Evaluation of the consequences associated with diffuse vascular disease history in patients diagnosed with peripheral arterial disease: estimates from Saskatchewan health data.

BACKGROUND: Peripheral arterial disease (PAD) is caused by narrowing of the arteries in the lower extremities. Limited data exist concerning the impact of diffuse vascular disease (DVD) on prognosis and costs. Thus, the objective of this study is to estimate the impact of DVD on morbidity, mortality and costs. METHODS: PAD was identified between 1985 and 1995 and classified by extent of DVD at diagnosis: none (PAD only, reference group), prior myocardial infarction (MI), prior stroke, prior MI and stroke (MI + stroke), prior transient ischemic attack (TIA). Deaths and hospitalizations were identified through December 2000. Hospitalization costs were estimated from the Ontario Case Cost Project, reported in 2002 $CAD. Proportional hazards analyses measured the impact of vascular involvement on mortality while controlling for risk factors (e.g., age, cardiovascular history). RESULTS: Overall, 16,439 patients with PAD were included; 14.8% had a prior MI, 10.2% a prior stroke, 2.6% prior MI + stroke, 6.4% prior TIA, two-thirds had PAD only. Median survival was shorter for patients with prior MI (9.3 yrs), TIA (6.3), stroke (4.7), and MI+stroke (4.1) versus the reference group (9.9, p < 0.05, all comparisons). Analyses revealed that the death risk was 60% higher in patients with prior stroke and 84% higher for MI + stroke. Atherothrombotic and bleeding event-related costs were $712, $337, $268, and $170 higher per patient/year of follow-up in patients with a history of MI+stroke, MI, stroke, and TIA, respectively. CONCLUSION: Patients diagnosed with PAD with DVD have higher risk of poor outcomes and increased costs.

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.

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.

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.

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 dollars and 4,246 dollars. 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.

A Canadian study of the cost-effectiveness of apixaban compared with enoxaparin for post-surgical venous thromboembolism prevention.

BACKGROUND: Occurrence of a venous thromboembolism (VTE) in patients undergoing major orthopedic surgery who are not given thromboprophylactic therapy presents considerable danger to patient medical outcomes and a significant economic burden to the health care system at large. Apixaban is a direct factor Xa inhibitor that has been shown in clinical trial use to safely reduce the composite of VTE and mortality rates in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA); however, the cost-effectiveness of apixaban treatment in Canadian settings has not been studied. Our study evaluated the cost-effectiveness of apixaban compared with enoxaparin as VTE preventive therapy in patients undergoing elective THA or TKA in Canada. METHODS: An economic model, including both a decision-tree component and a Markov model, was created. The decision tree considered VTE, bleeding, and mortality incidence that occurred in patients within 90 days post-surgery using data from the Apixaban Versus Enoxaparin for Thromboprophylaxis After Knee or Hip Replacement (ADVANCE) trials, which compared apixaban therapy with 30-mg twice daily and 40-mg daily enoxaparin treatment. The Markov model provided the option to simulate events that may occur over the long term, such as recurrent VTE and post-thrombotic syndrome. Outcomes during the short-term phase directly impact the risk of events occurring during the long-term phase (5 years post-surgery). RESULTS: The results of our analysis indicated that apixaban is dominant (ie, more effective and less expensive) than enoxaparin in treating patients undergoing THA and TKA. There were fewer occurrences of VTEs, bleeding events, recurrent VTEs, and post-thrombotic syndrome events in the TKA population with apixaban therapy. Similar results were seen in patients undergoing THA, with the exception of bleeding events, which were more common with apixaban treatment. Savings of $180 to $270 per patient are expected with apixaban treatment compared with enoxaparin treatment, and health outcomes in general are better with apixaban use. Sensitivity analyses yielded consistent results across the THA and TKA populations. CONCLUSION: : This is the first economic evaluation of apixaban use for VTE thromboprophylaxis in the Canadian setting, and our study results show apixaban to be a cost-effective treatment alternative to preventive treatment with enoxaparin.

Economic evaluation of clopidogrel plus aspirin for secondary prevention of cardiovascular events in Canada for patients with established cardiovascular disease: Results from the CHARISMA trial.

BACKGROUND: The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial found a statistically significant reduction in cardiovascular events when clopidogrel was added to aspirin in a prespecified subgroup of patients with established cardiovascular disease. However, the economic implications of such a strategy for the Canadian health care system are unknown. METHODS: For each patient in the CHARISMA trial with established cardiovascular disease, costs were estimated by multiplying resource utilization by unit costs derived from populations of Canadian patients in 2008 dollars. Changes in life expectancy due to nonfatal events were estimated with parametric regression models based on the Saskatchewan Health database. RESULTS: For patients with established cardiovascular disease, a strategy of clopidogrel plus aspirin for median duration of 28 months was associated with a 12.5% relative reduction in cardiovascular death, myocardial infarction, or stroke compared with aspirin alone (6.9% vs 7.9%, P =.048). Mean cost per patient was CAD$1,488 higher for clopidogrel plus aspirin, and life expectancy increased by 0.057 years. The resulting incremental cost-effectiveness ratio for adding clopidogrel was CAD$25,969 per life-year gained or CAD$21,549 per quality-adjusted life-year. These results were sensitive to the cost of clopidogrel but relatively insensitive to plausible variations in discount rate, costs other than clopidogrel, and the prognostic impact of nonfatal events. CONCLUSION: Among the subgroup of patients with established cardiovascular disease in the CHARISMA trial, adding clopidogrel to aspirin increases life expectancy at a cost generally considered acceptable in Canada.

Assessing the economics of vaccination for Neisseria meningitidis in industrialized nations: a review and recommendations for further research.

OBJECTIVES: To review the existing health economic literature on meningococcal disease vaccination. METHODS: A Medline search for economic evaluations of vaccination programs for meningococcal disease in developed countries was conducted. All identified studies were reviewed. RESULTS: Nine published studies were identified examining either mass vaccination during outbreaks or routine vaccination. Although net expenses were estimated in almost all studies, the resulting cost-effectiveness ratios varied widely. Vaccination of college-age students was found to be potentially cost-effective in Australia but not in the United States. With one exception, routine vaccination of children and adolescents in Europe was predicted to be cost-effective. Many simplifying assumptions were made, and important elements were often left out, in particular the potential for reduced transmission of disease. CONCLUSIONS: The methods used and the vaccination strategies vary widely, and results do not provide strong grounds for making conclusions as to whether vaccination is cost-effective. Furthermore, in all instances, transmission of disease, changes in population carriage rates, and outbreaks are either ignored, dealt with using very broad simplifying assumptions, or are not necessarily generalizable to other settings. The analyses provide some insight into the potential cost-effectiveness of vaccination, but more importantly, they highlight areas requiring further study. Economic evaluations based on observed outcomes from recently implemented strategies would be helpful, as would more sophisticated health economic models. The choice of vaccination strategies cannot be based on the results of existing economic analyses.