Cost-effectiveness of folfirinox for first-line treatment of metastatic pancreatic cancer.

BACKGROUND: The accord 11/0402 trial demonstrated that folfirinox (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is significantly more efficacious than gemcitabine monotherapy in the first-line treatment of metastatic pancreatic cancer (mpc). The present study assessed the cost-effectiveness of first-line folfirinox compared with first-line gemcitabine for public payers in Canada. METHODS: A Markov model simulated the movement of mpc patients from first-line treatment until death. Overall survival (os) and progression-free survival (pfs) data were derived from accord. Published utility data and Canadian costs were applied based on time in each health state and on treatment-related adverse event (ae) rates. Costs included first- and second-line therapy, monitoring, and costs to treat aes. Two separate analyses were performed. Analysis 1 was based on trial data [first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by second-line platinum-based chemotherapy, with use of granulocyte colony-stimulating factor (g-csf) allowed], and analysis 2 used Ontario treatment patterns before folfirinox funding (first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by best supportive care, no use of g-csf). RESULTS: Compared with first-line gemcitabine, first-line folfirinox resulted in more life-years and quality adjusted life-years (qalys). Probabilistic sensitivity analysis results showed that, for analyses 1 and 2 respectively, folfirinox has a greater than 85% probability and an approximately 80% probability of being cost-effective at the $100,000 threshold. CONCLUSIONS: Compared with gemcitabine, first-line folfirinox significantly prolongs median os. Given the favourable cost per qaly, the improvement in clinical efficacy, and the limited available treatment options, folfirinox represents an attractive cost-effective treatment for mpc.

Cost effectiveness of TAC versus FAC in adjuvant treatment of node-positive breast cancer.

BACKGROUND: This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi-Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (TAC) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) following primary surgery for breast cancer in women with operable, axillary lymph node-positive breast cancer. METHODS: A Markov model looking at two time phases-5-year treatment and long-term follow-up-was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were "no recurrence," "locoregional recurrence," "distant recurrence," and "death." Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration costs, relapse and follow-up costs, costs for management of adverse events, and costs for granulocyte colony-stimulating factor (G-CSF) prophylaxis. A 5% discount rate was applied to costs and outcomes alike. Health utilities were obtained from published sources. RESULTS: For TAC as compared with fac, the incremental cost was $6921 per life-year (LY) gained and $6,848 per quality-adjusted life-year (QALY) gained. The model was robust to changes in input variables (for example, febrile neutropenia rate, utility). When G-CSF and antibiotics were given prophylactically before every cycle, the incremental ratios increased to $13,183 and $13,044 respectively. CONCLUSIONS: Compared with FAC, TAC offered improved response at a higher cost. The cost-effectiveness ratios were low, indicating good economic value in the adjuvant setting of node-positive breast cancer patients.

Cost-effectiveness of oxaliplatin in the adjuvant treatment of colon cancer in Canada.

OBJECTIVE: The cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5FU/LV)-the FOLFOX regimen-was compared with that of 5FU/LV alone as adjuvant therapy for patients with stage III colon cancer, from the perspective of the Cancer Care Ontario New Drug Funding Program. In the mosaic (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) trial, the FOLFOX regimen significantly improved disease-free survival. The mosaic trial formed the basis of the present analysis. METHODOLOGY: Extrapolated patient-level data from the mosaic trial were used to model patient outcomes from treatment until death. Utilities were obtained from the literature. Resource utilization data were derived from the mosaic trial and supplemented with data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, the London Health Sciences Centre, and the literature. RESULTS: Lifetime incremental cost-effectiveness ratios for FOLFOX compared with 5fu/lv were CA$14,266 per disease-free year, CA$23,598 per life-year saved, and CA$24,104 per quality adjusted life-year (QALY) gained, discounting costs and outcomes at 5% per annum. These results were stable for a wide range of inputs; only utility values associated with relapse seemed to influence the cost-effectiveness ratios observed. CONCLUSIONS: With an incremental cost of CA$24,104 per QALY gained, FOLFOX is a cost-effective adjuvant treatment for stage iii colon cancer. Compared with 5fu/lv alone, this regimen offers better clinical outcomes and provides good value for money.

Propentofylline treatment for Alzheimer disease and vascular dementia: an economic evaluation based on functional abilities.

A Canadian economic evaluation of propentofylline (a therapy shown to be effective for patients with mild to moderate Alzheimer disease and/or vascular dementia) versus standard care was conducted. Patients were categorized by functional abilities according to the Alberta Resident Classification System by translating measures that were originally captured through the Gottfries-Bråne-Steen scale. The Alberta Resident Classification System was then linked to a community dataset of home care costs for a population with dementia. Cost and cost-effectiveness analyses were performed from the perspective of the Ministry of Health, the caregiver, and society using an intent-to-treat analysis for propentofylline versus placebo. Results, limited to the 48-week clinical trial duration, indicated that propentofylline improved health outcomes of persons with dementia as statistically significant treatment effects were found. However, although an incremental cost for the propentofylline intervention was incurred from the Ministry of Health perspective, home care and, to a larger extent, caregiver costs were reduced. Savings in these areas may have partially offset annual treatment medication costs because a non-statistically significant cost difference was observed from a societal perspective.

