Cost effectiveness of treatments for wet age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in people aged >= 50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination and Cochrane Library databases were searched for all wet AMD health technology assessments (HTAs). Overall, 44 publications were evaluated in full and included in this review. A broad range of cost-effectiveness analyses were identified for the most commonly used therapies for wet AMD (pegaptanib, ranibizumab and photodynamic therapy [PDT] with verteporfin). Three studies evaluated the cost effectiveness of bevacizumab in wet AMD. A small number of analyses of other treatments, such as laser photocoagulation and antioxidant vitamins, were also found. Ranibizumab was consistently shown to be cost effective for wet AMD in comparison with all the approved wet AMD therapies (four of the five studies identified showed ranibizumab was cost effective vs usual care, PDT or pegaptanib); however, there was considerable variation in the methodology for cost-effectiveness modelling between studies. Findings from the HTAs supported those from the PubMed and EM BASE searches; of the seven HTAs that included ranibizumab, six (including HTAs for Australia, Canada and the UK) concluded that ranibizumab was cost effective for the treatment of wet AMD; most compared ranibizumab with PDT and/or pegaptanib. By contrast, HTAs at best generally recommended pegaptanib or PDT for restricted use in subsets of patients with wet AMD. In the literature analyses, pegaptanib was found to be cost effective versus usual/best supportive care (including PDT) or no treatment in one of five studies; the other four studies found pegaptanib was of borderline cost effectiveness depending on the stage of disease and time horizon. PDT was shown to be cost effective versus usual/best supportive care or no treatment in five of nine studies; two studies showed that PDT was of borderline cost effectiveness depending on baseline visual acuity, and two showed that PDT was not cost effective. We identified no robust studies that properly evaluated the cost effectiveness of bevacizumab in wet AMD

Cost-effectiveness of ranibizumab in treatment of diabetic macular oedema (DME) causing visual impairment : evidence from the RESTORE trial

Background/aims To evaluate the cost-effectiveness of ranibizumab as either monotherapy or combined with laser therapy, compared with laser monotherapy, in the treatment of diabetic macular oedema (DME) causing visual impairment from a UK healthcare payer perspective. Methods A Markov model simulated long-term outcomes and costs of treating DME in one eye (BCVA <= 5 letters) based on data from the RESTORE Phase III trial. Outcomes measured in quality-adjusted life-years (QALYs) were simulated for a 15-year time horizon based on 12-month follow-up from RESTORE and published long-term data. Costs included treatment, disease monitoring, visual impairment and blindness (at 2010 price levels). Results Ranibizumab monotherapy resulted in a 0.17 QALY gain at an incremental cost of 4191 pound relative to laser monotherapy, yielding an incremental cost-effectiveness ratio (ICER) of 24 pound 028. Probabilistic sensitivity analysis showed a 64% probability of being cost-effective at a threshold of 30 pound 000 per QALY. Combined ranibizumab and laser therapy resulted in a 0.13 QALY gain at an incremental cost of 4695 pound relative to laser monotherapy (ICER 36 pound 106; 42% probability of ICER <30 pound 000). Conclusions Based on RESTORE 1-year follow-up data, ranibizumab monotherapy appears to be cost-effective relative to laser monotherapy, the current standard of care. Cost-effectiveness of combination therapy is less certain. Ongoing studies will further inform on disease progression and the need for additional ranibizumab treatment

Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel

BACKGROUND: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. OBJECTIVE: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. METHODS: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. RESULTS: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. CONCLUSION: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time

Pharmaceutical Restrictions: Possible Effect on Patient/Physician Buy-In of Disease Management Programs

Restrictions on the use of pharmaceuticals (such as those for low molecular weight heparins) are commonly imposed by healthcare organizations to combat rising health care costs. These restrictions can be system-based which are established by imposing specific coverage policies by insurance companies and payors or can be patient-based which are those that limit certain therapeutic agents to specified patient populations. Disease management (DM) programs are implemented by healthcare organizations to improve patient care while utilizing resources efficiently. From a payor perspective, restricted use of pharmaceuticals would conform to the goals of DM. However, from a practitioner's perspective, restrictions on the use of medications could sometimes be viewed as conflicting with their goal of providing appropriate patient care. Formularies and prior-authorization programs may sometimes impede physicians' clinical autonomy and may hinder physicians' willingness to participate in DM protocols with such drug restrictions. Furthermore, direct-to-patient advertisements and patient education are encouraging patients to participate actively in the drug selection process. When pharmaceutical restrictions prevent patients from receiving their drug of choice, patients may perceive that their treatment is suboptimal and unfavorable. Despite implementing a fine disease management protocol, imposing rigid drug-use restrictions could hinder physicians' and patients' buy-in of DM programs.Disease management programmes, Healthcare expenditure, Pharmacoeconomics

