Pharmacoeconomic analysis of empirical therapy with ceftazidime alone or combination antibiotics for febrile neutropenia in cancer patients

There is evidence to suggest that single-agent broad spectrum antibacterials may be cost-effective alternatives to combination antibiotics for the empirical management of febrile neutropenia in cancer patients. The objectives of the present study were 2-fold. The first objective was to compare the clinical effectiveness of ceftazidime monotherapy with that of 2 combination antibiotic regimens in cancer patients with febrile neutropenia. The 2 comparator regimens consisted of tobramycin plus piperacillin, either with (regimen 'CAP') or without (regimen 'AP') cefazolin. The second objective was to perform a cost-effectiveness analysis of the 3 regimens. Meta-analysis of randomised comparative trials between the 3 therapy groups was performed to determine the average overall response rate after 3 to 5 days of treatment. Seven clinical studies were selected for analysis. The overall incidence of adverse drug reactions (ADRs) was determined using the results of comparative and noncomparative studies. A comparative cost-analytic model was applied from a hospital perspective. The costs of primary therapy, hospitalisation, laboratory tests, routine patient care and treating ADRs were calculated, as were future costs. Monotherapy with ceftazidime was associated with an overall response rate of 63.5% and mean per-patient costs of $Can12,000 to $Can14,000. In comparison, regimen AP was associated with an overall response rate of 58.8% and mean costs of $Can13,000 to $Can16,000 per patient. The overall response rate in patients receiving CAP was 75.3%, and the mean cost per patient was $Can11,000 to $Can12,000. Thus, regimen CAP was the most cost-effective therapy from a hospital perspective.     

Effect of lenograstim on the cost of autologous bone marrow transplantation. A preliminary communication

High dose chemotherapy and autologous bone marrow transplantation (BMT) can produce prolonged remission in patients with malignant lymphoma or solid tumours. However, neutropenia is a serious complication of treatment in patients with these diseases. In this study, we investigated the costs and effects of using lenograstim, a recombinant human granulocyte colony-stimulating factor, to treat neutropenia in 16 patients with lymphoma or solid tumours. The cost of lenograstim was not included in the calculations. The duration of neutropenia and hospitalisation were both lower in patients who received lenograstim compared with no treatment. The mean cost of autologous BMT was FF142,000 in patients who received lenograstim, compared with FF166,000 in patients who did not. Savings were largely attributable to decreased expenditure on hospitalisation in the lenograstim-treated group. The cost of 14 days' treatment with lenograstim was estimated at FF10,500, based on a daily dosage of 150 micrograms/m2/day.     

Mobilization of peripheral blood stem cells by granulocyte-colony stimulating factors: comparison of a standard dose of glycosylated and mutated granulocyte-colony stimulating factor in non-Hodgkin's lymphoma patients following CHOP therapy

The effects of granulocyte-colony stimulating factor (G-CSF) have been studied in several clinical settings. G-CSFs are widely used to stimulate the production of granulocytes and are well known to mobilize peripheral blood stem cells (PBSCs). However, very few studies have examined differences among G-CSFs. The aim of this study was to compare the mobilization of PBSCs induced by a standard dose of two G-CSFs following biweekly cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. Using a standard dose of G-CSF, we conducted a randomized, crossover trial that compared the efficacy of two kinds of G-CSF, glycosylated [lenograstim (2 micrograms/kg)] and mutated [nartograstim (1 microgram/kg)], on PBSC mobilization in 10 patients with non-Hodgkin's lymphoma after biweekly CHOP chemotherapy. Lenograstim (2 micrograms/kg) was more effective in shortening the duration of neutropenia than nartograstim (1 microgram/kg) (3.8 days vs. 5.0 days, p < 0.05, the number of days for the neutrophil count to reach 5 x 10(9)/l from nadir). The number of CD34+ cells and granulocyte-macrophage colony forming units (GM-CFU) was higher for lenograstim but no statistically significant difference between the two groups was found. Glycosylated G-CSF is more effective than mutated G-CSF in shortening the duration of neutropenia. As for the mobilization of CD34+ cells and the number of CFU-GM, there was a tendency to increase in the lenograstim group but no statistically significant differences were found.     

Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective

BACKGROUND: The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) reduces the severity and duration of neutropenia and reduces the incidence of febrile neutropenia after cancer chemotherapy. However, the use of G-CSFs, particularly filgrastim, to treat established neutropenia remains controversial. A recent meta-analysis of randomised controlled trials (RCTs) evaluating G-CSF treatment for established febrile neutropenia demonstrated a reduction in prolonged hospitalisations. Because more than one-third of patients in the analysis were hospitalised for at least 10 days, this finding has broad pharmacoeconomic and clinical significance. This analysis presents the potential cost implications of G-CSF treatment for established neutropenia among hospitalised patients. METHODS: Direct medical costs ($US, year 2003 values) related to hospitalisation for established neutropenia were modelled using a hospital perspective and according to two treatment options: (i) no use of G-CSF during the neutropenic episode (control); and (ii) addition of daily G-CSF until neutrophil recovery. Within each option, we modelled the probability of a long stay (>or=10 days) and patient survival. The model used three data sets: discharge data from a consortium of academic medical institutions, drug cost data (filgrastim) from Federal payers, and estimates of G-CSF efficacy derived from a meta-analysis of RCTs of treatment in patients with established febrile neutropenia. The lowest expected total cost was predicted for both treatment options; sensitivity analyses and Monte Carlo simulations were used to evaluate the robustness of the model. RESULTS: The G-CSF arm produced the lowest expected cost, and predicted net estimated savings of $US1046 per neutropenic episode compared with the control strategy. G-CSF was less expensive than the control for most reasonable estimates of cost per day and all lengths of stay (LOS) >or=10 days. G-CSF was the least costly strategy for 73.5% of 10,000 Monte Carlo iterations, while the no-G-CSF control strategy predicted savings in 26.5% of iterations. CONCLUSIONS: This pharmacoeconomic model suggests that therapeutic use of G-CSF should be considered for patients with established neutropenia in order to reduce overall hospital cost. G-CSF treatment may offer substantial potential savings for hospitalised patients with established neutropenia over a wide range of model assumptions. Therapeutic G-CSF use among patients hospitalised for established neutropenia may complement the recommended prophylactic use of these agents for the prevention of neutropenic episodes.     

An economic evaluation of the use of granulocyte colony-stimulating factor after bone marrow transplantation in children

Studies that have assessed the use of granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation have shown a significantly reduced time to neutrophil recovery with the use of this agent, which may translate into a reduced duration of antimicrobial therapy and hospitalisation. We performed a pharmacoeconomic study evaluating the elective use of G-CSF after bone marrow transplantation in children. 22 consecutive children who underwent bone marrow transplantation and received G-CSF 5 micrograms/kg/day were compared with 18 such children (control group) who did not receive G-CSF. Despite a significant reduction in time to recovery of the absolute neutrophil count (ANC) to > 0.5 x 10(9)/L in G-CSF recipients compared with the control group (14 days vs 20.9 days; p < 0.0001), there was only a trend towards a reduction in the duration of intravenous antimicrobial therapy (14.5 days vs 18.6 days; p = 0.15), and there was no significant difference in the duration of hospitalisation (25.3 days vs 29.8 days). Reasons for prolonged hospitalisation beyond ANC recovery included continued use of total parenteral nutrition, treatment of graft-versus-host disease and treatment of ongoing infection. Overall, the mean total cost for patients receiving G-CSF was Pounds 15001, compared with Pounds 15482 for the control group (1995 values). In conclusion, while there appears to be no benefit in financial terms, the release of a child from strict isolation as a result of early ANC recovery must be taken into consideration.     

Modelling the potential economic impact of viral load-driven triple drug combination antiretroviral therapy

