The epidemiological and economic impact of a quadrivalent human papillomavirus vaccine (6/11/16/18) in the UK.

OBJECTIVE: To assess the potential epidemiological and economic impact of a prophylactic quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), CIN1 and genital warts. DESIGN: Cost-utility analysis. SETTING: UK. POPULATION: Female and male UK population 12 years or older. METHODS: We adapted a previously developed multi-HPV type dynamic transmission to compare four female vaccination strategies, routine vaccination at age 12 years, and routine vaccination at age 12 years combined with temporary catch-up vaccination at ages 12-14, 12-17 and 12-24 years. MAIN OUTCOMES MEASURES: Costs, cases avoided, incremental cost per quality-adjusted life year (QALY). RESULTS: The model projected that at year 100, each vaccination strategy could reduce the number of HPV 6/11/16/18-related cervical cancer, CIN2/3, CIN1 and genital wart cases among women by 86, 85, 79 and 89% respectively. Over 25 years, routine vaccination at age 12 years combined with a 12- to 24-year-old catch-up programme was the most effective strategy, reducing the cumulative number of cases of cervical cancer, CIN2/3, CIN1 and genital warts by 5800, 146 000, 28 000, and 1.1 million respectively. Over 100 years, the incremental cost-effectiveness ratios across all strategies ranged from pound5882 to pound11,412 per QALY gained. CONCLUSION: In the UK, a quadrivalent HPV vaccination programme that includes a catch-up strategy can reduce the incidence of cervical cancer, CIN and genital warts at a cost per QALY ratio within the range typically regarded as cost-effective.

The effect of alendronate on fracture-related healthcare utilization and costs: the fracture intervention trial.

The Vertebral Fracture Arm (VFA) of the Fracture Intervention Trial (FIT) study demonstrated that alendronate reduced the incidence of spine, forearm and hip fractures in women with low bone mass and existing vertebral fractures by about 50%. The objective of the present study was to determine the effects of alendronate therapy versus placebo on fracture-related healthcare utilization and costs. Participants were randomly assigned to double-masked treatment with alendronate (5 mg/day for 2 years and then 10 mg/day for 1 year) or placebo for 3 years. For each patient experiencing a clinical fracture, we determined whether treatment in an emergency room, hospital, nursing home and/or rehabilitation hospital was a consequence of the fracture. The VFA of the FIT Study enrolled 2027 women aged 55-81 years with low bone mass and pre-existing vertebral fractures from population-based listings in 11 metropolitan areas of the United States. We measured (1) the proportion of patients who had any fracture-related healthcare event and (2) the estimated cost of fracture-related healthcare services. Alendronate significantly reduced the proportion of patients utilizing fracture-related healthcare (emergency room, hospital, rehabilitation hospital or nursing home) by 25% (p = 0.038). Alendronate significantly reduced the costs associated with hip-fracture-related care by 58%, or $181 per patient randomized (p = 0.036). The reduction in fracture-related total costs was 35% ($190 per patient randomized) in the alendronate group relative to the placebo group (p = 0.114). Alendronate thus not only reduces the incidence of clinical fractures and associated morbidity, but reduces the proportion of patients utilizing the associated healthcare resources.

An economic overview of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity. Relatively few pharmacoeconomic studies have been conducted on this disease. This article reviews available information about the utilisation of healthcare resources and cost of care, and the cost or cost effectiveness of therapeutic interventions reported for this disease. Burden-of-illness data indicate that hospital care, medications and oxygen therapy were the major cost drivers in these studies. Mean annual Medicare expenditures in the US were $US11,841 (2000 values) for patients with COPD compared with $US4,901 for all covered patients. Utilisation was skewed; the most expensive 10% of the Medicare beneficiaries accounted for nearly 50% of total expenditures for this disease. Costs are associated with health status, age, physician specialty, geographic location and type of insurance coverage. Six types of interventions were assessed in the literature--pharmacotherapy, oxygen therapy, home care, surgery, exercise and rehabilitation and health education. The studies used different analytic strategies (e.g. cost-minimisation and cost-effectiveness analyses) and even within the realm of cost-effectiveness analyses, no uniformity existed as to how outcome was measured. Patient severity was not always delineated, and the length of the follow-up period, while quite short, varied. Only 11 of the 34 evaluations were based on randomised controlled trials. Cost-minimisation studies generally found no significant difference in the cost of antimicrobial treatment for first-line, second-line and third-line agents. Studies of bronchodilators indicated that ipratropium bromide alone or in combination with salbutamol (albuterol) was the preferred medication. The major area for achieving cost savings is by reducing hospital utilisation. As the annual rate of hospitalisation is relatively low, large patient samples will be required to demonstrate an economic advantage for a new therapy. The major challenges will be financing such a study, and selecting an outcome measure that satisfies both clinical and economic conventions.

