Bridging the osteoporosis treatment gap: performance and cost-effectiveness of a fracture liaison service.

Individuals who sustain fragility fractures are at high risk of refracture. However, osteoporosis treatment rates remain low for these patients. Therefore, we aimed to assess the performance and cost-effectiveness of introducing a fracture liaison service (FLS) into a tertiary hospital. In "nonhospitalized" ambulatory patients who had sustained fragility fractures, we assessed baseline osteoporosis investigation and treatment rates, and subsequently, the impact of introducing an orthopedic osteoporosis policy and an FLS. Outcomes measured were uptake of osteoporosis intervention, patient satisfaction, and quality-adjusted life years (QALYs) gained. QALYs were calculated over 5 years using predicted fracture risks without intervention and estimated fracture risk reduction with intervention. At baseline (n = 49), 2% of ambulatory patients who had sustained fragility fractures underwent dual-energy X-ray absorptiometry (DXA) and 6% received osteoporosis-specific medication. After introduction of an osteoporosis policy (n = 58), 28% were investigated with DXA (p < 0.0001). However, treatment rates were unchanged. An FLS was introduced, reviewing 203 new patients over the inaugural 2 years (mean age [standard deviation], 67 (11) years; 77% female). All underwent DXA, and criteria for osteoporosis and osteopenia were identified in 44% and 40%, respectively. Osteoporosis medications were prescribed to 61% patients (risedronate: 22%, alendronate: 16%, strontium ranelate: 13%, zoledronic acid: 8%, other: 2%). Eighty-five of 90 questionnaire respondents were very satisfied or satisfied with the FLS. With the treatment prescribed over 5 years, we conservatively estimated that this FLS would reduce nonvertebral refractures from 59 to 50, improving QALYs by 0.054 and costing $1716 per patient (incremental cost-effectiveness ratio: $31749). This FLS model improves uptake of osteoporosis intervention guidelines, is popular among patients, and improves cost-effectiveness. Thus, it has the capacity to substantially improve health in a cost-effective way.

Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

BACKGROUND: The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available. OBJECTIVE: To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS. DESIGN: Decision-analytic model. DATA SOURCES: Published literature, Medicare claims, and life tables. TARGET POPULATION: Patients having percutaneous coronary intervention for ACS. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel. OUTCOME MEASURES: Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor). RESULTS OF SENSITIVITY ANALYSIS: Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor. LIMITATION: No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor. CONCLUSION: Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.

Random CNT network and regioregular poly(3-hexylthiophen) FETs for pH sensing applications: a comparison.

BACKGROUND: Nowadays, there is a tremendous need for cheap disposable sensing devices for medical applications. Materials such as Carbon Nanotubes (CNTs) and regioregular P3HT are proven to offer a huge potential as cost-effective and solution processable semiconductors for (bio)sensing applications. METHODS: CNT-based field-effect transistors (CNT-FETs) as well as regioregular P3HT-based ones (P3HT-FETs) are fabricated and operated in the so-called electrolyte-gated configuration. The active layer of the P3HT-FETs consists of a spin-coated regioregular P3HT layer, which serves on one hand as the active sensing element and on the other hand as passivation layer for the transistor's metal contacts. The active layer of the nanotube transistors consists of a randomly distributed single walled CNT-network (>90% semiconducting tubes) deposited from a CNT-ink solution by spin-coating. RESULTS: We compare both devices concerning their stability in aqueous environment and their response when exposed to buffers with different pH. We found that even if P3HT shows lower stability its pH sensitivity is reproducible even after long-term measurements. CONCLUSION: CNT-FETs and P3HT-FETs offer different advantages and drawbacks concerning their stability in solution and the ease of fabrication. A discussion of their different sensing mechanisms as well as sensitivity is given here. GENERAL SIGNIFICANCE: This work reports on fast and cost-effective production of solution processable thin-film transistors based on carbon nanotubes and regioregular P3HT and demonstrates their suitability as reliable pH sensors. This article is part of a Special Issue entitled Organic Bioelectronics - Novel Applications in Biomedicine.

