Communicating the parameter uncertainty in the IQWiG efficiency frontier to decision-makers.

The Institute for Quality and Efficiency in Health Care (IQWiG) developed-in a consultation process with an international expert panel-the efficiency frontier (EF) approach to satisfy a range of legal requirements for economic evaluation in Germany's statutory health insurance system. The EF approach is distinctly different from other health economic approaches. Here, we evaluate established tools for assessing and communicating parameter uncertainty in terms of their applicability to the EF approach. Among these are tools that perform the following: (i) graphically display overall uncertainty within the IQWiG EF (scatter plots, confidence bands, and contour plots) and (ii) communicate the uncertainty around the reimbursable price. We found that, within the EF approach, most established plots were not always easy to interpret. Hence, we propose the use of price reimbursement acceptability curves-a modification of the well-known cost-effectiveness acceptability curves. Furthermore, it emerges that the net monetary benefit allows an intuitive interpretation of parameter uncertainty within the EF approach. This research closes a gap for handling uncertainty in the economic evaluation approach of the IQWiG methods when using the EF. However, the precise consequences of uncertainty when determining prices are yet to be defined.

Discrete event simulation: the preferred technique for health economic evaluations?

OBJECTIVES: To argue that discrete event simulation should be preferred to cohort Markov models for economic evaluations in health care. METHODS: The basis for the modeling techniques is reviewed. For many health-care decisions, existing data are insufficient to fully inform them, necessitating the use of modeling to estimate the consequences that are relevant to decision-makers. These models must reflect what is known about the problem at a level of detail sufficient to inform the questions. Oversimplification will result in estimates that are not only inaccurate, but potentially misleading. RESULTS: Markov cohort models, though currently popular, have so many limitations and inherent assumptions that they are inadequate to inform most health-care decisions. An event-based individual simulation offers an alternative much better suited to the problem. A properly designed discrete event simulation provides more accurate, relevant estimates without being computationally prohibitive. It does require more data and may be a challenge to convey transparently, but these are necessary trade-offs to provide meaningful and valid results. CONCLUSION: In our opinion, discrete event simulation should be the preferred technique for health economic evaluations today.

NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used?

The National Institute for Health and Clinical Excellence (NICE) recently issued updated guidance on the use of cholinesterase inhibitors in the treatment of Alzheimer's disease. NICE initially recommended that cholinesterase inhibitors no longer be used, but final guidance restricted treatment to patients with disease of a moderately severe stage. This decision was based largely on results from a heavily criticised economic evaluation that used an adaptation of the Assessment of Health Economics in Alzheimer's Disease (AHEAD) model. As the developers of the AHEAD model, we examined the appropriateness of NICE's economic analyses and presentation of results. We attempted to replicate NICE's results by modifying the original AHEAD model. Sensitivity analyses were then run using the modified AHEAD model to evaluate the extent of uncertainty in predictions. The AHEAD(NICE) analyses resulted in an incremental cost-effectiveness ratio for galantamine of 82,000 pound per QALY gained (year 2003 values) from the perspective of the UK NHS and Personal Social Services. This was later revised to 46,000 pound per QALY, compared with < 9000 pound per discounted QALY gained (year 2001 values) in the original AHEAD model. Using our modified AHEAD with effectiveness estimates matching those of AHEAD(NICE), we show that NICE's choice and presentation of sensitivity analyses obscured the instability of their estimates. In the final NICE evaluation, the recommendation to delay treatment with cholinesterase inhibitors until patients have moderately severe disease was based on critical assumptions in the economic analyses that had little evidence to support them. The case of NICE's guidance on cholinesterase inhibitors highlights the importance of transparent and valid economic evaluations and the dangers of using inappropriate modelling technologies, basing analyses on a limited subset of the available data, and insufficiently reflecting the uncertainty in estimates that are intended to inform decision makers.

Direct medical cost of managing deep vein thrombosis according to the occurrence of complications.

BACKGROUND: Management of deep vein thrombosis (DVT) has evolved from hospitalisation for intravenous heparin therapy to treatment options that include acute management as an outpatient. While efficacy and safety remain the principal basis for choosing a therapy, the economic consequences of that choice should be considered as well. OBJECTIVE: To estimate the average cost of various DVT management options from the perspective of US health payers. DESIGN: Inpatient and outpatient management strategies were examined. Inpatient cases were identified by International Classification of Diseases, 9(th) Edition, Clinical Modification codes and were classified into subgroups according to complication status. A cost estimate was developed by applying unit costs to the corresponding course of treatment. Cost estimates included initial acute care and that occurring in the following 6 months. Resource use profiles and unit costs were derived from several statewide inpatient, emergency room and ambulatory care databases supplemented by national fee schedules, published reports and peer-reviewed literature. All costs are reported in 1999 US dollars. RESULTS: The mean 6-month treatment costs for inpatient management ranged from US dollars 3906 to US dollars 17,168, depending on complication status. For outpatient management, the cost ranged from US dollars 2394 to US dollars 3369, depending on frequency of low molecular weight heparin (LMWH) injection and need for professional assistance. CONCLUSIONS: The management strategy selected for DVT has an important economic impact. Self-administered LMWH in a homecare setting results in the lowest cost. However, as some patients either cannot, or will not, be treated this way, it is important for decision makers to consider the costs of other strategies.

Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder.

