Search

I. INTRODUCTION At present, the United Kingdom devotes approximately 6% of its annual gross domestic product to public health care, via the National Health Service (NHS). After staffing, drugs constitute [...]

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.

In the light of evidence which suggests that the use of medicines is in some degree predictable from the demographic structure of practice populations,(1) a move has been made towards […]

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.

IMPORTANCE Few data are available on relative changes in vision-related function after treatment for diabetic macular edema (DME). OBJECTIVE To determine the impact of intravitreal ranibizumab, 0.5 mg, compared with laser on patient-reported visual function. DESIGN Phase 3, randomized, double-masked, 12-month study (RESTORE). SETTING Outpatient retina practices in Australia, Canada, and Europe. PARTICIPANTS Patients 18 years or older with type 1 or 2 diabetes mellitus and visual impairment due to DME. INTERVENTIONS Patients were randomized to ranibizumab plus sham laser (n = 116), ranibizumab plus laser (n = 118), or sham injections plus laser (n = 111). Ranibizumab and sham injections were given for 3 consecutive months then as needed; laser or sham laser treatment was given at baseline then as needed. MAIN OUTCOMES AND MEASURES National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) scores at 0, 3, and 12 months for patients receiving 1 or more study treatments with 1 or more postbaseline NEI VFQ-25 assessments and last observation carried forward for missing data. RESULTS Mean baseline NEI VFQ-25 composite scores were 72.8, 73.5, and 74.1 in the ranibizumab, laser, and ranibizumab plus laser groups, respectively. At 12 months, the mean composite scores (95% CIs) improved by 5.0 (ranibizumab vs laser, 2.6 to 7.4; P = .01 vs laser) and 5.4 (ranibizumab plus laser vs laser alone, 3.3 to 7.4; P = .004 vs laser) from baseline in the ranibizumab and ranibizumab plus laser groups, respectively, compared with 0.6 (−1.8 to 3.0) for the laser group. Near activities scores improved by 9.0 (ranibizumab vs laser, 5.0 to 13.0; P = .01) and 9.1 (ranibizumab plus laser vs laser, 5.6 to 12.6; P = .006) compared with 1.1 (−3.0 to 5.2) for the laser group, whereas distance activities scores improved by 5.3 (ranibizumab vs laser, 1.8 to 8.9; P = .04) and 5.6 (ranibizumab plus laser vs laser, 2.3 to 9.0; P = .03) compared with 0.4 (−3.1 to 3.8) for the laser group. Patients with better baseline visual acuity or lower central retinal thickness had greater improvements with ranibizumab treatment compared with laser in composite and some subscale scores compared with patients with worse visual acuity or higher central retinal thickness. CONCLUSIONS AND RELEVANCE These data provide vision-related, patient-reported outcome evidence that mirrors visual acuity outcomes and supports benefits from ranibizumab or ranibizumab plus laser treatment for patients with DME and characteristics similar to those enrolled in this randomized clinical trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00687804

Health Technology Assessment (HTA) has been formally used in the United Kingdom for more than 10 years to help determine evidence‐based decisions on the access to new drugs, based on evidence of clinical and cost‐effectiveness. Separate HTA systems have developed in England and Wales (NICE, AWMSG), and Scotland (SMC). The primary clinical evidence desired for technology appraisal by the HTA bodies is the comparative randomized controlled trial because of its good internal validity, but the role and value of observational study designs for providing data on real‐world effectiveness have been recognized in the methods guidance of these bodies. To date HTA has had a fairly limited impact on drug development and clinical trial design in the United Kingdom, coupled with limited use to date of non‐RCT data for assessing treatment effect and outcomes in NICE/SMC appraisals. Nonetheless, with new initiatives such as closer regulatory and HTA coordination in Europe, and “conditional market access” schemes such as the Innovation Pass in the United Kingdom, in the future pharmaceutical companies are likely to need to adopt a more flexible approach to drug development and clinical data collection involving RCT, observational data collection, and indirect comparisons to meet the needs to provide relevant clinical and cost‐effectiveness evidence at drug launch and post launch. Drug Dev Res 71: 478–484, 2010. © 2010 Wiley‐Liss, Inc.

Abstract: Aim: Clinical trials have demonstrated the efficacy of the tetravalent human papillomavirus (HPV) vaccination in the prevention of cervical cancer and genital warts associated with HPV types 6, 11, 16 and 18. We used an empirically calibrated Markov cohort model of the natural history of HPV to assess the cost-effectiveness of the vaccine administered to 12-year-old girls alongside existing cervical screening programmes in Germany. Subjects and methods: The model estimated cervical cancer (CC), cervical intraepithelial neoplasia (CIN) and genital wart lifetime risks and total lifetime health care costs, life years gained and quality-adjusted life years (QALY) gained. The analysis was conducted from the perspective of the German health care payer. Results: In the base case (considering a lifetime duration of protection and 100% efficacy) it was estimated that 2,835 cervical cancer cases and 679 deaths could be prevented among a cohort of 400,000, at an incremental cost per QALY gained of 10,530 €. A total of 120 girls needed to be vaccinated to prevent 1 case of CC. Cost-effectiveness is sensitive to a duration of protection of less than 20 years and to the discount rate for costs and benefits. Conclusion: A policy of vaccinating adolescent girls has been recommended by the German Standing Committee on Vaccinations. This study has demonstrated that such a policy is cost-effective based on thresholds of cost-effectiveness that apply in Germany.

