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PubMed2001

Recombinant human follicle-stimulating hormone: a scientific step to clinical improvement.

Urinary-derived follicle-stimulating hormone (FSH) preparations have been used clinically for many years. Although effective, these have a number of disadvantages, not least of which is their variable composition. The availability of recombinant human FSH (r-hFSH), produced from CHO cells, with its constant composition and exceptionally high purity, has, therefore, aroused great interest. This review focuses on the use of r-hFSH for ovarian stimulation in assisted reproduction technology protocols and the treatment of World Health Organization Group I and II anovulation. The use of r-hFSH has been shown to lead to improvements in efficacy over urinary-derived preparations, particularly in assisted reproductive treatment, and a recent meta-analysis has shown higher ongoing pregnancy rates with the recombinant product. Although the two available recombinant products from CHO cells (follitropin alpha [Gonal-F((R))] and beta [Puregon((R))]) are similar from a physicochemical perspective, some minor advantages have been reported for follitropin alpha in relation to pregnancy rates and better local tolerance to injections. The apparent higher bioactivity of r-hFSH has led to reduced total FSH consumption over shorter treatment periods compared with conventional preparations, thus reducing overall exposure for patients. This is likely to confer not only safety benefits, but also cost-effectiveness as demonstrated through pharmaco-economic modelling.

Journal Article↗
PubMed2001

Dialysis for end-stage renal disease. Determining a cost-effective approach.

OBJECTIVE: Renal replacement therapy (RRT) is essential for maintenance of life for those with end-stage renal disease. However, there remain many areas of uncertainty about which method of RRT should be chosen. This paper reports an economic model based on a systematic review that attempts to determine which method of dialysis, continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis, a patient should have as the initial method of RRT. METHODS: A systematic review and a costing exercise carried out in a Scottish hospital were used to populate a Markov model. Scenario analysis was used to model plausible variations in variables included in the model. RESULTS: In 8 of the 16 scenarios developed hemodialysis dominated CAPD. In a further eight scenarios, the cost per life-year displayed considerable variability, ranging from between 5,000 Pounds to 51,000 Pounds. The higher costs per life-year were associated with minimum estimates of additional survival for a patient starting RRT on hospital hemodialysis. CONCLUSION: It may be more cost-effective to manage patients starting on RRT with hospital hemodialysis than CAPD. This has particular implications for the United Kingdom, given that up to 50% of new patients receive CAPD.

Cost-Benefit Analysis↗
PubMed2004

Cost effectiveness of tension-free vaginal tape for the surgical management of female stress incontinence.

OBJECTIVES: Stress urinary incontinence affects between 10 percent and 50 percent of women. Surgery is commonly recommended for troublesome incontinence that does not respond to nonsurgical management. Tension-free vaginal tape (TVT) is a newer, minimal access surgical sling procedure, which is being increasingly adopted worldwide. The cost-effectiveness of TVT in comparison with other surgical procedures, particularly open colposuspension, is assessed. METHODS: Effectiveness estimates came from a systematic review of TVT compared with other surgical procedures (open and laparoscopic colposuspension, traditional slings, and injectables). Deterministic and probabilistic analyses were used to assess the likelihood of TVT being cost-effective. Sensitivity analyses assessed the impact of changing assumptions about cure rates and costs for TVT, cure rates for retreatment open colposuspension, and proportions of women who choose retreatment. RESULTS: Reliable estimates of relative effectiveness were difficult to derive because the few randomized controlled comparisons had not been optimally analyzed or fully reported. Results of the economic model suggested that TVT dominates open colposuspension (lower cost and same quality of life years [QALYs]) within 5 years after surgery. Stochastic analysis indicated that the likelihood of TVT being cost-effective was 100 percent if decision-makers are unwilling to pay for additional QALYs. TVT's dominance depended on the assumption fact that retreatment open colposuspension has lower cure rates than a first colposuspension. CONCLUSIONS: Analysis based on current short-term data indicates dominance of TVT over open colposuspension from approximately 5 years. There is a need for longer-term follow-up data from methodologically rigorous randomized trials to provide a sounder basis for estimating the relative benefits and cost implications.

