Search

The National Institute for Health and Care Excellence (NICE) is only one of several organisations internationally that uses economic evaluation as part of decision making regarding funding and pricing of new medical technologies. However, it can be argued that NICE has developed a more prominent international profile than most in their use of economics. After 20 years of operation, it is timely to assess the extent of NICE's achievements, including the economic evaluation methods it has used and its willingness to adapt these as new evaluative approaches emerge and when NICE faces particular policy challenges. This paper considers some of the important policy and contextual developments in the UK over the last 20 years and how these may have shaped NICE's approach to economic evaluation. It then assesses key areas of NICE methods, including perspective, defining benefits, modelling and uncertainty. The paper concludes that NICE has provided important support for the development of new methods, in particular through its role in identifying priorities for methods research funding and its sponsorship of the NICE Decision Support Unit. However, potentially important developments in methods in a number of important areas have yet to be formally included in NICE's methods guidance and this should be addressed in the Institute's 2019/2020 methods review. [ABSTRACT FROM AUTHOR]

There is a growing appetite for large complex databases that integrate a range of personal, socio-demographic, health, genetic and financial information on individuals. It has been argued that 'Big Data' will provide the necessary catalyst to advance both biomedical research and health economics and outcomes research. However, it is important that we do not succumb to being data rich but information poor. This paper discusses the benefits and challenges of building Big Data, analysing Big Data and making appropriate inferences in order to advance cancer care, using Cancer 2015 (a prospective, longitudinal, genomic cohort study in Victoria, Australia) as a case study. Cancer 2015 has been linked to State and Commonwealth reimbursement databases that have known limitations. This partly reflects the funding arrangements in Australia, a country with both public and private provision, including public funding of private healthcare, and partly the legislative frameworks that govern data linkage. Additionally, linkage is not without time delays and, as such, achieving a contemporaneous database is challenging. Despite these limitations, there is clear value in using linked data and creating Big Data. This paper describes the linked Cancer 2015 dataset, discusses estimation issues given the nature of the data and presents panel regression results that allow us to make possible inferences regarding which patient, disease, genomic and treatment characteristics explain variation in health expenditure. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of women at risk of pre-eclampsia could enhance appropriate application of antenatal care, management and treatment. Very little is known about the cost effectiveness of these and other tests for pre-eclampsia, mainly because there is no clear treatment path. The aim of this study was to provide a comprehensive overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia.Methods: We searched three electronic databases (PubMed, EMBASE and the Cochrane Library) for studies on screening, diagnosis, treatment or prevention of pre-eclampsia, published between 1994 and 2014. Only full papers written in English containing complete economic assessments in pre-eclampsia were included.Results: From an initial total of 138 references, six papers fulfilled the inclusion criteria. Three studies were on the cost effectiveness of treatment of pre-eclampsia, two of which evaluated magnesium sulphate for prevention of seizures and the third evaluated the cost effectiveness of induction of labour versus expectant monitoring. The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term pre-eclampsia was more cost effective than expectant monitoring. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia.Discussion: This study is the first to provide a comprehensive overview on the economic aspects of pre-eclampsia in its broadest sense, ranging from screening to treatment options. The main limitation of the present study lies in the variety of topics in combination with the limited number of papers that could be included; this restricted the comparisons that could be made. In conclusion, novel biomarkers in screening for and diagnosing pre-eclampsia show promise, but their accuracy is a major driver of cost effectiveness, as is prevalence. Universal screening for pre-eclampsia, using a biomarker, will be feasible only when accuracy is significantly increased. [ABSTRACT FROM AUTHOR]

The objective of the paper is to assess the cost-effectiveness of targeted respiratory syncytial virus (RSV) prophylaxis based on a validated prediction rule with 1-year time horizon in moderately preterm infants compared to no prophylaxis. Data on health care consumption were derived from a randomised clinical trial on wheeze reduction following RSV prophylaxis and a large birth cohort study on risk prediction of RSV hospitalisation. We calculated the incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no prophylaxis per quality-adjusted life year (QALYs) using a societal perspective, including medical and parental costs and effects. Costs and health outcomes were modelled in a decision tree analysis with sensitivity analyses. Targeted RSV prophylaxis in infants with a first-year RSV hospitalisation risk of > 10% resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional cost of €472 compared to no prophylaxis (ICER €214,748/QALY). The ICER falls below a threshold of €80,000 per QALY when RSV prophylaxis cost would be lowered from €928 (baseline) to €406 per unit. At a unit cost of €97, RSV prophylaxis would be cost saving.Conclusions: Targeted RSV prophylaxis is not cost-effective in reducing RSV burden of disease in moderately preterm infants, but it can become cost-effective if lower priced biosimilar palivizumab or a vaccine would be available. [ABSTRACT FROM AUTHOR]