SUMMARYThe 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 ofcancer 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 survey of the functioning of the six communication aid centres (CACs) in England and Wales was undertaken. All CACs are specialist units drawing clients from a wide area of the country which means that referrals are more likely to come from outside, rather than from within the districts in which the CACs are located. All CACs have developed individual assessment procedures, with some CACs undertaking continuous assessment of clients, and others recommending an aid after a single session. Funding of aids was often a problem because CACs were only able to recommend aid provision and did not supply them; their stocks of aids were used in assessment sessions or for interim loan to clients until a definitive aid had been acquired. CAC staff engaged in a variety of other functions including the organisation of courses, acting as an advice and information service, and undertaking research.Il s'agit &dcarune enquete sur le fonctionnement de six Centres &dcarAide à la Communication (CAC) &dcarAngleterre et du Pays de Galles. Tous sont des unités spécialisées qui tirent lews clientèles de vastes zones du pays, ce qui signifie que les cas qui leur sont adressés ont davantage de chances de venir &dcarau-delà des limites des districts où les CAC sont silués que de intérieur de ces districts. Tous les CAC ont mis au point lews propres méthodes &dcarévaluation, certains faisant une évaluation continue de leurs clients, tandis que pour &dcarautres une session suffit pour recommander un appareil. Le financement des appareils est souvent chose difficile du fait que les CAC sont seulement habilités à recommander octroi &dcarun appareil, mais ce ne sont pas eux qui les fournissent. Leurs stocks &dcarappareils servent awe sessions &dcarexamens ou à des prets temporaires en attendant acquisition &dcarun appareil définitifpar le client. Le personnel des CAC se livre à un certain nombre &dcarautres activatés, comme organisation de cows, des services de conseils et de renseignements, et la recherche.Eine Überblicksuntersuchung der Funktion und Leistung von sechs Zentren für Kommunikationshilfen (communication aid centres = CACs) in England und Wales wurde durchgeführt. Alle untersuchten CACs sind Spezialeinheiten, deren Klienten aus vielen Teilen des Landes kommen. Demzufolge ist die Wahrscheinlichkeit groβ, daβ eine Überweisung von auswärts und nicht von innerhalb des Einzugsgebiets des CACs kommt. Alle CACs haben Verfahren für die Individualbewertung von Palienten entwickelt, wobei einige eine kontinuierliche Bewertung vornehmen. während andere nach einer einmaligen Untersuchung eine Hilfe empfehlen. Die Finanzierung von Hilfen ist oft problematisch, well CACs die Hilfen nur empfehlen sie jedoch nicht zur Verfügung stellen können. Die vorhandenen Hilfen werden bei der Bewertungsprozedur eingesetzt bzw. vorübergehend an Klienten ausgeliehen. bis eine endgültige Hilfe zur Verfügung gestellt werden kann. CAC-Angestellte haben eine Reihe von Zusatzfunktionen, darunter die Organisation von Kursen. die Ausführung eines Beratungs-und Fnformationsdienstes und Forschung.

In April 1991, the fundholding and indicative prescribing schemes introduced budgets for expenditure on prescribed drugs into UK general practice. Although both schemes were designed to be equally effective at containing prescribing-cost inflation, several studies suggest that expenditure growth has been lower in fundholding practices, compared with nonfundholding practices. This study attempts to ascertain how fundholding practices control their expenditure by examining data from a rural English health authority for the financial year 1993 to 1994. The fundholding practices sampled were found to control their expenditure through: (i) reduced overprescribing; (ii) using fewer drugs that have limited clinical value; (iii) substituting similar, but less expensive, drugs; (iv) more generic prescribing; and (v) appropriate use of expensive preparations. However, whether the cost differential between fundholding and nonfundholding practices is sustained in future years will depend upon: (i) the ability of fundholding practices to generate further savings; (ii) the characteristics of the practices that enter the fundholding scheme in subsequent waves; (iii) the way in which the scheme is organised; and (iv) the level at which budgets are set.

The recent licensing of interferon-β for use in patients with multiple sclerosis has caused concern, in view of the equivocal evidence of efficacy, pressure of public expectation towards its use and the high expected cost if widespread use were to be sanctioned. Whether such alarm is justified remains a moot point. Owing to the limited range of circumstances of proven efficacy and the lack of cost-effectiveness data, it remains unclear whether sanctioned usage will proliferate to the anticipated extent. Unit costs may well fall in the future owing to competition in the pharmaceutical market. Interferon-β is simply one example of a growing trend in actively promoted high-cost preparations over which rationing decisions will have to be reached.

