Mapping EQ-5D utility scores from the Incontinence Quality of Life Questionnaire among patients with neurogenic and idiopathic overactive bladder.

OBJECTIVES: To provide a mapping algorithm for estimating EuroQol five-dimensional (EQ-5D) questionnaire index scores from the Incontinence-specific Quality of Life questionnaire (I-QOL) based on nationally representative samples of patients with idiopathic or neurogenic overactive bladder (OAB) using EQ-5D questionnaire preference valuations based on both the UK and US general populations. METHODS: Analyses were conducted for 2505 patients from the Adelphi Overactive Bladder Disease Specific Programme, a cross-sectional study of patients with idiopathic or neurogenic OAB, undertaken in the United States and Europe in 2010. A range of statistical modeling techniques was used. Tenfold cross-validation techniques were used to calculate mean absolute error (MAE) and root mean squared error (RMSE) goodness-of-fit statistics. Various predictor lists, together with a method combining stepwise selection with multivariable fractional polynomial techniques to allow nonlinear relationships to feature, were pursued. RESULTS: Choice of predictors was consistent for both the UK and US EQ-5D questionnaire tariffs. For idiopathic, the best model included the I-QOL total score and age (both modeled nonlinearly.) For neurogenic, the best model was the I-QOL social embarrassment domain score modeled linearly only. Best-fit results were better in the idiopathic (n = 2351; MAE = 0.10; RMSE = 0.14) than in the neurogenic sample (n = 254; MAE = 0.17; RMSE = 0.22). CONCLUSIONS: This research provides algorithms for mapping EQ-5D questionnaire index scores from the I-QOL, allowing calculation of appropriate preference-based health-related quality-of-life scores for use in cost-effectiveness analyses when only I-QOL data are available. The strongest results were for idiopathic patients, but those for neurogenic are consistent with those of other published mapping studies.

Model parameters influencing the cost-effectiveness of sacubitril/valsartan in heart failure: evidence from a systematic literature review.

OBJECTIVES: To summarize cost-effectiveness (CE) evidence of sacubitril/valsartan for the treatment of heart failure (HF) patients with reduced ejection fraction (HFrEF). The impact of different modeling approaches and parameters on the CE results is also described. METHODS: We conducted a systematic literature review using multiple databases: Embase®; MEDLINE®; MEDLINE®-In Process; NIHR CRD database including DARE, NHS EED, and HTA databases; and the Cost Effectiveness Analysis registry. We also reviewed HTA countries' websites to identify CE reports of sacubitril/valsartan, published up to 25-July-2021. Articles published in English as full-texts, conference-abstracts, or HTA reports were included. RESULTS: We included 44 CE models [39 from 37 publications (22 full-texts; 15 conference-abstracts) and 5 HTAs; Europe, n = 20; North and South Americas, n = 14; Asia and Australia, n = 10]. Most models adopted a Markov structure with constant transition probabilities of events (n = 27) or a mix of Markov and regression-based models (n = 16), with variations in structural assumptions and chosen parameters. Study authors concluded sacubitril/valsartan to be a cost-effective therapy in 37/41 models in chronic HFrEF patients and 2/3 models in hospitalized patients stabilized after an acute decompensation for HF. CE models showing sacubitril/valsartan not to be a cost-effective treatment generally modeled a shorter time horizon. Effect of sacubitril/valsartan on cardiovascular and all-cause mortality, cost, duration of effect and time horizon was the main model drivers. CONCLUSIONS: Most evidence indicated sacubitril/valsartan is cost-effective in HFrEF. The use of a lifetime horizon is recommended in future models as HF is a chronic disease. Data on the CE of sacubitril/valsartan in the inpatient setting were limited and further research is warranted.

Exploring the impact of excessive daytime sleepiness caused by obstructive sleep apnea on patient and partner quality of life: a time trade-off utility study in the UK general public.