The purpose of this study is to model the potential economic impact of viral load-driven triple drug combination (including a protease inhibitor) antiretroviral therapy on incremental drug and hospitalisation costs among individuals with HIV disease. Individuals included in the study were HIV-positive men and women from the province of British Columbia, Canada, who were aged 18 years or older and had given consent to access their medical records. The study employed pharmacoeconomic modelling of drug- and hospital-utilisation patterns among a population-based cohort with free access to antiretroviral therapy. Protease inhibitor use and associated costs based on actual use in a subsequent period was modelled upon men and women who were able to maintain stable CD4+ cell counts (slope > or = 0) for at least 6 months (baseline period) with an average follow-up period of 30 months (protease-like group). A control was modelled upon individuals with declining CD4+ cell counts (slope < 0) during similar baseline and follow-up periods. The primary outcome measure was average annual incremental cost of triple drug therapy net of hospitalisation and testing costs in 1996 Canadian dollars ($Can). The utilisation pattern of drugs and hospitals was modelled from actual use among a total of 1271 individuals who were eligible for this analysis. Programme participants who gave consent to access their medical records were more likely to be men (p < 0.001), older (p < 0.020), and on antiretroviral therapy (p < 0.001) than programme participants who did not give consent. No differences were observed between the protease-like and comparison groups with respect to age (p = 0.65) and CD4+ cell count (p = 0.30) at study entry. Over a period of 1 year, the protease-like group was shown to spend less time in hospital (2.7 vs 6.6 days; p < 0.001). This difference in hospitalisation remained in multivariate models, adjusting for prior AIDS-defining illnesses and gender. The average annual incremental cost of adding a protease inhibitor to a 2-drug antiretroviral regimen was estimated to be $Can2318 per person. The cost implications of hospital stay while using a protease inhibitor drug and 2 nucleosides translated into an average annual incremental cost (savings if negative) of between -$Can4798 and -$Can2227 per person. The overall average annual incremental cost impact per person associated with triple drug therapy with a protease inhibitor varied between -$Can2288 to $Can283. Negative incremental costs imply overall savings from adopting triple combination therapy. This modelling exercise demonstrated that the cost of triple drug combination antiretroviral therapy with a protease inhibitor among HIV-positive men and women was considerably less than the expected acquisition cost of the drug alone due to hospitalisation savings in the province of British Columbia.     

Cost analyses of adjunct colony stimulating factors for older patients with acute myeloid leukaemia : can they improve clinical decision making?

Colony stimulating factors (CSF) have been shown to reduce the duration of neutropenia following intensive chemotherapy in a variety of settings, with many of these studies targeting older patients with leukaemia. We review the clinical and economic findings for use of growth factors for older adults with acute myelogenous leukaemia (AML). The cost analyses were based on the perspective of the third party payer. One study, conducted by the Southwest Oncology Group (SWOG) randomised 207 AML patients to receive granulocyte colony-stimulating factor (G-CSF) or placebo and found no significant difference in number of infections and in days of hospitalisation, 3 fewer days with an absolute neutrophil count <500 cells/microL with G-CSF, and an estimated incremental cost of only US 120 dollars with G-CSF over placebo (1997 costs). A second study, conducted by the Eastern Cooperative Oncology Group (ECOG), randomised 119 AML patients to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo and found a reduction in severe infections, 4 fewer days with an absolute neutrophil count <500 cells/microL, no significant difference in the duration of hospitalisation, and estimated cost savings of US 2310 dollars with GM-CSF (1997 costs). These data may be useful to physicians faced with concerns over clinical and economic factors associated with CSF use as adjunct therapy for older persons with AML.     

Cost effectiveness of cephalosporin monotherapy and aminoglycoside/ureidopenicillin combination therapy. For the treatment of febrile episodes in neutropenic patients

OBJECTIVE: To assess the relative cost effectiveness of cephalosporin monotherapy options and aminoglycoside/ureidopenicillin combination therapy for the treatment of febrile episodes in adult patients with neutropenia. DESIGN AND SETTING: This was a retrospective cost-effectiveness analysis conducted from the institutional perspective. METHODS: The analysis was based on 741 febrile episodes in adult patients with neutropenia enrolled in 5 randomised trials: 3 comparing monotherapy with ceftazidime or cefepime, and 2 comparing cefepime monotherapy versus aminoglycoside/ureidopenicillin combination therapy. Resource utilisation included costs for study antibacterials, treatment of adverse effects and failures, and hospitalisation. The primary end-point was the overall cost of treatment per patient. Cost-effectiveness ratios were also analysed. RESULTS: No significant differences in clinical success rates were detected. Median per-patient costs in the monotherapy comparisons were $US7849 for cefepime and $US7788 for ceftazidime [1997 values; not significantly different (NS)]. Corresponding costs for the monotherapy versus combination therapy comparisons were $US9780 for cefepime and $US10 159 for gentamicin/ureidopenicillin (NS). Despite a higher acquisition cost for cefepime, there were no statistically significant differences in cost effectiveness compared with either ceftazidime monotherapy or gentamicin/ureidopenicillin combination therapy. Sensitivity analyses revealed that monotherapy can be cost effective compared with combination therapy in many situations. CONCLUSION: There were no economic differences between the 3 regimens tested. Therefore drug cost should not be a deciding factor when choosing antibacterial therapy for the treatment of febrile episodes in adult patients with neutropenia.     

