Age, time living with diagnosed HIV infection, and self-rated health.

OBJECTIVES: An increasing proportion of people living with HIV are older adults, who may require specialized care. Adverse physical and psychological effects of HIV infection may be greatest among older people or those who have lived longer with HIV. METHODS: The ASTRA study is a cross-sectional questionnaire study of 3258 HIV-diagnosed adults (2248 men who have sex with men, 373 heterosexual men and 637 women) recruited from UK clinics in 2011-2012. Associations of age group with physical symptom distress (significant distress for at least one of 26 symptoms), depression and anxiety symptoms (scores ≥ 10 on PHQ-9 and GAD-7, respectively), and health-related functional problems (problems on at least one of three domains of the Euroqol 5D-3L)) were assessed, adjusting for time with diagnosed HIV infection, gender/sexual orientation and ethnicity. RESULTS: The age distribution of participants was: < 30 years, 5%; 30-39 years, 23%; 40-49 years, 43%; 50-59 years, 22%; and ≥ 60 years, 7%. Overall prevalences were: physical symptom distress, 56%; depression symptoms, 27%; anxiety symptoms, 22%; functional problems, 38%. No trend was found in the prevalence of physical symptom distress with age [adjusted odds ratio (OR) for trend across age groups, 0.96; 95% confidence interval (CI) 0.89, 1.04; P = 0.36]. The prevalence of depression and anxiety symptoms decreased with age [adjusted OR 0.86 (95% CI 0.79, 0.94; P = 0.001) and adjusted OR 0.85 (95% CI 0.77, 0.94; P = 0.001), respectively], while that of functional problems increased (adjusted OR 1.28; 95% CI 1.17, 1.39; P < 0.001). In contrast, a longer time with diagnosed HIV infection was strongly and independently associated with a higher prevalence of symptom distress, depression symptoms, anxiety symptoms, and functional problems (P < 0.001 for trends, adjusted analysis). CONCLUSIONS: Among people living with HIV, although health-related functional problems were more common with older age, physical symptom distress was not, and mental health was more favourable. These results suggest that a longer time with diagnosed HIV infection, rather than age, is the dominating factor contributing to psychological morbidity and lower quality of life.

A discrete choice experiment to assess people living with HIV's (PLWHIV's) preferences for GP or HIV clinic appointments.

OBJECTIVES: To understand which aspects of general practitioner (GP) and HIV clinic appointments people living with HIV (PLWHIV) most value when seeking advice for new health problems. METHODS: A discrete choice experiment using a convenience sample of people diagnosed with HIV. Participants were recruited from 14 general HIV clinics in the South East of England between December 2014 and April 2015. ORs were calculated using conditional logit (CLOGIT) and latent class models (LCMs). RESULTS: A total of 1106 questionnaires were returned. Most participants were male (85%), white (74%) and were men who have sex with men (69%). The CLOGIT analysis showed people particularly valued shorter appointment waiting times (ORs between 1.52 and 3.62, p<0.001 in all instances). The LCM analysis showed there were two distinct classes, with 59% and 41% of respondents likely to be in each. The first class generally preferred GP to HIV clinic appointments and particularly valued 'being seen quickly'. For example, they had strong preferences for shorter appointment waiting times and longer GP opening hours. People in the second class also valued shorter waiting times, but they had a strong general preference for HIV clinic rather than GP appointments. CONCLUSIONS: PLWHIV value many aspects of care for new health problems, particularly short appointment waiting times. However, they appear split in their general willingness to engage with GPs.

Which aspects of health care are most valued by people living with HIV in high-income countries? A systematic review.

BACKGROUND: Increasing numbers of people with HIV are living into older age and experiencing comorbidities. The development of new models of care to meet the needs of this population is now a priority. It is important that the views and preferences of patients inform the development of services in order to maintain high levels of patient satisfaction and engagement. The aim of this systematic review was to determine which aspects of healthcare are particularly valued by people living with HIV. METHODS: We searched electronic databases and reference lists of relevant articles. The search strategy was developed to identify articles reporting on HIV positive patients' perceptions, evaluations or experiences of healthcare services and factors associated with satisfaction with care. Peer-reviewed papers and conference abstracts were included if the study reported on aspects of health care that were valued by people living with HIV, data were collected during the era of combination therapy (from 1996 onwards), and the paper was published in English. A thematic approach to data synthesis was used. RESULTS: Twenty-three studies met the inclusion criteria. Studies used both qualitative and quantitative methods. Six studies specifically reported on relative importance to patients of different aspects of care. The valued aspects of care identified were grouped into seven themes. These highlighted the importance to patients of: a good health care professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and involvement in decisions about treatment and care. We were unable to determine the relative importance to patients of different aspects of care because of methodological differences between the studies. CONCLUSIONS: This review identified several attributes of healthcare that are valued by people living with HIV, many of which would be relevant to any future reconfiguration of services to meet the needs of an ageing population. Further research is required to determine the relative importance to patients of different aspects of care.