STUDY OBJECTIVES: This study aimed to quantify the impact of excessive daytime sleepiness (EDS) on patient and patient's partner health-related quality of life in the form of utility values typically used in health economic evaluations. METHODS: A time trade-off study was conducted in a UK general population sample (representing a societal perspective) to elicit utility values, measured on a 0 to 1 scale, for health states with varying obstructive sleep apnea-associated EDS severity. In a time trade-off study, health states are described, and participants "trade off" time in a specific higher severity state for a shorter amount of time in full health. RESULTS: Overall, the sample consisted of 104 participants, who were interviewed and took part in the time trade-off exercise to elicit utility values for patient and partner residual EDS health states. The average utility score declined with increasing obstructive sleep apnea-associated EDS severity for both patient (no EDS, 0.926; mild EDS, 0.794; moderate EDS, 0.614; severe EDS, 0.546) and partner (no EDS, 0.955; mild EDS, 0.882; moderate EDS, 0.751; severe EDS, 0.670) health states. CONCLUSIONS: These results demonstrate the high impact that EDS in obstructive sleep apnea is estimated to have on patient and partner health-related quality of life. CITATION: Tolley K, Noble-Longster J, Mettam S, et al. Exploring the impact of excessive daytime sleepiness caused by obstructive sleep apnea on patient and partner quality of life: a time trade-off utility study in the UK general public. J Clin Sleep Med. 2022;18(9):2237-2246.

Cost-effectiveness of lanthanum carbonate in the treatment of hyperphosphatemia in chronic kidney disease before and during dialysis.

OBJECTIVES: Hyperphosphatemia is a common and harmful condition in patients with chronic kidney disease (CKD). We determined the cost-effectiveness of the noncalcium-based phosphate binder lanthanum carbonate (LC) as second-line treatment of hyperphosphatemia after therapy failure with calcium-based binders (CB). METHODS: Two CKD populations were modeled: 1) predialysis CKD patients and 2) incident dialysis patients. Patients not responding to CB with a serum phosphate (SP) level >5.5 mg/dl received a trial with LC. Patients not responding to LC (SP >4.6 mg/dl) returned to CB treatment. Patient-level data were obtained from clinical trials in predialysis and dialysis. Time-dependent, life-long Markov models (discounting at 3.5% annually) were developed, using a UK National Health Service perspective. RESULTS: The health gains with second-line LC treatment compared to CB treatment were 44 and 56 quality-adjusted life-years (QALYs) for the predialysis and incident dialysis populations, respectively. Second-line LC was a cost-saving strategy in the predialysis population because of the cost-savings of delayed CKD progression. Second-line LC was cost-effective at £6900 (90% probability interval: £5800-£8300) per QALY gained in the dialysis population. Results were robust to plausible variations in other model parameters; inclusion of future unrelated dialysis costs had a large influence on cost-effectiveness estimates. CONCLUSIONS: Second-line treatment with LC is associated with considerable clinical benefits and good value for money in CKD, irrespective of dialysis status. These results support Kidney Disease Outcomes Quality Initiative guidelines to treat CKD patients with hyperphosphatemia irrespective of dialysis status.

An economic evaluation of short-acting opioids for treatment of breakthrough pain in patients with cancer.

OBJECTIVE: Breakthrough cancer pain (BTCP) represents a considerable economic burden. A decision-analysis model was developed to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS) compared with oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT) for the treatment of BTCP. METHODS: The model was parameterized for Sweden to estimate the costs and benefits associated with treatments. Expected reductions in pain intensity (PI; measured on a numeric rating scale ranging from 0 to 10) per BTCP episodes were translated into resource use and quality-adjusted life years (QALYs). Relative analgesic efficacy of interventions was derived from a mixed treatment comparison of six randomized controlled trials. The relationship between PI and utility was obtained from a time-trade off study in the general population. Resource use and unit cost data were obtained from the literature and validated by Swedish clinical experts. The base case scenario assumed three BTCP episodes/day, a background PI of 2, and a time horizon of 180 days. Prices of INFS and OTFC were assumed to be equal with FBT ∼14% less. Uncertainty in the source data was incorporated by probabilistic sensitivity analyses and different scenario analyses. RESULTS: With INFS, 55% of BTCP (95% uncertainty interval [UI]: 46-68%) was avoided, which is greater than expected with OTFC (29%; UI 22-38%) or FBT (31%; UI 25-39%). INFS was dominating OTFC (resulting in 0.046 QALY gain and saving 174 Euros with a time horizon of 180 days) and cost-effective versus FBT (incremental cost-effectiveness ratio 12203 Euros/QALY). Despite uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. CONCLUSION: Given inherent limitations of modelling studies, the greater efficacy of INFS translates to cost and QALY advantages over competing interventions in the treatment for BTCP in Sweden.