Incremental cost analysis of ambulatory clinic and home-based intravenous therapy for patients with multiple myeloma

BACKGROUND: Patients with multiple myeloma and other forms of cancer receiving pamidronate via intravenous (IV) infusion at the Hamilton Regional Cancer Centre in Hamilton, Ontario, Canada face 2 treatment options: they can have their entire treatment completed at the clinic using traditional IV therapy (e.g. IV bag and pole) or they can have the treatment initiated at the clinic and then return home to complete the treatment utilising a portable and disposable IV therapy device. OBJECTIVE: To perform a cost analysis of these 2 treatment options. PERSPECTIVE: Societal. METHODS AND PATIENTS: Data on all patients with multiple myeloma who attended the Hamilton Regional Cancer Centre for pamidronate therapy from November 1, 1997 to October 31, 1998 were collected from clinic records. As almost all of these patients with multiple myeloma completed their IV therapy at home, comparison to clinic-based therapy was based on derived cost estimates. Cost data, where possible, were acquired from the Hamilton Regional Cancer Centre's records. A sensitivity analysis was also conducted. RESULTS: In the base-case scenario for the study period, the incremental cost of the infusion device and training in Canadian dollars ($Can; 1998 values) for the 48 patients (299 cycles) who had their infusion initiated at the clinic but completed at home was $Can 5.50/cycle ($Can 4,636 for the 299 cycles). If these 48 patients had had their entire infusion at the clinic, the incremental costs of overtime treatment, parking, clinic overheads and lost work or leisure time would have been $Can 68.49/cycle ($Can 20,477 for the 299 cycles). Therefore, shifting treatment from the clinic to the home resulted in net cost savings to society of $Can 52.98/cycle ($Can 15,841 for the 299 cycles). Sensitivity analysis of best- and worst-cost scenarios did not alter the substantive findings although the relative difference between treatment options varied. In the best-case scenario, home treatment was $Can 95.97/cycle ($Can 28,696 for the 299 cycles) less costly than clinic treatment, while in the worst-case scenario, home treatment was $Can 17.19/cycle ($Can 5,141 for the 299 cycles) less costly than clinic treatment. The results also demonstrated that clinic overheads, the cost of a portable and disposable infusion device and the cost of lost work and leisure time had the greatest impact on incremental costs for each treatment option. CONCLUSION: Subject to study limitations, a significant cost advantage was demonstrated through the home-based treatment option for patients with multiple myeloma. Key issues that must be addressed in future evaluations include the precise determination of clinic overheads, the valuation of lost work and/or leisure time and the direct cost of portable and disposable infusion devices.     

Cost analysis of 2 empiric antibacterial regimens containing glycopeptides for the treatment of febrile neutropenia in patients with acute leukaemia.