Byggande av kulsinteranläggning MK3 : processdesign, samverkansformer och IT-stöd

Denna rapport beskriver de studier som en grupp av forskare vid Institutionen för Samhällsbyggnad, Luleå tekniska universitet, genomfört beträffande vissa centrala delar av projektupplägget vid byggandet av kulsinteranläggning MK3 vid LKAB:s anläggningar i Vitåfors under perioden Nov. 2004 till Dec. 2006. Vid tidpunkten för investeringsbeslutet för kulsinterverket MK3, som är det första i en rad av planerade stora investeringar, var LKAB i en situation där man hade dragit ner egna projekterings- och projektledningsresurser efter att ha genomfört stora investeringar under 1990-talet. I det läget var det en strategiskt viktig beslutsfråga för företagsledning och styrelse hur MK3 projektet skulle styras och organiseras för att säkerställa projektets höga målsättningar beträffande tid, funktion och ekonomi. Dessutom är projekt av typen MK3 ofta dynamiska till sin natur (kort ledtid, snabba informations- och kommunikationsbehov), tekniskt och administrativt komplexa och med många risker och osäkerhetsfaktorer som måste hanteras kontinuerligt under projekttiden. LKAB har för projekt MK3 valt att söka samverkanslösningar för att med be- gränsade egna resurser kunna följa upp och påverka projektets funktionsut- formning, tid för genomförande samt projektets investeringskostnader. Sålunda har byggdelen av MK 3 upphandlats med transparent ersättningsform och strukturerad samverkansform, typ partnering. Genomförandeformen är totalentreprenad (ABT 94) där byggentreprenören administrativt ansvarar för detaljprojekteringen. Till huvudentreprenör på byggdelen och med samordningsansvar även för installationsfasen av separat upphandlade processdelar har valts NCC. Enligt de resultat från genomförda studier som redovisas i denna rapport anser en stor majoritet av i projekt MK3 medverkande beställar-, entreprenörs- och konsultrepresentanter att valet av upphandlingsmodell med klar samverkansprofil för projektet varit lyckad. En majoritet anser också att detta varit av avgörande betydelse för att kunna nå projektets målsättningar beträffande funktion, tid och ekonomi. Bland de fördelar som upphandlingsmodellen medfört är att samarbetsklimatet mellan aktörerna upplevts som bättre än vid konventionellt upphandlade projekt. Detta har ett egenvärde i sig men är framförallt en nödvändig förutsättning för att kunna nyttja strategiska viktiga kompetenser och kunskaper på ett effektivt sätt för att projektets målsättningar skall säkerställas. Effekterna av det goda samarbetsklimatet är speciellt tydliga i det sätt projekteringen av anläggningen kunnat bedrivas i effektiv samverkan mellan kund, entreprenör och konsulter (Concurrent engineering). Vid projektgenomförandet har även De IT-stödsystem, speciellt 3D modellering och VR använts på innovativt sätt som kommunikations- och informationsverktyg. Användandet av detta i projekteringen har på många sätt bidragit till att skapa mervärde för kunden och minska byggfelen i produktionen. Enbart besparingarna i en effektivare projektsamordning torde ha bekostat investeringen i 3D och VR med råge.Godkänd; 2007; 20070523 (ysko

Functional Impairment, Healthcare Costs and the Prevalence of Institutionalisation in Patients with Alzheimer's Disease and Other Dementias

Introduction: The progressive decline in functional status for patients with Alzheimer's disease and other dementias (ADOD) is well documented. However, there is limited information on the economic benefits of interventions improving functional status in an ADOD population. This study estimated the relationship between the degree of functional impairment in patients with ADOD and their healthcare costs and prevalence of institutionalisation. Methods: Retrospective cross-sectional analyses of the Medicare Current Beneficiary Survey (MCBS) were performed. A nationally representative sample of Medicare beneficiaries with ADOD was identified from the 1995-8 waves of the MCBS (n = 3138): 34% in the community, 57% institutionalised and 9% residing in both settings during the year. Three measures of functioning were used: the number of activities of daily living (ADLs) and independent ADLs (IADLs) impaired; an index summarising number and severity of ADL and IADL impairments; and the Katz Index of ADLs. Healthcare costs included costs for all healthcare services received in all settings, regardless of whether they were covered by insurance or paid out of pocket. The relationships between each measure of impairment and healthcare costs and prevalence of institutionalisation were estimated using linear and logistic regression. Results: Healthcare costs (1995-8 values) for all ADOD patients increased by $US1958 (p_Alzheimer's-disease, Cost-analysis, Dementia

