Ginkgo biloba extract EGb 761 in the treatment of dementia: a pharmacoeconomic analysis of the Austrian setting.

OBJECTIVE: We used efficacy data from three clinical trials to investigate the pharmacoeconomic implications of treating noninstitutionalized Austrian dementia patients with a drug based on EGb 761R, a standardized extract from Gingkgo biloba. In a separate analysis, we compared the pharmacoeconomic aspects of achieving treatment success with EGb 761R and cholinesterase inhibitors. METHODS: A fixed-effect model was used to conduct a metaanalysis of activities of daily living data from 1,201 patients diagnosed with dementia and treated with either EGb 761R (240 mg/day) or matched placebo for 22 or 24 weeks under double-blind conditions. From this analysis, the delay in activities of daily living (ADL)-based disease progression was estimated. Current Austrian drug reimbursement prices, physician fees, and federal subsidies for seven stages of home care were applied to calculate overall costs in four scenarios. For the comparison with cholinesterase inhibitors, metaanalysis data pertaining to overall clinical impression as published by the Cochrane Group were compared to corresponding data from our EGb 761R studies. RESULTS AND DISCUSSION: The benefit of treatment with EGb 761R (240 mg/day) corresponds to a delay in ADL deterioration by 22.3 months compared to placebo. Overall net savings with EGb 761R treatment ranged from EUR 3,692 to EUR 29,577, mainly driven by delays in progression towards higher home care subsidies. For one additional therapy success with EGb 761R, EUR 530.88 was required. In a tentative cost comparison, cholinesterase inhibitors required higher expenses to achieve treatment success.

Adecuación del uso de ketorolaco en un hospital de traumatología / Appropriateness of ketorolac use in a trauma hospital

Objetivo: Adecuar la prescripción y el uso de ketorolaco, así como los demás antiinflamatorios no esteroideos (AINE) y analgésicos disponibles en la "Guía farmacoterapéutica" del hospital (GFT). Material y métodos: Este trabajo se estructuró siguiendo los pasos que integran un ciclo de mejora (PDCA). Se analizó el problema mediante un diagrama de Ishikawa. Se elaboraron tanto indicadores de calidad cualitativos, que medían la calidad de la prescripción, como cuantitativos (dosis diaria definida [DDD]/100E), que medían el consumo de medicamentos, y se marcaron los objetivos a alcanzar. Dichos indicadores se cuantificaron en el periodo previo y posterior a la implantación de las estrategias de mejora. La población estudiada fueron los pacientes ingresados en los servicios de traumatología y cirugía plástica con sistema de distribución de medicamentos en dosis unitaria. La estrategia de mejora consistió en el aporte de información mediante sesiones informativas y entrega de documentación a los médicos prescriptores en el periodo preintervención. Los resultados obtenidos se compararon con los objetivos iniciales para comprobar su cumplimiento. Resultados: Indicadores cualitativos: se incrementó el uso de ketorolaco intravenoso hasta2 días en el 25,5% (p < 0,001), y en pacientes de 65 años o más a dosis ≤ 60 mg/día un27,7% (p < 0,05). Indicadores cuantitativos: el consumo de ketorolaco descendió (cirugía plástica, 61,8 DDD/100E a 14,8), y el consumo de tramadol, ibuprofeno y metamizol aumentó (cirugía plástica, de 0 a 14,1; de 8,7 a 48,6 y de 50,1 a 71, respectivamente). Conclusiones: Se ha adecuado la prescripción y el uso de ketorolaco, AINE y tramadol, lo que proporciona mayor seguridad al paciente. Las estrategias utilizadas han sido efectivas (AU)

Objective: To evaluate the suitability of ketorolac and non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesic drugs currently used in the hospital. Material and method: We have followed the steps to develop a PDCA cycle (plan, do, check, act) or quality improvement cycle. The quality problem was analysed using anIshikawa diagram. We defined both qualitative quality indicators, those that measure prescription quality, and quantitative ones (defined daily dose, DDD/100BDs), which measure drug consumption, being the objectives to achieve. The study was conducted in all patients admitted to the hospital and who were admitted to orthopaedic and trauma surgery and plastic surgery departments with unit-dose dispensing systems. The strategy used was to give information to physicians through meetings and documentation. Finally, the results were analysed and compared with the initial objectives. Results: The study was performed on 260 patients in the first study period and 292 in the second. Qualitative indicators: intravenous ketorolac use ≤ 2 days, increased in 25.5% (p< 0.001); in patients ≥ 65 years old at dose ≤ 60 mg/day it increased 27.7% (p < 0.05). Quantitative indicators: in the second study period, ketorolac use decreased (plastic surgery department: 61.8 DDD/100BDs to 14.8), whereas tramadol, ibuprofen and metamizole increased (plastic surgery department: 0 to 14.1 in tramadol, 8.7 to 48.6 in ibuprofen and 50.1 to 71 in metamizole). Conclusions: Appropriateness of ketorolac, NSAIDs and tramadol use has been achieved, thus improving patient safety. Strategies have been effective (AU)

Effects of the German reference drug program on ex-factory prices of prescription drugs: a panel data approach.

