The application of pharmacoeconomic modelling to estimate a value-based price for new cancer drugs.

RATIONALE, AIMS AND OBJECTIVES: Value-based pricing has recently been discussed by international bodies as a means to estimate a drug price that is linked to the benefits it offers patients and society. The World Health Organization (WHO) has recommended using three times a country's per capita gross domestic product (GDP) as the threshold for economic value. Using the WHO criteria, pharmacoeconomic modelling was used to illustrate the application of value-based price towards bevacizumab, a relatively new drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC). METHODS: A decision model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from Canadian cancer centres. Utility estimates were determined by interviewing 24 oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of $CAD117,000 per quality adjusted life year gained, which is three times the Canadian per capita GDP. RESULTS: For a 1.4-month survival benefit, a price of $CAD830 per dose would be considered cost-effective from the Canadian public health care perspective. If the drug were able to improve patient quality of life or survival from 1.4 to 3 months, the drug price could increase to $CAD1560 and $CAD2180 and still be considered cost-effective. DISCUSSION: The use of the WHO criteria for estimating a value-based price is feasible, but a balance between what patients/governments can afford to pay and the commercial viability of the product in the reference country would be required.

Economic analysis of albumin-bound paclitaxel for the treatment of metastatic breast cancer.

BACKGROUND: An albumin-bound formulation of paclitaxel (nab-paclitaxel) was developed to provide additional efficacy and to overcome the safety drawbacks of paclitaxel and docetaxel in patients with metastatic breast cancer. To provide health economic data for the Canadian setting, an economic analysis comparing each of nab-paclitaxel and docetaxel, both as alternatives to paclitaxel in metastatic breast cancer was conducted. METHODS: The clinical and safety data were obtained from a meta-analysis of randomized trials comparing either nab-paclitaxel (260 mg/m(2) q3wk) or docetaxel (100 mg/m( 2) q3wk), to standard paclitaxel (175 mg/m(2) q3wk). Health care resource use for the delivery of chemotherapy and the management of grade III/IV toxicity was collected from the oncology literature. Treatment preferences and health state utilities were obtained from 24 female oncology nurses and pharmacists using the time trade-off technique. RESULTS: Nab-paclitaxel had the lowest incidence of grade III/IV toxicity. This translated to lower overall costs for managing the grade III/IV events relative to both docetaxel and paclitaxel ($597 vs. $2626 vs. $1227). Using the median number of cycles administered and the cost impact of grade III/ IV toxicity, the overall cost for nab-paclitaxel would be $15,105 compared to $15,268 for docetaxel and $3557 for paclitaxel. When treatment preferences were assessed, 20 of 24 (83.3%) respondents selected nab-paclitaxel as their preferred choice compared to only 4 who selected docetaxel. These corresponded to a gain of 0.203 and 0.016 QALYs for nab-paclitaxel and docetaxel, respectively. With these utility benefits, the incremental cost per QALY gained was more favorable for nab-paclitaxel than docetaxel ($56,800 vs. $739,600). CONCLUSIONS: Nab-paclitaxel would be an economically reasonable alternative to docetaxel in MBC patients. As an alternative to paclitaxel, formulary committees must decide if the $56,800 cost per QALY represents good value in their health care setting.

Effectiveness of traffic management in Salt Lake City, Utah.

PROBLEM: The effectiveness of speed humps, 14 ft (4.3 m) wide by 3.5 in (8.9 cm) high, and tables, 22 ft (6.7 m) wide, on 12 streets in Salt Lake City, Utah was investigated. Mean and 85th percentile spot speeds, speed limit compliance, motor-vehicle crashes, and resident opinions were considered. METHOD: Spot speeds were collected at 18 "between-hump" locations. Motor-vehicle crash data were obtained for "before" and "after" periods of equal duration. A total of 436 residents were surveyed; 184 responded. RESULTS: The mean and 85th percentile speeds decreased at 14 and 15 locations, respectively. The average reduction in the 85th percentile speed (3.4 mph or 5.4 km/h) was significant in flat and rolling terrain, but not on uphill or downhill segments. The number of sites with 50% speed limit compliance increased from 4 to 12. The number of motor-vehicle crashes decreased from 10 to 9; the change was not significant, but injury crashes decreased from five to one. Regarding the residents, 30% were positive, 25% were negative, and 45% offered suggestions, some of which were conflicting. DISCUSSION: Further study is needed on speed hump spacing and speed tables in hilly terrain. Example results should be shared with residents to inform their decision-making. SUMMARY: At least 78% of the sites experienced a decrease in the mean or 85th percentile speed, or an increase in speed limit compliance. IMPACT ON INDUSTRY: These findings should be useful to agencies that are planning or implementing traffic calming projects, and to analysts.

Rotation to methadone after opioid dose escalation: How should individualization of dosing occur?

Methadone is a synthetic opioid agonist and N-methyl-D-aspartate (NMDA) receptor antagonist that is being increasingly used in pain management, particularly for pain that is resistant to conventional opioids. We describe two patients with neurotoxic side effects on escalating doses of parenteral hydromorphone with uncontrolled cancer pain who were successfully converted to oral methadone at a dose much smaller than predicted. The phenomenon of increasing pain despite opioid dose escalation is discussed and the rationale for the use of methadone in this situation is described. While methadone is useful for patients with unremitting pain on another opioid, existing conversion regimens do not specifically take into account the setting of dose escalation. Clinical guidelines for rotation to methadone after dose escalation of the previous opioid are needed to avoid toxicity including respiratory depression. A possible conversion method for rotation to methadone for patients with escalating pain and opioid use is suggested.

