomy plus reconstruction ($31,047, P < .05). The 2-year cost for immediate reconstruction was $8200 less than for delayed procedures and was similar to the cost of BCS. CONCLUSIONS: Age was the driving force in reconstruction decisions. Clinical factors such as tumor size and nodal status were more important for the choice between BCS and mastectomy. There are significant cost differences between the various procedures. For a similar cosmetic outcome, BCS is less expensive than breast reconstruction. When reconstruction is required, a simultaneous procedure is less expensive.

Predictors of Medicare costs in elderly beneficiaries with breast, colorectal, lung, or prostate cancer.

BACKGROUND: Determining the apportionment of costs of cancer care and identifying factors that predict costs are important for planning ethical resource allocation for cancer care, especially in markets where managed care has grown. DESIGN: This study linked tumor registry data with Medicare administrative claims to determine the costs of care for breast, colorectal, lung and prostate cancers during the initial year subsequent to diagnosis, and to develop models to identify factors predicting costs. SUBJECTS: Patients with a diagnosis of breast (n = 1,952), colorectal (n = 2,563), lung (n = 3,331) or prostate cancer (n = 3,179) diagnosed from 1985 through 1988. RESULTS: The average costs during the initial treatment period were $12,141 (s.d. = $10,434) for breast cancer, $24,910 (s.d. = $14,870) for colorectal cancer, $21,351 (s.d. = $14,813) for lung cancer, and $14,361 (s.d. = $11,216) for prostate cancer. Using least squares regression analysis, factors significantly associated with cost included comorbidity, hospital length of stay, type of therapy, and ZIP level income for all four cancer sites. Access to health care resources was variably associated with costs of care. Total R2 ranged from 38% (prostate) to 49% (breast). The prediction error for the regression models ranged from < 1% to 4%, by cancer site. CONCLUSIONS: Linking administrative claims with state tumor registry data can accurately predict costs of cancer care during the first year subsequent to diagnosis for cancer patients. Regression models using both data sources may be useful to health plans and providers and in determining appropriate prospective reimbursement for cancer, particularly with increasing HMO penetration and decreased ability to capture complete and accurate utilization and cost data on this population.

Cost-effectiveness assessment of interferon alfa-2b as adjuvant therapy of high-risk resected cutaneous melanoma.

The use of interferon alfa-2b (IFN-alpha 2b) as adjuvant therapy of high-risk resected cutaneous melanoma was recently found to significantly improve relapse-free and overall survival in the Eastern Cooperative Oncology Group trial 1684 (E1684). However, treatment toxicities and costs may limit its widespread use. A cost-effectiveness and cost-utility analysis of this therapy was conducted using a hypothetical cohort of patients as if they had entered E1684. Survival and recurrence rates were calculated at 7 and 35 years for typical 50-year-old melanoma patients based on the clinical results of E1684 and natural history databases. Costs included all treatment-related costs (i.e. drug acquisition and administration, monitoring and treatment-related toxicity) and the costs of treating recurrences. Estimated utility values were assigned based on data from other oncology trials. The model predicted that IFN-alpha 2b provided an extra 0.52 years of life compared with observation at 7 years; however, at 35 years, the survival benefit of IFN-alpha 2b increased almost 4-fold to nearly 2 years. At 7 years, the cost per year of life gained was U.S. $32,600 and the cost per quality-adjusted life-year (QALY) gained was U.S. $43,200. At 35 years, these costs decreased to U.S. $13,700 and $15,200, respectively. These costs are comparable with those of other well-established medical interventions. Although these results require confirmation in a prospective study, it appears that the use of high-dose IFN-alpha 2b for patients with high-risk melanoma is cost-effective.

Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: report of a workshop.

In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed.