[Urinary tract infections: Economical impact of water intake]. / Infections des voies urinaires : impact économique de la consommation d'eau.

BACKGROUNDS: This study aims to estimate the impact of preventing urinary tract infections (UTI), using a strategy of increased water intake, from the payer's perspective in the French health care system. METHODS: A Markov model enables a comparison of health care costs and outcomes for a virtual cohort of subjects with different levels of daily water intake. The analysis of the budgetary impact was based on a period of 5years. The analysis was based on a 25-year follow-up period to assess the effects of adequate water supply on long-term complications. RESULTS: The authors estimate annual primary incidence of UTI and annual risk of recurrence at 5.3% and 30%, respectively. Risk reduction associated with greater water intake reached 45% and 33% for the general and recurrent populations, respectively. The average total health care cost of a single UTI episode is €1074; for a population of 65 millions, UTI management represents a cost of €3.700 millions for payers. With adequate water intake, the model indicates a potential cost savings of €2.288 millions annually, by preventing 27 million UTI episodes. At the individual level, the potential cost savings is approximately €2915. CONCLUSIONS: Preventing urinary tract infections using a strategy of adequate water intake could lead to significant cost savings for a public health care system. Further studies are needed to assess the effectiveness of such an approach.

Increased water intake as a prevention strategy for recurrent urolithiasis: major impact of compliance on cost-effectiveness.

PURPOSE: We evaluated the economic impact of preventing recurrent stones using a strategy of increased water intake and determined the impact of compliance on cost-effectiveness for the French health care system. MATERIALS AND METHODS: A Markov model was constructed to compare costs and outcomes for recurrent kidney stone formers with less than 2 L vs 2 L or more daily fluid intake. Model assumptions included an annual prevalence of 120,000 stone episodes in France, 14.4% annual risk of stone recurrence and a 55% risk reduction in subjects with adequate water intake. Costs were based on resource use as estimated by a panel of experts and official national price lists. Outcomes were from the perspective of the public health payer, and encompassed direct and indirect costs. RESULTS: The total cost of an episode of urolithiasis was estimated at €4,267 including the cost of treatment and complications. This corresponds to an annual budget impact of €88 million for recurrent stones based on 21,000 stone events. Assuming 100% compliance with fluid intake recommendations of 2 L daily, 11,572 new stones might be prevented, resulting in a cost savings of €49 million. Compliance with water intake in only 25% of patients would still result in 2,893 fewer stones and a cost savings of €10 million. Varying the costs of managing stones had a smaller impact on outcomes since in many patients stones do not form. Varying the incidence of complications did not change the incidence of stones and had a negligible effect on overall cost. CONCLUSIONS: Preventing recurrent urolithiasis has a significant cost savings potential for a payer as a result of a reduced stone burden. However, compliance is an important factor in determining cost-effectiveness.

Workshop Report: concepts and methods in the economics of nutrition--gateways to better economic evaluation of nutrition interventions.

Improving health through better nutrition of the population may contribute to enhanced efficiency and sustainability of healthcare systems. A recent expert meeting investigated in detail a number of methodological aspects related to the discipline of nutrition economics. The role of nutrition in health maintenance and in the prevention of non-communicable diseases is now generally recognised. However, the main scope of those seeking to contain healthcare expenditures tends to focus on the management of existing chronic diseases. Identifying additional relevant dimensions to measure and the context of use will become increasingly important in selecting and developing outcome measurements for nutrition interventions. The translation of nutrition-related research data into public health guidance raises the challenging issue of carrying out more pragmatic trials in many areas where these would generate the most useful evidence for health policy decision-making. Nutrition exemplifies all the types of interventions and policy which need evaluating across the health field. There is a need to start actively engaging key stakeholders in order to collect data and to widen health technology assessment approaches for achieving a policy shift from evidence-based medicine to evidence-based decision-making in the field of nutrition.

Nutrition economics - characterising the economic and health impact of nutrition.

There is a new merging of health economics and nutrition disciplines to assess the impact of diet on health and disease prevention and to characterise the health and economic aspects of specific changes in nutritional behaviour and nutrition recommendations. A rationale exists for developing the field of nutrition economics which could offer a better understanding of both nutrition, in the context of having a significant influence on health outcomes, and economics, in order to estimate the absolute and relative monetary impact of health measures. For this purpose, an expert meeting assessed questions aimed at clarifying the scope and identifying the key issues that should be taken into consideration in developing nutrition economics as a discipline that could potentially address important questions. We propose a first multidisciplinary outline for understanding the principles and particular characteristics of this emerging field. We summarise here the concepts and the observations of workshop participants and propose a basic setting for nutrition economics and health outcomes research as a novel discipline to support nutrition, health economics and health policy development in an evidence and health-benefit-based manner.

Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-alpha2a compared with sunitinib.

BACKGROUND: Bevacizumab plus interferon-alpha2a (IFN) prolongs progression-free survival to >10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing adverse events may be an important factor in selecting therapy. METHODS: Costs of managing adverse events affecting patients with metastatic RCC eligible for treatment with bevacizumab plus IFN or sunitinib were evaluated using a linear decision analytical model. Management costs were calculated from the published incidence of adverse events and health-care costs for treating adverse events in the United Kingdom, Germany, France and Italy. RESULTS: Adverse event management costs were higher for sunitinib than for bevacizumab plus IFN. The average cost per patient for the management of grade 3-4 adverse events was markedly lower with bevacizumab plus IFN compared with sunitinib in the United Kingdom (euro1475 vs euro804), Germany (euro1785 vs euro1367), France (euro2590 vs euro1618) and Italy (euro891 vs euro402). The main cost drivers were lymphopaenia, neutropaenia, thrombocytopaenia, leucopaenia and fatigue/asthaenia for sunitinib; and proteinuria, fatigue/asthaenia, bleeding, anaemia and gastrointestinal perforation for bevacizumab plus IFN. CONCLUSION: The costs of managing adverse events are lower for bevacizumab plus IFN than for sunitinib. The potential for cost savings should be considered when selecting treatments for RCC.

The view of European experts regarding health economics for medical nutrition in disease-related malnutrition.

Health-care systems are currently facing tremendous budget constraints resulting in growing pressure on decision makers and health-care providers to obtain the maximum possible health benefits of the resources available. Choices have to be made, and health economics can help in allocating limited health-care resources among unlimited wants and needs. Attempts to achieve cost reductions often focus on severe pathologies and chronic diseases as they commonly represent high health-care expenditures. In this context, awareness of the considerable financial burden caused by disease-related malnutrition (DRM) is lacking. Possibilities of reducing costs by optimising the management of DRM through medical nutrition will mostly not even be taken into account. During a European expert meeting, the total evaluation of medical nutrition was viewed and discussed. The aim of this meeting was to gain an experts' outline of the key issues relating to the health economic assessment of the use of medical nutrition. This article provides a summary of the observations per discussed item and describes the next steps suggested.

Bridging decision analytic modelling with a cross-sectional study. Application to Parkinson's disease.

The ideal study design for demonstrating the possible health outcomes and costs associated with a new drug would be a naturalistic prospective study. However, it is not often feasible to derive the required information from scientifically sound prospective studies. In these cases, decision analytic models may provide some of the missing information. However, the use of a Delphi panel to gather data for these models is a major concern because of potential bias and data accuracy. Because reimbursement of pharmaceuticals is often based on economic data derived from modelling studies, it is obvious that potential bias due to the use of Delphi panels should be minimised. In this manuscript we present an alternative data source for modelling studies: the cross-sectional study. Data from such studies can be used to yield costs and utilities for Markov health states. The overall combined design may be considered a hybrid between a naturalistic prospective study and a modelling study by maximising the pros and minimising the cons of both types of design, including an increase of external validity. This hybrid design is based on bridging the probabilities derived from the literature and clinical trials with information on costs and utilities from a cross-sectional study. This design also has logistical advantages, namely a shorter required study duration compared with prospective naturalistic studies for chronic diseases. This combined design was illustrated using a Markov model for Parkinson's disease.

Measuring sensitivity in pharmacoeconomic studies. Refining point sensitivity and range sensitivity by incorporating probability distributions.

OBJECTIVE: The aim of the present study is to describe a refinement of a previously presented method, based on the concept of point sensitivity, to deal with uncertainty in economic studies. DESIGN: The original method was refined by the incorporation of probability distributions which allow a more accurate assessment of the level of uncertainty in the model. In addition, a bootstrap method was used to create a probability distribution for a fixed input variable based on a limited number of data points. The original method was limited in that the sensitivity measurement was based on a uniform distribution of the variables and that the overall sensitivity measure was based on a subjectively chosen range which excludes the impact of values outside the range on the overall sensitivity. PATIENTS AND PARTICIPANTS: The concepts of the refined method were illustrated using a Markov model of depression. MAIN OUTCOME MEASURES AND RESULTS: The application of the refined method substantially changed the ranking of the most sensitive variables compared with the original method. The response rate became the most sensitive variable instead of the 'per diem' for hospitalisation. CONCLUSIONS: The refinement of the original method yields sensitivity outcomes, which greater reflect the real uncertainty in economic studies.