In most economic evaluations. future monetary costs and benefits and future health benefits are discounted at the same rate. The purpose of this article is to question such current practice. The primary reason behind discounting costs and benefits is to allow for individuals’ preferences over the timing of such events, i.e. to represent social time preference. We argue that the social time preference rate for health benefits is unlikely to be the same as that for monetary costs and benefits. The results of a sensitivity analysis of pharmacoeconomic analyses of drug treatments for hypertension illustrate how the choice of discount rate can affect the conclusions. As no definite conclusions can be drawn regarding the magnitude of the discount rate for health benefits, we recommend that analysts conduct sensitivity analyses employing differential discount rates for health benefits as well as monetary costs and benefits.

Tolley: Tolley Health Economics: Consultancy. Off Label Use: ICT for patients with iron overload due to blood transfusion in patients with MDS. Vieira:Novartis: Employment. Strickson:Tolley Health Economics: Consultancy. Kundishora:Novartis: Employment.

The article presents the author's perspectives on the dividing line drawn by most people in the church between evangelism and discipleship. He states that the dividing line is based on whether or not the person has created a personal decision of accepting by faith Jesus Christ as Lord and personal Savior. He mentions that distinguishing the scope of evangelism based on a point-in-time decision can really result to the false impression that the main purpose of the gospel is a conversion decision.

Background: Invasive fungal infections present a leading cause of mortality and morbidity in neutropenic patients treated for hematologic malignancies. As the diagnosis and management of invasive fungal infections is difficult, effective antifungal prophylaxis is desirable. Itraconazole is a broad spectrum antifungal agent with activity against Candida species as well as Aspergillus species, whereas fluconazole primarily targets Candida. There is no published data comparing cost-effectiveness of both antifungal agents. Objective: To asses the cost-effectiveness of itraconazole compared with (i) prophylactic fluconazole and with (ii) no prophylaxis in the prevention of invasive fungal infections in Germany, the Netherlands and the UK. Methods: A probabilistic decision model was designed to evaluate the incremental cost-effectiveness of itraconazole versus fluconazole and versus no prophylaxis (see Figure). Baseline risks for invasive fungal infections and risk reductions for itraconazole (>200mg/day) and fluconazole (400mg/day PO or 200mg/day IV) were taken from studies recently published in two meta-analyses. Costs were evaluated from the health care perspective. Drug acquisition costs for the two prophylactic regimens were calculated using 2003 prices. We estimated the increase in the length of stay as a result of an invasive infection using local or national databases and costed this using reference prices. Results: The meta-analysis revealed that itraconazole is effective in averting invasive fungal disease, in particular aspergillosis. The mean increase in the length of stay for invasive fungal infections was estimated at 9.3 days (rather similar for all 3 countries). As an illustration for our findings: in the Netherlands, itraconazole prophylaxis was expected to be cost-saving compared to fluconazole and provided limited extra costs compared to no prophylaxis at all. Cost-effectiveness was €470 per invasive infection averted for the itraconazole compared to no prophylaxis (95%-CI ranging from cost-saving to €5926 per infection averted). Other country-specific results will be presented at the conference. Discussion & Conclusions: Our study shows that itraconazole prophylaxis is effective and is clinically likely to result in cost-savings or provide an acceptable cost-effectiveness. Itraconazole should be the first choice in the prophylaxis of invasive fungal infections in neutropenic patients with hematologic malignancies, from the clinical and economic point of view. Figure Figure

Background An earlier paper published in this journal suggested that fundholding practices in Lincolnshire had managed to constrain the growth in their prescribing costs more successfully than had non-fundholders, largely on the basis of restricting the number of items prescribed per patient. At that time, insufficient data were available to explore the impact of a change in status from non-fundholding to fundholding on prescribing behaviour. Method Time-series prescribing data for the fourth-wave of Lincolnshire fundholders are analysed, and comparisons are made between this group, non-fundholders and the fundholders of the earlier waves. Results In their first year of fundholding, fourth-wave practices adopted the prescribing strategies employed previously by existing fundholders, namely, reductions in the number of items prescribed per patient and substantial increases in generic prescribing. The hypothesis that prospective fundholders inflate their prescribing budget before attaining fundholding status is not generally supported by the Lincolnshire data. Evidence is presented which suggests that the prescribing cost economies accruing to fundholding status may be short term. Conclusions With the acquisition of fundholding status, the structure of incentives facing practices changes. Our results suggest that, with respect to prescribing, practices adjust rapidly to the new incentive structure.

Background Medicines prescribed by general practitioners constitute a major item of National Health Service expenditure and evidence suggests that prescribing patterns vary considerably between practices. This study attempts to assess the impact of the introduction of fundholding on prescribing costs in one health authority Method Both time-series and cross-section data for Lincolnshire are analysed with a view to determining prescribing cost trends over time and identifying differences in characteristics which might explain why fundholding practices differ from non-fundholders in respect of prescribing costs. Results Since the introduction of fundholding, Lincolnshire fundholders have clearly emerged as the low-cost prescribes. Cost economies are accomplished by prescribing fewer items per patient across the majority of prescribing chapters. Fundholders cannot be distinguished from non-fundholders in terms of environmental characteristics, such as the composition of practice lists, although there exist several significant organizational differences between fundholders and non-fundholders, for example, the use of computers in prescribing. Conclusion In Lincolnshire, fundholders have been more successful than non-fundholders in meeting prescribing budget targets