Cost-Benefit Analysis↗
PubMedDate not supplied

Does the incidence of group health insurance fall on individual workers?

Economic models predict that the cost of health insurance is borne by workers. In this paper we ask two questions. First, is cost shifting individual-specific: does a worker with higher expected medical expenses bear this cost? Second, how do explicit employee contributions affect cost shifting? We estimate wage change regressions that include as explanatory variables changes in health insurance coverage, changes in employee premium contributions, health status, and an interaction between health insurance changes and health status. We find no evidence of a significant wage offset at either the individual or group level and conclude that changes in health insurance status are not exogenous.

Cost Sharing↗
PubMed1999

Cocaine self-administration under conditions of restricted and unrestricted food access.

Four rhesus monkeys (Macaca mulatta), maintained at reduced body weight and restricted food availability, had access to a 0.8-mg/ml cocaine solution and vehicle under a concurrent fixed-ratio (FR) 8 schedule. Over days, the cocaine concentration was reduced (0.57, 0.4, 0.2, 0.1, 0.05, 0.025) and then returned, gradually over days, to 0.8 mg/ml. The ratio value was then varied (to 16, 32, 64, 128, and 8). Food access was unrestricted, and the ratio and the concentration manipulations were then repeated. During food restriction cocaine served as a reinforcer for all monkeys, whereas during free feeding cocaine functioned as a reinforcer for 3 of 4 monkeys; with these monkeys, the dose-response curve obtained under free feeding was shifted to the right of that obtained under food restriction. There were no differences in FR response curves obtained during food restriction and unrestricted feeding. These data suggest that food restriction increases cocaine's reinforcing effects and that the higher the cocaine dose, the greater are the reinforcing effects. A demand curve analysis was completed, and data are discussed in terms of microeconomic principles.

Algorithms↗
PubMed2003

Effectiveness and cost-effectiveness of prognostic markers in prostate cancer.

This paper demonstrates how economic modelling can be used to derive estimates of the cost-effectiveness of prognostic markers in the management of clinically localised and moderately graded prostate cancer. The model uses a Markov process and is populated using published evidence and local data. The robustness of the results has been tested using sensitivity analysis. Three treatment policies of 'monitoring' (observation), radical prostatectomy, or a selection-based management policy using DNA-ploidy as an experimental marker, have been evaluated. Modelling indicates that a policy of managing these tumours utilising experimental markers has an estimated cost per quality-adjusted life year (QALY) of pound 12 068. Sensitivity analysis shows the results to be relatively sensitive to quality-of-life variables. If novel and experimental markers can achieve specificity in excess of 80%, then a policy of radical surgery for those identified as being at high risk and conservative treatment for the remainder would be both better for patients and cost-effective. The analysis suggests that a radical prostatectomy treatment policy for the moderately graded tumours (Gleason grades -7) modelled in this paper may be inferior to a conservative approach in the absence of reliable prognostic markers, being both more costly and yielding fewer QALYs.

Cost-Benefit Analysis↗
PubMed2006

Using contrast sensitivity to estimate the cost-effectiveness of verteporfin in patients with predominantly classic age-related macular degeneration.