Cost-effectiveness of dabigatran and rivaroxaban compared with warfarin for stroke prevention in patients with atrial fibrillation.

PURPOSE: This study aimed to evaluate the cost-effectiveness of dabigatran and rivaroxaban compared with warfarin for the prevention of stroke in patients with atrial fibrillation (AF) in Singapore. METHODS: A Markov model was constructed to compare the lifetime costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) of dabigatran 110 and 150 mg, rivaroxaban 20 mg and adjusted-dose warfarin from the perspective of the Singapore healthcare system, using clinical data from published studies, utilities from a patient-reported survey and costs from hospital databases. The target population was a hypothetical cohort of 65-year-old AF patients with no contraindications to anticoagulation. RESULTS: In the base-case analysis, the QALYs were 8.75 with warfarin, 8.73 with dabigatran 110 mg, 8.82 with dabigatran 150 mg, and 9.33 with rivaroxaban. The costs were Singapore dollar (SG$) 34,648 for warfarin, SG$54,919 for dabigatran 110 mg, SG$50,484 for dabigatran 150 mg and SG$51,975 for rivaroxaban. The ICER of rivaroxaban versus warfarin was SG$29,697 (US$26,727) per QALY. Rivaroxaban and warfarin had extended dominance over the high-dose dabigatran. The low-dose dabigatran was dominated by warfarin. Deterministic sensitivity analyses showed that the ICER of rivaroxaban versus warfarin was sensitive to cost of rivaroxaban and utilities for rivaroxaban and warfarin. Probability sensitivity analysis demonstrated that the probability of rivaroxaban being the optimal choice was 97.8% and 99.5% at a willingness-to-pay threshold of SG$65,000 (US$58,500) and SG$130,000 (US$117,000) per QALY, respectively. CONCLUSION: Rivaroxaban may be a cost-effective alternative to warfarin for the prevention of stroke in patients with AF in Singapore.

Cost-effectiveness of different strategies for stroke prevention in patients with atrial fibrillation in a health resource-limited setting.

PURPOSE: To compare the lifetime cost and effectiveness of five alternative chronic atrial fibrillation (AF) management strategies: rivaroxaban, warfarin, aspirin plus clopidogrel, aspirin and no prevention. METHODS: An individual-level state-transition model was developed to track the lifetime disease course associated with AF. The clinical and utility data were derived from published studies. The cost data were estimated based on local charges and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty on the results. RESULTS: For base-case patients with a CHADS2 score of 3, the cost per additional quality-adjusted life-years (QALYs) gained for rivaroxaban compared with no prevention, aspirin, aspirin plus clopidogrel and warfarin was $116,884, $153,944, $155,979 and $216,273, respectively. CHADS2 score had a substantial impact on the model outcomes for different prevention strategies. The time distribution of warfarin international normalised ratio (INR), stroke and intracranial haemorrhage (ICH) risks, cost of rivaroxaban and utility of warfarin therapy had substantial impacts on the results. Based on a willingness-to-pay threshold of $16,350/QALY, no prevention strategy was the preferred therapy for a patient with a low risk for stroke and a high risk for ICH; aspirin was preferred for patients with a moderate risk for stroke and ICH; and warfarin was preferred for patients with a high risk for stroke and a low risk of ICH. CONCLUSION: In the context of limited health resources, rivaroxaban is unlikely to be cost-effective, although it provided more health benefits comparing with other strategies. Additionally, warfarin with good INR control might be more suitable for AF patients in developing regions.

Duloxetine use in employees with low back pain: treatment patterns and direct and indirect costs.

