Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil

Objective: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. Method: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. Results: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. Conclusions: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil.

OBJECTIVE: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. METHOD: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. RESULTS: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. CONCLUSIONS: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Trends in Drug Prescription Rates for Dementia: An Observational Population-Based Study in France, 2006-2014.

BACKGROUND: Since the 2011 French guidance updates, cholinesterase inhibitors and memantine are considered optional in the management of dementia and leave physicians free to prescribe based on their clinical expertise. OBJECTIVES: The aims of this study were to analyze the influence of these recent guidance updates on the prescription rates of these drugs and to quantify the impact of potential changes on healthcare expenditures. METHODS: Patients over 65 years old from a representative sample of a national administrative claims database, the French national health insurance database, were retrospectively included from 2006 to 2014. Trends of annual prescription rates were tested using adjusted segmented regression analysis. Drug costs with and without prescribers' behavioral changes were estimated. RESULTS: A total of 119,731 individuals were included and followed during the study period. Among them, 5514 individuals were treated for dementia. According to the unadjusted segmented regression model, there was a significant increase in prescription rates between 2006 and 2010, from 2.23% (95% confidence interval 2.13-2.34) to 2.73% (95% confidence interval 2.62-2.84) of the study population. Since 2011, the trend has reversed with a significant decrease until 2014, from 2.64% (95% confidence interval 2.54-2.75) to 1.92% (95% confidence interval 1.84-2.01). In the multivariate analysis, we also found a gradual decline since 2011, particularly for patients aged 65-69 years and with one or more other chronic diseases. Cost savings associated with prescribers' behavioral changes were estimated at €108 million. CONCLUSION: Drugs prescribed for dementia are on a declining trend with important cost savings, and this was concomitant with guidance updates that left physicians to rely on their clinical expertise while managing dementia.

Medical Resource Value Appraisal for Leucojum aestivum in Turkey.

In this study, we investigate the medical and economical value of Leucojum aestivum. Leucojum aestivum contains the alkaloid galanthamine, which is one of the main active substances in Reminyl, a commonly used drug for the treatment of Alzheimer's disease (AD). In this analysis, we estimate that there are 13 million mild to moderate patients with Alzheimer's who use Reminyl. Our results suggest that the market change value of L aestivum required for 1 unit of Reminyl is US$62. The value of total change of galanthamine and L aestivumis estimated to be US$18.6 billion per year. Alzheimer's drugs that use L aestivum are relatively expensive, ranging in cost from US$183 to more than US$400 per month. The minimum annual cost of this is US$2196 per person for "patients with mild and moderate stage AD." The using value of 6 million units of L aestivum bulbs, which is the amount exported from Turkey, is estimated to be US$27 million per year. The determined value for L aestivum is equivalent to the value of a rare flower that can be used to treat the serious illness of AD.

Use of cognitive enhancers and associated medical care costs among patients with dementia: a nationwide study in Taiwan.

BACKGROUND: Pharmaceutical therapy for patients with dementia including cholinesterase inhibitors (ChEI) and memantine is covered by Taiwan's National Health Insurance (NHI) but with strict reimbursement criteria. This study compared utilization of selected cognitive enhancers among elderly patients with dementia and estimated associated differences in medical care costs. METHODS: This study used medical claims and pharmacy claims from the NHI Research Database of Taiwan from 2009 to 2011, which included all patients 65 years or older diagnosed with dementia in their outpatient or inpatient claims. Both individual-level and market-level analysis were performed to calculate the average medical costs per person and the share of drug expenditures. Generalized linear models with propensity score adjustment estimated differences in medical care costs by use of selected cognitive enhancers. RESULTS: Users of ChEI had the highest medication and outpatient costs but the lowest inpatient costs among all users of cognitive enhancers. However, annual adjusted total medical care costs per ChEI user were not significantly different from those who used cerebral vasodilators (CBV). In 2011, 52.4% of the elderly with dementia in Taiwan used cognitive enhancers, but among them 88.3% used CBV while 9.2% used ChEI. Among patients with dementia who used at least one cognitive enhancer, the aggregated expenditure as a share of their total drug expenditures was 9.7% in 2011. CONCLUSION: Given that CBV had a much higher utilization rate than ChEI or memantine among elderly people with dementia, the strict reimbursement policy for ChEI and memantine may need to be revisited to increase access to those drugs by patients with dementia in Taiwan.

