An economic evaluation of early assessment for Alzheimer's disease in the United Kingdom.

BACKGROUND: Diagnosing and treating patients with Alzheimer's disease (AD) at an early stage should improve the quality of life of the patient and caregiver. In the United Kingdom, cost-effectiveness of early assessment of individuals presenting with subjective memory complaints and treating those with AD with donepezil was evaluated. METHODS: A discrete event simulation of AD progression and the effect of treatment interventions was developed. Patient-level data from donepezil trials and a 7-year follow-up registry were used to model correlated longitudinal rates of change in cognition, behavior, and function. Other epidemiological and health services data, including estimates of undiagnosed dementia and delays in diagnosis, were based on published sources. Simulated individuals were followed up for 10 years. RESULTS: In the base-case estimates, 17 patients need to be assessed to diagnose one patient with AD, resulting in an average assessment cost of £4100 ($6000; $1 US = £0.68 UK) per patient diagnosed (2007 cost year). In comparison with a scenario without early assessment or pharmacologic treatment, early assessment reduces health care costs by £3600 ($5300) per patient and societal costs by £7750 ($11,400). Savings are also substantial compared with treatment without early assessment, averaging £2100 ($3100) in health care costs, and £5700 ($8400) in societal costs. Results are most sensitive to estimates of patient care costs and the probability of patients reporting subjective memory complaints. In probabilistic sensitivity analysis, early assessment leads to savings or is highly cost-effective in the majority of cases. CONCLUSIONS: Although early assessment has significant up-front costs, identifying AD patients at an early stage results in cost savings and health benefits compared with no treatment or treatment in the absence of early assessment.

Treating relapsing multiple sclerosis with subcutaneous versus intramuscular interferon-beta-1a: modelling the clinical and economic implications.

The EVIDENCE trial concluded that administering high-dose/high-frequency subcutaneous (SC) interferon-beta-1a (IFNb1a) was more effective in preventing relapses among patients with relapsing multiple sclerosis (MS) than low-dose weekly intramuscular (IM) IFNb1a after 64 weeks. This analysis utilized discrete-event simulation (DES) to model the potential longer-term clinical and economic implications of this trial. A DES predicting the course of relapsing MS and incorporating the effect of IFNb1a therapy was developed. The model began by randomly reading in actual patient data from the trial to create 1000 patients. Each simulated patient was replicated - one was assigned to receive SC IFNb1a three times a week and the other to receive IM IFNb1a once a week. During the simulation, patients may (i) experience relapses, with associated short- and long-term impacts on costs and disability; (ii) develop new T2 lesions detected by a magnetic resonance imaging scan; (iii) discontinue treatment because of adverse events or lack of response; (iv) advance to secondary progressive MS; or (v) die. Model inputs were mainly obtained from the EVIDENCE trial, but were taken from published literature if they could not be obtained from the trial. Direct medical costs ($US, year 2006 values) to the US payers were primarily obtained by updating a published cost analysis. Costs and benefits were discounted at 3% per annum. Extensive sensitivity analyses were conducted to test the robustness of the model results. Based on 100 replications of 1000 patient pairs over 4 years, SC IFNb1a was predicted to enable more patients to avoid relapse (216 vs 147). Total mean costs per patient (discounted) were $US79 890 with SC IFNb1a versus $US74 485 with IM administration, a net increase of $US5405 per patient. However, SC IFNb1a was estimated to prevent 0.50 relapses and save 23 relapse-free days per patient, yielding incremental cost-effectiveness ratios of $US10 755 per relapse prevented and $US232 per relapse-free day gained. Sensitivity analyses revealed that the result was most sensitive to the treatment efficacy, model time horizon and cost of IFNb1a treatment. Based on the results observed in the EVIDENCE trial, the model predicted that SC IFNb1a would yield greater health benefits over 4 years than IM IFNb1a, at a cost that would seem to be a reasonable trade-off.

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

INTRODUCTION: This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. METHODS: A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. RESULTS: Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. CONCLUSION: Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

Clinical and economic burden of infused iron chelation therapy in the United States.