OBJECTIVE: The study aims to examine real-world effects of duloxetine treatment for low back pain (LBP). METHODS: The study identified employees with ≥1 LBP diagnosis and ≥1 duloxetine prescription within a year after LBP diagnosis from a privately insured claims database (2004-2007). Duloxetine-treated employees were propensity score matched to employees initiating another pharmacological/noninvasive treatment in the same month from LBP diagnosis. Treatment patterns and costs were compared over the 6 months following treatment initiation. RESULTS: Relative to controls, duloxetine-treated employees (N = 753) had significantly lower rates of other pharmacological/noninvasive therapies and a similar LBP surgery rate (1.7% vs 2.8%, P = 0.1573). Duloxetine-treated employees, despite higher pharmacy costs, had similar direct (health care) costs ($4,935 vs $5,649, P = 0.2662), and significantly lower indirect (workloss) costs ($1,723 vs $2,198, P = 0.0036). CONCLUSIONS: Duloxetine treatment in LBP employees was associated with reduced rates of many nonsurgical therapies and lower indirect costs. The findings are limited by the observational study design and unmeasured potential confounders.

Potential drug-drug and drug-condition interactions among fibromyalgia patients initiating pregabalin or duloxetine: prevalence and health care expenditure impact.

OBJECTIVE: To quantify the prevalence of potential drug-drug/drug-condition interactions (DDI/DCI) among fibromyalgia patients initiating pregabalin or duloxetine, and to determine the impact of potential DDI/DCI on health care expenditures. DESIGN: Retrospective cohort study. SETTING: U.S. clinical practice, as reflected within a large administrative claims database. SUBJECTS: Fibromyalgia patients newly initiating pregabalin or duloxetine between July 1, 2008 and October 1, 2010 (initiation date = index). OUTCOME MEASURES: Potential DDI measured using clinical software that identifies co-prescription of medications that potentially interact with pregabalin or duloxetine. Potential DCI, drawn from the contraindications and warnings and precautions sections of pregabalin and duloxetine prescribing information, measured using administrative claims-based algorithms. All-cause health care expenditures measured throughout a 6-month postindex period. Analyses included univariate, bivariate, and multivariable statistical approaches. RESULTS: Seven thousand seven hundred fifty-one pregabalin and 7,785 duloxetine initiators were selected for study: mean age 49 years, 88% female. Only 1.4% of pregabalin initiators had ≥1 potential pregabalin DCI; none had potential pregabalin DDI. In contrast, 67% of duloxetine initiators had potential duloxetine DDI/DCI, driven mostly by potential duloxetine DDI (62% of duloxetine initiators). Compared between pregabalin and duloxetine initiators, differences in the prevalence of potential DDI/DCI were statistically significant (P < 0.001). Multivariable analyses indicated that, among duloxetine initiators, those with potential duloxetine DDI/DCI had postinitiation health care expenditures that were $670 higher (P < 0.001) than those without potential duloxetine DDI/DCI. Among pregabalin initiators, potential pregabalin DDI/DCI were not associated with health care expenditures. CONCLUSIONS: Among fibromyalgia patients initiating pregabalin or duloxetine, potential duloxetine DDI could be highly prevalent. Among duloxetine initiators, potential duloxetine DDI/DCI were significantly associated with increased health care expenditures.

Comparison of cost-effectiveness of anticoagulation with dabigatran, rivaroxaban and apixaban in patients with non-valvular atrial fibrillation across countries.