Predicting the outcomes of using longer-acting prophylactic factor VIII to treat people with severe hemophilia A: a hypothetical decision analysis.

Essentials No randomized trials have compared long-acting factor VIII (FVIII) with currently used products. A comparison was undertaken using a decision model to predict FVIII use and number of bleeds. In the base case, longer acting FVIII reduced factor use by 17% while resulting in similar bleeds. The value of longer acting FVIII will be largely determined by existing regimens and unit price. Click to hear Prof. Makris's presentation on new treatments in hemophilia SUMMARY: Background Recently, factor VIII (FVIII) products with longer half-lives, such as recombinant FVIII Fc fusion protein (rFVIIIFc), have become available. Use of longer-acting FVIII products will largely depend on effectiveness and cost; no direct evaluations have compared these parameters between conventional and longer-acting FVIII therapies. Objectives To present a hypothetical decision analysis, combining evidence from multiple sources to estimate bleeding frequency, resource use and cost of longer-acting prophylactic products, such as rFVIIIFc, vs. conventional recombinant FVIII (rFVIII). Patients/Methods The decision model used published pharmacokinetic parameters, bleeding frequency vs. time information below a 1-IU dL-1 FVIII trough level, and adherence. Prophylactic treatment scenarios were modelled for a hypothetical patient with severe hemophilia A (<1 IU/dL) receiving rFVIIIFc or rFVIII. Results Infusing twice weekly with rFVIIIFc 42.7 IU kg-1 per dose required less clotting factor than infusing every 56 h with rFVIII 33.75 IU kg-1 per dose; annual bleeding rates were similar. Base case analysis suggested that total FVIII costs were equated when rFVIIIFc cost 1.18 times more per IU than rFVIII, assuming similar adherence. Other modelled scenarios produced similar results, although differences in FVIII consumption were particularly sensitive to assumptions regarding frequency and dose of the rFVIII and rFVIIIFc regimens. For example, decreasing rFVIII from 33.75 IU kg-1 to 30 IU kg-1 per dose decreased the price factor to 1.05. Conclusions Longer-acting FVIII products may reduce FVIII consumption and infusion frequency without compromising hemostatic effect; this should be considered along with other factors (e.g. adherence and underlying FVIII regimen) when evaluating a suitable price for these agents.

Assessing the cost-effectiveness of finding cases of hepatitis C infection in UK migrant populations and the value of further research.

Hepatitis C (HCV) infection can cause cirrhosis, liver cancer and death in the absence of treatment. Many people living in the UK but born overseas are believed to be infected with HCV although many are unlikely to know they are infected. The aim of this study is to assess the potential for a case-finding approach to be cost-effective and to estimate the value of further research. An economic evaluation and value of information analysis was undertaken by developing a model of HCV disease progression and by populating it with evidence from the published literature. They were performed from a UK National Health Services cost perspective, and outcomes were expressed in terms of quality-adjusted life-years (QALYs). The comparator intervention was defined as the background rate of testing (i.e. no intervention). The base case results generated an incremental cost-effectiveness ratio (ICER) of about £23,200 per additional QALY. However, the ICER was shown to be particularly sensitive to HCV seroprevalence, the intervention effect / cost and the probability of treatment uptake. The value of information analysis suggested that approximately £4 million should be spent on further research. This evaluation demonstrates that testing UK migrants for HCV could be cost-effective. However, further research, particularly to refine estimates of the probability of treatment uptake once identified, the utility associated with sustained virological response and the cost of the intervention, would help to increase the robustness of this conclusion.