BACKGROUND: Patients requiring chronic blood transfusions are at risk for iron overload, which, if not treated by iron chelation therapy (ICT), can create serious organ damage and reduce life expectancy. Current ICT requires burdensome 8- to 12-hour infusions five to seven times per week. STUDY DESIGN AND METHODS: A naturalistic study of the burden of infused ICT was conducted in four US centers. Data from the initial and most recent years of ICT were collected from medical charts of consenting thalassemia (n = 40) and sickle cell disease (n = 9) patients. Quality of life (QoL), treatment satisfaction, and ICT-related resource utilization data were also collected from a patient interview. RESULTS: Mean serum ferritin levels during the initial (2519 +/- 1382 ng/mL) and most recent (2741 +/- 2532 ng/mL) years remained unacceptably high and increased over time (306 +/- 2200 ng/mL; mean of 20+/- years of therapy). Within 30 days before interview, 55 percent of patients suffered at least one ICT-related adverse event; 76 percent missed at least one dose. QoL, measured by the SF-36, and treatment satisfaction appear compromised in this cohort. Although total annual costs of ICT were estimated at USD $30,000 to $35,000, drug accounted for only 50 to 60 percent of this amount. CONCLUSIONS: Infused ICT may not provide adequate effectiveness in the real world. High ferritin levels seem to be associated with ICT noncompliance, likely in relation to the bothersome mode of administration and side effects. The total cost of ICT appears to well exceed that of drug alone.

The time course of subsequent hospitalizations and associated costs in survivors of an ischemic stroke in Canada.

BACKGROUND: Documentation of the hospitalizations rates following a stroke provides the inputs required for planning health services and to evaluate the economic efficiency of any new therapies. METHODS: Hospitalization rates by cause were examined using administrative data on 18,695 patients diagnosed with ischemic stroke (first or subsequent, excluding transient ischemic attack) in Saskatchewan, Canada between 1990 and 1995. Medical history was available retrospectively to January 1980 and follow-up was complete to March 2000. Analyses evaluated the rate and timing of all-cause and cardiovascular hospitalizations within discrete periods in the five years following the index stroke. Cardiovascular hospitalizations included patients with a primary diagnosis of ischemic stroke, transient ischemic attack, myocardial infarction, stable or unstable angina, heart failure or peripheral arterial disease. RESULTS: One-third (36%) of patients were identified by a hospitalized stroke. Mean age was 70.5 years, 48.0% were male, half had a history of stroke or a transient ischemic attack at the time of their index stroke. Three-quarters of the patients (72.7%) were hospitalized at least once during a mean follow-up of 4.6 years, accruing CAD $24 million in the first year alone. Of all hospitalizations, 20.4% were related to cardiovascular disease and 1.6% to bleeds. In the month following index stroke, 12.5% were admitted, an average of 1.04 times per patient hospitalized. Strokes accounted for 33% of all hospitalizations in the first month. The rate diminished steadily throughout the year and stabilized in the second year when approximately one-third of patients required hospitalization, at a rate of about one hospitalization for every two patient-years. Mean lengths of stay ranged from nine days to nearly 40 days. Close-fitting Weibull functions allow highly specific probability estimates. Other cardiovascular risk factors significantly increased hospitalization rates. CONCLUSION: After stroke, there are frequent hospitalizations accounting for substantial additional costs. Though these rates drop after one year, they remain high over time. The number of other cardiovascular causes of hospitalization confirms that stroke is a manifestation of disseminated atherothrombotic disease.

Assessment of compliance with osteoporosis treatment and its consequences in a managed care population.

OBJECTIVE: To evaluate non-compliance with osteoporosis medications as well as its implications for health and economic outcomes in actual practice. STUDY DESIGN: Data on demographics, prescription drug dispensing, physician services and hospitalizations were obtained from a US managed care database for women with osteoporosis who were dispensed an osteoporosis medication between 1997 and 2002. METHODS: Each subject's pattern of osteoporosis medication use was reconstructed using dispensing records. Subjects were considered compliant over a given period if their medication possession ratio (MPR) was >or=80% and gradients of compliance (<50% poor, 50-80% medium, 80-90% good, >90% excellent) were also examined. Using proportional hazards, the association between compliance over time and fracture rates was examined; Poisson regression was used for hospitalization and log-linear regression for medical costs. RESULTS: 38,120 women with osteoporosis were identified with a mean age of 66 years and an average follow-up of 1.7 years. Three quarters of them had an MPR below 80% when their entire follow-up was considered. Low compliance was associated with a 17% (95% CI 9-25%) increase in the fracture rate, adjusting for other known risk factors. Controlling for the specific drug regimen did not alter the association. Low compliance was also associated with a 37% (95% CI 32-43%) increase in the risk of all-cause hospitalization; and average monthly costs for all medical services combined were higher: 600 US dollars vs. 340 US dollars (P < 0.0001). Similar associations were observed when using the gradients of compliance. CONCLUSIONS: The desired goal of keeping patients with osteoporosis on chronic treatment is not being achieved adequately in actual practice and the potential social and economic implications of this behavior are substantial. Until compliance is improved, society will continue to fail in meeting an important public health goal.