Cost effectiveness of itraconazole in the prophylaxis of invasive fungal infections.

BACKGROUND: Invasive fungal infections in neutropenic patients treated for haematological malignancies are associated with a high mortality rate and, therefore, require early treatment. As the diagnosis of invasive fungal infections is difficult, effective antifungal prophylaxis is desirable. So far, fluconazole has been the most commonly used. OBJECTIVE: To assess the cost effectiveness of itraconazole compared with both fluconazole and no prophylaxis for the prevention of invasive fungal infections in haematological patients, mean age 51 years, in Germany and The Netherlands. STUDY DESIGN: We designed a probabilistic decision model to fully incorporate the uncertainty associated with the risk estimates of acquiring an invasive fungal infection. These risk estimates were extracted from two meta-analyses, evaluating the effectiveness of fluconazole and itraconazole and no prophylaxis. The perspective of the analysis was that of the healthcare sector; only medical costs were taken into account. All costs were reported in euro, year 2004 values.Cost effectiveness was expressed as net costs per invasive fungal infection averted. No discounting was performed, as the model followed patients during their neutropenic period, which was assumed to be less than 1 year. RESULTS: According to our probabilistic decision model, the monetary benefits of averted healthcare exceed the costs of itraconazole prophylaxis under baseline assumptions (95% CI: from cost-saving to euro 5000 per invasive fungal infection averted). Compared with fluconazole, itraconazole is estimated to be both more effective and more economically favourable, with a probability of almost 98%. CONCLUSIONS: In specific groups of neutropenic patients treated for haematological malignancies, itraconazole prophylaxis could potentially reduce overall healthcare expenditure, without harming effectiveness, in settings where fluconazole is common practice in the prophylaxis of invasive fungal infections.

An assessment of innovative pricing schemes for the communication of value: is price discrimination and two-part pricing a way forward?

INTRODUCTION: With the introduction of new expensive medicines, traditional pricing schemes based on constructs such as price per pill/vial have been challenged. Potential innovative schemes could be either financial-based or performance-based. Within financial-based schemes the use of price discrimination is an emerging option, which we explore in this assessment. AREAS COVERED: In the short term the price per indication approach is likely to become more prevalent for high cost, high benefit new pharmaceuticals, such as those emerging in oncology (e.g. new combination immunotherapies). 'Two-Part Pricing' (2PP) is a frequently used payment method in other industries, which consists of an Entry Fee, giving the buyer the right to use the product, and a Usage Price charged every time the product is purchased. Introducing 2PP into biopharma could have cross-stakeholder benefits including broader patient access, and improvement in budget/revenue predictability. A concern however is the potential complexity of the negotiation between manufacturer and payer. EXPERT COMMENTARY: We believe 'price discrimination' and 2PP in particular can be relevant for some new, expensive specialist medicines. A recommended first step would be to initiate pilots to test to what degree the 2PP approach meets stakeholder objectives and is practical to implement within specialty care.

Comparative Effectiveness of Adding Alogliptin to Metformin Plus Sulfonylurea with Other DPP-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy. METHODS: A systematic literature review was conducted to identify published papers of randomized controlled trials (RCTs) that compared alogliptin with other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) at their Summary of Product Characteristics (SmPC) recommended daily doses, added on to metformin and SU. Comprehensive comparative analysis involving frequentist meta-analysis and Bayesian NMA compared alogliptin to each DPP-4 inhibitor separately and collectively as a group. Quasi-random effect models were introduced when random effect models could not be estimated. RESULTS: The review identified 2186 articles, and 94 full-text articles were assessed for eligibility. Eight RCTs contained appropriate data for inclusion in the NMA. All analyses over all trial population sets produced very similar results, and show that alogliptin 25 mg is as least as effective (as measured by change in HbA1c from baseline, but supported by other outcome measures: change in body weight and FPG from baseline) and safe (as measured by incidence of hypoglycemia and adverse events leading to study discontinuation) as all the other DPP-4 inhibitors in triple therapy. CONCLUSION: This decision-focused systematic review and NMA demonstrated alogliptin 25 mg daily to have similar efficacy and safety compared to other DPP-4 inhibitors, for the treatment of T2DM in adults inadequately controlled on metformin and SU. (Funded by Takeda Development Centre Americas; EXAMINE ClinicalTrials.gov number, NCT00968708).