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

BACKGROUND: National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. OBJECTIVES: In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). DATA SOURCES: A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. REVIEW METHODS: Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. RESULTS: The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from priorities expressed in the stakeholder survey. LIMITATIONS: We did not conduct systematic reviews to inform the model parameters, and so the results might not reflect all current evidence. Data limitations and time constraints restricted the number of analyses that we could conduct. We were also unable to obtain feedback from guideline stakeholders about the usefulness of the models within project time scales. CONCLUSIONS: Discrete event simulation can be used to model full guideline pathways for CEA, although this requires a substantial investment of clinical and analytic time and expertise. For some topics lack of data may limit the potential for modelling. There are also uncertainties over the accessibility and adaptability of full guideline models. However, full guideline modelling offers the potential to strengthen and extend the analytical basis of NICE's CGs. Further work is needed to extend the analysis of our case study models to estimate population-level budget and health impacts. The practical usefulness of our models to guideline developers and users should also be investigated, as should the feasibility and usefulness of whole guideline modelling alongside development of a new CG. FUNDING: This project was funded by the Medical Research Council and the National Institute for Health Research through the Methodology Research Programme [grant number G0901504] and will be published in full in Health Technology Assessment; Vol. 17, No. 58. See the NIHR Journals Library website for further project information.

Economic evaluations of prophylaxis with clotting factor for people with severe haemophilia: why do the results vary so much?

A number of studies examining the cost effectiveness of haemophilia prophylaxis have been published, but they report a wide range of results. The aim of this study was to explain why the results from existing economic evaluations of prophylaxis with clotting factor vary so much and to suggest areas of further research that will help to generate stronger economic evidence. Results from a previous systematic review were updated using a textword search of a number of electronic databases. Eleven economic evaluations were identified. They reported incremental cost-effectiveness ratios for prophylaxis ranging from 'cost saving and clinically beneficial' (i.e. 'dominant') to over €1 million per additional quality-adjusted life year (QALY) if prophylaxis replaces treatment following a bleed. A number of reasons are likely to explain this breadth of results, most notably differences in choice of time horizon, estimates of treatment effect, clotting factor unit cost, discount rates and definitions of prophylaxis. Although the existing cost-effectiveness literature for haemophilia prophylaxis appears to report a wide range of results, closer inspection suggests that differences are largely explained by a number of design features. Some are likely to reflect local economic conditions and should be expected. However, others, such as differences in the choice of appropriate time horizon, are more concerning as they reflect differences in opinion over appropriate methodology. A number of studies to help address these evidence gaps are suggested: however, it is also recommended that analysts continue to adhere to established conventions when conducting and reporting economic evaluations.

Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials.

Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine.

The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model.

BACKGROUND: Alzheimer's disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. OBJECTIVES: Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009). DATA SOURCES: Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects. REVIEW METHODS: The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE). INTERVENTIONS: mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE < 10)--memantine. Comparators: mild AD (MMSE 21-26)--placebo or best supportive care (BSC); moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine, memantine, placebo or BSC; severe AD (MMSE < 10)--placebo or BSC. The outcomes were clinical, global, functional, behavioural, quality of life, adverse events, costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology assessment report, based upon time to institutionalisation, parameterised with updated estimates of effectiveness, costs and utilities. RESULTS: Notwithstanding the uncertainty of our results, we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay (WTP) of £'30,000 per qualityadjusted life-year (QALY) for people with mild-to-moderate AD. For this class of drugs, there is a > 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £'30,000 per QALY (27% at a WTP of £'20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£'69,592 vs £'69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £'30,000 per QALY is 38% (and 28% at a WTP of £'20,000 per QALY). The deterministic ICER for memantine is £'32,100 per/QALY and the probabilistic ICER is £'36,700 per/QALY. LIMITATIONS: Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters. CONCLUSIONS: The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug's use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. RESEARCH PRIORITIES: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Adaptive e-learning to improve dietary behaviour: a systematic review and cost-effectiveness analysis.