OBJECTIVE: Patients with cancer-associated neutropenia are at high risk of developing severe infections which can be fatal if treatment is not promptly administered. For this reason, fever is treated as soon as possible with broad spectrum antibacterial therapy. The objective of this study was to conduct a cost analysis in Italy comparing 2 empiric glycoprotein-containing antibacterial regimens for the treatment of febrile neutropenia in patients with acute leukaemia. DESIGN AND SETTING: A retrospective cost analysis was conducted, using the records of 527 febrile neutropenic patients with acute leukaemia who participated in an 18-month multicentre (29 Italian haematological units) randomised trial during 1991. All patients received either of the following 2 empiric intravenous regimens, each containing 3 antibacterial agents: ceftazidime (2 g, 3 times daily) and amikacin (15 mg/kg/day, in 3 separate doses) plus teicoplanin (6 mg/kg, in a single dose) or vancomycin (30 mg/kg/day, in 2 separate doses). Economic analyses were carried out from a hospital perspective. Only the direct costs per patient, i.e. mean antibacterial treatment and management cost, mean overall treatment failure cost and mean cost of adverse effects, were included. MAIN OUTCOME MEASURES AND RESULTS: No differences were found in the clinical response, defined as the improvement in the rate of fever or infection (if documented), between the 2 regimens. However, tolerability, defined as the incidence of adverse effects probably or definitely related to the assigned treatment, was reported to be better with the teicoplanin-rather than the vancomycin-containing regimen. CONCLUSIONS: Thus retrospective cost analysis showed that despite the higher acquisition cost of teicoplanin relative to vancomycin, the lower incidence of adverse effects associated with teicoplanin and its ease of administration (single daily dose) resulted in equivalent overall treatment costs between teicoplanin- and vancomycin containing regimens.     

Economic evaluation of oral sumatriptan compared with oral caffeine/ergotamine for migraine

We conducted an economic comparison of oral sumatriptan with oral caffeine/ergotamine in the treatment of patients with migraine. Cost-effectiveness, cost-utility and cost-benefit analyses were conducted from societal and health-departmental perspectives. A decision tree was used. Utilities were assigned to health states using the Quality of Well-Being Scale. Simple and probabilistic sensitivity analyses were also carried out. From a societal perspective, using sumatriptan instead of caffeine/ergotamine resulted in an incremental cost-effectiveness ratio of -25 Canadian dollars ($Can) per attack aborted, an incremental cost-utility ratio of -$Can7507 per quality-adjusted life-year (QALY), and a net economic benefit of $Can42 per patient per year (1995 values). From the perspective of the health department, the incremental cost-effectiveness ratio was $Can98 per attack aborted, the incremental cost-utility ratio was $Can29,366 per QALY; the grade of recommendation based on past decisions regarding health technology for adoption into health insurance plans was 'moderate'. Sensitivity analysis showed that the results were robust to relatively large changes in the input variables. The incremental health benefits obtained from using oral sumatriptan rather than oral caffeine/ergotamine were achieved at moderately acceptable incremental costs, if past decisions on the adoption of other health technologies are used as a guide.     

Cost effectiveness of multi-therapy treatment strategies in the prevention of vertebral fractures in postmenopausal women with osteoporosis.

OBJECTIVE: The aim of this study was to evaluate the cost effectiveness of multi-therapy treatment strategies in the prevention of vertebral fractures in postmenopausal women with osteoporosis. DESIGN: A retrospective, incremental cost-effectiveness analysis was conducted from a societal perspective. It compared 9 treatment strategies over 3 years and incorporated the willingness of patients to initiate and continue each therapy. MAIN OUTCOME MEASURES AND RESULTS: Four nondominated strategies formed the efficient frontier in the following order: (i) calcium-->no therapy; (ii) ovarian hormone therapy (OHT)-->calcium-->no therapy [166 Canadian dollars ($Can)]; (iii) OHT-->etidronate-->calcium-->no therapy ($Can2331); and (iv) OHT-->alendronate-->calcium-->no therapy ($Can40,965). The figures in parentheses are the incremental costs per vertebral fracture averted to move to that strategy from the previous strategy for patients who had undergone a hysterectomy. CONCLUSIONS: We identified 4 efficient multi-therapy strategies for the treatment of vertebral osteoporosis in postmenopausal women, 2 of which were consistent with the practice guidelines of the Osteoporosis Society of Canada. Decision-makers may select from among these efficient strategies on the basis of incremental cost effectiveness.     