The multinational impact of migraine symptoms on healthcare utilisation and work loss.

OBJECTIVE: To compare self-reported healthcare resource utilisation, paid work loss, unpaid work loss and loss of effectiveness at work due to migraine in a clinic-based adult migraine population. METHODS: The Migraine Background Questionnaire (MBQ) was translated and pilot-tested for use in 25 countries. The questionnaire was then self-administered by patients at a screening visit for 3 phase III clinical trials of rizatriptan [a selective serotonin (5-hydroxytryptamine) 5-HT1B/1D receptor agonist] in 23 US and 78 non-US sites. PARTICIPANTS: Persons 18 to 65 years of age with at least a 6-month history of moderate to severe migraines prior to the screening visit were surveyed. RESULTS: A total of 2670 persons (54.7% Europe, 16.5% Latin America, 23.1% North America, 5.5% other countries) completed the MBQ and had responses which could be analysed. On average, each patient reported 2.78 doctor visits, 0.53 emergency room visits and 0.06 hospitalisations related to migraine per year. Patients self-reported being only 46% effective while on the job with migraine symptoms. Extrapolation of patient self-reported work and productivity loss for the last 4 weeks to an annual basis suggested that clinic-based patients with migraine lose 19.5 workday equivalents (8.3 days due to absenteeism, 11.2 days due to reduced workday equivalents) due to migraine per year. In the US, the annual employer cost of this total migraine-related work loss is estimated to be $US3309 (2000 values) per patient with migraine. The levels of self-reported healthcare resources utilised for migraine and work loss were generally consistent across geographic regions. CONCLUSIONS: The impact of migraine symptoms on healthcare resource utilisation and work loss was similar across most measures in Europe, Latin America, North America and other countries. Total migraine-related work loss due to absenteeism and reduced workday equivalents accounts for most of the economic burden of migraine, regardless of country, in a clinic-based migraine population.

Mortality and costs of acute renal failure associated with amphotericin B therapy.

To assess the mortality and resource utilization that results from acute renal failure associated with amphotericin B therapy, 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital. Main outcome measures were mortality, length of stay, and costs; we controlled for potential confounders, including age, sex, insurance status, baseline creatinine level, length of stay before beginning amphotericin B therapy, and severity of illness. Among 707 admissions, there were 212 episodes (30%) of acute renal failure. When renal failure developed, the mortality rate was much higher: 54% versus 16% (adjusted odds of death, 6.6). When acute renal failure occurred, the mean adjusted increase in length of stay was 8.2 days, and the adjusted total cost was $29,823. Although residual confounding exists despite adjustment, the increases in resource utilization that we found are large and the associated mortality is high when acute renal failure occurs following amphotericin B therapy.

Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy.

OBJECTIVE: To measure health-related quality-of-life (HRQoL) in elderly symptomatic heart failure patients following treatment with an angiotensin II receptor antagonist (losartan) vs. an angiotensin-converting-enzyme (ACE) inhibitor (captopril). METHODS: Patients (age > or = 65 years) were randomised to losartan, titrated to 50 mg once daily, or captopril, titrated to 50 mg three times daily, as tolerated. Sickness Impact Profile (SIP) and Minnesota Living with Heart Failure (LIhFE) questionnaires were administered at baseline, weeks 12 and 48. Composite hypothesis testing of change in HRQoL from baseline for completers, and withdrawal for unfavourable events (death, clinical/laboratory adverse experience) was used to account for differential dropout rates. RESULTS: In 203 patients completing the substudy (week 48), significant and comparable improvements in HRQoL from baseline were observed for both treatment groups (p < or = 0.001). Although there was a trend favouring losartan vs. captopril for the composite HRQoL endpoint (unadjusted p = 0.018, one-sided), this was not considered significant after adjusting for multiple testing. Significantly more captopril patients in the substudy subset withdrew for unfavourable reasons (19.6 vs. 10.9%, p = 0.038). CONCLUSIONS: Significant improvements in HRQoL were observed in elderly patients with symptomatic heart failure treated with losartan and captopril long-term. A trend favouring losartan in the composite measure of drug tolerability/quality of life was not significant, but losartan was generally better tolerated than captopril in that significantly fewer losartan patients discontinued therapy.