Pharmacoeconomic evaluations in the treatment of actinic keratoses.

Actinic keratoses (AKs) develop as a consequence of chronic ultraviolet (UV) exposure and exist on a continuum with squamous cell carcinoma (SCC). As one of the most common conditions treated by dermatologists, AK places a significant burden on patients and the healthcare system. A range of treatments are used, including topical treatments that target the visible and subclinical lesions. The goal of such therapies is to achieve complete clearance of AKs and eliminate the risk of progression to SCC. Robust meta-analyses of trial data can provide valuable information for the optimal management of AK and cost-effectiveness evaluations of topical treatments, such as ingenol mebutate gel and diclofenac. These outcomes can facilitate prescribing physicians' decisions and shape therapeutic guidelines. Peer-reviewed meta-analysis publications and treatment guidelines favoured ingenol mebutate efficacy over diclofenac and the relative cost-effectiveness of ingenol mebutate. We discuss and critique recent evidence, from a cost-effectiveness analysis of 3% diclofenac sodium and ingenol mebutate in the treatment of AK in Italy, which has challenged this view.

Unlocking the potential of established products: toward new incentives rewarding innovation in Europe.

Background: Many established products (EPs - marketed for eight years or more) are widely used off-label despite little evidence on benefit-risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods: Targeted literature search and expert panel meetings. Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients' access to treatment options. Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems.

A cost-utility analysis of ingenol mebutate gel for the treatment of actinic keratosis: a Scottish perspective.

BACKGROUND: Actinic keratosis (AK) is a UV-induced, pre-malignant skin condition that is common in adults over 60 years of age with fair skin in Scotland. The most commonly prescribed first-line treatment for AK in Scotland is currently diclofenac gel (3 %). Ingenol mebutate gel is a recently developed topical therapy available in two strengths for the treatment of AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days). OBJECTIVE: To compare the cost-effectiveness of two strengths of ingenol mebutate gel developed to treat AK lesions on the face and scalp (150 mcg/g once daily for 3 consecutive days) or trunk and extremities (500 mcg/g once daily for 2 consecutive days) with other first-line AK therapies including diclofenac gel, 5-FU, 5-FU/salicylic acid, and cryotherapy for the first-line treatment of AK in adult patients, from the perspective of the National Health Service (NHS) in Scotland. METHODS: A cost-utility analysis was conducted using a decision-tree approach to calculate the costs and benefits of different treatment strategies for AK on the face and scalp or trunk and limbs over a 12-month time horizon. Data on the relative efficacy of treatments were obtained from a systematic literature review and meta-analysis. Utility scores and resource-use data were obtained from published sources. RESULTS: Over 12 months, ingenol mebutate 150 mcg/g gel and 500 mcg/g gel were cost-effective compared with the most commonly used topical therapy in Scotland, diclofenac (3 %) gel, at a willingness-to-pay threshold of £20,000 per QALY, with a minimal additional cost of £43 and £105, respectively per QALY gained. CONCLUSIONS: Ingenol mebutate gel is a cost-effective therapy for the first-line treatment of AK from a Scottish NHS perspective.

Determining the value of medical technologies to treat ultra-rare disorders: a consensus statement.