Cost analysis of ropinirole versus levodopa in the treatment of Parkinson's disease

BACKGROUND: Not all patients with Parkinson's disease (PD) respond to levodopa and others develop dyskinesias. Ropinirole, a dopamine agonist, is associated with fewer dyskinesias than levodopa. OBJECTIVE: To examine the economic impact of reducing dyskinesias using ropinirole instead of levodopa plus benserazide in PD was examined. The research question addressed was: is the added cost of ropinirole offset by savings due to avoided cases of dyskinesia? METHODS: A cost-minimisation analysis was performed from both the societal and Ministry of Health (MoH) of Ontario, Canada perspectives, using 5-year data from a study of dyskinesia outcomes comparing ropinirole with levodopa plus benserazide. A predictive model was developed to capture resource utilisation over 5 years, such as medication costs, medical consultations, hospital admissions, nursing home admissions, caregiver time and productivity loss. The model was based on a previously reported clinical trial which determined dyskinesia rates to be 20% for ropinirole and 45% for levodopa. Standard costing lists were used, and costs were discounted at various rates. Constant 1999 Canadian dollars ($Can) were applied, and no increases were assumed over the time horizon of the analysis. A multivariate sensitivity analysis with changes in key parameters was also performed. RESULTS: From a societal perspective, ropinirole was cost saving. From the MoH perspective, the analysis yielded an incremental expected daily cost/patient of $Can4.41 for substituting levodopa plus benserazide with ropinirole. Ropinirole resulted in daily savings/patient of $Can0.17 in non-drug healthcare costs. In the sensitivity analysis, the direction of results did not change despite changes of 15 to 20% in key parameters, suggesting robustness of the model. CONCLUSIONS: From the societal perspective, in comparison with levodopa plus benserazide, the added cost of ropinirole is offset by savings due to avoided cases of dyskinesia.     

Economic evaluation of norethisterone acetate/ethinylestradiol (FemHRT) for women with menopausal symptoms

INTRODUCTION: The objective of this study was to assess the cost effectiveness of a continuous combined oral preparation of norethisterone (norethindrone) acetate and ethinylestradiol (NA/EE) [FemHRT] as both a first-line and second-line therapy for menopausal women. PERSPECTIVE: Third-party payer. METHODS: The cost effectiveness of NA/EE was assessed as both a first- and second-line therapy in comparison with conjugated equine oestrogen 0.625mg and medroxyprogesterone acetate 2.5mg (CEE/MPA) and no therapy. Analysis was conducted within a Markov model with states relating to the presence and absence of vaginal bleeding, menopausal symptoms and hip fracture. Analysis forecasted life expectancy, QALYs and lifetime costs for a 50-year-old menopausal woman. Compliance was modelled related to menopausal symptoms and vaginal bleeding. For the base-case analysis, it was assumed that compliant women would take therapy for up to 5 years. Sensitivity analysis assumed therapy was taken only for 1 year. RESULTS: Compared with both CEE/MPA and no therapy, NA/EE led to an increase in both costs and QALYs, both as a first- and second-line therapy. For first-line therapy, the incremental cost per QALY gained for NA/EE was $2200 Canadian dollars ($Can; 1999 values) [compared with no therapy] and was $Can20 300 (compared with CEE/MPA). For second-line therapy, the incremental cost per QALY gained for NA/EE was $Can900 (compared with no therapy) and was $Can16 400 (compared with CEE/MPA). Results were robust to most sensitivity analyses. CONCLUSIONS: NA/EE is a cost-effective therapy for women with menopausal symptoms both as a first-line and second-line therapy.     

Granulocytic growth factors and cancer-related neutropenia: limited effects

(1) Cancer chemotherapy often causes haematological complications, in particular neutropenia, which can have grave consequences in terms of the risk of infections (increasing with the degree and duration of neutropenia) and the need for modifications in chemotherapy protocols (longer intervals between cycles or dose reductions). (2) In France, three haematopoietic growth factors are licensed to stimulate leukocyte production: filgrastim (unglycosylated granulocyte colony-stimulating factor (G-CSF)), pegfilgrastim (pegylated filgrastim), and lenograstim (glycosylated G-CSF). (3) The main adverse effects of these three growth factors are joint and bone pain, a flu-like syndrome, and reactions at the injection site. (4) G-CSF has provided disappointing results in primary prevention, and its use is only justified for patients receiving chemotherapy that causes febrile neutropenia in at least 40% of cases: patients with acute leukaemia, elderly patients, and patients with cancer-related neutropenia or poor general status, etc. In these patients, G-CSF reduces the incidence of febrile neutropenia and, possibly, the risk of hospitalisation. A meta-analysis of 11 comparative trials involving about 1500 patients with non Hodgkin's lymphoma showed only a reduction in the incidence of febrile neutropenia and infections. (5) In the prevention of recurrences of neutropenia on continuing chemotherapy, only one trial, involving patients aged over 60 with high-grade non Hodgkin's lymphoma, showed an improvement in survival time with filgrastim (survival rate: 64.3% with filgrastim versus 49% with placebo, after a median follow-up of 40 months). Until these results are confirmed in other clinical trials, reduction in the intensity of chemotherapy (dosage, frequency) is generally recommended. (6) Curative treatment of neutropenia with G-CSF is only warranted for febrile patients with a high risk of severe infections requiring lengthy hospitalisation. Two meta-analyses, one including 8 trials and the other including 13 trials, involving a total of about 1500 patients, only showed a reduction in the length of hospitalisation.     