Background: The techniques of laparoscopic liver resection (LLR) have developed rapidly in selected centers, while global adoption of this approach has been cautious. The costs of LLR compared to open resection (OLR) are considered an important metric in evaluating this approach and may be a barrier to adoption in some centers.Methods: To formulate a consensus statement using the Zurich-Danish consensus model to the question of "What are the comparative outcomes of cost for LLR and OLR, minor and major?" a systematic search of the literature was conducted. Results were presented to the jury in September 2014 and updated in August 30, 2015. Adjustments for currency conversions and inflation were not performed due to limitations in available data.Results: Thirty-four studies were reviewed, and 11 relevant papers were selected for inclusion. No randomized control studies were found. Five studies were case-matched comparisons, while the remaining studies were retrospective reviews. The number of patients in each study ranged from 28 to 74, and the cumulative number of patients was 643 comparing 350 OLR to 293 LLR. Overall median hospital stay was lower for LLR at 4.6 versus 7.4 days. This remained valid when only the case-matched studies were analyzed, 4.6 (n = 178) versus 6.6 days (n = 266). The median overall total costs were 16.3 % lower (range 0 to -22 %) for LLR compared to OLR. This remained valid in the subgroup analysis of the case-matched studies, with a median 17.4 % lower costs for the LLR. Median OR costs were 3 % higher for LLR (range -9 to 40 %) but 32.9 % lower for hospital ward costs (range 0 to -60 %) when compared to OLR.Conclusions: Currently, the published literature indicates that overall hospital costs are less for LLR when compared to OLR (Level of evidence 3a and 3b). This evidence is strongest for minor hepatic resections. The decreased cost is based on savings in hospital ward costs and likely related to a significantly shorter hospital stay for LLR. [ABSTRACT FROM AUTHOR]

Purpose: In a randomised controlled trial, patients were offered financial incentives to improve their adherence to anti-psychotic maintenance medication. Compared to a control group without the incentives, they had an improved adherence and also better subjective quality of life (SQOL) after 1 year. This paper explores the question as to whether this improvement in SQOL was associated with the amount of money received or with the improved adherence itself.Method: A secondary analysis was performed using data of the experimental group in the trial. Adherence was assessed as the percentage of all prescribed long-acting anti-psychotic injections that were taken by the patient. In regression models, we tested whether changes in medication adherence and/or the amount of incentives received over the 12-month period was associated with SQOL, as rated on the DIALOG scale.Results: Adherence changed from 68.49 % at baseline to 88.23 % (mean difference in adherence = 19.59 %, SD = 17.52 %). The total amount of incentives received within the 1-year study period varied between £75 and £735, depending on the treatment cycle and the number of long-acting injections taken. Improvement in adherence was found to be a significant predictor of better subjective quality of life (β = 0.014, 95 % CI 0.003-0.025, p = 0.014), whilst the amount of incentives received was not (β = 0.0002, 95 % CI -0.002 to 0.002, p = 0.818).Conclusion: Improved medication adherence is associated with a more favourable SQOL. This underlines the clinical relevance of improved adherence in response to financial incentives in this patient group. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. As it is detected incidentally through the evaluation of liver function tests or at the time of blood donor testing, it is usually clinically silent until the advanced stages of liver disease have occurred, when treatment is less effective and shortages of donor liver organs limit the therapeutic options. Combination therapy with ribavirin and pegylated interferon has resulted in sustained viral negative response rates of 54–61%. Because treatment is expensive and not uniformly effective, and because not all chronically infected patients will develop complications, concerns have arisen regarding the cost effectiveness of combination therapy.This paper reviews the public health and individual implications of HCV infections. Because of the latency of infection, numerous country-specific population analyses suggest that HCV will cause an increasing number of liver-related deaths over the next 10 years, despite the dramatic drop in incidence over the past 10–15 years. These deaths will be related to prevalent HCV infection from transfusion and injection drug use prior to identification of the virus and availability of screening tests in the late 1980s and early 1990s. HCV can reduce life expectancy and impair quality of life, yet not all patients will develop progressive liver disease, and antiviral treatment may have associated adverse effects.Finally, to assess the value of antiviral drugs for HCV infection, this paper reviews studies examining the costs of antiviral drugs and of the disease itself along with response to antiviral therapy and the cost effectiveness of antiviral therapy. Although antiviral therapy appears to be expensive, when also considering the likelihood of sustained viral response to therapy, and the cost savings, quality-of-life improvement and prolongation of life expectancy from the prevention of HCV complications, antiviral treatment for HCV appears to be cost effective when compared with other well accepted medical interventions. [ABSTRACT FROM AUTHOR]

Purpose: The Strengths and Difficulties Questionnaire (SDQ) is a behavioural screening tool for children. The SDQ is increasingly used as the primary outcome measure in population health interventions involving children, but it is not preference based; therefore, its role in allocative economic evaluation is limited. The Child Health Utility 9D (CHU9D) is a generic preference-based health-related quality of-life measure. This study investigates the applicability of the SDQ outcome measure for use in economic evaluations and examines its relationship with the CHU9D by testing previously published mapping algorithms. The aim of the paper is to explore the feasibility of using the SDQ within economic evaluations of school-based population health interventions.Methods: Data were available from children participating in a cluster randomised controlled trial of the school-based roots of empathy programme in Northern Ireland. Utility was calculated using the original and alternative CHU9D tariffs along with two SDQ mapping algorithms. t tests were performed for pairwise differences in utility values from the preference-based tariffs and mapping algorithms.Results: Mean (standard deviation) SDQ total difficulties and prosocial scores were 12 (3.2) and 8.3 (2.1). Utility values obtained from the original tariff, alternative tariff, and mapping algorithms using five and three SDQ subscales were 0.84 (0.11), 0.80 (0.13), 0.84 (0.05), and 0.83 (0.04), respectively. Each method for calculating utility produced statistically significantly different values except the original tariff and five SDQ subscale algorithm.Conclusion: Initial evidence suggests the SDQ and CHU9D are related in some of their measurement properties. The mapping algorithm using five SDQ subscales was found to be optimal in predicting mean child health utility. Future research valuing changes in the SDQ scores would contribute to this research. [ABSTRACT FROM AUTHOR]