Bipolar disorder (or manic depression) is a lifelong, severe and complex psychiatric illness characterized by recurrent episodes of depression and mania. The aim of this study is to explore the cost-effectiveness of quetiapine compared with other alternatives for the treatment of acute manic episodes in bipolar I disorder, with a specific focus on serious side effects. Four trials investigating quetiapine monotherapy and adjunctive therapy were performed to investigate the efficacy of quetiapine in patients with bipolar I disorder. Data were derived from The Netherlands Mental Health Survey and Incidence Study and used to construct a study population for the model. To assess the cost-effectiveness of quetiapine in the management of acute mania in bipolar I disorders, a discrete event simulation model of seven monotherapy and combination treatment options was developed. A comparison of the total costs demonstrates that all of the monotherapy options and placebo are more costly than the combination therapy options. The combinations of lithium with risperidone (euro2365) and with olanzapine (euro2429) are estimated to be less costly per patient than the combination of lithium with quetiapine (euro2555). A group of 10,000 patients switching from olanzepine/lithium to quetiapine/lithium would involve extra costs of euro1,260,000, but would prevent an estimated number of 362 serious side effects. Switching from risperidone/lithium to quetiapine/lithium would cost an additional euro1,900,000 and would prevent 1580 serious side effects. In terms of serious side effects, the combination of lithium/quetiapine was superior to the combination of lithium with olanzapine or risperidone. It must be considered whether the decreased likelihood of developing a severe side effect is worth the extra costs incurred with the combination of quetiapine/lithium.

Are hypoglycaemia and other adverse effects similar among sulphonylureas?

This review provides an updated overview of the adverse effects of sulphonylureas and identifies factors associated with variation in adverse effect rates among sulphonylureas published by different studies. A search of Medline, Embase, Current Contents and Cochrane Library was conducted to identify all papers related to sulphonylureas and adverse effects published from 1950-2001. The reference lists of all relevant papers were also searched for additional articles. The frequency of sulphonylurea-induced hypoglycaemia varied from 1.8-59%. Severe hypoglycaemia due to sulphonylurea use has been reported from 1.9-3.5%. Variation in hypoglycaemia rates may be due to differences in definitions, methods to detect and to collect information, patient characteristics, patient knowledge of the condition, threshold for symptoms, and activity level during hypoglycaemia. Other adverse effects associated with sulphonylurea use include bodyweight gain, gastrointestinal distress, disulphiram-like syndrome, dermatological reactions, haematological changes, ocular problems, and the syndrome of inappropriate secretion of antidiuretic hormone. Bodyweight gain has been reported to vary from 1.7-4.8 kg, according to the United Kingdom Prospective Diabetes Study (UKPDS-33). Controversy exists regarding cardiovascular adverse effects, but the consensus is to exercise caution in the use of these drugs as first-line therapy for patients with diabetes mellitus and coronary artery disease. The benefits of sulphonylurea treatment should be weighed against the risks associated with them. More work in this area is needed to homogenise the definition of hypoglycaemia, to get consensus on the methods for detection and data collection, as well as to further patient and physician education.

Lung cancer screening: will the controversy extend to its cost-effectiveness?

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in the US. It has been shown that when treated in its early stages, survival rates improve. Despite this, controversy remains regarding screening for the early detection of lung cancer, primarily because mortality reductions were not observed in the trials that studied chest x-ray and sputum cytology. Nevertheless, renewed interest in screening, due in part to better screening options, has prompted further research exploring the potential cost-effectiveness of implementing lung cancer screening programs. This article provides a critical review of the literature of economic evaluations of lung cancer screening programs. The focus of this review is the methodology implemented in these studies. Based on an electronic search of the literature (Pubmed, Medline and CancerLit) from Sep 1988-Sep 2001, seven articles that quantified the cost-effectiveness of lung cancer screening programs were identified. For most of the studies, the cost-effectiveness aspect was a minor component with little or no description of the methods. Although some studies focused more on estimating the economic efficiency of screening, their methodology was weak and still not well documented. Only two studies implemented fully a cost-effectiveness analysis and provided the necessary level of detail. If consensus can be reached regarding the clinical benefit of lung cancer screening, future studies related to cost-effectiveness would have to be implemented on much sounder methodology. The publications reviewed do provide preliminary support for the economic efficiency of screening for lung cancer.

Assessing the economics of vaccination for Neisseria meningitidis in industrialized nations: a review and recommendations for further research.

OBJECTIVES: To review the existing health economic literature on meningococcal disease vaccination. METHODS: A Medline search for economic evaluations of vaccination programs for meningococcal disease in developed countries was conducted. All identified studies were reviewed. RESULTS: Nine published studies were identified examining either mass vaccination during outbreaks or routine vaccination. Although net expenses were estimated in almost all studies, the resulting cost-effectiveness ratios varied widely. Vaccination of college-age students was found to be potentially cost-effective in Australia but not in the United States. With one exception, routine vaccination of children and adolescents in Europe was predicted to be cost-effective. Many simplifying assumptions were made, and important elements were often left out, in particular the potential for reduced transmission of disease. CONCLUSIONS: The methods used and the vaccination strategies vary widely, and results do not provide strong grounds for making conclusions as to whether vaccination is cost-effective. Furthermore, in all instances, transmission of disease, changes in population carriage rates, and outbreaks are either ignored, dealt with using very broad simplifying assumptions, or are not necessarily generalizable to other settings. The analyses provide some insight into the potential cost-effectiveness of vaccination, but more importantly, they highlight areas requiring further study. Economic evaluations based on observed outcomes from recently implemented strategies would be helpful, as would more sophisticated health economic models. The choice of vaccination strategies cannot be based on the results of existing economic analyses.