Burden of aspergillosis-related hospitalizations in the United States.

In the United States in 1996, there were an estimated 10,190 aspergillosis-related hospitalizations (95% confidence interval [CI], 9000-11,380); these resulted in 1970 deaths (95% CI, 1659-2280), 176,272 hospital days (95% CI, 147,163-206,275), and $633.1 million in costs (95% CI, $492.0-$780.2 million). The average hospitalization lasted 17.3 days (95% CI, 16.1-18.6) and cost $62,426 (95% CI, $52,670-$72,181). Although aspergillosis-related hospitalizations account for a small percentage of hospitalizations in the United States, patients hospitalized with the condition have lengthy hospital stays and high mortality rates.

Effect of future costs on cost-effectiveness of medical interventions among young adults: the example of intensive therapy for type 1 diabetes mellitus.

OBJECTIVES: Recent research based on a lifetime utility maximization model has suggested that cost-effectiveness analyses should account for all future costs, including medical costs for related and unrelated illnesses and nonmedical costs. This work has also shown that analyses that omit future costs are biased to favor interventions among the elderly that extend life over interventions that improve quality of life. However, the effect of including future costs on the cost-effectiveness of interventions among the young has not been studied. This article examines the effect of including future costs on the cost-effectiveness of intensive therapy for type 1 diabetes mellitus among young adults. METHODS: By modifying a cost-effectiveness model based on the Diabetes Control and Complications Trial to include future costs, the effect of including future costs on the cost-effectiveness of intensive therapy for type 1 diabetes mellitus among young adults was examined. Future costs added to the model included future costs for medical expenditures for illnesses unrelated to diabetes and future nonmedical expenditures net of earnings. RESULTS: Intensive therapy among young adults led to approximately equal increases in the expected number of years lived before age 65, when people generally produce more than they consume, and after age 65, when the opposite tends to hold. Because the discounted value of savings due to lower mortality before age 65 exceeded the discounted value of later increases in costs due to lower mortality after age 65, accounting for future costs decreased the cost-effectiveness ratio from $22,576 to $9,626 per quality-adjusted life-year. CONCLUSIONS: The inclusion of future costs can significantly improve the cost-effectiveness of interventions that decrease mortality among young adults. The common practice of excluding future costs may bias cost-effectiveness analyses against such interventions.

Work and productivity loss in the rizatriptan multiple attack study.

The objective of this study was to measure the self-reported effect of acute migraine and its treatment on paid work and productivity loss. Patients self-administered a questionnaire in which the impact of a recent migraine on paid work and productivity activities was assessed. We included the questionnaire in a randomized, double-blind, placebo-controlled, crossover, out-patient study designed to examine the safety and efficacy of rizatriptan (5-HT1B/1D receptor agonist) 10 mg p.o. in patients treating four separate migraine attacks. A total of 407 patients, aged 18-65 years, suffering from moderate to severe migrainous headaches was studied. Patients receiving rizatriptan compared with placebo reported 0.7 fewer hours (P < 0.01) of paid worked missed due to absenteeism, 0.4 fewer hours (P < 0.05) of productive time lost on the job, and 1.1 fewer total hours (P < 0.01) of work loss per migraine attack. Rizatriptan compared with placebo significantly reduced migraine-related work loss associated with absenteeism and decreased effectiveness on the job.

The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure.

The Losartan Heart Failure ELITE Study recently found that in patients with symptomatic heart failure and a left ventricular ejection fraction of /=65 years with symptomatic heart failure. Data on health care resource utilization were collected as part of the trial. We conducted a cost-effectiveness analysis to estimate the lifetime benefits of treatment and the associated costs. We observed no differences between treatments in the number of hospitalizations, hospital days, and emergency room visits per patient over the trial period. We estimated the total cost of losartan to be USD 54 (95% CI: USD -1,717, USD 1,755) less per patient than captopril over this time frame. We also estimated that over the projected remaining lifetime of the study population, losartan compared to captopril would increase survival by 0.20 years (undiscounted) at an average cost of USD 769 (discounted) more per patient. This cost increase translated into a cost-effectiveness ratio of USD 4,047 per year of life gained for losartan relative to captopril. In patients with symptomatic heart failure, losartan compared to captopril increased survival with better tolerability at a cost well within the range accepted as cost-effective.