The selection of data sources for use in modelling studies.

Economic analysis has become increasingly important in healthcare in general, and particularly with respect to pharmaceuticals. Therefore, it is vital that the methods used in such evaluations are carefully scrutinised and refined. However, guidelines contain only a limited number of recommendations for the use of secondary data in modelling studies. In this manuscript, the selection of data sources in modelling studies will be addressed. The objectives of this manuscript are as follows: (i) to present a general strategy on how to determine the appropriateness of a data source for a model; and (ii) to present recommendations on a transparent reporting format for the selection of data sources.

Measuring sensitivity in pharmacoeconomic studies. An integration of point-sensitivity and range-sensitivity.

The level of uncertainty with regard to the outcomes of pharmacoeconomic studies cannot be completely covered by the statistical methods routinely employed to handle uncertainty in clinical research. Sensitivity analysis is the most common methodology to deal with the extra uncertainty associated with pharmacoeconomics, and has also been incorporated in recent guidelines on healthcare evaluation. However, the execution of a sensitivity analysis and the interpretation of its results have not yet been standardised, which may lead to subjectivity and consequently weaken the value of economic evaluations. This article presents a method of dealing more systematically with uncertainty and eliminating potential bias in sensitivity analysis, with regard to the measurement of sensitivity and the comparison of the degree of sensitivity between variables. An assessment of the disadvantages of using slope as a measure of sensitivity leads to 2 types of sensitivity analyses (point-sensitivity and range-sensitivity), which are integrated into one method for the measurement of sensitivity.

Applications of modelling studies.

There is increasing use of economic evaluation to support decision-makers in health services for allocation of scarce healthcare resources. However, information necessary for economic evaluations cannot always be derived from well-conducted prospective clinical studies, and decision-analytical models can be used to provide some of the missing information. A number of applications of decision-analytical models are discussed, including submissions to authorities for reimbursement purposes, pharmacoeconomic programme development, portfolio investment decisions, marketing and communication strategies, and applications in disease management.

A Markov process analysis comparing the cost effectiveness of maintenance therapy with citalopram versus standard therapy in major depression.

The objective of this study was to demonstrate the cost effectiveness of long term maintenance treatment with citalopram versus standard therapy (defined as short term antidepressant treatment) in patients with major depression in Germany. We chose doxepin, amitriptyline and trimipramine as standard therapy because these drugs are the leading antidepressants in that country. A Markov process analysis was used to model health status and economic outcomes as they accrued over a 1-year follow-up period. The main outcome measures were time without depression, direct costs and indirect costs (work days lost). All costs were in 1993 Deutsche marks. The clinical data were obtained from the published literature and US clinical practice guidelines; the associated unit costs of the medical resources used were derived from official German tariff lists. The results show that, compared with standard therapy, long-term maintenance treatment with citalopram is associated with a mean increase in time without depression of 7.9% (8.2 vs 7.6 months). The total costs of maintenance treatment with citalopram were substantially lower than with standard therapy (DM7985 vs DM11,948 per patient per year. In addition, both the direct and indirect costs of maintenance treatment with citalopram (DM3764 vs DM4221 per patient, respectively) were lower than with standard therapy (DM4577 vs DM7371 per patient, respectively). In conclusion, the study demonstrates that one year's maintenance treatment with citalopram is both more effective and less costly than standard therapy in the treatment of patients with major depression.

Cost effectiveness of letrozole in the treatment of advanced breast cancer in postmenopausal women in the UK.