BACKGROUND: In most jurisdictions, policies have been adopted to encourage the development of treatments for rare or orphan diseases. While successful as assessed against their primary objective, these policies have prompted concerns among payers about the economic burden that might be caused by an annual cost per patient in some cases exceeding 100,000 Euro. At the same time, many drugs for rare disorders do not meet conventional standards for cost-effectiveness or 'value for money'. Owing to the fixed (volume-independent) cost of research and development, this issue is becoming increasingly serious with decreasing prevalence of a given disorder. METHODS: In order to critically appraise the problems posed by the systematic valuation of interventions for ultra-rare disorders (URDs), an international group of clinical and health economic experts was convened in conjunction with the Annual European ISPOR Congress in Berlin, Germany, in November 2012. Following this meeting and during subsequent deliberations, the group achieved a consensus on the specific challenges and potential ways forward. RESULTS: The group concluded that the complexities of research and development for new treatments for URDs may require conditional approval and reimbursement policies, such as managed entry schemes and coverage with evidence development agreements, but should not use as justification surrogate end point improvement only. As a prerequisite for value assessment, the demonstration of a minimum significant clinical benefit should be expected within a reasonable time frame. As to the health economic evaluation of interventions for URDs, the currently prevailing logic of cost-effectiveness (using benchmarks for the maximum allowable incremental cost per quality-adjusted life year gained) was considered deficient as it does not capture well-established social preferences regarding health care resource allocation. CONCLUSION: Modified approaches or alternative paradigms to establish the 'value for money' conferred by interventions for URDs should be developed with high priority.

Reimbursement of targeted cancer therapies within 3 different European health care systems.

PURPOSE: Targeted cancer therapies (TCTs) are drugs that specifically act on molecular targets within the cancer cell, causing its regression and/or destruction. Although TCTs offer clinically important gains in survival in one of the most challenging therapeutic areas, these gains are followed by considerable increases in health care expenditures. The aim of this study was to identify differences in the recommendations for TCTs in 3 European health care systems (Serbian, Scottish, and Dutch) and to examine the role of pharmacoeconomic (PE) assessments in such recommendations. METHODS: A list of currently approved TCTs cited from the European Medicines Agency was cross-referenced with drug reimbursement reports issued by the National Health Insurance Fund for Serbia, the Scottish Medicines Consortium for Scotland, and the National Health Institute for the Netherlands. The following key variables were gathered from the reports: drug indication, registration status, reimbursement status, and outcome of the PE evaluation. FINDINGS: There were 41 TCTs approved by the European Medicines Agency for 70 cancer indications. Of the total number of TCT indications, 20 were reimbursed in Serbia, and 25 are still without a decision from the national agency. The remaining TCT indications (n = 25) are not registered in Serbia. None of the submissions or the PE analyses were publicly available. The Scottish Medicines Consortium positively assessed 26 TCT indications and rejected 30. All appraisals were published, and the majority contained full PE assessments. Finally, the Dutch agency accepted 60 TCT indications and disapproved the use of 1. The majority of reimbursed drugs were exempted from PE evaluation in accordance with 2 recent policies regarding expensive hospital drugs. IMPLICATIONS: In the 3 examined health care systems, the reimbursement status of the TCTs differed significantly. Level of PE application within the TCT evaluation procedures seemed to largely affect the final reimbursement decisions. Although, there are special policies in the Netherlands that enabled fast access for 98% of the TCTs that applied for reimbursement, a clear definition of cost-effectiveness threshold and strict requirements for full cost utility assessments in Scotland led to acceptance of only 46% of the TCT submissions. More precise PE guidelines must still be designed for TCT reimbursement in Serbia. Guidelines must account for specific epidemic and economic conditions of the country and could build on the experiences of Scotland and the Netherlands.

A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis.

Subcutaneous pegylated interferon beta-1a (peginterferon beta-1a [PEG-IFN]) 125 µg every two or four weeks has been studied in relapsing-remitting multiple sclerosis (RRMS) patients in the pivotal Phase 3 ADVANCE trial. In the absence of direct comparative evidence, a network meta-analysis (NMA) was conducted to provide an indirect assessment of the relative efficacy, safety, and tolerability of PEG-IFN versus other injectable RRMS therapies. Systematic searches were conducted in MEDLINE, Embase, and the Cochrane Library, and conference proceedings from relevant annual symposia were hand-searched. Included studies were randomized controlled trials evaluating ≥1 first-line treatments including interferon beta-1a 30, 44, and 22 µg, interferon beta-1b, and glatiramer acetate in patients with RRMS. Studies were included based on a pre-specified protocol and extracted by a team of independent reviewers and information scientists, utilizing criteria from NICE and IQWiG. In line with ADVANCE findings, NMA results support that PEG-IFN every 2 weeks significantly reduced annualized relapse rate, and 3- and 6-month confirmed disability progression (CDP) versus placebo. There was numerical trend favoring PEG-IFN every 2 weeks versus other IFNs assessed for annualized relapse rate, and versus all other injectables for 3- and 6-month CDP (6-month CDP was significantly reduced versus IFN beta-1a 30 µg). The safety and tolerability profile of PEG-IFN beta-1a 125 µg every 2 weeks was consistent with that of other evaluated treatments. Study limitations for the NMA include variant definitions of relapse and other systematic differences across trials, assumptions that populations were sufficiently similar, and inability to perform NMA of adverse events. With similar efficacy compared to other RRMS treatments in terms of annualized relapse rate and 3- and 6-month CDP, a promising safety profile, and up to 93% reduction in number of injections (which may improve adherence), PEG-IFN every 2 weeks offers a valuable alternative treatment option for patients with RRMS.