BACKGROUND: UK public health policy strongly advocates dietary change for the improvement of population health and emphasises the importance of individual empowerment to improve health. A new and evolving area in the promotion of dietary behavioural change is 'e-learning', the use of interactive electronic media to facilitate teaching and learning on a range of issues including health. The high level of accessibility, combined with emerging advances in computer processing power, data transmission and data storage, makes interactive e-learning a potentially powerful and cost-effective medium for improving dietary behaviour. OBJECTIVE: This review aims to assess the effectiveness and cost-effectiveness of adaptive e-learning interventions for dietary behaviour change, and also to explore potential psychological mechanisms of action and components of effective interventions. DATA SOURCES: Electronic bibliographic databases (Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Dissertation Abstracts, EMBASE, Education Resources Information Center, Global Health, Health Economic Evaluations Database, Health Management Information Consortium, MEDLINE, PsycINFO and Web of Science) were searched for the period January 1990 to November 2009. Reference lists of included studies and previous reviews were also screened; authors were contacted and trial registers were searched. REVIEW METHODS: Studies were included if they were randomised controlled trials, involving participants aged ≥ 13 years, which evaluated the effectiveness of interactive software programs for improving dietary behaviour. Primary outcomes were measures of dietary behaviours, including estimated intakes or changes in intake of energy, nutrients, dietary fibre, foods or food groups. Secondary outcome measures were clinical outcomes such as anthropometry or blood biochemistry. Psychological mediators of dietary behaviour change were also investigated. Two review authors independently screened results and extracted data from included studies, with any discrepancies settled by a third author. Where studies reported the same outcome, the results were pooled using a random-effects model, with weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated. Cost-effectiveness was assessed in two ways: through a systematic literature review and by building a de novo decision model to assess the cost-effectiveness of a 'generic' e-learning device compared with dietary advice delivered by a health-care professional. RESULTS: A total of 36,379 titles were initially identified by the electronic searches, of which 43 studies were eligible for inclusion in the review. All e-learning interventions were delivered in high-income countries. The most commonly used behavioural change techniques reported to have been used were goal setting; feedback on performance; information on consequences of behaviour in general; barrier identification/problem solving; prompting self-monitoring of behaviour; and instruction on how to perform the behaviour. There was substantial heterogeneity in the estimates of effect. E-learning interventions were associated with a WMD of +0.24 (95% CI 0.04 to 0.44) servings of fruit and vegetables per day; -0.78 g (95% CI -2.5 g to 0.95 g) total fat consumed per day; -0.24 g (95% CI -1.44 g to 0.96 g) saturated fat intake per day; -1.4% (95% CI -2.5% to -0.3%) of total energy consumed from fat per day; +1.45 g (95% CI -0.02 g to 2.92 g) dietary fibre per day; +4 kcal (95% CI -85 kcal to 93 kcal) daily energy intake; -0.1 kg/m2 (95% CI -0.7 kg/m2 to 0.4 kg/m2) change in body mass index. The base-case results from the E-Learning Economic Evaluation Model suggested that the incremental cost-effectiveness ratio was approximately £102,112 per quality-adjusted life-year (QALY). Expected value of perfect information (EVPI) analysis showed that although the individual-level EVPI was arguably negligible, the population-level value was between £37M and £170M at a willingness to pay of £20,000-30,000 per additional QALY. LIMITATIONS: The limitations of this review include potential reporting bias, incomplete retrieval of completed research studies and data extraction errors. CONCLUSION: The current clinical and economic evidence base suggests that e-learning devices designed to promote dietary behaviour change will not produce clinically significant changes in dietary behaviour and are at least as expensive as other individual behaviour change interventions. FUTURE WORK RECOMMENDATIONS: Despite the relatively high EVPI results from the cost-effectiveness modelling, further clinical trials of individual e-learning interventions should not be undertaken until theoretically informed work that addresses the question of which characteristics of the target population, target behaviour, content and delivery of the intervention are likely to lead to positive results, is completed. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Revisiting the cost-effectiveness of primary prophylaxis with clotting factor for the treatment of severe haemophilia A.

Severe haemophilia A is a lifelong condition that requires treatment with exogenous clotting factor. While primary prophylaxis is the clinically preferred method of delivering treatment, its provision is costly. A 2002 evaluation of primary prophylaxis suggested an incremental cost-effectiveness of approximately 50,000 pounds per additional quality-adjusted life-year (QALY). However, since this time, preferable evaluative methods have been developed and means of assessing the value of future research also now exist. Thus, the primary aims of this study were to update a previously published cost-effectiveness analysis of primary prophylaxis vs. treating on-demand in terms of methods and to estimate the value of undertaking further primary research. The base case incremental cost-effectiveness ratio was shown to be approximately 37,000 pounds, 10,000 pounds lower than the value published in 2002. The main reason for this difference was the use of different structural assumptions and methods to fit the various model parameters. At a willingness to pay per additional QALY threshold of 30,000 pounds, the probability prophylaxis is cost-effective was 13%. However, this increased to over 90% when alternative structural assumptions were employed, such as the rate at which future QALYs are discounted. The value of further research to increase the precision of this newly calculated cost-effectiveness estimate was high at a threshold willingness to pay values of 30,000- 40,000 pounds per QALY, particularly for the utilities associated with the health states. Thus, there is considerable value in conducting further primary research related to economic aspects of primary prophylaxis.