AIMS: To re-evaluate the cost-effectiveness of photodynamic therapy with verteporfin (Visudyne, Novartis AG, Switzerland) in patients with predominantly classic and classic choroidal neovascularization (CNV) owing to age-related macular degeneration (AMD), using new evidence on the impact of contrast sensitivity on health status. METHOD: A health economic model is used to synthesise the evidence on contrast sensitivity and treatment rates from the TAP Investigation with health state utilities and costs. Impairment of visual function is estimated using a Markov model to predict transitions between states of contrast sensitivity. Each state is associated with costs and a health state utility. Total expected costs and benefits for a cohort of patients over a defined number of cycles are calculated. The expected health state utility for each disease state was estimated using results from a study of 209 patients with AMD in Sheffield. The model includes the costs associated with treatment and monitoring in the verteporfin treatment arm and costs offset by delaying the deterioration of visual function. RESULTS: Beyond 3 years, the annual costs of the verteporfin arm are estimated to be less than the annual costs of the control arm, owing to the cost associated with higher blindness prevalence in the control arm. Over time, the results show that both the incremental utility and cost decreases. By 10 years, the estimated incremental cost-effectiveness is approximately pound20 996 per Quality-Adjusted Life Years. CONCLUSION: The results of this study suggest that the verteporfin therapy in the treatment for patients with predominantly classic and classic CNV owing to AMD is encouraging.

Aged↗
PubMed2003

The rate of fibrosis progression is an independent predictor of the response to antiviral therapy in chronic hepatitis C.

The response to antiviral therapy and the rate of fibrosis progression in chronic hepatitis C virus (HCV) infection are related to common factors, including age and gender. The aim of this study was to evaluate the relationship between the rate of fibrosis progression and the sustained virologic response (SVR) to interferon (IFN)-based treatment. A total of 332 patients treated for chronic HCV infection were evaluated. Using multivariate logistic regression analysis, the impact of the rate of fibrosis progression (defined as the stage of liver fibrosis according to the Metavir system/duration of infection) on the rate of SVR (negative HCV RNA at least 6 months following the end of treatment), was determined. The median age of the patients was 44 (range 25-77) years, 64% were male, and 66% were infected with genotypes 1, 4, 5 or 6. The median rate of fibrosis progression was 0.083 (range 0-2) Metavir units/year; 158 patients (48%) had F2-F4 fibrosis. After a median of 48 (range 2-126) weeks of therapy (IFN, n=190; IFN and ribavirin, n=96; pegylated IFN, n=20; pegylated IFN and ribavirin, n=26), 93 patients (28%) achieved an SVR. In univariate analysis, the rate of SVR was higher in slow [< 0.083 Metavir units/year (n=162)] than rapid progressors [> or = 0.083 Metavir units/year (n=170)] (35%vs 22%, P=0.01). After controlling for age, gender, genotype, viral load, and treatment regimen and duration, the rate of fibrosis progression remained an independent predictor of SVR (slow vs rapid progressors, OR 2.74; 95% CI 1.27-5.92; P=0.01). Hence the rate of fibrosis progression is an independent predictor of SVR to IFN-based therapy in patients with chronic hepatitis C. This additional factor should be considered in economic models evaluating this condition.

Adult↗
PubMedDate not supplied

Clinical and economic benefits of ramipril: an Australian analysis of the HOPE study.

BACKGROUND: The Heart Outcomes Prevention Evaluation (HOPE) study has demonstrated that ramipril 10 mg/day for 5 years in an at-risk population results in clinically and statistically significant reductions in the occurrence of cardiovascular death, myocardial infarction (MI), stroke and revascularization procedures. The likely impact of the intervention in Australia, in terms of the number of potential events avoided and the cost per life-year saved, has previously not been determined. AIMS: To assess the clinical and economic impacts of the use of daily ramipril in the Australian at-risk population from the perspective of the public health-care budget. METHODS: The clinical benefits were calculated from endpoints used in the trial, which were converted to the 'number needed to treat'. These were then applied to the at-risk population, which was determined nationally from the relevant Australian statistics. The result of this calculation is the potential number of events avoided in Australia. The economic benefits were established by undertaking an incremental cost-effectiveness analysis. The economic model considered the clinical benefits and the costs (and cost offsets) arising from ramipril 10 mg/day therapy for 5 years. Life-years saved was determined by calculating the difference in total years survived between the ramipril and control arms of the study. Net costs divided by life-years saved is the cost per life-year saved, and this is reported in Australian dollars as the incremental cost effectiveness. RESULTS: The clinical benefits over a 5-year period were expressed as the number of potential events avoided and comprised approximately: 9188 strokes; 14 658 MI; 14 317 revascularization procedures; and 12,534 cardiovascular-related deaths, nationally. The incremental cost-effectiveness analysis showed the estimated cost per life-year saved to be 17,214 Australia dollars. CONCLUSION: The use of ramipril 10 mg/day over a 5-year period in the at-risk Australian population could prevent many thousands of cardiovascular events, including 12,534 cardiovascular-related deaths. The cost per life-year saved compares favourably to other health care interventions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