Treatment costs and quality of life with granulocyte-macrophage colony-stimulating factor in patients with antineoplastic therapy-related febrile neutropenia. Results of a randomised placebo-controlled trial

This study examined the costs of treatment of, and quality of life in, patients with antineoplastic therapy-induced neutropenic fever who were treated with antibacterials, with or without granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients with haematological malignancies (n = 47) or solid tumours (n = 87) who had severe neutropenia (neutrophil count < 0.5 x 10(9)/L) and fever (> 38.5 degrees C once, or > 38 degrees C twice, in a 12-hour observation period) were randomised to receive subcutaneous GM-CSF 5 micrograms/kg/day (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibacterials. GM-CSF enhanced neutrophil recovery compared with placebo. Median neutrophil counts at day 4 were 2.9 (range 0 to 25) x 10(9)/L in the GM-CSF arm and 1.3 (range 0 to 9) x 10(9)/L in the placebo group (p < 0.001). No significant difference was observed with regard to median days with neutrophil count < or = 1.0 x 10(9)/L or in time to resolution of fever. Quality-of-life scores in 90 patients demonstrated significant differences in favour of the placebo group. The results for the oncology and haematology patients were similar to the results for the total group. Patients in the GM-CSF and placebo groups had a mean hospital stay of 7.25 and 8.33 days, respectively. Hospital costs were higher for the GM-CSF-treated patients when GM-CSF was included in the price [mean costs: GM-CSF arm $US 5177 vs placebo arm $US 4178 (p < 0.05; 1992 values)]. The haematology patients stayed longer in hospital than the oncology patients, resulting in higher total costs for the former group. These results indicate that GM-CSF does not affect the number of days required for resolution of fever of the hospitalisation period for this patient group, and does not provide a cost-effective contribution to the treatment of these patients. Sensitivity analyses indicate that GM-CSF would produce savings if the duration of hospitalisation with GM-CSF was < or = 76.5% of that in the placebo group.     

Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication

OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment. DESIGN: A decision-analytical model was developed to estimate expected per patient costs [1998 Canadian dollars ($ Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). MAIN OUTCOME MEASURES AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216). CONCLUSION: From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both. More data on the clinical and statistical differences in H. pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.     

Recombinant granulocyte colony-stimulating factor (rG-CSF): pharmacoeconomic considerations in chemotherapy-induced neutropenia

Recombinant granulocyte colony-stimulating factor (rG-CSF) therapy is associated with a dose-proportional reduction in the frequency, duration and severity of neutropenia associated with cytotoxic chemotherapy. This is associated with a decrease in the incidence of infection, with subsequent reductions in the number of hospitalisations, days of hospitalisation and antibiotic requirements. These effects produce marked reductions in costs, and could contribute substantially towards offsetting the costs of rG-CSF, although the magnitude of the savings will vary between institutions and with the chemotherapy regimen used. Other benefits include a reduction in the frequency and severity of mucositis, and an improved patient quality of life. However, further research is required to evaluate other potentially important considerations including the targeting of specific patient populations (e.g. those receiving regimens with a curative intent), and additional improvements in patient quality of life and, perhaps, mortality. Thus, although specific pharmacoeconomic analyses are limited, preliminary evidence indicates that rG-CSF, administered prior to the onset of neutropenia in patients receiving cytotoxic chemotherapy, can provide cost reductions both from an institutional and a payor perspective, with even greater potential savings from a societal viewpoint.