OBJECTIVE: To simulate the treatment of postmenopausal women with advanced breast cancer from second-line hormone therapy to death, and to generate estimates of the cost and effectiveness of letrozole and megestrol in order to determine the incremental cost effectiveness of letrozole, expressed as cost per life-years gained. DESIGN: A decision-analytic model, using Markov process techniques, was designed to evaluate the lifetime clinical and economic consequences of treatment with letrozole compared with standard care with megestrol. The model was based on clinical trial results showing a clear advantage of letrozole in terms of time to progression and duration of response. SETTING: The setting of the study was that of the UK healthcare system in 1996. PATIENTS AND PARTICIPANTS: A hypothetical cohort of patients, identical to the patients recruited for the AR/BC2 clinical trial, who were postmenopausal women with advanced breast cancer who had previously failed to respond to first-line or adjuvant anti-estrogen therapy. INTERVENTIONS: The dosages of medications were 2.5 and 160 mg/day for letrozole and megestrol, respectively. The analysis covered the period from treatment initiation until death (lifetime model). Effectiveness was expressed as survival and time without progression, and the model also included all relevant economic measures. MAIN OUTCOME MEASURES AND RESULTS: Based on the model, the average survival time of the letrozole group was 2.1 years (25.3 months) versus 1.9 years (21.5 months) for the megestrol group, a gain in survival of 2.4 months (10.5%). The average time without progression, cumulatively calculated over the different treatment options, amounted to 20.2 months for letrozole and 17.8 months for megestrol, an increase of 13.7% for the former patients. The total average cost per patient for the treatment of advanced breast cancer starting from second-line hormone therapy until death was higher in the letrozole group at 7547 Pounds versus 6820 Pounds for the megestrol group (discounted at an annual rate of 5%), leading to an incremental cost-effectiveness ratio of 3588 Pounds per life-year gained (1996 values). CONCLUSIONS: Based on the assumptions used in this model, letrozole offers a suitable alternative to megestrol in the treatment of second-line hormone therapy.

Cost effectiveness of fluvoxamine in the treatment of recurrent depression in France.

OBJECTIVE: The objective of this study was to examine the cost effectiveness of fluvoxamine compared with tricyclic antidepressants (TCAs) in the treatment of patients with depressive episodes. DESIGN AND SETTING: A Markov process model was constructed to model the effectiveness, as measured by time without depression, and the costs of both treatments. The model examined a period of 18 months in order to capture the influence of both relapses and recurrences on the outcomes. Data for the construction of the model came from the published literature, an expert panel and a large multicentre randomised clinical trial. Costs were obtained from published sources. The setting for this study was France. MAIN OUTCOME MEASURES AND RESULTS: The results of the baseline analysis showed that the use of fluvoxamine in the maintenance treatment (recurrence prevention) of depressive disorders was less costly than TCAs with total costs (direct and indirect costs) of 40,232.40 French francs (FF) and FF52,257.53, respectively (1996 values). In addition, due to the prevention of relapse and recurrence, effectiveness favoured fluvoxamine as it was associated with a longer period of time without depression when compared with TCAs (79% of the study period vs 71%). Sensitivity analyses confirmed the robustness of these findings. CONCLUSION: In conclusion, on the basis of the assumptions used in the model, the use of fluvoxamine as maintenance therapy is clinically and economically justified in patients with depressive disorders.

A cost-cost study comparing etanercept with infliximab in rheumatoid arthritis.

OBJECTIVE: The objective of this study was to compare the total costs associated with the administration of two different tumour necrosis factor (TNF) strategies used in the treatment of rheumatoid arthritis (RA): etanercept, a soluble TNF receptor that can be administered at home by subcutaneous injection, versus infliximab, an antibody that requires an intravenous infusion in a hospital outpatient setting. DESIGN AND SETTING: The main analytical framework of the study was a cost-cost analysis comparing the total annual costs associated with the administration of etanercept and infliximab in adult RA patients. The perspective of the study was that of the Dutch society. An economic model was constructed to determine the costs of both treatments. The cost evaluation included direct medical costs, direct nonmedical costs and indirect costs. The base-case analysis compared monotherapy with etanercept versus a combination therapy with infliximab and methotrexate. Data for the economic model came from published literature, expert opinion and official price and tariff lists. All costs were in 1999 values. PATIENTS AND PARTICIPANTS: The analysis was performed for the adult RA population eligible for treatment with etanercept or infliximab in The Netherlands. MAIN OUTCOME MEASURES AND RESULTS: The analysis showed that the total annual drug costs per patient do not differ substantially between infliximab and etanercept, with costs of Netherland guilders (NLG)31,526 (12,610 US dollars) and NLG31,334 (12,534 US dollars), respectively. However, the other medical costs (i.e. excluding the costs of the two drugs themselves) are substantially higher for infliximab due to the additional costs associated with administration in an outpatient clinic and the use of methotrexate [NLG 12,621 (5048 US dollars) versus NLG269 (107 US dollars) for etanercept]. The impact of direct nonmedical costs (transportation) and indirect costs were negligible. Overall treatment with infliximab is more expensive than treatment with etanercept with total costs of NLG45 115 (18,046 US dollars) and NLG3I,621 (12,648 US dollars), respectively (42.7% increase). CONCLUSIONS: Based on the assumptions used in the model, we may conclude that the use of etanercept compares favourably with infliximab from a budgetary and health economic perspective: the total costs are substantially lower when the efficacy of etanercept is assumed to be at least equivalent to the efficacy of infliximab.