This paper examines effects of the German social health insurance system's reference drug program (RDP) for prescription drugs on ex-factory prices. Moreover, we analyze whether manufacturers adapt prices of their products that are not subject to reference pricing as a consequence of changes in reference prices of their products that are subject to reference pricing. We use econometric panel data methods based on a large panel data set of nearly all German prescription drugs on a monthly basis between October 1994 and July 2005. They provide information on ex-factory prices, reference prices, manufacturers, type of prescription drug, and market entries and exits. Our results show that there is no full price adjustment: A 1%-change in reference prices leads to a 0.3%-change in market prices. Price adjustment, however, is fast - it mostly happens in the first month. Furthermore, the first introduction of a reference price reduces market prices of the affected products by approximately 7%. Finally, we observe a significant time effect that is positive in the market without reference prices and negative in the market with reference prices.

Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium.

OBJECTIVES: Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payer's perspective. METHODS: We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. RESULTS: In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. CONCLUSIONS: The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

BACKGROUND: Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. OBJECTIVE: To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. METHODS: A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. RESULTS: Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. CONCLUSION: Results of this analysis of the cost effectiveness of oral deferasirox versus infusional deferoxamine suggest that deferasirox is a cost effective iron chelator from a US healthcare perspective.

Cost-effectiveness as an outcome in randomized clinical trials.

BACKGROUND: Economic outcomes are now included in many contemporary randomized trials and provide an additional dimension to the assessment of interventions. Economic data collection and analysis pose several methodologic challenges, however. PURPOSE: This paper reviews methods of incorporating economic outcomes in clinical trials. RESULTS: Data on medical resource utilization and cost can readily be collected along with data on clinical outcomes. The cost of planned interventions can be measured with reasonable accuracy, but costs due to unplanned clinical events are more difficult to measure reliably. The total cost depends critically on these relatively infrequent, yet costly, adverse outcomes, which may partially, or even completely, offset any difference between the planned costs of the randomized therapies. Newer therapies are typically more expensive than older therapies, so the most important question is whether patient outcomes are improved sufficiently to justify the added expense. Cost-effectiveness analysis helps gauge the value provided by a new therapy. The cost-effectiveness of an intervention compared with an alternative is defined as the ratio of the incremental costs and the incremental clinical benefits, measured as dollars per quality-adjusted life-year added. The follow-up period in most clinical trials is generally long enough to measure the added cost of therapy, but may not capture the full benefits of treatment. The limited time horizon of clinical trials makes it necessary to use a model to extrapolate the observed effect of treatment and project the increase in life expectancy. The resulting cost-effectiveness ratio is sensitive to assumptions about the long-term efficacy of treatment, particularly whether the treatment effect will continue or dissipate over time. CONCLUSION: Economic outcomes can be measured alongside clinical outcomes in randomized trial. While the use of cost-effectiveness models falls outside the strictly empirical, within-trial analysis framework that is embraced by most clinical trialists, it provides an explicit approach to assessing whether the intervention under study provides a clinically meaningful improvement in outcome that is worthwhile.

Cost-effectiveness analysis of rizatriptan and sumatriptan versus Cafergot in the acute treatment of migraine.