Many healthcare organizations are now making good use of electronic health record (EHR) systems to record clinical information about their patients and the details of their healthcare. Electronic data in EHRs is generated by people engaged in complex processes within complex environments, and their human input, albeit shaped by computer systems, is compromised by many human factors. These data are potentially valuable to health economists and outcomes researchers but are sufficiently large and complex enough to be considered part of the new frontier of 'big data'. This paper describes emerging methods that draw together data mining, process modelling, activity-based costing and dynamic simulation models. Our research infrastructure includes safe links to Leeds hospital's EHRs with 3 million secondary and tertiary care patients. We created a multidisciplinary team of health economists, clinical specialists, and data and computer scientists, and developed a dynamic simulation tool called NETIMIS (Network Tools for Intervention Modelling with Intelligent Simulation; http://www.netimis.com ) suitable for visualization of both human-designed and data-mined processes which can then be used for 'what-if' analysis by stakeholders interested in costing, designing and evaluating healthcare interventions. We present two examples of model development to illustrate how dynamic simulation can be informed by big data from an EHR. We found the tool provided a focal point for multidisciplinary team work to help them iteratively and collaboratively 'deep dive' into big data. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and the NICE's subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer's decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack of response made long-term effectiveness estimates unreliable, e.g. overall survival (OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model, which increased the ICER to £68,125 per quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend lenalidomide as a cost-effective treatment. Subsequently, the manufacturer submitted a Patient Access Scheme (PAS) that provided lenalidomide free of charge for patients who remained on treatment after 26 cycles. This PAS improved the ICER to £25,300, although the AC considered the proportion of patients who received treatment beyond 26 cycles, and hence the ICER, to be uncertain. Nevertheless, the AC accepted a commitment from the manufacturer to publish, once available, data on the proportion of patients eligible for the PAS, and believed this provided reassurance that lenalidomide was a cost-effective treatment for low- or intermediate-1-risk MDS patients. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE) invited Dendreon, the company manufacturing sipuleucel-T, to submit evidence for the clinical and cost effectiveness of sipuleucel-T for asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer patients in whom chemotherapy is not yet clinically indicated, as part of NICE's single technology appraisal process. The comparator was abiraterone acetate (AA) or best supportive care (BSC). The School of Health and Related Research at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper describes the company submission (CS), ERG review, and subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost-effectiveness evidence of sipuleucel-T based upon the CS. Clinical-effectiveness data relevant to the decision problem were taken from three randomised controlled trials (RCTs) of sipuleucel-T and a placebo (PBO) comparator of antigen-presenting cells (APC) being re-infused (APC-PBO) (D9901, D9902A and D9902B), and one RCT (COU-AA-302) of AA plus prednisone vs. PBO plus prednisone. Two trials reported a significant advantage for sipuleucel-T in median overall survival compared with APC-PBO: for trial D9901, an adjusted hazard ratio (HR) 0.47; (95 % confidence interval [CI] 0.29, 0.76) p < 0.002; for D9902B, adjusted HR 0.78 (95 % CI 0.61, 0.98) p = 0.03. There was no significant difference between groups in D9902A, unadjusted HR 0.79 (95 % CI 0.48, 1.28) p = 0.331. Sipuleucel-T and APC-PBO groups did not differ significantly in time to disease progression, in any of the three RCTs. Most adverse events developed within 1 day of the infusion, and resolved within 2 days. The CS included an indirect comparison of sipuleucel-T (D9902B) and AA plus prednisone (COU-AA-302). As trials differed in prior use of chemotherapy, an analysis of only chemotherapy-naïve patients was included, in which the overall survival for sipuleucel-T and AA was not significantly different, HR 0.94 (95 % CI 0.69, 1.28) p = 0.699. The ERG had several concerns regarding the data and assumptions incorporated within the company's cost-effectiveness analyses and conducted exploratory analyses to quantify the impact of making alternative assumptions or using alternative data inputs. The deterministic incremental cost-effectiveness ratio (ICER) for sipuleucel-T vs. BSC when using the ERG's preferred data and assumptions was £ 108,585 per quality-adjusted life-year (QALY) in the whole licensed population and £ 61,204/QALY in the subgroup with low prostate-specific antigen at baseline. The ERG also conducted an incremental analysis comparing sipuleucel-T with both AA and BSC in the chemotherapy-naïve subgroup. Sipuleucel-T had a deterministic ICER of £ 111,682/QALY in this subgroup, when using the ERG's preferred assumptions, and AA was extendedly dominated. The ERG also concluded that estimates of costs and benefits for AA should be interpreted with caution given the limitations of the indirect comparison. The AC noted that the ICER for sipuleucel-T was well above the range usually considered cost effective, and did not recommend sipuleucel-T for the treatment of asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: The Swedish Dental and Pharmaceutical Benefits Agency (TLV) is the government body responsible for deciding whether outpatient drugs are to be included in the pharmaceutical benefits scheme. This paper analyzes the impact of cost effectiveness and severity of disease on reimbursement decisions for new pharmaceuticals.Methods: Data has been extracted from all decisions made by the TLV between 2005 and 2011. Cost effectiveness is measured as the cost per quality-adjusted life-year (QALY) gained, whereas disease severity is a binary variable (severe-not severe). In total, the dataset consists of 102 decisions, with 86 approved and 16 declined reimbursements.Results: The lowest cost per QALY of declined reimbursements is Swedish kronor (SEK) 700,000 (€ 79,100), while the highest cost per QALY of approved reimbursements is SEK1,220,000 (€ 135,600). At a cost per QALY of SEK702,000 Swedish kronor (non-severe diseases) and SEK988,000 (severe diseases), the likelihood of approval is estimated to be 50/50 (€ 79,400 and € 111,700).Conclusions: The TLV places substantial weight on both the cost effectiveness and the severity of disease in reimbursement decisions, and the implied willingness to pay for a QALY is higher than the often cited 'rule of thumb' in Swedish policy debates. [ABSTRACT FROM AUTHOR]