Modeling the long-term outcomes and costs of HIV antiretroviral therapy using HIV RNA levels: application to a clinical trial.

A model was developed to gain insight into the potential clinical and economic impact of antiretroviral therapy for HIV-infected patients. Observed HIV RNA levels and CD4 cell counts are used in the model to estimate the probability that an individual progresses from asymptomatic infection to the first AIDS-defining illness and death and to estimate the total net cost of care and long-term cost-effectiveness of antiretroviral therapy. The model was applied to patients in a clinical trial (Merck protocol 035) that compared the surrogate marker response to triple therapy with indinavir (IDV; 800 mg every 8 hr) plus zidovudine (ZDV; 200 mg every 8 hr) plus lamivudine (3TC; 150 mg twice a day) to double therapy with ZDV+3TC. The model projected that for an individual without AIDS who received triple therapy the progression to AIDS and death would be delayed more than for a patient who received double therapy with ZDV+3TC if no other treatment options were offered. Because of this delay in disease progression, the total discounted cost over the initial 5-year period was projected to be $5100 lower for patients who received triple therapy compared with double therapy if suppression with triple therapy lasts up to 3 years. If suppression with triple therapy lasts up to 5 years, costs were projected to be higher with the triple combination, but 81% of the cost is offset by lower disease costs as a result of fewer patients progressing to AIDS. Over 20 years, total discounted cost was projected to be higher for the triple-therapy regimen primarily because of a longer estimated survival time. At 20 years, the incremental cost per life-year gained by adding IDV to a ZDV+3TC regimen was estimated at $13,229, which is well within the range of other widely accepted medical interventions.

The cost-effectiveness of intensive therapy for diabetes mellitus.

Although persons with diabetes constitute only 3.1% of the US population, costs for their care account for 11.9% of total US health care expenditures. Approximately half of the expenditures for medical care for diabetes are for treatment of the metabolic condition and half for the treatment of chronic complications. Intensive therapy for persons with diabetes uses more resources and is more expensive than conventional therapy. On the other hand, intensive therapy is associated with a lower incidence of costly chronic complications. Formal economic analyses have demonstrated that intensive therapy is cost-effective for the treatment of diabetes. In IDDM, intensive therapy costs approximately $20,000 per QALY gained; in NIDDM, it costs approximately $16,000 per QALY gained. From an economic perspective, intensive therapy for persons with diabetes compares favorably with pharmacologic therapy for high-risk individuals with hypertension and hypercholesterolemia. Health policy should foster the use of such therapy for persons with diabetes mellitus.

Model of complications of NIDDM. I. Model construction and assumptions.

OBJECTIVE: To develop a model of NIDDM for analyzing prevention strategies for NIDDM. RESEARCH DESIGN AND METHODS: A Markov type model with Monte Carlo techniques was used. Age, sex, and ethnicity of cohort was based on U.S. data. Incidence rates of complications were also based on community and population studies. RESULTS: Nonproliferative retinopathy, proliferative retinopathy, and macular edema are predicted in 79, 19, and 52%, respectively, of people with NIDDM; 19% are predicted to develop legal blindness. Microalbuminuria, gross proteinuria, and end-stage renal disease related to diabetes are predicted in 53, 40, and 17%, respectively. Symptomatic sensorimotor neuropathy and lower-extremity amputation are predicted in 31 and 17%, respectively. Cardiovascular disease is predicted in 39%. Higher rates of complications (1.1-3.0x) are predicted in minority populations. Predicted average life expectancy is 17 years after diagnosis. CONCLUSIONS: A probabilistic model of NIDDM predicts the vascular complications of NIDDM in a cohort representative of the incident cases of diabetes in the U.S. before age 75 years. Predictions of complications and mortality are consistent with the known epidemiology of NIDDM. The model is suitable for evaluating the effect of preventive interventions on the natural history of NIDDM.

Model of complications of NIDDM. II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia.