Compliance with refilling prescriptions for atypical antipsychotic agents and its association with the risks for hospitalization, suicide, and death in patients with schizophrenia in Quebec and Saskatchewan: a retrospective database study.

OBJECTIVE: The objective of this analysis was to describe the patterns of compliance with atypical antipsychotics among patients with schizophrenia in actual practice in 2 Canadian provinces and to examine the relation between degrees of compliance and the risks of hospitalization, suicide, and death. METHODS: Adults with a diagnosis of schizophrenia who filled at least 1 prescription for risperidone, olanzapine, or quetiapine were identified in the Quebec public prescription drug insurance plan database (from July 1, 2001, to December 31, 2004) and the Saskatchewan Health database (from January 1, 1999, to December 31, 2003). Compliance was assessed based on the medication possession ratio, which was estimated as the proportion of days for which medication was available over each month of follow-up (> or = 80% = good compliance; 50%-79% = moderate compliance; < 50% = poor compliance). The association between the early and long-term effects of compliance and the risks of hospitalization, suicide, and death were examined using Cox regression, with adjustment for baseline age, sex, and use of antidepressants, sedatives, and lithium (Quebec only). RESULTS: respective 41,754 and 3291 patients were identified from the Quebec and Saskatchewan databases. Approximately half of the patients in each cohort were male and were aged < 45 years. Many patients had good compliance over the full follow-up period (Quebec, 61%; Saskatchewan, 45%); however, poor compliance was seen in 23% of patients from Quebec and 34% of those from Saskatchewan. Compared with poor compliance, the long-term effect of good compliance was associated with a significantly decreased risk of all-cause hospitalization (Quebec: adjusted hazard ratio [HR] = 0.60; 95% CI, 0.57-0.64; Saskatchewan: adjusted HR = 0.81; 95% CI, 0.69-0.95) and psychosis-related hospitalization (Quebec: adjusted HR = 0.37; 95% Cl, 0.34-0.40; Saskatchewan: adjusted HR = 0.45; 95% CI, 0.32-0.64). The Quebec data also indicated a significant association between good versus poor compliance and a decreased risk of death (adjusted HR = 0.58; 95% CI, 0.51-0.66) and suicide (adjusted HR = 0.68; 95% CI, 0.55-0.84) that was not observed in Saskatchewan. CONCLUSION: In this retrospective analysis of patients with schizophrenia in Quebec and Saskatchewan, good compliance with atypical antipsychotic medications was associated with substantial reductions in the risk for all-cause and psychosis-related hospitalizations.

Costs and medical care consequences associated with the diagnosis of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is increasingly recognised as an indicator of disseminated atherothrombosis, but its impact on use of healthcare resources is not well understood. OBJECTIVE: To provide a quantitative description of the resource utilisation and costs incurred following PAD. METHODS: Hospitalisations, physician visits and the corresponding direct medical costs were examined in 16,440 patients with a diagnosis of PAD (1985--1995) in Saskatchewan, Canada, and compared with 15,590 reference patients with a diagnosis of myocardial infarction (MI) [1990--1995]. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up to December 2000. Rates and timing of all-cause and cardiovascular hospitalisations and physician visits within discrete periods in the 10 years following PAD diagnosis, and 5 years following MI, were evaluated, as were lengths of stay and predictors of hospitalisation. RESULTS: Average follow-up was 5.9 years among patients with PAD and 3.6 years for MI. Half (55%) of patients with PAD were male versus 64% of reference patients. The mean ages were 67.3 and 66.9 years, respectively. Patients with PAD were hospitalised most frequently soon after diagnosis, with rates subsequently decreasing to 0.14 per month. These rates were similar in the reference group except for the period immediately following MI. The average 5-year cost post-diagnosis (2002 Can dollars) per patient was 41,968 Can dollars vs 48,578 Can dollars for the reference population. CONCLUSIONS: A diagnosis of PAD not only imposes a severe burden on patients and their families, but it also significantly increases the use of healthcare resources and the associated costs. By the end of year 1, this burden is comparable with a diagnosis of MI.

