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.

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 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.

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.

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.

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.

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.

Assessing the relationship between productivity levels and severity of haemophilia.

In this study, we assessed whether severity of haemophilia was associated with levels of productivity. Productivity levels were assessed by sending a 'time-use' questionnaire to 228 individuals with mild, moderate and severe haemophilia. The results showed that, after adjusting for differences in age and HIV serostatus, there were no differences between individuals with severe and mild/moderate haemophilia in terms of completed levels of education, employment status, absenteeism from work over the previous 2 weeks, the number of hours each week spent performing unpaid tasks and how efficiently individuals performed these tasks. The data did suggest, however, that a significantly larger proportion of individuals with severe haemophilia (32%) required help from family or friends to perform routine household tasks each week than individuals with mild/moderate haemophilia (13%). In conclusion, it is possible that individuals with severe haemophilia have similar levels of productivity compared to individuals with mild/moderate haemophilia or that treatment with secondary prophylaxis has helped to reduce differences between the two patient groups.

The cost of HIV treatment and care. A global review.

This review of published studies on the costs of HIV treatment and care describes some of the recent developments that have influenced these costs in industrialised and industrialising countries, especially within the context of changing drug treatments. Some of the different approaches to estimating the economic impact of HIV infection are briefly presented. The methods used to review the literature are described, particularly the criteria of a scoring system that was specifically developed to systematically screen some of the studies identified. The mean review score for studies dealing with direct hospital costs increased significantly (p = 0.003) over the 3 periods analysed (before 1987, 1987 to 1995, and 1996 and beyond), indicating that the overall 'quality' of studies increased over time. All cost estimates, other than those from non-industrialised regions, were converted to 1996 US dollars using country-specific total health expenditure inflaters and country-specific Gross Domestic Product Purchasing Power Parity converters. A summary of hospital cost estimates over time and by region demonstrated that the costs of treating asymptomatic individuals and people with symptomatic non-AIDS increased over the period, but that the costs of treating individuals with AIDS appears to have stabilised since the late 1980s. As fewer studies could be identified on the costs of community and informal care, indirect productivity costs and population cost estimates, and costs of care for children with HIV infection, all of these studies were reviewed without the use of the scoring system. Finally, the discussion explores the evidence on the global costs of HIV in non-industrialised economies and the affordability of HIV treatment and care. Some suggestions for the direction of future HIV costing studies are also presented. A need remains for good quality cost data. Adequate research effort should be directed to improving the scope and quality of information on costs of HIV service provision around the world.

Primary prophylaxis for individuals with severe haemophilia: how many hospital visits could treatment prevent?

OBJECTIVES: To assess how many hospital visits primary prophylaxis with clotting factor could prevent. DESIGN: The potential for reducing hospital visits was assessed by comparing rates of in-patient, Out-patient and day-case visits per patient-year for individuals with severe (< 1 IU dL-1) haemophilia who had never received primary prophylaxis with attendance rates for individuals with mild/moderate (1-50 IU dL-1) haemophilia. Hospital attendance data were collected retrospectively for the period 1988-97 inclusive for individuals who were aged 18 years or over. SETTING: Data were obtained on patients who were registered at the Katharine Dormandy Haemophilia Centre (KDHC), London, UK. OUTCOME MEASURES: In-patient stays, Out-patient and day-case visits. RESULTS: Individuals with mild/moderate haemophilia were 45% (31-56), 36% (30-41) and 70% (68-73) less likely to have required in-patient, Out-patient and day-case visits than were individuals with severe haemophilia. HIV serostatus and age were also shown to be significant and independent predictors of the rate of Out-patient and day-case visits, but not the rate of in-patient stays. CONCLUSION: These results suggest that primary prophylaxis for individuals with severe haemophilia could significantly reduce the demand for in-patient stays, and Out-patient and day-case visits.

The cost-effectiveness of triple nucleoside analogue therapy antiretroviral regimens in the treatment of HIV in the United Kingdom.

PURPOSE: Treatment of HIV infection has improved markedly in recent years due to the use of combination antiretroviral therapies. However, the cost of these treatments remains a concern for those who fund health services. This article reports the results of an economic evaluation to determine the incremental cost-effectiveness of triple combination nucleoside analogue (NA) therapy compared with dual NA therapy. METHOD: A Markov model was developed to assess the incremental cost effectiveness of triple therapy treatment versus dual therapy treatment. Clinical data was derived from published clinical trials and large observational cohorts whilst cost data was derived from a prospective database that monitors health care resource use in the UK HIV population. RESULTS: The model predicted that triple NA combination treatment extended life expectancy by an additional 1.2 years compared with dual therapy NA treatment with an incremental cost-effectiveness ratio of 8,419 pounds per life-year saved. The incremental cost per quality-adjusted life-year (QALY) was estimated to be between 10,072-16,168 pounds per QALY gained depending on the assumptions. CONCLUSION: The results show triple nucleoside analogue therapy to be a cost effective means of delaying HIV progression and extending life expectancy. However, further research into this issue is warranted.

Audit of clinical management of von Willebrand disease during 1997 at a single institution and review of treatment patterns between 1980 and 1997.