The influence of case mix, site selection, and methods biases on costs of hospitalization for acute exacerbations of chronic obstructive airways disease and lower respiratory tract infections.

OBJECTIVE: To compare costs of hospitalization for lower respiratory tract infection (LRTI) in patients who received antibiotics before admission to those who did not, and in patients with and without underlying chronic obstructive airways disease (COAD) or diabetes mellitus. METHODS: All hospitalizations in a population of 366,849 residents in Tayside Scotland from 1993 to 1994 were analyzed. Three groups of patients were identified by primary discharge diagnosis in 1993/94 and previous admissions from 1980 to 1992: 1) acute exacerbation of COAD; 2) LRTI plus a secondary diagnosis of COAD or previous admission with COAD; 3) LRTI but no secondary COAD or previous admission with COAD. Setting specific costs were applied (e.g., general medicine, intensive care, geriatrics). Dispensed antibiotic prescribing in the 28 days before admission was identified from all community pharmacies. Nonparametric statistical tests were used. RESULTS: Patients with COAD were more likely to have received antibiotics before admission: COAD (n = 893) 49%; COAD + LRTI (n = 316) 43%; LRTI only (n = 822) 33%. Patients who received antibiotics before admission had lower hospital costs than patients who did not. Mean total costs per admission: COAD pound1604 versus pound1625 (p = .5); COAD + LRTI pound2281 versus pound2297 (p = .5); LRTI only pound2365 versus pound3233; (p = .009). Increasing age and diabetes mellitus were associated with higher hospital costs in all three groups. CONCLUSION: Economic models of the value of preventing hospital admissions for COAD or LRTI will be subject to case mix bias unless they adjust for age, community antibiotic use, and comorbidity.

Journal Article↗
PubMed2002

Impact of chest pain on cost of migraine treatment with almotriptan and sumatriptan.

Chest-related symptoms occur with all triptans; up to 41% of patients with migraine who receive sumatriptan experience chest symptoms, and 10% of patients discontinue treatment. Thus, the cost of chest pain-related care was estimated in migraineurs receiving almotriptan 12.5 mg versus sumatriptan 50 mg. A population-based, retrospective cohort study used data to quantify the incidence and costs of chest pain-related diagnoses and procedures. An economic model was constructed to estimate annual cost savings per 1000 patients receiving almotriptan versus sumatriptan based on the reported rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives. Among a cohort of 1390 patients, the incidence of chest pain-related diagnoses increased significantly by 43.6% with sumatriptan (P=.003). Aggregate costs for chest pain-related diagnoses and procedures increased from $22,713 to $30,234. Payments for inpatient hospital services, costs for primary care visits, and costs for outpatient hospital visits increased by over 100%, 53.1%, and 14.4%, respectively. The model predicted $11,215 in direct medical cost savings annually per 1000 patients treated with almotriptan versus sumatriptan. Annual direct medical costs avoided totaled $194,358, and when applied to recent estimates of 86 million lives currently covered by almotriptan treatment, translates into an annual cost savings of just under $17 million for chest pain and associated care. Thus, using almotriptan in place of sumatriptan will likely reduce the cost of chest pain-related care.

Adolescent↗
PubMed2004

The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis.

BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.

Clinical Trials as Topic↗
PubMed2004

An adaptive way for improving noise reduction using local geometric projection.

