Evaluating the cost effectiveness of donepezil in the treatment of Alzheimer's disease in Germany using discrete event simulation.

BACKGROUND: Previous cost-effectiveness studies of cholinesterase inhibitors have modeled Alzheimer's disease (AD) progression and treatment effects through single or global severity measures, or progression to "Full Time Care". This analysis evaluates the cost-effectiveness of donepezil versus memantine or no treatment in Germany by considering correlated changes in cognition, behavior and function. METHODS: Rates of change were modeled using trial and registry-based patient level data. A discrete event simulation projected outcomes for three identical patient groups: donepezil 10 mg, memantine 20 mg and no therapy. Patient mix, mortality and costs were developed using Germany-specific sources. RESULTS: Treatment of patients with mild to moderately severe AD with donepezil compared to no treatment was associated with 0.13 QALYs gained per patient, and 0.01 QALYs gained per caregiver and resulted in average savings of €7,007 and €9,893 per patient from the healthcare system and societal perspectives, respectively. In patients with moderate to moderately-severe AD, donepezil compared to memantine resulted in QALY gains averaging 0.01 per patient, and savings averaging €1,960 and €2,825 from the healthcare system and societal perspective, respectively.In probabilistic sensitivity analyses, donepezil dominated no treatment in most replications and memantine in over 70% of the replications. Donepezil leads to savings in 95% of replications versus memantine. CONCLUSIONS: Donepezil is highly cost-effective in patients with AD in Germany, leading to improvements in health outcomes and substantial savings compared to no treatment. This holds across a variety of sensitivity analyses.

Accounting for the relationship between per diem cost and LOS when estimating hospitalization costs.

BACKGROUND: Hospitalization costs in clinical trials are typically derived by multiplying the length of stay (LOS) by an average per-diem (PD) cost from external sources. This assumes that PD costs are independent of LOS. Resource utilization in early days of the stay is usually more intense, however, and thus, the PD cost for a short hospitalization may be higher than for longer stays. The shape of this relationship is unlikely to be linear, as PD costs would be expected to gradually plateau. This paper describes how to model the relationship between PD cost and LOS using flexible statistical modelling techniques. METHODS: An example based on a clinical study of clevidipine for the treatment of peri-operative hypertension during hospitalizations for cardiac surgery is used to illustrate how inferences about cost-savings associated with good blood pressure (BP) control during the stay can be affected by the approach used to derive hospitalization costs.Data on the cost and LOS of hospitalizations for coronary artery bypass grafting (CABG) from the Massachusetts Acute Hospital Case Mix Database (the MA Case Mix Database) were analyzed to link LOS to PD cost, factoring in complications that may have occurred during the hospitalization or post-discharge. The shape of the relationship between LOS and PD costs in the MA Case Mix was explored graphically in a regression framework. A series of statistical models including those based on simple logarithmic transformation of LOS to more flexible models using LOcally wEighted Scatterplot Smoothing (LOESS) techniques were considered. A final model was selected, using simplicity and parsimony as guiding principles in addition traditional fit statistics (like Akaike's Information Criterion, or AIC). This mapping was applied in ECLIPSE to predict an LOS-specific PD cost, and then a total cost of hospitalization. These were then compared for patients who had good vs. poor peri-operative blood-pressure control. RESULTS: The MA Case Mix dataset included data from over 10,000 patients. Visual inspection of PD vs. LOS revealed a non-linear relationship. A logarithmic model and a series of LOESS and piecewise-linear models with varying connection points were tested. The logarithmic model was ultimately favoured for its fit and simplicity. Using this mapping in the ECLIPSE trials, we found that good peri-operative BP control was associated with a cost savings of $5,366 when costs were derived using the mapping, compared with savings of $7,666 obtained using the traditional approach of calculating the cost. CONCLUSIONS: PD costs vary systematically with LOS, with short stays being associated with high PD costs that drop gradually and level off. The shape of the relationship may differ in other settings. It is important to assess this and model the observed pattern, as this may have an impact on conclusions based on derived hospitalization costs.

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.

Invasive meningococcal disease epidemiology and control measures: a framework for evaluation.