Cost effectiveness of lanthanum carbonate in chronic kidney disease patients in Spain before and during dialysis.

AIMS: In Spain, the first line treatment of hyperphosphatemia in Chronic Kidney Disease (CKD) consists of calcium-based phosphate binders (CB). However, their use is associated with vascular calcification and an increased mortality risk. The aim of this study was to assess the incremental cost-effectiveness of second-line Lanthanum Carbonate (LC) treatment in patients not responding to CB (calcium carbonate and calcium acetate). MATERIAL AND METHODS: A lifetime Markov model was developed considering three health states (predialysis, dialysis and death). Transitions between states and efficacy data were obtained from randomized clinical trials and the European Dialysis and Transplant Association Annual report. Mortality rate was adjusted with the relative risk related to serum phosphorus levels. According to the Spanish healthcare system perspective, only medical direct costs were considered. Dialysis costs (2013 prices in Euros) were obtained from diagnosis-related groups. Drug costs were derived from ex-factory prices, adjusted with 7.5% mandatory rebate. Quality of life estimates were based on a published systematic review. Costs and benefits were discounted at 3%. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: At the end of simulation, costs per patient with LC therapy were 1,169 and 5,044 with CB alone. 4.653 Quality Adjusted Life Years (QALYs) were gained per patient treated with LC, and 4.579 QALYs with CB. CB therapy is dominated by the LC strategy (i.e. lower costs, higher QALYs). Assuming a 30,000/QALY threshold, LC was dominant in 100% of PSA simulations. CONCLUSIONS: LC is a cost-effective second line treatment of hyperphosphatemia in CKD patients irrespective of dialysis status in Spain.

Treatment of anaemia in cancer patients: implications for supportive care in the National Health Service Cancer Plan.

The National Health Service (NHS) Cancer Plan published in 2000 has a short-term focus on the most pressing problems of improving survival rates and replacing equipment. It also mentioned as a target 'improved quality of life for those affected by cancer'. Continuity of care for longer-term care programmes was seen predominantly in terms of palliative care. Recent National Institute for Clinical Excellence (NICE) reports may have reinforced this approach by focussing on the clinical and cost effectiveness of chemotherapy for late-stage cancer. The impact on local decision-makers has been that drug funds have been prioritised for use on survival-enhancing interventions, with few resources left for short and longer-term supportive care targeted primarily on improving quality of life. Within supportive care, resources are particularly limited for funding treatments such as erythropoietin for the management of cancer-related anaemia, a common and very debilitating side-effect of intensive therapy. The need for a re-focusing on supportive care is associated with cancer becoming, in many instances, a longer-term illness. The prevalence of cancer is rising markedly due to increased survival rates. However, this creates a new challenge of reducing disability and improving quality of life. In surveys, patients have rated fatigue associated with anaemia as one of the most debilitating effects of their cancer and its treatment with chemotherapy. This paper reviews the evidence demonstrating the quality of life benefits of erythropoietin, and then considers the policy constraints that have limited the adoption of this treatment within the NHS. Through co-ordinated planning there are opportunities for cancer networks and primary care trusts (PCTs) working with cancer centres to develop more support in ways which are feasible and fundable. The case is argued that PCTs and cancer networks, in implementing the Cancer Plan locally, need to integrate short- and longer-term supportive care into their cancer service development plans, and recognise the importance of anaemia management as an integral part of this. Lessons can be learnt from UK renal services where anaemia management with erythropoietin is standard practice.