Do physicians follow systemic treatment and funding policy guidelines?

BACKGROUND: The use of bisphosphonates for the prevention of skeletal related events in women with bone metastases from breast cancer is well established. We undertook an evaluation of bisphosphonate use in clinical practice in three Canadian cancer centres. In addition we assessed whether or not physicians at these centres are following their local treatment guidelines and funding policies. METHODS: Charts and electronic files of patients who had received either clodronate or pamidronate at any time between January 2000 and December 2001 at three Canadian cancer centres were retrospectively reviewed. RESULTS: There has been a marked improvement in the time between the diagnosis of bone metastases and the commencement of bisphosphonates from a median of 155 days in 1998 to 24 days in 2001. However, despite a local funding policy requiring that oral clodronate be the first bisphosphonate used, this was the case in only 67% of patients. In addition, despite one centre's guidelines recommending that bisphosphonates be stopped once the patient was progressing, 90% of their patients remained on bisphosphonates until they died. CONCLUSIONS: A considerable amount of effort is spent on the creation of "evidence based" treatment guidelines. Funding agencies develop policies based on these treatment guidelines, but often funding is more restrictive than the treatment guideline would suggest. It is clear from this review that physicians still appear to manage a substantial proportion of patients outside of funding policies, but within evidence based recommendations. Therefore, a need exists for either the creation of guidelines and policies that physicians will follow or the implementation of methods to ensure that restrictive policies are actually followed.

Measuring treatment preferences and willingness to pay for docetaxel in advanced ovarian cancer.

BACKGROUND: Docetaxel is an equally active alternative to paclitaxel in advanced ovarian cancer but has a different adverse effect profile. Whilst paclitaxel is associated with less haematological toxicity, such as febrile neutropenia and anaemia, docetaxel causes less sensory and motor neuropathy. OBJECTIVE: To measure the economic value and preference scores for docetaxel as an alternative to paclitaxel in patients with advanced ovarian cancer. DESIGN AND SETTING: A cost-benefit analysis using a consumer-based willingness-to-pay (WTP) approach was conducted. The study population consisted of a patient surrogate sample comprised of 80 oncology pharmacists and nurses from eight Canadian provinces. Background information on ovarian cancer was provided including its current management, and differences in adverse effects between docetaxel and paclitaxel. Respondents were then asked what their preferred product would be if they were diagnosed with ovarian cancer and how much they would be willing to pay per cycle for six cycles in the form of a co-payment (i.e. user's fee) for the product of their choice. The maximum willingness to pay for docetaxel was then compared against the incremental cost (acquisition and administration) of the drug. STUDY PERSPECTIVE: Canadian healthcare system perspective. MAIN OUTCOME MEASURES AND RESULTS: The WTP survey instrument was simple to administer and easily understood by participants. Respondents ranked motor neuropathy as being the most unpleasant adverse effect of treatment. Of the sample, 63.8% preferred to use docetaxel instead of paclitaxel (p = 0.075). The patient surrogate sample was willing to pay a mean of 64 Canadian dollars (dollars Can; 2003 values) [95% CI dollars Can33, dollars Can92] per cycle for the benefits offered by docetaxel as an alternative to paclitaxel. This estimate was marginally lower than the incremental cost of dollars Can87 per cycle of docetaxel. CONCLUSION: A substantial portion of Canadian patients with ovarian cancer would likely prefer to be treated with docetaxel instead of paclitaxel for the management of their disease and would be willing to pay a portion of the incremental cost. Therefore, both options should be offered to patients, and selection of treatment can be based on reducing the risk of the toxicity that concerns the patient the most.

Cost-effectiveness of chemotherapy for nonsmall-cell lung cancer.

After decades of research into its prevention and treatment, lung cancer remains the leading cause of cancer death in North America and Europe. Approximately 75% of all new lung cancer diagnoses are of the nonsmall-cell subtype, and less than 25% of these patients are potentially operable upon first detection. First-generation cisplatin-based chemotherapy regimens for patients with metastatic disease achieved a median survival of 175 days, with 15 to 20% of patients alive at 1 year.In recent years, vinorelbine, gemcitabine, paclitaxel, and docetaxel have emerged as promising agents in the treatment of advanced nonsmall-cell lung cancer. Evidence from randomized trials demonstrates that when these agents are combined with cisplatin, the objective tumor response is 25 to 40%, with a median overall survival approaching 300 days. In addition, recent studies have shown that single-agent docetaxel improves survival and quality of life in patients with platinum-refractory nonsmall-cell lung cancer. Since these modest but important improvements in the management of nonsmall-cell lung cancer are achieved at a significant cost, cost has emerged as a major consideration in health policy decision-making. This article reviews the pharmacoeconomic literature to provide guidance on the cost-effective use of chemotherapy in the treatment of advanced nonsmall-cell lung cancer.