We did a cost-utility analysis for the new oral anticoagulants (NOACs) in the German population based on the quality-adjusted life years (QALY), total costs, and incremental cost-effectiveness ratios (ICER). The aim of our investigation was to examine cost-utility for current German drug market costs and compared to other countries. Outcome data were taken from dabigatran's RE-LY, rivaroxaban's ROCKET AF, and apixaban's ARISTOTLE trials. A Markov decision model, the Monte Carlo simulation (MCS), and further sensitivity analyses were used to simulate comparisons between NOACs over a follow up period of 20 years. The main perspective used for the analyses is from a German public health care insurance perspective. The base-case analyses of a 65 years old person with a CHADS2 score >1 resulted in 7.56-7.64 QALYs gained for warfarin. NOACs added 0.04-0.19 QALYs. Total costs for warfarin ranged from 7622 to 9069 and for NOACs from 19537 to 20048. The sensitivity analysis indicated that current German market costs for the NOACs exceed a willingness-to-pay threshold of (hypothetical) 50000/QALY in all treatment regimen. The MCS showed willingness-to-pay thresholds from 60500/QALY for apixaban to 278000/QALY for dabigatran 110 mg bid, with values for dabigatran 150 mg bid and rivaroxaban in between. In conclusion, from a German public health care insurance perspective current market costs are high in relation to the quality of life gained. These results from clinical studies (efficacy) remain to be confirmed under real life conditions (effectiveness).

Conventional and new oral anticoagulants in the treatment of chest disease and its complications.

Oral anticoagulants block the coagulation cascade either by an indirect mechanism (e.g., vitamin K antagonists) or by a direct one (e.g., the novel oral anticoagulants). Vitamin K antagonists are widely used as treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. Although low molecular weight heparin remains the first line in venous thromboembolism prophylaxis, more recently the novel oral anticoagulants such as dabigatran (initial dose of 110 mg within 1-4 h after surgery, followed by the full dose of 220 mg once daily), rivaroxaban (dose of 10 mg once daily, with the first dose administered 6-10 h after the surgery), and apixaban (dose of 2.5 mg twice daily, starting 12-24 h after surgery, but available only in Europe) are approved for prophylaxis in patients undergoing major orthopedic surgery. The period in which thromboembolic risk abates remains uncertain, and trials of extended therapy are still ongoing. After showing at least noninferiority to warfarin in RE-LY, ROCKET-AF, and ARISTOTLE trials, dabigatran (110 or 150 mg twice daily), rivaroxaban (20 or 15 mg once daily), and apixaban (5 mg twice daily), respectively, were approved also for stroke prevention in patients with atrial fibrillation. While awaiting long-term safety data, the choice among all these available therapies should be based on patient preferences, compliance, and ease of administration, as well as on local factors affecting cost-effectiveness.

Direct medical costs and medication compliance among fibromyalgia patients: duloxetine initiators vs. pregabalin initiators.

OBJECTIVES: To assess and compare direct medical costs and medication compliance between patients with fibromyalgia who initiated duloxetine and patients with fibromyalgia who initiated pregabalin in 2008. METHODS: A retrospective cohort study design was used based on a large US national commercial claims database (2006 to 2009). Patients with fibromyalgia aged 18 to 64 who initiated duloxetine or pregabalin in 2008 and who had continuous health insurance 1 year preceding and 1 year following the initiation were selected into duloxetine cohort or pregabalin cohort based on their initiated agent. Medication compliance was measured by total supply days, medication possession ratio (MPR), and proportion of patients with MPR ≥ 0.8. Direct medical costs were measured by annual costs per patient and compared between the cohorts in the year following the initiation. Propensity score stratification and bootstrapping methods were used to adjust for distribution bias, as well as cross-cohort differences in demographic, clinical and economic characteristics, and medication history prior to the initiation. RESULTS: Both the duloxetine (n = 3,033) and pregabalin (n = 4,838) cohorts had a mean initiation age around 49 years, 89% were women. During the postindex year, compared to the pregabalin cohort, the duloxetine cohort had higher totally annual supply days (273.5 vs. 176.6, P < 0.05), higher MPR (0.7 vs. 0.5, P < 0.05), and more patients with MPR ≥ 0.8 (45.1% vs. 29.4%, P < 0.05). Further, relative to pregabalin cohort, duloxetine cohort had lower inpatient costs ($2,994.9 vs. $4,949.6, P < 0.05), lower outpatient costs ($8,259.6 vs. $10,312.2, P < 0.05), similar medication costs ($5,214.6 vs. $5,290.8, P > 0.05), and lower total medical costs ($16,469.1 vs. $20,552.6, P < 0.05) in the postinitiation year. CONCLUSIONS: In a real-world setting, patients with fibromyalgia who initiated duloxetine in 2008 had better medication compliance and consumed less inpatient, outpatient, and total medical costs than those who initiated pregabalin.