BACKGROUND: Both ergotamine and selective serotonin 5-HT(1B/1D) receptor agonists ('triptans') are currently used in the treatment of moderate to severe migraine. Ergotamine is a traditional therapy with a lower drug acquisition cost compared with triptans. It has been shown that triptans are more efficacious than ergotamine, but the higher acquisition costs and shorter duration of action are disadvantages of triptans compared with ergotamine. OBJECTIVE: The purpose of this study was to provide a comparison of the cost-effectiveness of rizatriptan 10 mg and sumatriptan 50 mg tablets with that of a fixed-dose combination of ergotamine tartrate plus caffeine (Cafergot) in the treatment of an acute migraine attack. The cost-effectiveness of rizatriptan in comparison with sumatriptan was also assessed. METHODS: Three separate decision tree models were developed (model 1: rizatriptan vs Cafergot; model 2: sumatriptan vs Cafergot; model 3: rizatriptan vs sumatriptan). The time horizon was 1 year. Cost-effectiveness analysis was conducted from the societal perspective using cost and effectiveness estimates from the literature. All costs were converted to US dollars (2003). The cost-effectiveness ratio was expressed as incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: Base case evaluation showed that both rizatriptan and sumatriptan dominated Cafergot. The net annual saving associated with use of rizatriptan was US dollars 622.98 per patient, with an incremental QALY of 0.001. Use of sumatriptan resulted in a saving of US dollars 620.90 and an increase in QALY. The cost-effective ratios were not sensitive to changes in key variables such as efficacy, utility, drug costs, hospitalisation cost and patient preference over alternative therapies. The study further showed that rizatriptan is more cost effective than sumatriptan, as evidenced by its lower cost and greater effectiveness. Sensitivity analysis showed that the cost-effectiveness ratios were sensitive to moderate changes in drug efficacy. CONCLUSION: Rizatriptan and sumatriptan were less costly and more effective than Cafergot in the treatment of an acute migraine attack. Rizatriptan was somewhat less costly and more effective than sumatriptan. Additional quality-of-life studies are needed to confirm the benefits of using triptans in the management of migraine.

Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection.

Palivizumab (Synagi) is a humanized monoclonal antibody that provides immunoprophylaxis against serious lower respiratory tract infections (LRTIs) caused by respiratory syncytial virus (RSV). RSV is the leading cause of hospitalization for LRTIs in infants, causing winter- or wet-season epidemics. In two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg every 30 days for 5 months significantly reduced RSV-related hospitalizations by 55% in 1502 infants with prematurity and/or bronchopulmonary dysplasia/chronic lung disease (BPD/CLD) and by 45% in 1287 infants with hemodynamically significant congenital heart disease (HSCHD). Reductions were statistically significant versus placebo in infants with BPD/CLD, with all degrees of prematurity, and with acyanotic/other heart disease. Palivizumab was generally well tolerated, with < or =1.9% of recipients discontinuing treatment for tolerability reasons. In placebo-controlled trials, the most common potentially drug-related adverse events were fever, nervousness, injection-site reactions, and diarrhea. Drug-related events occurred in 7.2-11% of palivizumab recipients in controlled trials (vs 6.9-10% with placebo) and 0-7.9% in open-label trials. Very few serious potentially drug-related adverse events occurred in clinical trials; four occurred in 2 of 285 patients in one open-label trial. No significant anti-palivizumab antibodies developed during palivizumab use. Palivizumab trough serum concentrations were below the recommended 40 microg/mL in about 33% and up to 14% of children prior to their second and third palivizumab injections. In pharmacoeconomic studies, the cost of palivizumab per hospitalization averted was generally lowest in the highest-risk infants. Drug cost was generally the most influential factor in sensitivity analyses. In conclusion, prophylaxis with palivizumab significantly reduces the incidence of RSV-related hospitalization relative to placebo and is generally well tolerated in high-risk infants aged <2 years, including those with prematurity and BPD/CLD or HSCHD, which are risk factors for early or serious RSV infection. Palivizumab is approved for use in these patients. Other high-risk infants in whom palivizumab has not been formally assessed, such as those with immunodeficiency, cystic fibrosis, or location-specific risk factors (including extended hospital stays) might potentially benefit from palivizumab. The use of palivizumab in these other high-risk populations is likely to be determined as much by pharmacoeconomic considerations as by efficacy outcomes.

Promotion of folate for the prevention of neural tube defects: knowledge and use of periconceptional folic acid supplements in Western Australia, 1992 to 1995.

To assess changes in knowledge and use of folic acid supplements in relation to a statewide health promotion project for the prevention of neural tube defects, we surveyed general practitioners, pharmacists, women of child-bearing age and pregnant women in Western Australia. We also collected data on wholesale sales of folic acid supplements. By the end of the project, 56.5 per cent of general practitioner respondents knew that the recommended dose of folic acid was 0.5 mg and 70 per cent offered folic acid supplements to women planning pregnancy, 82.5 per cent of responding pharmacists knew the recommended dose, and 87.5 per cent reported an increase in sales of 0.5 mg folic acid. Wholesale sales of 0.5 mg folic acid increased markedly in Western Australia compared with other states. From shopping centre surveys of women of child-bearing age we estimated that their knowledge of the association between folate and spina bifida increased from 8.2 per cent before the project to 67.5 per cent 2.5 years later, and doctors were a major source of information for women. In a 1995 survey of a sample of pregnant women, 43.1 per cent with planned pregnancies had taken folic acid supplements periconceptionally, compared with 19.1 per cent in a similar survey in 1993.