The morbidity and mortality following a diagnosis of peripheral arterial disease: long-term follow-up of a large database.

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased.

Estimating survival for cost-effectiveness analyses: a case study in atherothrombosis.

BACKGROUND: Economic evaluations typically require estimates of survival beyond the limited follow-up in clinical trials. The objective of this study was to demonstrate a data-driven approach to deriving these estimates. METHODS: To provide survival estimates for analyses of the CAPRIE trial, data were obtained from Saskatchewan on more than 50,000 patients like those in the trial: diagnosed with peripheral arterial disease (PAD), myocardial infarction, or ischemic stroke between 1985 and 1995; follow-up to December 31, 2000. Mean survival was estimated by integrating the full survival curve derived by applying hazard functions over time. Cox proportional hazards analyses were carried out in each of four periods defined to ensure proportionality. RESULTS: Adjusting for mean age in CAPRIE, mean survival ranged from 12.1 years after index stroke to 13.6 years after diagnosis of PAD. Comorbidities reduced mean survival by 1 to 2 years. Subsequent events had a marked detrimental effect, decreasing life-expectancy by 50% or more, and disease in multiple vascular beds led to survival of less than 5 years. DISCUSSION: These analyses demonstrate the analytic methods required to accurately estimate survival. The trial ages were much lower than in the observational study. Thus, the estimates are optimistic for the general population. CONCLUSIONS: Accurate valuation of interventions depends on valid survival estimates. These analyses confirm that survival is significantly reduced in patients with atherothrombotic disease, particularly with additional comorbidities.

The impact of compliance with osteoporosis therapy on fracture rates in actual practice.

BACKGROUND: Clinical trials have demonstrated that drug therapy can reduce osteoporosis-related fracture risk in women over 50 years of age. Noncompliance could considerably limit the effectiveness observed in actual practice, however. The objective of this study was therefore to estimate fracture risk in relation to compliance with osteoporosis medication in actual practice. METHODS: Demographic, prescription drug use, physician services, and hospitalization information for women with osteoporosis who were dispensed an osteoporosis medication between 1996 and 2001 was obtained from the Saskatchewan health data files. Compliance to treatment was defined as drug available to cover 80% of the time. Subsequent fractures were identified via hospitalizations or physician contacts with a relevant diagnostic or procedure code. The risk of fractures in relation to compliance was examined using a Cox proportional hazards model with time-dependent covariates. The impact of other patient characteristics, including age, having suffered a prior fracture, and prior use of osteoporosis medication and steroids, was also examined. RESULTS: 11,249 women suffering from osteoporosis were identified with a mean age at the time of the index prescription of 68.4 years and average follow-up of 2 years. The overall fracture rate was 4.5% per year. Patients who complied experienced a 16% lower fracture rate. This association was maintained within subgroups and after controlling for other patient characteristics that independently predict the fracture rate. CONCLUSION: These results indicate that improving compliance in actual practice may significantly decrease osteoporosis-related fracture risk.

Modeling the efficiency of reaching a target intermediate end point: a case study in type 2 diabetes in the United States.

OBJECTIVE: The objective of this study was to describe an approach to modeling the efficiency of an intervention by focusing on an established intermediate end point directly. A case study addresses the economic efficiency of obtaining dual glycemic control over time, according to initial choice of treatment. METHODS: From the perspective of a payer in the United States, instead of the usual approach of basing the model on projecting long-term diabetic complications from glycemic control, this model focuses directly on glycemic control. Treatment changes and associated health-care utilization needed to address postprandial glucose. After assigning each of 10000 drug-naïve patients, HbA1c, age, race, and sex based on distributions from a randomized clinical trial, the model applies the efficacy of nateglinide compared to metformin. Sensitivity analyses were carried out for all parameters. Costs are reported in year 2000 US dollars and discounted at 3%. RESULTS: In the base case, starting on nateglinide and increasing the time in dual glycemic control over 3 years by 2.4 months led to savings of US dollars 295 compared to starting on metformin. Savings increased with stricter treatment criteria but decreased if glycemic control was better initially. CONCLUSIONS: This study illustrates the use of an efficiency model that focuses directly on the relevant short-term end point: glycemic control. Starting patients with nateglinide is shown to be an efficient way of obtaining dual glycemic control during the first 3 years 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.