Denis Getsios

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

OBJECTIVESnTo argue that discrete event simulation should be preferred to cohort Markov models for economic evaluations in health care.nnnMETHODSnThe 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.nnnRESULTSnMarkov 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.nnnCONCLUSIONnIn our opinion, discrete event simulation should be the preferred technique for health economic evaluations today.

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.

Assessment of Health Economics in Alzheimer's Disease (AHEAD): Treatment with Galantamine in Sweden

AbstractBackground: 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.n Objective: To estimate the long-term health and economic impact of galantamine from the perspective of the public health payer in Sweden.n 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.n 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 (EUR5594) 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.n 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.

Economic Analysis of Galantamine, a Cholinesterase Inhibitor, in the Treatment of Patients with Mild to Moderate Alzheimer’s Disease in The Netherlands

Background: The economic impact of dementia on the Dutch health and social services is substantial. Objective: To predict the long-term economic impact of galantamine, a cholinesterase inhibitor, in the treatment of Dutch patients with mild to moderate Alzheimer’s disease. Method: A pharmacoeconomic model was used to predict long-term outcomes. It has two components: an initial module based on clinical trials of galantamine and a subsequent module that predicts when a patient will deteriorate to a level where full time care (FTC) is needed. The analyses take a broad perspective that includes all formal (paid) care, not just those covered by the Dutch health care system. Direct cost estimates were based on resource use profiles of patients with Alzheimer’s disease in the Netherlands. Key inputs were tested in sensitivity analyses. Results: After 10.5 years all patients are predicted to require FTC. For every hundred patients starting treatment on galantamine at the mild to moderate stage, it is predicted that 18 person-years of FTC will be avoided (14.4 discounted) and about 5 quality-adjusted years of life will be gained (3.9 discounted). Net savings for those starting treatment with galantamine are estimated at NLG 3,050 (1,676 UDS). The cost of galantamine accounts for only about 5.0% of the total cost of care for treated Alzheimer’s patients. The direction of these results remained unchanged when input values and assumptions were tested in sensitivity analyses. Conclusions: The cholinesterase inhibitor galantamine is expected to bring savings in the direct cost of caring for patients with Alzheimer’s disease in the Netherlands.

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

BACKGROUNDnAlzheimers 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.nnnOBJECTIVEnThe 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).nnnMETHODSnCalculations were made using the Assessment of Health Economics in Alzheimers 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%.nnnRESULTSnIn 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.nnnCONCLUSIONSnThese 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.

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

Cost Effectiveness of Donepezil in the Treatment of Mild to Moderate Alzheimer’s Disease

6000 to

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

22,000 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.

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

Background: Recommendations in the UK suggest restricting treatment of Alzheimer’s disease with cholinesterase inhibitors, on cost-effectiveness grounds, to patients with moderate cognitive decline. As the economic analyses that informed these recommendations have been the subject of debate, we sought to address the potential limitations of existing models and produce estimates of donepezil treatment cost effectiveness in the UK using the most recent available data and simulation techniques.Methods: A discrete-event simulation was developed that predicts progression of Alzheimer’s disease through correlated changes in cognition, behavioural disturbance and function. Patient-level data from seven randomized, placebo-controlled donepezil trials and a 7-year follow-up registry provided the basis for modeling longitudinal outcomes. Individuals in the simulation were assigned unique demographic and clinical characteristics and then followed for 10 years, with severity of disease tracked on continuous scales. Patient mix and costs were developed from UK-specific literature. Analyses were run for severity subgroups to evaluate outcomes for sub-populations with disease of mild versus moderate severity from both a healthcare payer and societal perspective. All costs are reported in £, year 2007 values, and all outcomes are discounted at 3.5% per annum.Results: Over 10 years, treatment of all patients with mild to moderate disease reduces overall direct medical costs by an average of over £2300 per patient. When unpaid caregiver time is also taken into consideration, savings increase to over £4700 per patient. Compared with untreated patients, patients receiving donepezil experience a discounted gain in QALYs averaging 0.11, with their caregivers gaining, on average, 0.01 QALYs. For the subset of patients starting treatment with more severe disease, savings are more modest, averaging about £1600 and £3750 from healthcare and societal perspectives, respectively. In probabilistic sensitivity analyses, donepezil dominated no treatment between 57% and 62% of replications when only medical costs were considered, and between 74% and 79% of replications when indirect costs were included, with results more favourable for treatment initiation in the mild versus moderate severity stages of the disease.Conclusions: Although the simulation results are not definitive, they suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer’s disease in the UK. They also indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer’s disease.

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

BackgroundPatients with Alzheimers 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 Alzheimers for patients, their families, and also health care providers. Understanding the relationship between a patients 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.MethodsData were obtained on 1,289 patients with mild-to-moderate Alzheimers disease studied in two randomised clinical trials of galantamine (Reminyl®). Cognition was assessed using the cognitive part of the Alzheimers 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.ResultsThe 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.ConclusionIn patients with mild-to-moderate Alzheimers disease, even relatively small degrees of poorer cognitive function increased the risk of losing the ability to live independently.