This paper outlines recent advances in the methods of cost-benefit analysis (CBA). Economic evaluations in healthcare can be criticised for, amongst other things, the inappropriate use of incremental cost-effectiveness ratios and the reporting of benefits in terms of cost savings, such as treatment costs averted. Many such economic evaluations are, according to the ‘scientific’ definition, CBAs. The ‘balance-sheet’ (or opportunity cost) approach is a form of CBA which can be used to identify who bears the costs and who reaps the benefits from any change. Whilst the next stage in a CBA, as defined in health economics, would require that all costs and benefits be valued in monetary terms, the balance-sheet approach, however, advocates that available monetary values can be augmented by other measures of cost and benefit. As such, this approach, which has a theoretical basis, is proposed as a practical prescription for CBA and highlights the notion that unquantified benefits are important and can be included within CBAs even when monetarisation is not possible. Recent methodological developments in monetary valuation for use in CBA are the development of the technique of willingness to pay, the use of conjoint analysis (CA) to elicit willingness-to-pay (WTP) values and advances in the debate on the inclusion of production gains in CBAs. Whilst acknowledging that there have been developments in each of these areas, it is claimed there has also been progress in using CBA as a framework for evaluation, as reflected by the balance-sheet approach. The paper concludes by stating that almost all types of economic evaluation have an element of the ‘cost-benefit’ approach in them. The important issue is to focus on the policy question to be addressed and to outline the relevant costs and benefits in a manner which assists the evaluation of welfare changes resulting from changes in healthcare delivery. The focus should not be on moulding a question to fit a hybrid definition of an analytical technique. [ABSTRACT FROM AUTHOR]

Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are licensed. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on the introduction of HPV vaccines in central Europe. Eight countries currently have medical representatives on CEVAG: the Czech Republic, Estonia, Hungary, Lithuania, Poland, Romania, Slovakia and Turkey. By raising awareness and disseminating information, CEVAG aims to promote the efficient and safe use of vaccines to prevent, control and if possible eliminate infectious diseases. In January 2008, the European Centre for Disease Prevention and Control published a report entitled Guidance for the Introduction of HPV Vaccines in EU Countries. Members of CEVAG have taken the information relevant to their countries from this report and, with consideration of local issues, produced these guidance recommendations for the introduction of HPV vaccines in the CEVAG region, which may be adapted for use in individual countries. [ABSTRACT FROM AUTHOR]

In many countries, including Thailand, there is an increasing impetus to use economic evaluation to allow more explicit and transparent healthcare priority setting. However, an important question for policy makers in low- and middle-income countries is whether it is appropriate and feasible to introduce economic evaluation data into healthcare priority-setting decisions. In addition to ethical, social and political issues, information supply challenges need to be addressed. This paper systematically reviewed the literature on economic evaluation of health technology in Thailand published between 1982 and 2005. Its aim was to analyse the quantity, quality and targeting of economic evaluation studies that can provide a framework for those conducting similar reviews in other settings. The review revealed that, although the number of publications reporting economic evaluations has increased significantly in recent years, serious attention needs to be given to the quality of reporting and analysis. Furthermore, there is an absence of economic evaluation publications for 15 of the top 20 major health problems in Thailand, indicating a poor distribution of research resources towards the determination of cost-effective interventions for diminishing the disease burden of certain major health problems. If economic evaluation is only useful for policy makers when performed correctly and reported accurately, these findings depict information barriers to using economic evaluation to assist health decision-making processes in Thailand. [ABSTRACT FROM AUTHOR]