BACKGROUND: Meningococcal disease can have devastating consequences. As new vaccines emerge, it is necessary to assess their impact on public health. In the absence of long-term real world data, modeling the effects of different vaccination strategies is required. Discrete event simulation provides a flexible platform with which to conduct such evaluations. METHODS: A discrete event simulation of the epidemiology of invasive meningococcal disease was developed to quantify the potential impact of implementing routine vaccination of adolescents in the United States with a quadrivalent conjugate vaccine protecting against serogroups A, C, Y, and W-135. The impact of vaccination is assessed including both the direct effects on individuals vaccinated and the indirect effects resulting from herd immunity. The simulation integrates a variety of epidemiologic and demographic data, with core information on the incidence of invasive meningococcal disease and outbreak frequency derived from data available through the Centers for Disease Control and Prevention. Simulation of the potential indirect benefits of vaccination resulting from herd immunity draw on data from the United Kingdom, where routine vaccination with a conjugate vaccine has been in place for a number of years. Cases of disease are modeled along with their health consequences, as are the occurrence of disease outbreaks. RESULTS: When run without a strategy of routine immunization, the simulation accurately predicts the age-specific incidence of invasive meningococcal disease and the site-specific frequency of outbreaks in the Unite States. 2,807 cases are predicted annually, resulting in over 14,000 potential life years lost due to invasive disease. In base case analyses of routine vaccination, life years lost due to infection are reduced by over 45% (to 7,600) when routinely vaccinating adolescents 12 years of age at 70% coverage. Sensitivity analyses indicate that herd immunity plays an important role when this population is targeted for vaccination. While 1,100 cases are avoided annually when herd immunity effects are included, in the absence of any herd immunity, the number of cases avoided with routine vaccination falls to 380 annually. The duration of vaccine protection also strongly influences results. CONCLUSION: In the absence of appropriate real world data on outcomes associated with large-scale vaccination programs, decisions on optimal immunization strategies can be aided by discrete events simulations such as the one described here. Given the importance of herd immunity on outcomes associated with routine vaccination, published estimates of the economic efficiency of routine vaccination with a quadrivalent conjugate vaccine in the United States may have considerably underestimated the benefits associated with a policy of routine immunization of adolescents.

Systematic Review of Model-Based Economic Evaluations of Treatments for Alzheimer's Disease.

BACKGROUND: Numerous economic evaluations using decision-analytic models have assessed the cost effectiveness of treatments for Alzheimer's disease (AD) in the last two decades. It is important to understand the methods used in the existing models of AD and how they could impact results, as they could inform new model-based economic evaluations of treatments for AD. OBJECTIVE: The aim of this systematic review was to provide a detailed description on the relevant aspects and components of existing decision-analytic models of AD, identifying areas for improvement and future development, and to conduct a quality assessment of the included studies. METHODS: We performed a systematic and comprehensive review of cost-effectiveness studies of pharmacological treatments for AD published in the last decade (January 2005 to February 2015) that used decision-analytic models, also including studies considering patients with mild cognitive impairment (MCI). The background information of the included studies and specific information on the decision-analytic models, including their approach and components, assumptions, data sources, analyses, and results, were obtained from each study. A description of how the modeling approaches and assumptions differ across studies, identifying areas for improvement and future development, is provided. At the end, we present our own view of the potential future directions of decision-analytic models of AD and the challenges they might face. RESULTS: The included studies present a variety of different approaches, assumptions, and scope of decision-analytic models used in the economic evaluation of pharmacological treatments of AD. The major areas for improvement in future models of AD are to include domains of cognition, function, and behavior, rather than cognition alone; include a detailed description of how data used to model the natural course of disease progression were derived; state and justify the economic model selected and structural assumptions and limitations; provide a detailed (rather than high-level) description of the cost components included in the model; and report on the face-, internal-, and cross-validity of the model to strengthen the credibility and confidence in model results. The quality scores of most studies were rated as fair to good (average 87.5, range 69.5-100, in a scale of 0-100). CONCLUSION: Despite the advancements in decision-analytic models of AD, there remain several areas of improvement that are necessary to more appropriately and realistically capture the broad nature of AD and the potential benefits of treatments in future models of AD.

Model-observational bridging study on the effectiveness of ezetimibe on cardiovascular morbidity and mortality in France: A population-based study.

BACKGROUND: To evaluate the real-life impact of ezetimibe on cardiovascular (CV) morbidity and mortality in France. OBJECTIVE: To estimate the number of non-fatal and fatal CV events that could be prevented and corresponding number of patients needed to treat (NNT) with ezetimibe to prevent one CV event over 5 years. METHODS: Non-interventional 48-month follow-up cohort conducted in hypercholesterolemic patients starting on ezetimibe <3 months at study entry, either as monotherapy or combined with statins. Prediction modeling using discrete event simulation with calibrated Framingham CV risk equations was applied to data from pivotal clinical trials on ezetimibe and real-life data derived from the cohort. RESULTS: A total of 3215 patients in the cohort accumulated 9314 person-years of follow-up for an average of 2.9 years. Mean age was 61.5 (standard deviation [SD] = 10.7), 54.6% were males, and 27.0% had a history of CV disease. Baseline LDL-cholesterol averaged 4.1 mmol/L (159 mg/dL; SD = 1.0) and HDL-C 1.6 mmol/L (62 mg/dL; SD = 0.5). LDL-C decreased in the first 12 months in ezetimibe-LLT (lipid-lowering therapy) initiators, switchers (monotherapy), and combination therapy with a statin by respectively 21.3%, 6.4%, and 29.1%. The corresponding predicted rate reductions of CV events (non-fatal and fatal) compared to no treatment or to a statin (combination therapy) were respectively 8, 2, and 12 per 1000 patients treated over 5 years, with a global NNT of 143 patients over 5 years. CONCLUSION: These results, accounting for observed CV event rates, risk factors evolution over time and adherence to treatment in real life, were consistent with those from clinical trials.

Economic burden of pertussis and the impact of immunization.

Although routine use of vaccines has diminished the incidence of pertussis disease, it has not eliminated the pathogen. Epidemiologic data confirm that pertussis remains a significant health problem in all age groups. Disease burden is highest in infants, in whom pertussis disease frequently leads to severe complications and mortality, although it is also a significant health burden in adolescents and adults, in whom the reported incidence of pertussis is increasing. The Global Pertussis Initiative reviewed the literature to find data that express the economic impact of this health burden and to review economic evaluations of pertussis immunization. Although only limited data on the direct and indirect costs of pertussis are available, they suggest that it poses a significant economic burden and indicate that the direct medical costs of pertussis depend on the rate of hospitalization and the severity of complications, and are highest in infants. The indirect costs of pertussis also appear to be considerable, particularly among adults, in whom the disease reduces work productivity, because of either personal illness or child care responsibilities. Several health economic models on the cost effectiveness of childhood immunization strategies have been published, and although constrained by missing data, have generally found childhood immunization strategies to be cost-effective. Economic analyses of adolescent and adult immunization strategies have also been conducted, but the findings of these studies have been inconsistent. The most recent evaluations, using much higher estimates of incidence than reported previously, suggest that immunization of adolescents and specific adult subgroups may be cost-effective. The literature review confirmed that the economic burden of pertussis is substantial, but there are gaps in existing information. In the short term, further economic analyses are required, particularly of adolescent and adult immunization. More importantly, collection of primary epidemiologic and economic data should be undertaken in parallel. Despite the existing gaps in data, further research using the most current data should facilitate decisions on new vaccination strategies by describing conditions for favorable results and quantifying the margin of uncertainty.

Pertussis immunization of adolescents in the United States: an economic evaluation.

The incidence of reported pertussis has increased during the past decade and poses a growing health and economic burden in developed countries, despite high rates of primary vaccination. Administration of a booster dose of acellular pertussis vaccine to adolescents may help reduce this burden, not only by reducing infections in vaccinated individuals but also by reducing transmission of Bordetella pertussis to other individuals, particularly infants. An epidemiologic model was created to assess the health and economic impact of implementing a program of routine acellular pertussis immunization in adolescents 11-18 years of age in the United States, considering both the reduction in cases in those vaccinated and among the unvaccinated population (due to herd immunity). Inputs for the base case were defined according to information derived from published literature and were supplemented by estimates provided by members of the Global Pertussis Initiative. Both direct and indirect costs were included (in 2002 US dollars) using U.S. data. Outcomes were evaluated over the lifetime of a cohort of potential adolescent vaccine candidates. Because of uncertainty in many of the inputs, extensive sensitivity analyses were conducted. With 80% vaccination coverage of adolescents and a 20% reduction of other cases because of herd immunity, >68,000 cases and 41 pertussis-related deaths would be avoided in the subsequent 10 years by routine administration of acellular pertussis boosters to a single cohort of adolescents in the United States. This strategy would be cost-effective, incurring from 6000 US dollars to 22,000 US dollars per life-year gained. The level of herd immunity attained and the true incidence of pertussis are critical determinants of cost effectiveness, as is the duration of immunity resulting from immunization. The cost of immunization and the discount rate also play a role. Although there is considerable uncertainty surrounding key inputs, the results indicate that the conditions required for adolescent immunization to be economically warranted are realistic.