[Cost-effectiveness of apixaban compared to other new oral anticoagulants in patients with non-valvular atrial fibrillation].

BACKGROUND: Atrial fibrillation is associated with development of thromboembolic events. New oral anticoagulants (apixaban, rivaroxaban and dabigatran) are recommended for antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF) with moderate and high risk of stroke. OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness ratio of apixaban compared to dabigatran and rivaroxaban in patients with NVAF from the Russian Federation national health care system perspective. METHODS: This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER) for apixaban compared to rivaroxaban and dabigatran 110 mg and 150 mg over lifetime horizon for patients with NVAF. The model enclosed cardiovascular event rates based on the results of the indirect treatment comparison that combined data from the randomized clinical trials comparing clinical effectiveness and safety of apixaban, rivaroxaban and dabigatran with warfarin (ARISTOTLE, ROCKET-AF, RE-LY). The following cardiovascular events were considered: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the new oral anticoagulants was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years) were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality-adjusted life year (QALY) gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. RESULTS: In the base case analysis it was demonstrated that apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban provided additional 0.101, 0.060 and 0.072 life years as well as additional 0.063; 0.038 and 0.041 QALYs respectively. Over lifetime horizon apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban required additional treatment costs equal to 22.78; 31.18 and 6.70 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban was 362.60, 805.54 and 162.45 thousands rubles per QALY correspondingly. CONCLUSION: Apixaban provided increased life expectancy compared to other new anticoagulants and may be considered as a cost-effective alternative to dabigatran 110 mg and 150 mg and rivaroxaban from the Russian Federation national health care system perspective.

Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation.

BACKGROUND AND PURPOSE: To estimate the cost-effectiveness of stroke prevention in patients with nonvalvular atrial fibrillation by using novel oral anticoagulants apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg compared with warfarin. METHODS: A Markov decision-analysis model was constructed using data from clinical trials to evaluate lifetime costs and quality-adjusted life-years of novel oral anticoagulants compared with warfarin. The modeled population was a hypothetical cohort of 70-year-old patients with nonvalvular atrial fibrillation, increased risk for stroke (CHADS2 ≥ 1), renal creatinine clearance ≥ 50 mL/min, and no previous contraindications to anticoagulation. The willingness-to-pay threshold was $50 000/quality-adjusted life-years gained. RESULTS: In the base case, warfarin had the lowest cost of $77 813 (SD, $2223), followed by rivaroxaban 20 mg ($78 738 ± $1852), dabigatran 150 mg ($82 719 ± $1959), and apixaban 5 mg ($85 326 ± $1512). Apixaban 5 mg had the highest quality-adjusted life-years estimate at 8.47 (SD, 0.06), followed by dabigatran 150 mg (8.41 ± 0.07), rivaroxaban 20 mg (8.26 ± 0.06), and warfarin (7.97 ± 0.04). In a Monte Carlo probabilistic sensitivity analysis, apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg, and warfarin were cost-effective in 45.1%, 40%, 14.9%, 0% of the simulations, respectively. CONCLUSIONS: In patients with nonvalvular atrial fibrillation and an increased risk of stroke prophylaxis, apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg were all cost-effective alternatives to warfarin. The cost-effectiveness of novel oral anticoagulantss was dependent on therapy pricing in the United States and neurological events associated with rivaroxaban 20 mg.

Cost-effectiveness of strontium ranelate in the treatment of male osteoporosis.