Objectives: In Australia, no therapeutic agents were subsidised for the treatment of idiopathic pulmonary artery hypertension (iPAH), a rare progressive and severe disease with short life expectancy, until 1 March 2004, when bosentan (a dual endothelin receptor antagonist of high cost) was listed on the Pharmaceutical Benefits Scheme (PBS). Bosentan, in addition to conventional therapy, has been shown to slow iPAH progression and improve clinical and haemodynamic status and symptomatology, compared with placebo and conventional therapy. The objective of this paper is to describe the process of the Australian Pharmaceutical Benefits Scheme listing for bosentan (Tracleer), which included a health economic model assessing the cost effectiveness of bosentan from a healthcare payer perspective, and a risk-sharing arrangement based on the establishment of a patient registry.Methods: The health economic model predicted the cost, hospitalisation and mortality rates of a population of iPAH patients treated with either the conventional therapy regimen used in Australia or bosentan plus the conventional therapy regimen. The model was implemented as a first-order Monte Carlo simulation with mortality modelled directly as the main clinical outcome. The impacts of proposed continuation criteria, restricting the ongoing use of the drug, were evaluated. Costs and outcomes were discounted at 5% and a sensitivity analysis examined the robustness of the key assumptions.Results: The model predicted that after 5, 10 and 15 years, the difference in average cumulative costs between bosentan plus conventional therapy and conventional therapy alone would be 116,929 Australian dollars (A dollars), A181,808 dollars and A216,331 dollars for each patient, respectively. There would be an associated increase in average life expectancy of 1.39, 2.93 and 3.87 years at 5, 10 and 15 years, respectively, with an incremental cost-effectiveness ratio at 15 years of A55,927 dollars for each life-year gained. Removing the continuation criteria from the model increased the incremental cost-effectiveness ratio to A62,267 dollars (1996-2002 values).Conclusions: Economic modelling based on improved survival suggests bosentan to be a potentially cost-effective treatment for iPAH. However, the structure of the model and its inputs should be reviewed and updated as more data become available. [ABSTRACT FROM AUTHOR]

A number of recent findings from the literature imply that the value of a QALY varies depending on the concentration or dispersion of that QALY over treated individuals. Given that funding decisions are currently made under either the assumption of distributive-neutrality or some combination of explicit decision criteria and implicit adjustment for distributional concerns, it is likely that substantial social welfare gains are available if distributional objectives could be more accurately reflected in funding decisions. This paper considers three alternative approaches to explicitly adjust for distributional concerns with regard to the concentration or dispersion of individual health gains. Including non-health arguments in the objective function by 'weighting' QALYs for distributional effects or imposing differential funding thresholds for interventions with different distributional effects might be considered first- and second-best solutions, and would likely deliver the greatest social welfare gains. However, there is some doubt that first- or second-best solutions would be: (i) feasible given current data gaps; and (ii) politically acceptable. Rather, a simple and transparent approach is suggested wherein the sponsors of interventions that deliver health gains that are of questionable 'welfare-significance' for the treated individual would be required to provide decision-makers with an estimate of willingness to pay for the QALYs in question and would only be eligible for funding in the event that the positive net present value criterion is met. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors (AIs) have been evaluated clinically in a wide range of breast cancer treatment settings. Although these agents appear to have clinical superiority, they are more expensive than the therapies (primarily tamoxifen) they have been compared with, thus economic evaluation is required to consider their incremental value to the payer. This paper reviews published economic evaluations of AIs as first-line therapy for advanced cancer, and as adjuvant therapy for early breast cancer. The evaluations in the advanced setting demonstrate a range of different modelling techniques and consider the payer's perspective in three healthcare systems. There is broad similarity in the application of standard cohort Markov modelling techniques to evaluate AIs in the early breast cancer setting, covering four separate health system perspectives. AIs appear cost effective compared with current practice. An analysis in the advanced setting suggests that letrozole may be the more cost-effective AI. No direct comparisons of alternative AIs in the adjuvant setting are reported, although indirect comparisons may be feasible. Future evaluations of treatment strategies over the entire course of the disease may also be needed. [ABSTRACT FROM AUTHOR]

Background: Rising public and private expenditure on antipsychotic medications is concentrated on the cost of second generation or 'atypical' medications, which are more expensive than first generation medications and make up a rapidly growing share of all antipsychotic prescriptions. Previous studies have examined whether the higher acquisition costs of atypicals are offset by other cost and/or utilisation benefits. This paper extends this literature by examining possible effects of atypicals on earnings and related measures of labour supply in a large naturalistic study with a long-term follow-up period.Methods: We analysed data on earnings and other characteristics from the Schizophrenia Care and Assessment Program (SCAP), a 3-year longitudinal study (with data collection during the years 1997-2003) of 2327 adults with schizophrenia (including schizoaffective and schizophreniform disorders) recruited from behavioural healthcare provider systems in six areas of the US. We used empirical criteria and data from the SCAP database to identify 336 patients aged < 50 years who were in the stable or 'maintenance' phase of their antipsychotic treatment during the 6 months prior to baseline. Effects of atypicals compared with typicals were estimated from Tobit regression models that included additional covariates and the baseline-dependent variable values. Regression-dependent variables were reported earnings per month, hours worked per month, days worked per month and a binary indicator of employment. To control for the effect of selection bias in choice of type of atypical, we employed an instrumental variables (IV) estimation procedure.Results: For all dependent variables, our IV Tobit regressions yielded consistently positive coefficient estimates for atypical use that were either marginally significant (p < 0.1) or significant (p < 0.05) for earnings, significant for hours and days of work and not as consistently significant for employment status. Results from these regressions imply a positive effect of atypical use on monthly earnings in the range of Dollars US 107-122. In regressions that did not control for selection bias by using IVs, coefficients for atypical use were often negative and never statistically significant.Conclusions: Our results indicate that higher drug costs of atypicals for maintenance-phase treatment are at least partially offset by higher earnings among patients. These effects represent benefits to consumers as well as savings to taxpayer-supported income transfer programmes. Future studies should seek to determine if treatment with atypicals increases patients' earnings via better control over negative symptoms and/or improved patient cognition. Both appear to be connected with employment and labour supply in patients with schizophrenia, and both may be improved through use of atypicals. [ABSTRACT FROM AUTHOR]