In 1997 the UK Haemophilia Centre Directors Organization published the guidelines for diagnosis and management of von Willebrand disease (vWD). The guidelines stated that desmopressin (DDAVP) should be used in type 1 and type 2N vWD, that it might be useful in other types 2 vWD and that it is ineffective in type 3 vWD. If patients are unresponsive to DDAVP or if it is contraindicated, the treatment of choice is clotting factor concentrates (CFC). In the light of these guidelines, we audited our practice for 1997. Furthermore, we undertook a retrospective review of the changing patterns of treatment of vWD between 1980 and 1997. During 1997, 10 patients with vWD received DDAVP and another 30 patients were treated with CFC (a total of 1.2 million IU): Haemate P (Centeon, Germany) and/or 8Y (BPL, Elstree, UK). Few patients had clear contraindications to DDAVP, but several patients with type 1 and 2 vWD received CFC on the basis of age or reduced levels of von Willebrand factor - where DDAVP was considered suboptimal for adequate haemostasis. However, this assumption was made without a preliminary test dose to assess the response to DDAVP. The analysis of treatment of vWD for the past 17 years showed that cryoprecipitate was discontinued from use in the early 1990s and that both DDAVP and CFC usage has been on the increase. In conclusion, the audit illustrated a general good adherence to guidelines but it highlighted the need for a DDAVP test before using CFC.

Assessing health-related quality-of-life in individuals with haemophilia.

The objectives of this study were to analyse current levels of health-related quality-of-life (HR-QoL) in individuals with severe haemophilia and to assess the scope for these levels to improve. To do this, 249 individuals with severe, moderate and mild haemophilia were asked to complete Medical Outcomes Study (MOS) Short-Form 36 (SF-36) and EuroQol (EQ-5D) questionnaires. Access was also gained to two appropriate normative data sets. The results from these questionnaires showed that HIV status, history of orthopaedic surgery and bleeding frequency in the previous calendar year were not strong predictors of HR-QoL for individuals with severe haemophilia. However, for the majority of scales, age was found to be a strong predictor of HR-QoL for this patient group. The results from the analysis also showed that compared to individuals with moderate/mild haemophilia and the UK male normative population, individuals with severe haemophilia generally recorded poorer levels of HR-QoL. These results suggest, therefore, that individuals with severe haemophilia have reduced levels of HR-QoL compared to individuals with moderate/mild haemophilia and the general population, irrespective of differences in age. The results also suggest that the scope for primary prophylaxis to increase HR-QoL in individuals with severe haemophilia is significant.

Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of prophylaxis with clotting factor against bleeding in patients with severe haemophilia and von Willebrand's disease (vWD). DESIGN: Treatment details that related to 179 patients with severe (< 1 u dL-1) haemophilia A, B and vWD were retrospectively examined for the period 1980-95. A subgroup of these patients, 25 adults and 22 children, who had previously received treatment on demand and who had switched to treating with prophylaxis, were studied in order to examine the effects of the change. The cost-effectiveness of prophylaxis was also analysed using another subgroup of 38 patients and by adjusting their treatment details by age and method of treatment. SETTING: Data were obtained on patients who were solely registered at the Royal Free Hospital Haemophilia Centre (RFHHC), London, UK. OUTCOME MEASURE: Bleeds. RESULTS: The median annual number of bleeds decreased from 23.5 (range 1-107) in 1980, to 14 (range 0-45) in 1995 (P < 0.0001). Switching from treating on demand to prophylaxis reduced bleeding frequency in 41 out of 47 patients within the period of 1 year. At the base scenario, switching to prophylaxis cost an additional pound547 per averted bleed; however, this figure was highly sensitive to certain variables. CONCLUSION: Prophylaxis can reduce bleeding frequency but requires more clotting factor than treatment on demand. More detailed proof of cost-effectiveness is likely to require the use of modelling techniques.

The changing patterns of factor VIII (FVIII) and factor IX (FIX) clotting factor usage in a comprehensive care centre between 1980 and 1994.

The annual amount of clotting factor used by patients at the Royal Free Haemophilia Centre increased significantly from 4 million iu in 1980 to over 15 million iu by 1994 (P < 0.0001). In order to assess the reasons for this increase, data on concentrate usage over this period were retrospectively collected for patients who had haemophilia or von Willebrand's disease. Only patients who were registered exclusively at the Centre were included in the study. In total, 498 patients met the inclusion criterion. The median age of the cohort on 1 January 1980 was 21 (range < 1-69) years. During the period there were 88 births and 45 deaths. The majority of patients had haemophilia A (55%). The median follow-up period per patient was 2.1 (range 0-14.8) years. Despite adjusting for increases in the number of patients and changes in body weight, statistically significant increases in clotting factor usage were detected for some subgroups of patients, in particularly for those with severe haemophilia A and B and from the late 1980s onwards, for patients with von Willebrand's disease. Two reasons for this increase in clotting factor usage were identified as being the introduction of improved products and prophylaxis. However, the increased cost of clotting factor provision that has resulted from these changes in treatment policy should not be analysed in isolation but should be balanced off against cost decreases in other areas and against increases in the effectiveness of treatment.