UNLABELLED: The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered a cost-effective strategy compared with no treatment for the treatment of osteoporotic men from a Belgian healthcare payer perspective. INTRODUCTION: This study was conducted to estimate the cost-effectiveness of strontium ranelate in the treatment of osteoporotic men. METHODS: A previously validated Markov microsimulation model was adapted to estimate the cost (2,010) per quality-adjusted life-year (QALY) gained of strontium ranelate compared with no treatment. Similar efficacy data on lumbar spine and femoral neck bone mineral density (BMD) between men with osteoporosis at high risk of fracture (MALEO Trial) and postmenopausal osteoporotic women (pivotal SOTI, TROPOS trials) supports the assumption, in the base-case analysis, of the same relative risk reduction of fractures in men as for women. Analyses were conducted, from a Belgian healthcare payer perspective, in the population from the MALEO Trial who is a men population with a mean age of 73 years, and BMD T-score ≤-2.5 or prevalent vertebral fracture (PVF). RESULTS: In the MALEO population, strontium ranelate compared with no treatment was estimated at 49,798 and 25,584 per QALY gained using efficacy data from the intent-to-treat analysis and the per-protocol analysis including only adherent patients, respectively. In men with a BMD T-score ≤-2.5 or with PVF, the cost per QALY gained of strontium ranelate fall below thresholds of 45,000 and 25,000 per QALY gained based on efficacy data from the entire population of the clinical trial and from the per-protocol analyses, respectively. CONCLUSIONS: The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered cost-effective compared with no treatment for male osteoporosis.

Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis.

UNLABELLED: The objective was to undertake a health economic analysis of denosumab for the treatment of osteoporosis in women from the UK, using the FRAX® tool. Denosumab was cost-effective in women with a risk of major osteoporotic fracture meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis, which has been shown to reduce the risk of fractures in a phase-III trial. The objective of the present study was to undertake a health economic analysis of denosumab in women from the UK. Ten-year probabilities of a major osteoporotic fracture at which denosumab is a cost-effective alternative to no treatment, generic alendronate, risedronate and strontium ranelate were estimated. METHODS: A previously published Markov model was adapted to incorporate fracture and mortality risk assessments based on absolute fracture probability, as estimated by FRAX®. The model included treatment persistence and residual effect after discontinuation. RESULTS: At a willingness-to-pay (WTP) of £30,000 per quality-adjusted life year and a 10-year fracture probability equivalent to a woman with a prior fragility fracture, denosumab was cost-effective compared to no treatment from the age of 70 years. At the same WTP, denosumab was-irrespective of age-cost-effective compared to no treatment at a major osteoporotic fracture probability of approximately 20%. Denosumab was estimated to cost-effectively replace strontium, risedronate and generic alendronate at 10-year probabilities exceeding 11, 19 and 32%, respectively. CONCLUSION: FRAX® facilitates the estimation of cost-effectiveness-based intervention thresholds applicable to patients with different combinations of clinical risk factors, which more closely matches the situation in clinical practice. Denosumab is cost-effective in patients with major osteoporotic fracture probabilities meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate.

The cost-effectiveness of duloxetine in chronic low back pain: a US private payer perspective.

