Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps

The growing understanding of the use of biomarkers in Alzheimer's disease (AD) may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET), is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Rational choice of cholinesterase inhibitor for the treatment of Alzheimer's disease in Canada: a comparative economic analysis

BACKGROUND: Cholinesterase inhibitors, such as galantamine, donepezil and rivastigmine are approved for symptomatic treatment of Alzheimer's Disease (AD) in Canada. In making choices amongst these drugs, one should consider their clinical merits and their economic implications. METHODS: Each drug's short-term efficacy was estimated based on independent Cochrane reviews of the clinical trials. Long-term clinical and economic outcomes were estimated using the Assessment of Health Economics in Alzheimer's Disease (AHEAD) model. RESULTS: While all treatments reduced the need for full-time care, only galantamine and donepezil 10 mg reduced the overall management costs of AD patients. The somewhat greater cognitive effect provided over six months by galantamine leads to the longest estimated delay before full-time care is required and, consequently to lower overall costs, with savings estimated at between $323 and$4,246. CONCLUSION: Although there is uncertainty in estimated results, the best information currently available suggests that the first choice for treatment of AD should be galantamine. These results should be interpreted with caution, however, as results are not based on direct comparisons among the drugs and the differences emerging from meta-analyses of the trials are relatively small

Adult Vaccination Strategies for the Control of Pertussis in the United States: An Economic Evaluation Including the Dynamic Population Effects

BACKGROUND: Prior economic evaluations of adult and adolescent vaccination strategies against pertussis have reached disparate conclusions. Using static approaches only, previous studies failed to analytically include the indirect benefits derived from herd immunity as well as the impact of vaccination on the evolution of disease incidence over time. METHODS: We assessed the impact of different pertussis vaccination strategies using a dynamic compartmental model able to consider pertussis transmission. We then combined the results with economic data to estimate the relative cost-effectiveness of pertussis immunization strategies for adolescents and adults in the US. The analysis compares combinations of programs targeting adolescents, parents of newborns (i.e. cocoon strategy), or adults of various ages. RESULTS: In the absence of adolescent or adult vaccination, pertussis incidence among adults is predicted to more than double in 20 years. Implementing an adult program in addition to childhood and adolescent vaccination either based on 1) a cocoon strategy and a single booster dose or 2) a decennial routine vaccination would maintain a low level of pertussis incidence in the long run for all age groups (respectively 30 and 20 cases per 100,000 person years). These strategies would also result in significant reductions of pertussis costs (between -77% and -80% including additional vaccination costs). The cocoon strategy complemented by a single booster dose is the most cost-effective one, whereas the decennial adult vaccination is slightly more effective in the long run. CONCLUSIONS: By providing a high level of disease control, the implementation of an adult vaccination program against pertussis appears to be highly cost-effective and often cost-saving

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

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 (Reminyl(®)). 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

Long-Term Effects of Second-Generation Cholinesterase Inhibitors on Clinical Outcomes and Costs of Alzheimer

Alzheimer Data on the effectiveness of these drugs from information beyond the short-term clinical trials (e.g. long-term clinical trials and non-trial data) are now emerging. In most cases, the results indicate that, at least for some patients, continued treatment with cholinesterase inhibitors is effective in slowing cognitive decline. Whether these results translate to clinically and economically relevant outcomes is less clear. The AD2000 trial in particular, a 1-year, placebo-controlled trial, seems to suggest that cognitive benefits, even if maintained over the mid-to-long term, may not adequately reflect overall deterioration in patients. Naturalistic studies, as well as analyses of administrative data, however, mostly suggest that these benefits are real and relevant. The cost effectiveness of treatment has been evaluated primarily through modeling. These studies have shown that the costs of treatment can be offset by savings in other areas as a result of slowed disease progression. When all medical costs are considered, relatively small delays in disease progression are required to offset treatment costs, but a large portion of these offsetting savings are a result of delayed institutionalization. To payors not responsible for institutional care costs, these predicted economic advantages are less relevant. While data are limited, some research indicates that reductions in other costs may be sufficiently large to fully offset the costs of treatment. Economic comparisons among active treatments have only been made in one study so far. Based on meta-analyses of trial data and a model estimating disease progression, that study concluded that galantamine provided the best health and economic projections. Head-to-head studies, however, are limited and provide conflicting results. While the treatment of patients with AlzheimerAlzheimer's-disease, Cholinesterase-inhibitors, Cost-analysis, Cost-effectiveness, Donepezil, Galantamine, Pharmacoeconomics, Rivastigmine

Discrete Event Simulation: The Preferred Technique for Health Economic Evaluations?

AbstractObjectivesTo argue that discrete event simulation should be preferred to cohort Markov models for economic evaluations in health care.MethodsThe 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.ResultsMarkov 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.ConclusionIn our opinion, discrete event simulation should be the preferred technique for health economic evaluations today

Managing Meningococcal Disease in the United States: Hospital Case Characteristics and Costs by Age

ABSTRACTObjectiveMeningococcal disease occurs worldwide. Approximately 1400 to 2800 cases are reported in the United States annually. The goal of this analysis was to examine hospitalized cases of meningitis and meningococcemia to identify case characteristics, resource use, and inpatient care costs.MethodsInternational Classification of Diseases-9th Revision-Clinical Modification diagnosis codes 036.0–036.9 were used to identify cases from roughly 1000 hospitals in four all payer state discharge databases. Multiyear data (1999–2001) were examined to identify demographics, admission month, health service utilization, and hospital costs by age group: infant (<1 years), children (1–10 years), adolescent (11–17 years), young adult (18–22 years), adults (23–49 years), and adults (≥50 years). Cost estimates include accommodations, ancillary and physician services, reported in 2003 US$.ResultsOf 1654 cases of meningococcal disease identified, meningococcemia was coded for 51$23,294 per patient. Infants had the lowest average cost per stay ($16,793) and adolescents had the highest ($28,202).ConclusionsThe presence of meningococcemia results in a greater death rate, longer length of stay, and increased care costs. Meningococcal disease has substantial economic, as well as profound clinical consequences for patients of all ages