Cost effectiveness of emedastine versus levocabastine in the treatment of allergic conjunctivitis in 7 European countries.

OBJECTIVE: To assess the cost effectiveness of emedastine, a new antihistamine, versus levocabastine in the treatment of acute allergic conjunctivitis (AAC) in Belgium, France, Germany, The Netherlands, Norway, Portugal and Sweden. DESIGN AND SETTING: Randomised double-blind multicountry clinical trial followed by economic modelling from the treatment provider perspective. PATIENTS: A total of 221 patients (109 emedastine, 112 levocabastine) with AAC were included. METHODS: The clinical trial compared the efficacy and safety of emedastine 0.05% and levocabastine 0.05%, both twice daily, for 42 days, using ocular redness, itching, days without symptoms and clinical failure as outcome measures. The cost of first-line treatment failure, including visits, drugs and laboratory examinations, was established in each country from a panel of ophthalmologists and general practitioners. Full sensitivity analyses were conducted. RESULTS: From day 7 to 42, patients treated with emedastine had less itching (p < 0.001) and less redness (p < 0.001). The failure rate was 10% less (p < 0.02) with emedastine and patients treated with emedastine had an incremental 8.5 days (p < 0.01) without symptoms. Emedastine and levocabastine were equally well tolerated. In all European countries, the cost of failure was lower with emedastine. Emedastine was found to be economically dominant relative to levocabastine, i.e. more effective and less expensive, in Belgium, Germany, Portugal and Sweden; in France, The Netherlands and Norway the incremental cost was low (less than 1 euro per additional symptom-free day). CONCLUSION: Through a model based on a randomised clinical trial and cost estimates of treatment failure derived from practitioner interviews, emedastine is a cost-effective treatment of AAC.

Introduction to the pharmacoeconomics of herbal medicines.

This article explores the need to perform pharmacoeconomic evaluations of herbal medicines and assesses the extent to which this approach has been applied so far to these products. There seems to be no compelling need for pharmacoeconomic analyses of herbal over-the-counter medicines, but such analyses are certainly warranted for herbal prescription medicines that have a high level of reimbursement. Such preparations are used in Germany, in particular, where physicians prescribed ginkgo, hawthorn, St John's wort, horse-chestnut and saw palmetto to a value of more than DM50 million each in 1996. In our survey, only a single pharmacoeconomic study, of uncertain quality, was found on these 5 herbs, whereas several pharmacoeconomic reports on synthetic competitors were retrieved. The time has come to submit highly reimbursed herbal prescription medicines to the same rigorous pharmacoeconomic evaluations as their synthetic competitors. At present, such studies are particularly important for Germany, but in the future they may also become relevant for other countries, inside as well as outside Europe.

Reporting format for economic evaluation. Part I: Application to the Dutch healthcare system.

This article presents the first version of the reporting format for economic valuation that was created in 1995 by a multidisciplinary taskforce. The members of this taskforce come from a broad spectrum of backgrounds within the healthcare field and participated in the exercise voluntarily. The format presented should be understood as the preferred Dutch structure for the reporting of any study on economic evaluation. In view of the many areas of contention that exist within the field, this format only gives normative directions in those areas in which consensus exists, as evidenced by the current published international guidelines. A regular review and adaptation of this format will be needed to reflect advances in the field.

Reporting format for economic evaluation. Part II: Focus on modelling studies.

This article presents the first version of a reporting format for modelling studies which is based on a general reporting format by our taskforce, which was published in the previous issue of this journal. The use of decision-analytical models for economic evaluations is increasing because, in practice, it is not always possible to derive information from prospective studies. However, the acceptance of modelling studies is generally lower than prospective studies not only because of the use of secondary data, but also because the reports of modelling studies do not always have sufficient transparency. Hence, a standardised reporting format may improve the transparency and, consequently, the acceptance of modelling studies. This article presents an example of a reporting format for economic evaluation based on modelling studies, which may facilitate the development of future guidelines for modelling studies. The format consists of a number of headings, which are followed by a brief recommendation on the content. This format does not deal with methodology and data management, but especially addresses validation and quality assurance, which may increase the transparency of the report.