Comparing estimates of cost effectiveness submitted to the National Institute for Clinical Excellence (NICE) by different organisations: retrospective study.

OBJECTIVE: To assess the association between different types of organisation and the results from economic evaluations. DESIGN: Retrospective pairwise comparison of evidence submitted to the technology appraisal programme of the National Institute for Clinical Excellence (NICE) by manufacturers of the relevant healthcare technologies and by contracted university based assessment groups. DATA SOURCES: Data from the first 62 appraisals. MAIN OUTCOME MEASURE: Incremental cost effectiveness ratios. RESULTS: Data from 27 of the 62 appraisals could be compared. The analysis of 54 pairwise comparisons showed that manufacturers' estimates of incremental cost effectiveness ratios were lower (suggesting a more cost effective use of resources) than those produced by the assessment groups (25 were lower, 29 were the same, none were higher, P < 0.01). Restriction of this dataset to include only one pairwise comparison per appraisal (27 pairs) produced a similar result (21 were lower, two were the same, four were higher, P < 0.001). CONCLUSIONS: The estimated incremental cost effectiveness ratios submitted by manufacturers were on average significantly lower than those submitted by the assessment groups. These results show that an important role of NICE's appraisal committee, and of decision makers in general, is to determine which economic evaluations, or parts of evaluations, should be given more credence.

Setting research priorities to improve cost-effectiveness estimations of primary prophylaxis with clotting factor for people with severe haemophilia.

Primary prophylaxis with clotting factor is the clinical treatment of choice for people with severe haemophilia, as evidence suggests it can prevent the onset and progression of joint- and muscle-related problems caused by bleeding episodes. However, the major limitation of this approach is that it requires considerably more clotting factor compared with treating on-demand. Thus, there is a need to establish its cost-effectiveness. The aim of this paper is to review the published evidence on the cost-effectiveness of prophylaxis and to highlight areas for future research that would decrease the uncertainty around these findings.

Assessment of health-related quality-of-life in males with Anderson Fabry Disease before therapeutic intervention.

Anderson Fabry Disease (AFD) is an extremely painful and debilitating multi-system X-linked disorder due to alpha-galactosidase enzyme deficiency. To date, no baseline data on health-related quality-of-life (HR-QoL) have been reported in males affected with this condition. In this study, 38 males with AFD completed Medical Outcomes Study Short Form, EuroQoL questionnaires and an AFD-specific questionnaire prior to the start of a trial involving replacement therapy with alpha-galactosidase. Results from these questionnaires were compared to the results from a similar HR-QoL study in males with severe haemophilia (factor VIII/IX deficiency) that used the same questionnaires and to the results of two large normative studies. The results on both questionnaires showed that in most instances males with AFD recorded significantly lower HR-QoL compared with males in the general population and individuals with severe haemophilia after adjusting for differences in age. These findings suggest therefore, that the scope for improvement in HR-QoL as a result of treatment with an appropriate agent is extremely large.

Experience of prophylaxis treatment in children with severe haemophilia.

The practice of prophylactic treatment of boys with severe haemophilia has been evaluated in our centre. Prophylaxis was started at the median age of 3.7 years (range 0.4-12.7 years) in 38/41 children (93%) under 17 years of age. Median follow-up was 4.1 years (range 0.4-12.7 years). The criteria of primary prophylaxis according to the definition by the European Paediatric Network of Haemophilia Management was fulfilled by 9/38 (24%). Although a majority [76%, 29/38] of the children started prophylaxis after a median number of joint bleeds of 3.5, 70% of the children in this group had clinical joint scores of 0. Intravenous catheter insertion was required at a median age of 15.5 months (range 5-36 months) in 21% of the children, resulting in a catheter infection rate of 1.74 per 1000 catheter days. None developed an inhibitor on prophylaxis and three patients who had low-titre inhibitors (< 5 Bethesda units) prior to prophylaxis had undetectable inhibitors after prophylaxis. The home-treatment training programme required considerable time and cost. As a result, 87% of the children used peripheral venous access and hospital visits declined as prophylaxis became established. Parents' incentives for prophylaxis were that the children undertook many physical activities and sports previously not recommended, there was less parental anxiety and an overall improvement in the quality of life for the whole family.