We propose an adaptive way to improve noise reduction by local geometric projection. From the neighborhood of each candidate point in phase space, we identify the best subspace that the point will be orthogonally projected to. The signal subspace is formed by the most significant eigendirections of the neighborhood, while the less significant ones define the noise subspace. We provide a simple criterion to separate the most significant eigendirections from the less significant ones. This criterion is based on the maximum logarithmic difference between the neighborhood eigendirection lengths, and the assumption that there is at least one eigendirection that corresponds to the noise subspace. In this way, we take into account the special characteristics of each neighborhood and introduce a more successful noise reduction technique. Results are presented for a chaotic time series of the Henon map and Ikeda map, as well as on the Nasdaq Composite index.

Algorithms↗
PubMed1993

Preattentive processing of object size: implications for theories of size perception.

Information about the visual angle size of objects is important for maintaining object constancy with variations in viewing distance. Although human observers are quite accurate at judging spatial separations (or cross-sectional size), they are prone to error when there are other spans nearby, as in classical illusions such as the Müller-Lyer illusion. It is possible to reconcile these aspects of size perception by assuming that the size domain is sampled sparsely. It was shown by means of a visual search procedure that the size of objects is processed preattentively and in parallel across the visual field. It was demonstrated that an object's size, rather than its boundary curvature or spatial-frequency content, provides the basis for parallel visual search. It was also shown that texture borders could be substituted for luminance borders, indicating that object boundaries at the relevant spatial scale provide the input to size perception. Parallel processing imposes a severe computational constraint which provides support for the assumption of sparse sampling. An economical model based on several broadly tuned layers of size detectors is proposed to account for the parallel extraction of size, the Weberian behaviour of size discrimination, and the occurrence of strong interference effects in the size domain.

Attention↗
PubMed1998

Funding arrangements for telehealth: encouraging efficiency rather than proliferation.

The use of telehealth as a basis for delivering health services is growing across Australia, and there is clear potential for these technologies to address some of the enduring issues of access and costs of service delivery. However, appropriate incentives must be created to encourage clinicians and managers to evaluate the true opportunity costs and benefits of delivering services in this way against the relevant alternative. This paper examines how different funding arrangements might encourage or discourage efficient use of telehealth.

Australia↗
PubMed2006

Under what conditions is feedback microwave thermotherapy (ProstaLund Feedback Treatment) cost-effective in comparison with alpha-blockade in the treatment of benign prostatic hyperplasia and lower urinary tract symptoms?

OBJECTIVE: Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are a common condition in men, and their incidence increases with age. The objective of this study was to evaluate the potential cost-utility of microwave thermotherapy, specifically the ProstaLund Feedback Treatment (PLFT), versus alpha-blockade in Swedish patients with LUTS due to BPH. MATERIAL AND METHODS: A health-economic simulation model, based on long-term disease progression and costs, was developed to analyse the cost-utility of PLFT in comparison with alpha-blockade over a 3-year period based on data from published literature, treatment programmes and official price lists. Outcome measures used in the analysis were quality of life, survival and reduction in International Prostate Symptom Score. Sensitivity analyses were performed for a number of essential variables. The perspective of the study is the healthcare sector. All costs are expressed as 2003 prices. RESULTS: Three years after an intervention with PLFT or initiation of drug treatment the cost-utility of PLFT was estimated at approximately euro 6600-9500 per quality-adjusted life-year gained. The cost-utility was further improved over a longer time period, and PLFT appears to be cost-saving after 5 years. One important finding from the model simulation was that PLFT also seems to be favourable in patients with less pronounced symptoms. This result may be further validated when additional results from controlled clinical trials become available. CONCLUSIONS: The present model simulation indicates that treatment with PLFT seems to be cost-effective compared with drug therapy with alpha-blockade. The result shows that the time-frame of the analysis has a great impact on the cost-effectiveness ratio.

Adrenergic alpha-Antagonists↗