OBJECTIVE: To analyze the health benefits and economics of treating NIDDM with the goal of normoglycemia. RESEARCH DESIGN AND METHODS: Incidence-based simulation model of NIDDM was used. Hazard rates for complications were adjusted for glycemia using risk gradients from the Diabetes Control and Complications Trial. Treatment costs were estimated from national survey data and clinical trials. Incremental costs and benefits were expressed in present value dollars (3% discount rate). Life-years were adjusted for quality of life, yielding quality-adjusted life-years (QALYs). RESULTS: Comprehensive treatment of NIDDM that maintains an HbA1c value of 7.2% is predicted to reduce the cumulative incidence of blindness, end-stage renal disease, and lower-extremity amputation by 72, 87, and 67%, respectively. Cardiovascular disease risk increased by 3% (no effect of treating glycemia is assumed). Life expectancy increased 1.39 years. The cost of treating hyperglycemia increased by almost twofold, which is partially offset by reductions in the cost of complications. The estimated incremental cost/QALY gained is $16,002. Treatment is more cost-effective for those with longer glycemic exposure (earlier onset of diabetes), minorities, and those with higher HbA1c under standard care. CONCLUSIONS: The incremental effectiveness of treating NIDDM with the goal of normoglycemia is estimated to be approximately $16,000/QALY gained, which is in the range of interventions that are generally considered cost-effective.

Self-rated health and mortality in people with diabetes.

OBJECTIVES: This study examined whether self-rated health is an independent and significant predictor of mortality in people with diabetes, using data collected in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. METHODS: Participants were asked to rate their health in comparison with others their age. A proportional hazards model was used to regress survival time on self-rated health and a number of covariates measuring physical health. RESULTS: People with younger onset diabetes (n = 891) who rated their health relative to their peers as "worse" or "don't know" were no more likely to die than those rating their health as "the same" or "better" when physical health status was controlled. In contrast, those with older onset diabetes (n = 987) who rated their health as "worse" or "don't know" were almost twice as likely to die as those rating their health as "the same" or "better" when physical health status was controlled. CONCLUSIONS: Self-rated health is a significant predictor of mortality in people with older onset diabetes but not in those with younger onset diabetes when physical health status is controlled.

Can quality care be planned?

Planning quality care can begin with planning a randomized controlled trial (RCT). Given that health-care services must compete for scarce resources, it is important that RCTs collect data to support an economic evaluation when the RCT ends. Economic data can be collected after an RCT ends; however, translating the clinical findings into clinical practice and health-care policy may be less efficient and less effective. Three types of data--economic, behavioral, and biological outcomes--should be collected during an RCT to conduct an economic evaluation at the end of an RCT. Economic outcomes represent the actual resources consumed by a health service, i.e., economic costs; behavioral outcomes include measures of longevity and health-related quality of life; and biological outcomes measure physiological state, e.g., retinopathy level.

The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors.

The Beaver Dam Health Outcomes Study (BDHOS) is an ongoing longitudinal cohort study of health status and health-related quality of life for a random sample of adults (age range at interview was 45 to 89 years; mean = 64.1, SD = 10.8) in a community population. In a face-to-face interview lasting approximately an hour, each participant responds to several batteries of questions. Included are a history of chronic medical conditions, current medications, and past surgeries; the SF-36 (a general health-status questionnaire); the Quality of Well-being index; self-rated health status on a five-point scale from "excellent" to "poor"; and evaluation of current health using the method of time tradeoffs. The authors present results from 1,356 interviews on these four principal measures, reporting mean scores by sex, by age, and for persons reporting being affected by various medical conditions. They believe data from the BDHOS will provide researchers and policy makers a reference collection of vital statistics for health-related quality of life. Additionally, the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS.

Disk-caused nerve compression in patients with acute low-back pain: diagnosis with MR, CT myelography, and plain CT.

Ninety-five patients with acute low-back and radicular pain underwent magnetic resonance (MR) imaging and either plain computed tomography (CT) (n = 32) or CT myelography (n = 63) for diagnosis of herniated nucleus pulposus-caused nerve compression (HNPNC). Patients were followed up for at least 6-12 months. Fifty-six patients underwent surgery, and 39 received conservative treatment. Receiver operating characteristic (ROC) analysis was performed on correlation of results of blinded image reading with "true" diagnoses determined by an expert panel [corrected]. Results in subgroup analysis for ROC curve areas were MR, 0.84, versus plain CT, 0.86; MR, 0.81, versus CT myelography, 0.83; and MR, 0.82, versus findings with both CT techniques, 0.85. Results indicate no statistically significant difference in diagnostic accuracy of HNPNC among the three modalities. Thus, factors of cost, radiation dose, and invasiveness influence selection of modality. On the basis of accuracy findings, the authors suggest that MR should replace CT myelography because of the invasiveness of myelography but that MR should not replace plain CT because plain CT is equally accurate and much less costly.