Ultrasonic beadtrapping for bioassays

This paper proposes a new dynamic mode of generating bioanalytical arrays based on ultrasonic trapping of microbeads in microfluidic systems. As compared to disposable glass slide microarrays, the proposed technology utilises exchangeable microbeads as the solid phase on which bioassays are performed. The use of microbeads in biochemical analysis is advantageous due to the increased surface area and thus the high binding capacity as compared to planar solid surfaces. By the integration of ultrasonic microtransducers in a microfluidic system, we have proved that it is possible to trap and manipulate microbead clusters by making use of acoustic standing wave forces. Functionalised microbeads have been trapped and moved between well-defined positions in a microchannel, thus for the first time showing trapping of microbeads within a flow-through device with individually controlled trapping sites in an array format. A device with three acoustic trapping sites was fabricated and evaluated. The lateral extension of each trapping site was essentially determined by the corresponding microtransducer dimensions, 0.8 x 0.8 mm2. The flow-through volume was approximately 1 µl and the active trapping site volumes about 100 nl each. The strength of trapping was investigated, showing that 50 % of the initially trapped beads were still trapped at a perfusion rate of 10 µl/min. Since the beads determine the chemical functionality in the device a high degree of flexibility is expected. A fluorescence based avidin bioassay was successfully performed on biotin-coated microbeads trapped in the flow-through device, providing a first proof of principle of the proposed dynamic arraying concept. The dynamic arraying is believed to be expandable to two dimensions, thus with a prospect of performing targeted and highly parallel protein analysis in microfluidics

Bioassays on ultrasonically trapped microbead clusters in microfluidic systems

The handling of biochemically functionalised beads or particles is becoming increasingly important in µTAS. Bead-based analysis of e.g. proteins can be made sensitive due to the large active surface area and flexible by chemical design of the bead surface. We have developed a microfluidic device utilising an array of integrated and individually controlled ultrasonic microtransducers for particle trapping [1]. Particles inserted in the device are subjected to acoustic radiation forces [2] confining them at localised trapping sites. We would now, for the first time at an international conference, like to present a technique for performing bioassays on such ultrasonically trapped beads in microfluidic systems. The microfluidic device is shown in Fig. 1, where the piezoceramic ultrasonic transducers can be seen in the channel crossings in the insert. The device is designed as an acoustic resonator, to obtain localised standing acoustic waves at each transducer with essentially one pressure node in the middle of the 72 µm deep channel when operated near 10 MHz. This configuration is chosen to keep trapped particles away from the interior surfaces of the device, thus enabling fast switching of beads with a minimum in carry-over between assays. The fluidic chip, shown in Fig. 2, is designed to allow injection of microbeads, washing fluid and sample to the three trapping sites. It has been shown that the microbead clusters, as shown in Fig. 3, can be trapped at considerably high perfusion rates, up to 10 µl/min, Fig 4. As a model bioassay, 6.7 µm biotin-covered beads (PC-B-6.0, Gerlinde Kisker, Germany) were injected and transported to one tapping site using washing fluid (water). Activating the transducer trapped the beads. A solution of FITC-tagged avidin was perfused over the bead bed at 3 µl/min, using the corresponding orthogonal sample channel. After 100 s the sample flow was turned off and the bead trap was washed by perfusing water at 3 µl/min. The fluorescence response from the trapped bead clusters was monitored during the assay, and the result is shown in Fig. 5. After excess avidin was washed from the bead trap, a measured step response . indicated that avidin had bound to the beads. Finally the possibility of moving trapped microbeads between the individually controlled trapping sites in the device is shown in Fig. 6, where the transducers are activated sequentially while keeping the bead carrying washing fluid at 3 µl/min during the experiment. Work in the near future will be focused on optimising the device with respect to the bioassay performance, and in a longer perspective on expanding the concept to two dimensions to enable a new dynamic mode of generating bioanalytical arrays

Cost Effectiveness of Once-Daily Oral Chelation Therapy with Deferasirox versus Infusional Deferoxamine in Transfusion-Dependent Thalassaemia Patients: US Healthcare System Perspective

Background: Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. Objective: To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. Methods: A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. Results: Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of$US126_018 per patient; the cost per QALY gained was $US28_255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. Conclusion: Results of this analysis of the cost effectiveness of oral deferasirox versus infusional deferoxamine suggest that deferasirox is a cost effective iron chelator from a US healthcare perspective.Children, Cost-utility, Deferasirox, Deferoxamine, Iron-overload, Research-and-development, Thalassaemia