OBJECTIVE: To assess the cost-effectiveness of duloxetine in the treatment of chronic low back pain (CLBP) from a US private payer perspective. METHODS: A cost-utility analysis was undertaken for duloxetine and seven oral post-first-line comparators, including nonsteroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids, and an anticonvulsant. We created a Markov model on the basis of the National Institute for Health and Clinical Excellence model documented in its 2008 osteoarthritis clinical guidelines. Health states included treatment, death, and 12 states associated with serious adverse events (AEs). We estimated treatment-specific utilities by carrying out a meta-analysis of pain scores from CLBP clinical trials and developing a transfer-to-utility equation using duloxetine CLBP patient-level data. Probabilities of AEs were taken from the National Institute for Health and Clinical Excellence model or estimated from osteoarthritis clinical trials by using a novel maximum-likelihood simulation technique. Costs were gathered from Red Book, Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project database, the literature, and, for a limited number of inputs, expert opinion. The model performed one-way and probabilistic sensitivity analyses and generated incremental cost-effectiveness ratios (ICERs) and cost acceptability curves. RESULTS: The model estimated an ICER of $59,473 for duloxetine over naproxen. ICERs under $30,000 were estimated for duloxetine over non-NSAIDs, with duloxetine dominating all strong opioids. In subpopulations at a higher risk of NSAID-related AEs, the ICER over naproxen was $33,105 or lower. CONCLUSIONS: Duloxetine appears to be a cost-effective post-first-line treatment for CLBP compared with all but generic NSAIDs. In subpopulations at risk of NSAID-related AEs, it is particularly cost-effective.

Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation.

OBJECTIVES: The primary objective was to assess the cost-effectiveness of new oral anticoagulants compared with warfarin in patients with nonvalvular atrial fibrillation. Secondary objectives related to assessing the cost-effectiveness of new oral anticoagulants stratified by center-specific time in therapeutic range, age, and CHADS2 score. METHODS: Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained. Analysis used a Markov cohort model that followed patients from initiation of pharmacotherapy to death. Transition probabilities were obtained from a concurrent network meta-analysis. Utility values and costs were obtained from published data. Numerous deterministic sensitivity analyses and probabilistic analysis were conducted. RESULTS: The incremental cost per QALY gained for dabigatran 150 mg versus warfarin was $20,797. Apixaban produced equal QALYs at a higher cost. Dabigatran 110 mg and rivaroxaban were dominated by dabigatran 150 mg and apixaban. Results were sensitive to the drug costs of apixaban, the time horizon adopted, and the consequences from major and minor bleeds with dabigatran. Results varied by a center's average time in therapeutic range, a patient's CHADS2 score, and patient age, with either dabigatran 150 mg or apixaban being optimal. CONCLUSIONS: Results were highly sensitive to patient characteristics. Rivaroxaban and dabigatran 110 mg were unlikely to be cost-effective. For different characteristics, apixaban or dabigatran 150 mg were optimal. Thus, the choice between these two options may come down to the price of apixaban and further evidence on the impact of major and minor bleeds with dabigatran.

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP.

BACKGROUND: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. METHODS/DESIGN: This study is a placebo controlled double blind, three armed randomized multi centre trial. Patients with (sub)chronic pain and a depressive disorder are randomized to either a) collaborative care with duloxetine, b) collaborative care with placebo or c) duloxetine alone. 189 completers are needed to attain sufficient power to show a clinically significant effect of 0.6 SD on the primary outcome measures (PHQ-9 score). Data on depression, anxiety, mental and physical health, medication adherence, medication tolerability, quality of life, patient-doctor relationship, coping, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months. DISCUSSION: This study enables us to show the value of a closely monitored integrated treatment model above usual pharmacological treatment. Furthermore, a comparison with a placebo arm enables us to evaluate effectiveness of duloxetine in this population in a real life setting. Also, this study will provide evidence-based treatments and tools for their implementation in practice. This will facilitate generalization and implementation of results of this study. Moreover, patients included in this study are screened for pain symptoms, differentiating between nociceptive and neuropathic pain. Therefore, pain relief can be thoroughly evaluated. TRIAL REGISTRATION: NTR1089.

Potential impact of new oral anticoagulants on the management of atrial fibrillation-related stroke in primary care.