Objective: To estimate the cost effectiveness (from the UK NHS and personal social services perspective) of the cholinesterase inhibitors donepezil, rivastigmine and galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease. Patients had a mean age of 74 years, a mean disease duration of 1 year and a mean Alzheimer's disease assessment scale-cognitive subscale score of 24.Methods: A pharmacoeconomic model was used to predict long-term outcomes over a 5-year time horizon and to estimate the cost effectiveness of cholinesterase inhibitors for the management of Alzheimer's disease. The model structure is informed by a systematic review of the literature on the clinical and cost effectiveness of cholinesterase inhibitors and a review of the literature on the costs and outcomes associated with treatment for Alzheimer's disease. The main outcome measure used was the cost per quality-adjusted life-year (QALY) gained. All healthcare costs (excluding cholinesterase inhibitor costs) were indexed to pounds sterling (2003 values). Drug costs are 2005 values. Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results.Results: The clinical benefits on cognition from treatment with cholinesterase inhibitors resulted in an incremental cost per QALY gained ranging from 53,780 pounds sterling to 74,735 pounds sterling, over 5 years (vs usual care). Uncertainty analysis suggests that the probability of any of these treatments having an incremental cost per QALY of < 30,000 pounds sterling is < 21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression.Conclusions: Results presented in this paper suggest that the use of cholinesterase inhibitors may not be a cost-effective use of NHS resources. Guidance from the National Institute for Health and Clinical Effectiveness (NICE) in the UK on their judgements surrounding the acceptability of technologies as an effective use of resources, indicates there would need to be special reasons for accepting cholinesterase inhibitors as a cost-effective use of NHS resources. [ABSTRACT FROM AUTHOR]

The anogenital human papillomavirus (HPV) is estimated to be the most commonly occurring sexually transmitted infection in the US. Comprehensive estimates of the annual economic burden associated with the prevention and treatment of anogenital HPV-related disease in the US population are currently unavailable. The purpose of this paper is to (i) outline an analytic framework from which to estimate the annual economic burden of preventing and treating anogenital HPV-related disease in the US; (ii) review available US literature concerning the annual economic burden of HPV; and (iii) highlight gaps in current knowledge where further study is particularly warranted. Among eight US studies identified that describe the annual economic burden pertaining to one or more aspects of anogenital HPV-related disease, three met the review eligibility criteria (published between 1990 and 2004, examined multiple facets of annual anogenital HPV-related economic burden, and clearly articulated the data and methods used in the estimation process). All costs were adjusted to 2004 US dollars. Estimates of the annual direct medical costs associated with cervical cancer were comparable across studies (range 300-400 million US dollars). In contrast, there was a wide range across studies for estimates of the annual direct medical costs associated with cervical intraepithelial neoplasia (range 700 million US dollars-2.3 billion US dollars). Only one study reported direct medical costs for anogenital warts (200 million US dollars) and routine cervical cancer screening (2.3 billion US dollars). No studies examined direct medical costs attributable to HPV-related anal, penile, vaginal or vulvar cancers, or the work and productivity losses resulting from time spent receiving medical care, morbidity or mortality. Current economic burden estimates would suggest annual direct medical costs associated with the prevention and treatment of anogenital warts and cervical HPV-related disease of at least 4 billion US dollars. This figure would likely rise to at least 5 billion US dollars per year if direct medical costs associated with other disease entities caused by the sexual transmission of HPV were included, with further additions to the economic burden totalling in the billions of dollars if work and productivity losses were incorporated, a research priority for future studies. [ABSTRACT FROM AUTHOR]

The economic burden of influenza-related illness has been estimated to be 71.3-166 billion US dollars in the US, the majority of which is attributable to indirect costs as a result of lost productivity. There are currently four antiviral drugs available for the treatment of influenza: two ion channel blockers, amantadine and rimantadine; and two neuraminidase inhibitors, zanamivir and oseltamivir. The objective of this paper was to review the studies evaluating the cost effectiveness of currently available antiviral treatment and prophylaxis management strategies for influenza. Published studies that reported both costs and effectiveness of influenza management were extracted using MEDLINE, pre-MEDLINE and EMBASE. To facilitate a broad comparison, all costs were inflated to 2003 US dollars. Fifteen studies met the inclusion criteria of the review, with 14 analyses based on decision-analytic modelling and one economic analysis performed alongside a clinical trial. Management strategies included antiviral influenza prophylaxis or vaccination, empiric treatment of suspected disease, or antiviral treatment following rapid influenza testing. Study populations included healthy adults, adults at risk of influenza-related adverse outcomes, institutionalised and non-institutionalised elderly, and children. The comparator in all studies was standard care (i.e. over-the-counter medications only), and analyses were carried out from both the societal and payer perspectives. The only dominant strategy relative to standard care was vaccination of the institutionalised elderly. All other strategies in all populations were both more costly and more effective than standard care. Depending on the population and the perspective, the incremental cost-effectiveness ratios (ICERs) for antiviral treatment strategies ranged from 5000 US dollars/QALY for amantadine in test-and-treat studies to >400,000 US dollars/QALY for zanamivir or oseltamivir treatment in children. Sensitivity analysis in all studies consistently reported a strong influence of the population prevalence or diagnostic accuracy of influenza on the cost effectiveness of all strategies. Baseline influenza prevalence varied widely between studies, ranging from 15% to 68%. There was also a wide variation in the assumption about the disutility of influenza (ranging from -0.137 to -0.983 for the elderly requiring hospitalisation), which also impacted the cost effectiveness. Given the variation in the ICERs of antiviral treatment and prophylaxis, the uncertainty around many model parameters, and the dynamic nature of influenza from year to year, one can only conclude that antiviral treatment or prophylaxis for influenza is likely to be more cost effective in specific populations at specific times during the influenza season, and during influenza seasons when the population prevalence reaches epidemic levels or there is mismatch between the vaccine and the circulating virus. [ABSTRACT FROM AUTHOR]