Pharmacological management of overactive bladder : a systematic and critical review of published economic evaluations.

Overactive bladder is a common condition, with recent findings estimating the prevalence in adults at about 15%. Symptoms, including urinary urgency, high voiding frequency and urge incontinence, have been shown to decrease patients' quality of life. Given its high prevalence, the economic burden of overactive bladder is also substantial, with a recent estimate placing the annual cost in the US at 9.1 billion US dollars (year 2000 values). The objective of this review is to provide a critical appraisal of published economic evaluations of pharmacological and non-pharmacological treatments for overactive bladder. Published economic evaluations of treatments for overactive bladder have focused entirely on pharmacological treatments -- mainly on the two most commonly used drugs, oxybutynin and tolterodine, each of which is available in immediate- and extended-release formulations. Ten economic evaluations (more than half are cost-effectiveness studies) have been published. Modelling with decision trees or Markov models has been the predominant method. Evaluations comparing drug therapy with no treatment have concluded that drug therapy is cost effective. Analyses comparing the formulations of oxybutynin and tolterodine have produced highly inconsistent results, largely due to the sources of data employed for effectiveness and treatment discontinuation rates. There are no evaluations of drugs relative to non-pharmacological treatment, and there are other significant gaps in the economic evaluations of treatment to date. These include gaps resulting from a lack of reliable data on the performance of these drugs in real-world settings, particularly data on long-term persistence with treatment. A more definitive pharmacoeconomic comparison of oxybutynin and tolterodine formulations, incorporating all available clinical data, and other treatment options would help direct treatment.

Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.

Instituting a routine varicella vaccination program in Canada: an economic evaluation.

BACKGROUND: After licensing of a varicella vaccine in Canada in 1998, Health Canada commissioned a study to evaluate options for a vaccination program. The evaluation of a program of vaccination of 12-month-old children, with and without a catch-up program for susceptible 12-year-olds, is presented here. METHODS: An economic model was developed simulating the expected experience, with and without vaccination, of cohorts of children susceptible to varicella. The cohorts were simulated for 70 years, and infection and complication rates were calculated along with the attendant costs, with an assumed vaccine cost of $60. RESULTS: With an 85% coverage rate vaccination is expected to reduce the number of chickenpox cases by approximately two-thirds and varicella-related complications by up to 75%. The overall costs of varicella are expected to drop by >$4 million (1998 Canadian dollars) per 100,000 eligible vaccinees, but costs to the health care system are expected to increase by >$2 million. From the health care system perspective, vaccination would cost approximately $42 per discounted case avoided. INTERPRETATION: Routine varicella vaccination would likely substantially reduce the overall costs of managing chickenpox but would result in an increase in health care expenditures. These findings are consistent with evaluations in other countries.

Canadian economic comparison of extended-release oxybutynin and immediate-release tolterodine in the treatment of overactive bladder.

BACKGROUND: Overactive bladder (OAB) is a condition characterized by urgency, increased frequency of micturition, or urge incontinence. It affects a considerable segment of the population, particularly with increasing age. Pharmacotherapy is one of the most common approaches to the treatment of OAB. OBJECTIVE: This article describes the development and results of a model comparing health-economic outcomes for the new extended-release (XL) formulation of oxybutynin and immediate-release (IR) tolterodine in a population of community-dwelling Canadian adults with OAB. METHODS: A Markov model was developed to compare health-economic outcomes over the course of 1 year. Effectiveness and treatment-persistence data were derived from the OBJECT (Overactive Bladder: Judging Effective Control and Treatment) trial, a 3-month comparison of oxybutynin XL 10 mg and tolterodine IR 4 mg, and were used, together with data from the literature (identified through a MEDLINE search of articles published between 1990 and 2003), to project outcomes beyond the trial period. Severity-specific cost profiles for incontinence were developed. In the principal analyses, cost items were limited to drug therapy, physician visits, use of pads or other protection, and laundry costs. Costs are reported in 2002 Canadian dollars. RESULTS: Costs after 1 year were estimated to be an average of $32 less per patient for oxybutynin XL compared with tolterodine IR, and 3.1 additional patients in every 100 who received oxybutynin XL were expected to attain complete continence compared with those who received tolterodine. During the course of 1 year, patients receiving oxybutynin XL were expected to have a mean 16.5 additional incontinence-free days compared with those receiving tolterodine IR. The results were sensitive to relative drug prices. In the other sensitivity analyses, however, oxybutyrin XL maintained its advantage over a wide range of inputs. CONCLUSION: The results of these analyses suggest that when priced equivalently, oxybutynin XL would reduce costs and provide better results than tolterodine IR over 1 year of treatment.

Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer's disease in the United States.

BACKGROUND: Alzheimer's disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with the cost of management increasing as the disease progresses. OBJECTIVE: The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care (FTC). METHODS: Calculations were made using the Assessment of Health Economics in Alzheimer's Disease model, which applies predictive equations to estimate the need for FTC and the associated costs. The predictive equations were developed from longitudinal data on patients with AD. Inputs to the equations were derived by analyzing the data from 2 randomized, placebo-controlled, galantamine clinical trials. Resource use (from a payer perspective) was estimated from US clinical trial data, and costs were estimated from several US databases. Analyses were carried out over 10 years, and costs and benefits were discounted at 3%. RESULTS: In the base case, 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC, depending on dose. Treated patients spent 7% to 8% more time pre-FTC and 12% to 14% less time requiring FTC, resulting in savings of 2408 to 3601 US dollars. Time horizons below 3 years, very high discontinuation rates, or increased survival with galantamine reversed the savings. Conversely, limiting treatment to responders delayed FTC by 6 to 7 months, with savings of approximately 9097 to 11,578 US dollars. CONCLUSIONS: These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly resources such as formal home care and nursing homes, leading to cost savings over time.

To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?

BACKGROUND: Patients with Alzheimer's disease experience a progressive loss of cognitive function, and the ability to independently perform activities of daily life. Sometimes a dependent stage is reached quite early in the disease, when caregivers decide that the patients can no longer be left alone safely. This is an important aspect of Alzheimer's for patients, their families, and also health care providers. Understanding the relationship between a patient's current cognitive status and their need for care may assist clinicians when recommending an appropriate management plan. In this study, we investigated the relationship of cognitive function to dependence on caregivers before the patients reach a severe stage of the disease. METHODS: Data were obtained on 1,289 patients with mild-to-moderate Alzheimer's disease studied in two randomised clinical trials of galantamine (ReminylcircledR;). Cognition was assessed using the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Mini-Mental State Examination (MMSE). Patients were considered dependent if they required >12 hours of supervision each day or had high care needs. The Disability Assessment for Dementia (DAD) scale was also used as a measure of dependence. Disability was predicted directly using MMSE and ADAS-cog and compared to predictions from converted scores. RESULTS: The odds ratio of dependence was significantly higher amongst the patients with worse cognitive impairment, adjusting for age, gender and antipsychotic medication use. For example, a 4-point difference in ADAS-cog score was associated with an increase of 17% (95% CI 11-23) in the adjusted odds for >12 hours of supervision, and of 35% (95% CI 28-43) for dependence. Disability predicted directly using actual ADAS-cog and scores converted from MMSE values had close agreement using the models developed. CONCLUSION: In patients with mild-to-moderate Alzheimer's disease, even relatively small degrees of poorer cognitive function increased the risk of losing the ability to live independently.

Assessing the health and economic impact of galantamine treatment in patients with Alzheimer's disease in the health care systems of different countries.

INTRODUCTION: Cholinesterase inhibitors have been shown to improve cognitive function and improve or maintain global function. OBJECTIVE: To estimate the long-term economic impact of treating patients with Alzheimer's disease with galantamine in seven healthcare systems: Australia, Canada, Finland, New Zealand, Sweden, the Netherlands and the UK. METHODS: The time until patients require full-time care (FTC), defined as the consistent requirement for a significant amount of care giving and supervision each day, and the associated costs were evaluated using the 'Assessment of Health Economics in Alzheimer's Disease (AHEAD)' model. Efficacy data were obtained from three clinical trials comparing galantamine with placebo and local cost and resource use data were determined for each country. Forecast costs reported in Euros (2001 value), were made for up to 10 years in each healthcare system. All costs were determined from a perspective somewhat broader than that of a comprehensive payer, including social services. Both benefits and costs were discounted at 3%. RESULTS: Galantamine (16 mg/day) is predicted to delay the need for FTC by 6.8%, thus the cumulative cost of care over 10 years is expected to be reduced, and this offsets much or all of the cost of galantamine. Approximately five patients need to be treated to avoid 1 year of FTC. In each healthcare system, FTC was estimated to account for 61-92% of the cost. Savings were estimated for most of the countries. For those countries with an expected expense, there were reasonable costs per FTC month avoided (euro553, discounted) and costs per quality-adjusted life year gained (euro25,000). CONCLUSION: In addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying FTC may offset the treatment costs.

Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis.

OBJECTIVE: To evaluate economic and health implications of tinzaparin sodium, a once a day low-molecular-weight heparin (LMWH), versus unfractionated heparin (UFH) in the treatment of acute deep vein thrombosis (DVT) from a US healthcare payer perspective. STUDY DESIGN: An economic model, composed of two submodules, was created: A short-term module based on clinical trial data covering the first 3 months and a long-term module that projects trial results based on published data for up to 50 years. METHODS: Clinical trial results were combined with data from long-term follow-up studies of DVT in a model that estimates the health and economic consequences of treatment. Both short- and long-term costs with tinzaparin sodium were compared with UFH, as were health outcomes and quality-adjusted life-years (QALYs). RESULTS: Patients treated with tinzaparin sodium are estimated to live a mean of 0.9 years longer on average (0.6 discounted), resulting in an increase of 0.8 QALYs (0.5 discounted). At the same time, lifetime savings are US dollars 621 per patient (1999 values), even when all patients receiving tinzapirin sodium are treated as inpatients. Early discharge of patients receiving tinzaparin sodium, or outpatient treatment, would save between US dollars 3000 and US dollars 5000 per patient. CONCLUSION: Tinzaparin sodium leads to better health outcomes and substantial economic savings compared with UFH treatment when all management costs are considered.

Assessment of Health Economics in Alzheimer's Disease (AHEAD): treatment with galantamine in Sweden.

BACKGROUND: Like other developed countries with aging populations, Sweden is expecting large increases in the prevalence of Alzheimer's disease and corresponding escalations in the cost of care for patients with this disease. Galantamine, a new acetylcholinesterase inhibitor and nicotinic modulator, has proved effective in managing patients with Alzheimer's disease in clinical trials. OBJECTIVE: To estimate the long-term health and economic impact of galantamine from the perspective of the public health payer in Sweden. DESIGN AND SETTING: The Assessment of Health Economics in Alzheimer's Disease (AHEAD) model compares galantamine treatment with no pharmacologic treatment. It consists of a module based on trial data followed by a projection module that uses the trial results to predict the time until patients require full-time care (FTC) or until their death. Forecasts were made for up to 10 years. The model was customised to Sweden by using Swedish resource use profiles obtained from the literature. RESULTS: Galantamine is predicted to reduce the time patients require FTC by almost 10%. Approximately 5.6 patients with mild-to-moderate disease would need to be treated to avoid one year of FTC. This would result in savings averaging 27 436 Swedish kronas (SEK) [3131 euros (EUR)] per patient over 10 years (1998 values). To avoid one year of FTC, 3.9 patients with moderate disease would need to be treated, with savings averaging SEK49 019 (EUR 5594) per patient over 10.5 years. Sensitivity analyses of key parameters, such as proportion of patients needing FTC treated in the community, cost of care in an institution, cost of FTC care in the community, the price of galantamine, and the discount rate, found savings with galantamine would occur under most circumstances. CONCLUSION: Galantamine can increase the time before patients require FTC, and may also lead to savings as treatment costs are offset by reductions in other healthcare expenditures and the costs associated with FTC.

Pharmacoeconomic evidence and considerations for triptan treatment of migraine.

The 5-hydroxytriptamine (5-HT)(1B/1D) agonists (i.e., the triptans) are highly effective in migraine but their high cost relative to other treatments necessitates careful analysis of their cost-effectiveness. The majority of pharmacoeconomic evaluations, nearly all of which deal with sumatriptan, indicate that from the societal perspective triptans are dominant: health outcomes are improved while the overall cost of migraine is reduced. However, the results are more ambiguous from the perspective of the health care payer: reductions in non-drug medical costs are unlikely to offset fully the high drug cost. Thus far, few analyses have explicitly included quality of life (QOL) in their analyses and pharmacoeconomic analyses comparing the different triptans are scant. More research is required in these areas.