Alzheimer's disease: a review of the disease, its epidemiology and economic impact.

This article consists of a critical review of Canadian, American and European studies published between 1976 and 1997 on the subject of Alzheimer's disease (AD), and its epidemiology, patterns of care, prognostic factors, and economic impact. As the population ages in North America and Europe, significant increases in the prevalence of AD over the next decades have been projected. The elderly population represents the largest consumer group of health care resources and the management of common diseases occurring in this population will have major medical, social, and economic implications. As a result, researchers will need to integrate the ever-increasing knowledge on AD when addressing governmental and societal concerns regarding its impact. Described herein is the study findings, limitations, and differences observed following the review of the diagnostic criteria, prevalence rates, incidence rates and risk factors. Highlighted are the areas where data is lacking. To refine current models of disease progression, and better address where health care resources and new therapies would be most beneficial, the review of predictors of institutionalization and predictive models of disease progression and survival, was performed. New research questions are indicated.

Pharmacokinetic origin of carbamazepine-induced resistance to vecuronium neuromuscular blockade in anesthetized patients.

BACKGROUND: Patients receiving chronic carbamazepine therapy have shortened recovery times from a neuromuscular block induced by vecuronium. The current study investigates the pharmacokinetic or pharmacodynamic mechanisms responsible for this observation. METHODS: Pharmacokinetics and pharmacodynamics of 0.1 mg/kg intravenous bolus vecuronium in ten epileptic patients receiving chronic carbamazepine therapy were compared to that of ten control subjects. All patients were scheduled for neurosurgery while anesthetized with isoflurane and sufentanil. Arterial blood samples were collected for 6 h. Plasma vecuronium concentrations were measured by high-performance liquid chromatography coupled to electrochemical detection. The adductor pollicis force of contraction was recorded after supramaximal ulnar nerve stimulation. Plasma vecuronium concentrations were fitted to a two-compartment pharmacokinetic model, and the effect compartment equilibration rate constant was derived with a nonparametric link model. The effect compartment concentrations were fitted to a sigmoid Emax model. Results were compared using Student's t-test for independent samples. RESULTS: In the carbamazepine group, the mean recovery times to T(1) 25% were shorter (28.1 +/- 3.4 vs. 47.3 +/- 5.1 min in control subjects; P=0.007), and the T(1) 25% to T(1) 75% recovery index was decreased (7.6 +/- 1.2 vs. 21.9 +/- 6.8 min in control subjects; P=0.025). No changes in onset times were observed. Clearance was 9.0 +/- 1.2 ml x kg-1 x min-1 versus 3.8 +/- 0.3 in the control group (P=0.003), whereas no changes in volumes of distribution at steady-state were observed. Therefore, the mean residence time was halved (17.8 +/- 2.5 vs. 31.9 +/- 2.5 min in control subjects; P=0.001). No differences in the effect compartment equilibration rate constant, vecuronium effect compartment concentration present at a 50% block (EC50), or slope of the sigmoid between the two groups were found. CONCLUSIONS: The twofold increase in clearance provides evidence of a pharmacokinetic origin to the carbamazepine-vecuronium interaction; however, the possibility of a concurrent pharmacodynamic alteration cannot be assessed. Greater knowledge of protein drug binding needs to be acquired to give a meaningful interpretation to the similar EC50 values observed in the two groups.

Measuring recovery from general anaesthesia using critical flicker frequency: a comparison of two methods.

Critical flicker frequency (CFF) is the frequency at which a flickering light appears steady. It is a sensitive measure for assessing recovery from anaesthesia. The CFF is almost always determined with the method of limits by which the flickering frequency is progressively decreased (or increased) until the patient reports a change from fusion to flicker (or flicker to fusion). This method has two disadvantages: it is influenced by the response bias (i.e., the subjective criterion used by the subject to decide that flicker is present or absent) and by the response delay (i.e., the interval between the perceptual change and the response). To avoid these problems, the method of forced choice is recommended. For each trial, the subject observes the light during two short successive periods. The light flickers during only one period, according to chance. The patient must indicate the period during which flickers occur. If uncertain, the patient has to make a guess. The aim of this study was to compare the two methods for assessing recovery from general anaesthesia. Two induction agents were used to obtain different recovery profiles. Twenty patients undergoing uncomplicated surgery lasting less than two hours were tested. They received either thiopentone or midazolam for induction, according to a randomized design. Vecuronium was used to facilitate tracheal intubation and anaesthesia was maintained with fentanyl, isoflurane and nitrous oxide. The CFF was measured before induction and at 60, 120 and 180 minutes after arrival in the recovery room. The person measuring CFF was unaware of the induction agent used.(ABSTRACT TRUNCATED AT 250 WORDS)