Treatment of Alzheimer disease.

Alzheimer disease is the most common form of dementia, affecting nearly one-half [corrected] of Americans older than 85 years. It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation, neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of Alzheimer disease. Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential. Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the clinical relevance of these effects is unclear. The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness, confusion, and cardiac arrhythmias. Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease. Memantine can also be used in combination with acetylcholinesterase inhibitors. Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is controversial. Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the progression of Alzheimer disease, no pharmacologic agents can reverse the progression. Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia. There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of Alzheimer disease. There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory drug therapy.

How do we treat people with dementia in Croatia.

The current clinical view on pharmacological treatment and the Croatian reality regarding approved antidementia drugs is presented. Dementia is a syndrome of high incidence and Alzheimer's disease is the most common cause of dementia. New data show that dementia prevalence will nearly double every 20 years, and we believe that current estimated number of persons with dementia (PWD) for Croatia is more than 80,000. The standard treatment with antidementia drugs is unavailable in Croatia, for the majority of PWD, because antidementia drugs are not on the reimbursement list, although Croatian algorithm for psychopharmacological treatment and Alzheimer Disease Societies Croatia recommend early and adequate treatment. Alzheimer's dementia is becoming a world's health priority in 21st century, so we strongly believe that antidementia drugs should be reimbursed in Croatia.

[A contribution to the current discussion on anti-dementia drugs in Germany]. / Ein Beitrag zur aktuellen Antidementivadiskussion in Deutschland.

In Germany, the role of acetylcholinesterase inhibitors in the treatment of Alzheimer's disease (AD) has become a topic of recent discussion. The present article addresses issues which, in the opinion of the authors, have not received sufficient attention. These include the distinction between statistical and clinical significance, outcome parameters, the duration of clinical trials, variability in treatment response and the definition of treatment responders. The authors argue that these issues need to be considered in an in-depth evaluation of acetylcholinesterase inhibitors in the treatment of AD.

[Treatment of Alzheimer's disease utilising the best available evidence-based medicine -- utopia?]. / Therapie der Alzheimer-Demenz mit der besten verfügbaren Evidenz -- eine Utopie?

STUDY OBJECTIVES: To practice evidence-based medicine is considered to improve health care, particularly of chronically ill patients. Taking Alzheimer's as an example the objective of this study is to explore as to how far ambulatory Alzheimer's patients receive the medical treatment with the best evidence available. METHOD: In 2000 and 2002 the health care situation of Alzheimer's disease patients was assessed by conducting telephone interviews with one hundred randomly selected general practitioners and specialists listed in the panel of the Institut fur Medizinische Statistik (IMS -- Institute for Medical Statistics). By means of a standardised questionnaire the interviewees' prescriptions were assessed as well as their knowledge of the medical therapy for Alzheimer's and the use of non-medical therapeutic measures. Besides, the interviewees' prescriptions were checked on the basis of quantitative data taken from the IMS panel. Cholinesterase inhibitors (ChE-I), which are accorded the best evidence presently available in the medical treatment of Alzheimer's, were seen as a marker for the improvement of health care in the course of the study. RESULTS AND CONCLUSIONS: The interviewed physicians considered the evidence of medical Alzheimer's disease therapy with cholinesterase inhibitors high. 67 % of the interviewees would use ChE-I as the drug of first choice if a near relative fell ill with Alzheimer's. However, the ChE-I prescriptions were limited to 13 % in the base year 2000 and to 24 % in the base year 2002. Obviously, the implementation of this medical therapy is hampered by budgetary regulations. The interviewees find it particularly disadvantageous that the prescription of ChE-I may overstrain the budgets allocated to their practices. As a consequence, the effort to improve the quality of health care by implementing evidence-based medicine is thwarted by the increasing pressure on German physicians to prescribe drugs according to economic viability.