Objectives: This study provides the results of a cost-effectiveness analysis of levetiracetam as an adjunctive treatment for refractory epilepsy from the Canadian Ministry of Health perspective. The main objective is to estimate the expected cost-effectiveness ratio expressed as the incremental cost per seizure-free day gained when using levetiracetam. In addition, this study examines the potential savings that might result by reducing the number of surgical evaluations and surgery when using levetiracetam.Methods: A 1-year dose escalation decision-tree model comparing levetiracetam plus standard therapy with standard therapy alone was designed in order to combine probability, resource use and unit cost data (1999 Canadian dollars [$Can]). The short-term outcomes were derived from three phase III randomised, double-blind, placebo-controlled trials performed in 904 patients, aged 16-70 years, with at least 1 year history of epilepsy, two to four partial seizures per month, and receiving a maximum of two classic antiepileptic drugs.Results: The average gain in seizure-free days attributed to levetiracetam was 19 days per patient per year and the incremental cost-effectiveness ratio (ICER) for levetiracetam add-on in the base-case scenario was $Can80.7 per seizure-free day gained per patient per year. Moreover, when surgical investigation and surgery are considered in the model, the use of levetiracetam may be dominant, with substantial savings to the overall healthcare budget. All univariate sensitivity analyses show that the model was robust to the assumptions made.Conclusions: The economic analysis presented in this paper suggests, given a wide range of assumptions, that the increased cost of treating patients (with refractory epilepsy) with levetiracetam may be partially offset by a reduction in other direct medical costs (from the Canadian Ministry of Health perspective), as a consequence of an increase in the number of seizure-free days. Moreover, potential cost savings may be foreseen when it is assumed that levetiracetam may reduce the number of candidates for surgical evaluation and surgery through a reduction of seizure frequency. [ABSTRACT FROM AUTHOR]

There is a lack of emphasis on health-related QOL (HR-QOL) changes associated with acute exacerbation of chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL instruments to evaluate acute exacerbation of CB or COPD, so as to form recommendations for future research. A literature search of papers published between 1966 and July 2003 identified more than 300 articles that used acute exacerbation of CB or COPD as the search term. However, only 21 of these studies employed HR-QOL measures as predictors of outcome or in the assessment of the impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of HR-QOL measures were used, both generic and disease specific. The disease-specific St George’s Respiratory Questionnaire (SGRQ), devised for patients with stable CB and with a recall period of 1–12 months, was the most widely used measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease-specific measures used. Most measures, both generic and disease specific, performed adequately when used during acute exacerbation of CB or COPD and indicated poor HR-QOL during acute exacerbation, which improved on resolution of the exacerbation. Relationships were evident between HR-QOL during an acute exacerbation and various outcomes, including post-exacerbation functional status, hospital re- admission for acute exacerbation or COPD, and mortality. There is a need for studies of treatments for acute exacerbation of CB or COPD to include an appropriate HR-QOL instrument to aid in the stratification of patients so as to target the right treatment to the right patient group. While a new instrument could be developed to measure HR-QOL during acute exacerbation of CB or COPD, currently available disease-specific measures such as the CRQ and the SGRQ appear to be acceptable to patients during acute exacerbation. However, the recall period of the SGRQ symptoms component should be shortened to make it more appropriate for use during acute exacerbation. [ABSTRACT FROM AUTHOR]

To date, decision trees and Markov models have been the most common methods used in pharmacoeconomic evaluations. Both of these techniques lack the flexibility required to appropriately represent clinical reality. In this paper an alternative, more natural, way to model clinical reality--discrete event simulation--is presented and its application is illustrated with a real world example.A discrete event simulation represents the course of disease very naturally, with few restrictions. Neither mutually exclusive branches nor states are required, nor is a fixed cycle. All relevant aspects can be incorporated explicitly and efficiently. Flexibility in handling perspectives and carrying out sensitivity analyses, including structural variations, is incorporated and the entire model can be presented very transparently. The main limitations are imposed by lack of data to fit realistic models. Discrete event simulation, though rarely employed in pharmacoeconomics today, should be strongly considered when carrying out economic evaluations, particularly those aimed at informing policy makers and at estimating the budget impact of a pharmaceutical intervention. [ABSTRACT FROM AUTHOR]