A multicentre study of patient survival, disability, quality of life and cost of care: among patients with AIDS in northern Italy.

OBJECTIVE: To describe the epidemiological, clinical and economic changes that occurred in the HIV epidemic in Italy prior to and after the introduction of highly active antiretroviral therapy (HAART). DESIGN: A prospective, observational, multicentre case-control study was conducted comparing data, collected over 6 months, from an AIDS cohort in 1998 with that of a cohort in 1994. Out of 77 patients with AIDS in the 1998 cohort, 74 survived. These 74 patients were matched for severity of illness with 74 patient survivors from the 1994 cohort to enable valid comparisons of mortality, disability-dependency (DD), health-related QOL (HR-QOL), and direct costs. RESULTS: Overall, a considerable difference was observed in mortality (33.8% in 1994 vs 3.9% in 1998) between unmatched patients of the two cohorts. As for matched patients, the number of hospital admissions was 1.7 in 1994 and 0.8 in 1998; the average length of stay was 28.1 days in 1994 and 12.6 days in 1998. The direct cost per patient per year was euro15 390 and euro11 465 for the 1994 and 1998 cohorts, respectively (1999 values). The 1998 patient cohort had significantly better HR-QOL at 6 months in two domains of the instrument used (emotional reaction and energy) and the percentage of totally dependent patients was significantly lower compared with the 1994 cohort (1.4% vs 6.8%). CONCLUSIONS: This is the first study to present a comprehensive comparison of direct costs, DD and HR-QOL of patients with AIDS between two time periods. The use of a case-control design has enabled changes in costs and outcomes to be linked to the introduction of HAART in Italy in 1997.

Cost-utility analysis of primary prophylaxis versus treatment on-demand for individuals with severe haemophilia.

OBJECTIVE: To assess the cost effectiveness of primary prophylaxis with clotting factor instead of treatment following a bleed (on-demand) for individuals with severe haemophilia. DESIGN: Different data sources on the clinical effects and costs of treatments were combined using a Markov model. SETTING: English treatment centres. PERSPECTIVE: UK societal. PARTICIPANTS: Hypothetical cohorts of 100 individuals with severe haemophilia A or B or severe von Willebrands disease. INTERVENTIONS: Primary prophylaxis treatment on-demand with clotting factor. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost per QALY in UK pounds ( pound, 1999/2000 values). RESULTS: The baseline results showed that treating individuals with severe haemophilia A/severe von Willebrands disease or severe haemophilia B with primary prophylaxis instead of treatment on-demand cost an additional pound 46500 and pound 8600 per QALY gained, respectively. However, the results were extremely sensitive to a number of factors including the clotting factor unit cost, the time between prophylactic doses and the discount rate. CONCLUSIONS: Despite the high costs of treatment, primary prophylaxis was cost effective compared with treatment on-demand in some scenarios. Primary prophylaxis is more likely to be cost effective for individuals with severe haemophilia B compared with individuals with severe haemophilia A/severe von Willebrands disease. Further research is required to assess the relationship between methods of clotting factor infusion and health-related quality-of-life.

A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe.

BACKGROUND: Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy. OBJECTIVES: To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe. METHODS: A network meta-analysis (NMA) was performed on the outcome "complete patient clearance". Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2-3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model. RESULTS: 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%). CONCLUSIONS: This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK.

Incremental cost per quality-adjusted life year gained? The need for alternative methods to evaluate medical interventions for ultra-rare disorders.

Drugs for ultra-rare disorders (URDs) rank prominently among the most expensive medicines on a cost-per-patient basis. Many of them do not meet conventional standards for cost-effectiveness. In light of the high fixed cost of R&D, this challenge is inversely related to the prevalence of URDs. The present paper sets out to explain the rationale underlying a recent expert consensus on these issues, recommending a more rigorous assessment of the clinical effectiveness of URDs, applying established standards of evidence-based medicine. This may include conditional approval and reimbursement policies, which should be combined with a firm expectation of proof of a minimum significant clinical benefit within a reasonable time. In contrast, current health economic evaluation paradigms fail to adequately reflect normative and empirical concerns (i.e., morally defensible 'social preferences') regarding healthcare resource allocation. Hence there is a strong need for alternative economic evaluation models for URDs.