AIM: Anticoagulant prophylaxis with vitamin K antagonists (such as warfarin) is effective in reducing the risk of stroke in patients with atrial fibrillation (AF). New oral anticoagulants have emerged as potential alternatives to traditional oral agents. The purpose of this review was to summarise the effectiveness and safety of rivaroxaban, dabigatran and apixaban in stroke prevention in patients with AF in phase III trials, evaluate their cost-effectiveness and consider the implications for primary care. METHODOLOGY: A literature search was performed between 2007 and 2012, selecting all phase III trials (ROCKET AF, RE-LY and ARISTOTLE) of new oral anticoagulants and relevant cost-benefit studies. RESULTS: Evidence shows that all three agents are at least as effective as warfarin in the prevention of stroke and systemic emboli, with similar safety profiles. Cost-benefit studies of rivaroxaban and dabigatran further confirm their potential use as alternatives to warfarin in clinical practice. These observations may allow stratification of the general practice AF population, to help prioritise which patients may benefit from receiving a new oral anticoagulant. CONCLUSION: The clinical and economic benefits of the new oral anticoagulants, along with appropriate risk stratification, may enable a higher number of patients with AF to receive effective and convenient prophylaxis for stroke prevention.

New anticoagulants as thromboprophylaxis after total hip or knee replacement.

OBJECTIVES: Due to a high risk of thromboembolism in patients undergoing major orthopedic surgery, it has become standard practice to give thromboprophylactic treatment. We assessed the relative efficacy and cost-effectiveness of two new oral anticoagulants, rivaroxaban and dabigatran, relative to subcutaneous enoxaparin for the prevention of thromboembolism after total hip replacement (THR) and total knee replacement surgery (TKR). METHODS: We conducted a systematic review of the literature to assess efficacy and safety, and evaluated quality of documentation using GRADE. Cost-effectiveness was assessed by developing a decision model. The model combined two modules; a decision tree for the short-term prophylaxis and a Markov model for the long-term complications and survival gain. RESULTS: For rivaroxaban compared with enoxaparin, we found statistically significant decreases in deep vein thrombosis, but also a trend toward increased risk of major bleeding. For mortality and pulmonary embolism there were no statistically significant differences between the treatments. We did not find statistically significant differences between dabigatran and enoxaparin for our efficacy and safety outcomes. Assuming a willingness to pay of EUR62,500 per QALY, rivaroxaban following THR had a probability of 38 percent, and enoxaparin following TKR had a probability of 34 percent of being cost-effective. Clinical efficacy had the greatest impact on decision uncertainty. CONCLUSIONS: Dabigatran and rivaroxaban are comparable with enoxaparin following THR and TKR regarding the efficacy and safety outcomes. However, there is great uncertainty regarding which strategy is the most cost-effective. More research on clinical efficacy of rivaroxaban and dabigatran is likely to change our results.

A clinical decision aid for the selection of antithrombotic therapy for the prevention of stroke due to atrial fibrillation.

AIMS: The availability of new antithrombotic agents, each with a unique efficacy and bleeding profile, has introduced a considerable amount of clinical uncertainty with physicians. We have developed a clinical decision aid in order to assist clinicians in determining an optimal antithrombotic regime for the prevention of stroke in patients who are newly diagnosed with non-valvular atrial fibrillation. METHODS AND RESULTS: The CHA(2)DS(2)-VASc and HAS-BLED scoring systems were used to assess patients' baseline risks of stroke and major bleeding, respectively. The relative risks of stroke and major bleeding for each antithrombotic agent were then used to identify the agent associated with the lowest net risk. Individual patient factors such as the treatment threshold, bleeding ratio, and cost threshold modified the recommendations in order to generate a final recommendation. By considering both patient factors and clinical research concurrently, this clinical decision aid is able to provide specific advice to clinicians regarding an optimal stroke prevention strategy. The resulting treatment recommendation tables are consistent with the recommendations of the European Society of Cardiology and Canadian Cardiovascular Society Guidelines, which can be incorporated into either a paper-based or electronic format to allow clinicians to have decision support at the point of care. CONCLUSION: The use of a clinical decision aid that considers both patient factors and evidence-based medicine will serve to bridge the knowledge gap and provide practical guidance to clinicians in the prevention of stroke due to atrial fibrillation.