Health-related quality of life in individuals infected with HIV in the era of HAART.

PURPOSE: To compare health-related quality of life (HR-QOL) in individuals infected with HIV to general population levels and to assess the relationship between HR-QOL and markers of disease progression in the era of highly active antiretroviral therapy (HAART). METHOD: This was a cross-sectional questionnaire-based study. This study included 154 individuals at least 18 years old with HIV who either were attending a London hospital or were visited by a community team in Brighton. Study participants were asked to complete two HR-QOL questionnaires. This study used HR-QOL, as measured using the Medical Outcome Study HIV Health Survey (MOS-HIV) and EuroQoL self-report (EQ-5D) questionnaires, as the main outcome measure. Responses on the EQ-5D were compared with a published general population data set. The relationships between scores on the MOS-HIV and EQ-5D questionnaires and a number of independent variables including CD4 count and viral load were also assessed. RESULTS: Each analysis was based on the results of at least 128 questionnaires. The mean MOS-HIV mental and physical component scores were 43.2 (SD = 12.2) and 41.8 (SD = 13.2), respectively. After adjusting for differences in age and gender, it was shown that individuals with HIV reported significantly lower EQ-5D(utility) ( p =.0001) and EQ-5D(VAS) ( p =.0001) compared with the general population. However, further analysis revealed few significant associations between markers of disease progression and HR-QOL. CONCLUSION: Individuals with HIV generally recorded significantly lower HR-QOL compared with the general population. Thus, prevention of further transmissions of the virus is still likely to prevent significant morbidity losses in addition to mortality losses, despite the availability of HAART. However, disease progression as measured is not clearly related to further reductions in HR-QOL.

Assessing the cost-effectiveness of HAART for adults with HIV in England.

OBJECTIVE: To assess the cost-effectiveness of highly active antiretroviral therapy (HAART) compared with two nucleoside reverse transcriptase inhibitors (NRTIs) for HIV infected individuals. DESIGN: Different data sources on the clinical effects and costs of treatments were combined using a Markov model. SETTING: English HIV treatment centres. Perspective UK public finance. INTERVENTIONS: HAART - dual NRTI therapy plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor - vs. dual NRTI therapy. PARTICIPANTS: Hypothetical cohorts of 1000 individuals infected with HIV. Outcome measures Projected life expectancy, cost-effectiveness in UK pound per life-year saved and per quality-adjusted life-years (QALYs) saved. RESULTS: Assuming a 2-year additional treatment effect of therapy with HAART produced incremental cost-effectiveness ratios of pound14 602 per life-year saved and pound17 698 per QALY saved. CONCLUSIONS: The results were sensitive to a number of assumptions including the cost of HAART and the discount rate, but they suggest that the use of HAART in England is at least moderately cost-effective compared with treatment with two NRTIs alone.

Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males.

OBJECTIVES: To determine the natural history of Anderson-Fabry disease (AFD) as a baseline for efficacy assessment of potentially therapeutic drugs. DESIGN: The first large cross sectional study of a patient cohort from the AFD clinical and genetic register (UK), maintained for the last 15 years. MEASURES: Prevalence, mortality, frequency of AFD manifestations, and impact of disease on patient lives, assessed from the AFD register and the disease specific questionnaire. RESULTS: The median cumulative survival was 50 years (n=51), which represents an approximately 20 year reduction of life span. Neuropathic pain was present in 77% (n=93) with mean pain score of 5 (scale 0-10) despite treatment with anticonvulsants and opiates. Pain stopped in only 11%. Cerebrovascular complications developed in 24.2% and renal failure in 30%. The onset and progression of serious AFD manifestations was highly variable. The relationship of gastrointestinal manifestations on weight, using body mass index (BMI), was significant (p=0.01). High frequency sensorineural deafness was confirmed in 78% of audiograms. Neuropathic pain and angiokeratoma were absent in five adult males (approximately 5%). Median age at diagnosis of AFD was 21.9 years (n=64). IMPACT OF DISEASE: Attendance at school, sports, and social activity were significantly affected by AFD. Only 56.6% (n=46) of patients were employed. Psychosexual effects of genital angiokeratoma, genital pain, and impotence were not previously recognised. CONCLUSION: The majority of males experience multiple disease manifestations and the duration of neuropathic pain was lifelong. The AFD register proved useful for the determination of baseline disease parameters in this cohort.