Canadian Outcomes Study in Dementia: study methods and patient characteristics.

OBJECTIVE: To describe the methods and patient characteristics of the Canadian Outcomes Study in Dementia (COSID). METHODS: COSID is a 3-year prospective study of dementia patients living in the community at the time of study registration. We assessed patients' cognition, behaviour, and functioning every 6 months, using the Modified Mini-Mental State Examination (3MS), the Neuropsychiatric Inventory (NPI), and the Functional Autonomy Measurement System (SMAF), respectively. We assessed caregivers, using the Zarit Burden Interview (ZBI). Additional information included the Global Deterioration Scale (GDS), patients' driving status, and clinical information including family history, dementia type, concomitant medications, and comorbid conditions. From the patient or caregiver, we collected details of inpatient and outpatient resources used by the patient and (or) caregiver. RESULTS: We enrolled 766 patients from 31 Canadian sites. Overall mean age was 76.8 years, and mean age of onset was 73.1 years. Of the total patients, 98% were white, 54% were women, and 84% were diagnosed with Alzheimer's disease. Mean baseline 3MS was 66.5, NPI was 9.5, and SMAF was 18.30. Of these patients, 48% reported a GDS score of 3 (that is, moderate), 16% reported a GDS score of 4 (that is, moderately severe), and the remaining 36% reported a GDS score of 1 or 2 (that is, mild or very mild). At baseline, 83% of patients received cholinesterase inhibitors, 46% received nonsteroidal antiinflammatory drugs, 39% received vitamin E, and 25% received antidepressants. Adult day care and home help were the largest cost factors in this population, with mean monthly costs of $65 and $64, respectively. We found interesting differences in the resources used among geographic regions and care settings. CONCLUSIONS: COSID is already generating valuable information about treatment patterns, outcomes, and resource use in Canadian patients with dementia. As the data mature, it will be possible to build robust models on treatment effectiveness and costs of care.

[Pharmacotherapy of patients with dementia]. / Pharmakotherapie bei Menschen mit Demenzerkrankungen.

Dementing illnesses present among the most frequent and most consequential psychiatric disorders in old age. They thus constitute a particular challenge for science politics and society as a whole. Knowledge about multifactorial etiological and pathological factors is still rather limited. By way of stratified diagnostic procedures various dementia disorders can be differentiated rather reliably. Anti-dementia drugs can enhance cognitive performance and temporarily slow down the progress of the most frequently occurring dementias (Alzheimer-dementia, vascular dementia). In the treatment of behavioral symptoms in dementia newly developed psychopharmological agents are of particular relevance. They constitute an important element of a multi-modal therapeutic strategy.

Acetylcholinesterase treatment--modelling potential demand and auditing practice.

BACKGROUND: Acetylcholinesterase inhibitors represent an entirely novel treatment option for patients with Alzheimer's disease (AD). As such they represent a significant change in practice and a significant cost pressure on funding bodies. OBJECTIVES: To assess the impact of cholinesterase inhibitors on routine clinical practice. METHODS: We estimated potential demand for the compounds taking into account eligibility criteria and prescribing practice agreed between clinicians and funders. We then audited actual prescribing practice assessing whether the estimated demand matched actual demand and whether practice and prescribing criteria were adhered to. RESULTS: Over a two-year period we estimated the demand for treatment at a total of 89 patient years for the population of the audit unit. In practice only 24.5 patient years of therapy were received, the short fall apparently being due to low referral rates for treatment. Prescribing by clinicians matched practice guidelines and a high proportion of three monthly assessments using scales for cognition, function and global state were performed. Using these assessment procedures treatment successes could be differentiated from primary and secondary treatment failures and, where apparently appropriate, treatment could be stopped. CONCLUSION: In the real world of clinical practice demand for treatment in AD is modest but likely to grow and assessment with an aim to identifying those receiving benefit from treatment can be achieved.