This paper presents the first full micro costing of a commonly used cancer genetic counselling and testing protocol used in the UK. Costs were estimated for the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a questionnaire to all staff, conducting an audit of clinic rooms and equipment and obtaining gross unit costs from the finance department. A total of 22 distinct event pathways were identified for patients at risk of developing breast, ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were pound sterling 97- pound sterling 151 for patients at moderate risk, pound sterling 975- pound sterling 3072 for patients at high risk of developing colorectal cancer and pound sterling 675- pound sterling 2909 for patients at high risk of developing breast or ovarian cancer. The most expensive element of cancer genetic services was labour. Labour costs were dependent upon the amount of labour, staff grade, number of counsellors used and the proportion of staff time devoted to indirect patient contact. With the growing demand for cancer genetic services and the growing number of national and regional cancer genetic centers, there is a need for the different protocols being used to be thoroughly evaluated in terms of costs and outcomes. [ABSTRACT FROM AUTHOR]

In schizophrenia, modelling techniques may be needed to estimate the long-term costs and effects of new interventions. However, it seems that a simple direct link between symptoms and costs does not exist. Decisions about whether a patient will be hospitalized or admitted to a different healthcare setting are based not only on symptoms but also on social and environmental factors. This paper describes the development of a model to assess the dependencies between a broad range of parameters in the treatment of schizophrenia. In particular, the model attempts to incorporate social and environmental factors into the decision-making process for the prescription of new drugs to patients. The model was used to analyse the potential benefits of improving compliance with medication by 20% in patients in the UK. A discrete event simulation (DES) model was developed, to describe a cohort of schizophrenia patients with multiple psychotic episodes. The model takes into account the patient's sex, disease severity, potential risk of harm to self and society, and social and environmental factors. Other variables that change over time include the number of psychiatric consultations, the presence of psychotic episodes, symptoms, treatments, compliance, side-effects, the lack of ability to take care of him/herself, care setting and risk of harm. Outcomes are costs, psychotic episodes and symptoms. Univariate and multivariate sensitivity analyses were performed. Direct medical costs were considered (year of costing 2002), applying a 6.0% discount rate for costs and a 1.5% discount rate for outcome. The timeframe of the model is 5 years. When 50% of the decisions about the patient care setting are based on symptoms, a 20% increase in compliance was estimated to save 16,147 pounds and to avoid 0.55 psychotic episodes per patient over 5 years. Sensitivity analysis showed that the costs savings associated with increased compliance are robust over a range of variations in parameters. DES offers a flexible structure for modelling a disease, taking into account how a patient's history affects the course of the disease over time. This approach is particularly pertinent to schizophrenia, in which treatment decisions are complex. The model shows that better compliance increases the time between relapses, decreases the symptom score, and reduces the requirement for treatment in an intensive patient care setting, leading to cost savings. The extent of the cost savings depends on the relative importance of symptoms and of social and environmental factors in these decisions. [ABSTRACT FROM AUTHOR]

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point 'relative effectiveness scale', which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts. [ABSTRACT FROM AUTHOR]

The resources available for healthcare are limited compared with demand, if not need, and all healthcare systems, regardless of their financing and organisation, employ mechanisms to ration or prioritise finite healthcare resources. This paper reviews alternative approaches that can be used to allocate healthcare resources. It discusses the problems encountered when allocating healthcare resources according to free market principles. It then proceeds to discuss the advantages and disadvantages of alternative resource allocation approaches that can be applied to public health systems. These include: (i) approaches based on the concept of meeting the needs of the population to maximising its capacity to benefit from interventions; (ii) economic approaches that identify the most efficient allocation of resources with the view of maximising health benefits or other measures of social welfare; (iii) approaches that seek to ration healthcare by age; and (iv) approaches that resolve resource allocation disputes through debate and bargaining. At present, there appears to be no consensus about the relative importance of the potentially conflicting principles that can be used to guide resource allocation decisions. It is concluded that whatever shape tomorrow's health service takes, the requirement to make equitable and efficient use of finite healthcare resources will remain. [ABSTRACT FROM AUTHOR]

The introduction of expensive disease-modifying agents for the treatment of multiple sclerosis (MS) has created the potential for patients with MS to become higher contributors to healthcare spending. In an attempt to make formulary and reimbursement choices for these agents, decision-makers may look to the literature for guidance. This critical review attempts to decipher a consistent message from the available economic literature regarding the relationship between disease severity and cost in MS. In the 2 studies that have examined MS disease severity, a positive correlation with total (direct and indirect) cost, indirect cost and some, if not all, components of direct cost was reported. In studies taking the societal perspective, the majority of total costs were indirect. This paper documents the high burden of MS on society and serves to guide the decision-maker in interpreting the MS economic literature such that this information can be optimally utilised to make informed resource allocation decisions. [ABSTRACT FROM AUTHOR]

This paper reviews evidence that behavioral family interventions are effective at improving child-rearing in distressed families and families with children exhibiting disruptive behavior. Essential therapeutic strategies offered within a collaborative therapeutic process are identified. Exemplary materials for parents and clinicians are identified. Differences between behavioral family interventions and two popular press parenting approaches are highlighted, including the lack of empirical support for these widely used programs and the advice they offer which runs counter to behavioral approaches. Recommendations are offered for combining behavioral family interventions with other empirically supported approaches, promoting more widespread use of empirically supported treatments, such as behavioral family interventions, and the need for a public health perspective on family functioning, involving collaboration among clinicians, policy makers, and researchers. [ABSTRACT FROM AUTHOR]