Keith Tolley

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.

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.

Cost-effectiveness and cost-benefit in the prevention of mother-to-child transmission of HIV in developing countries

Approximately 25-30% of infants born to HIV-infected mothers in developing countries are infected with HIV. A range of approaches exists to reduce the rate of mother-to-child transmission (MCT). Currently however the only therapeutic approach proven to reduce such vertical transmission is the administration of zidovudine therapy during pregnancy delivery and the neonatal period in the absence of breast-feeding. The authors review economic evaluation as an approach to help guide the development of policies on preventing MCT in developing countries drawing from studies evaluating anti-retroviral therapy in sub-Saharan Africa and Thailand. Principles of economic evaluation are discussed followed by a review of available evidence and the consideration of the sensitivity of estimates to parameter variation the reliability of parameter estimates model completeness and comparability and affordability. Future evaluations of MCT interventions should include economic evaluation to determine whether the intervention if found to be effective can or should be implemented as a public health measure. Such economic evaluations should be clear and include a sensitivity analysis of the most important variables thought to influence effectiveness and costs. Affordability should also be considered and multiple outcome measures and frames of reference used.

A Network Meta-Analysis of the Relative Efficacy of Treatments for Actinic Keratosis of the Face or Scalp in Europe

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

Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness study using a decision analysis model.

Abstract Objective: To determine how small differences in the efficacy and cost of two antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost effectiveness of H pylori eradication in duodenal ulcer disease. Design: A decision analysis to examine the cost effectiveness of eight H pylori eradication strategies for duodenal ulcer disease with and without 13C-urea breath testing to confirm eradication. Main outcome measures: Cumulative direct treatment costs per 100 patients with duodenal ulcer disease who were positive for H pylori. Results: In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone was the most cost effective of the four strategies assessed. The addition of the 13C-urea breath test and a second course of omeprazole, clarithromycin, and metronidazole achieved the highest eradication rate (97%) but was the most expensive (£62.63 per patient). The cost of each additional effective eradication was £589.00 (incremental cost per case) when compared with the cost of treating once only with omeprazole, clarithromycin, and metronidazole; equivalent to the cost of a patient receiving ranitidine for duodenal ulcer relapse for more than 15 years. Eradication strategies of omeprazole, amoxycillin, and metronidazole were less cost effective than omeprazole, clarithromycin, and metronidazole alone. In model 2 the addition of the 13C-urea breath test after treatment, and maintenance treatment, increased the cost of all the strategies and reduced the cost advantage of omeprazole, clarithromycin, and metronidazole alone. Conclusion: Small differences in efficacy can influence the comparative cost effectiveness of strategies for eradicating H pylori. Of the strategies tested the most cost effective (omeprazole, clarithromycin, and metronidazole alone) was neither the least expensive (omeprazole, amoxycillin, and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and metronidazole with further treatment for patients found positive for H pylori on 13C-urea breath testing). Cost effectiveness should be an important part of choosing an eradication strategy for H pylori. Key messages It is unlikely that randomised controlled trials to examine the effect of small differences in efficacy and cost between eradication regimens will ever be performed because of the large numbers of patients required Decision analysis models show that relatively small differences in efficacy and cost between several strategies for eradication of H pylori in patients with duodenal ulcer disease lead to large differences in their relative cost effectiveness The most cost effective strategy was neither the least expensive nor the most effective for eradication of H pylori For uncomplicated duodenal ulcer disease performing a 13C-urea breath test to identify patients failing eradication treatment is not cost effective if patients only receive acid suppression treatment for relapses that produce symptoms Performing a 13C-urea breath test to identify patients failing eradication treatment may only be cost effective in high risk patients

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

Abstract. Miners AH, Sabin CA, Tolley KH, Lee CA (Royal Free Hospital School of Medicine, London; University of Nottingham, Nottingham; and Royal Free Hampstead NHS Trust, London, UK). Primary prophylaxis for individuals with severe haemophilia: how many hospital visits could treatment prevent? J Intern Med 2000; 247: 493–499.

Economic impact of the AIDS epidemic in the european community : towards multinational scenarios on hospital care and costs

OBJECTIVE To underpin multinational public-health HIV/AIDS strategy planning in the European Community (EC) by integrating national studies on HIV/AIDS in scenario analysis. METHOD Three types of data are used: routine surveillance data, information on disease progression and observational studies on the economic impact. The HIV/AIDS epidemic is simulated using two models (MIDAS and PC-Based AIDS Scenarios). Selected simulations, consistent with surveillance data, are connected to economic impact (hospital-bed needs and annual hospital costs for AIDS patients). Parameter values expressing per person-year economic impacts are derived from a structured review of publications on economic aspects of AIDS. RESULTS Evaluation of published studies on hospital resource use and costs in EC countries shows that there are significant differences between both countries and studies, even after conversion to similar measures (for example, using purchasing power parities). These differences are partly due to factors such as the composition of the patient population. Differences in methodology may also have influenced the results. Economic impact is analysed for combinations of three factors; survival time after AIDS diagnosis, hospital inpatient days needed per person-year and corresponding hospital costs per person-year. All scenarios indicate 1995 hospital-bed needs above the 1990 level of 5400 beds. Hospital cost projections for 1995 vary (up to US

Hospital costs of treating haemophilic patients infected with HIV

1050 million). CONCLUSIONS (1) For economic impact assessment, there are important gaps in epidemiological and economic data, and in the methods for linking these. (2) Standardization of studies on the resource use and costs of HIV/AIDS is necessary to provide a sound basis for multinational scenarios. (3) Preliminary multinational scenarios show that by 1995 hospital-bed needs for AIDS might reach 0.45% of all hospital beds available in the EC, and that hospital cost projections for AIDS in that year will range from 0.15% to 0.30% of EC health-care expenditure.

The Use and Cost of HIV Service Provision in England in 1996

ObjectiveTo calculate the costs of treating HIV-infected haemophilic patients. DesignTwo-year retrospective study of hospital-based resource use and costs, from April 1991 to March 1993. SettingHaemophilia Centre and Haemostasis Unit, Royal Free Hospital and School of Medicine, London, UK. PatientsSixty patients infected with HIV between October 1979 and July 1985. ResultsDuring the 2-year period a total of 1668 hospital visits were made by patients. The mean number of episodes per patient-year (PY) was 0.6 inpatient admissions, 11.5 outpatient visits and 1.8 day cases. The mean cost per PY was £32528, with the majority of this spent on clotting factor concentrate products and haemophilia inpatient admissions (81%). A mean cost for HIV-related treatment of £6050 was estimated. The additional cost incurred in switching this group of haemophilic patients from intermediate-purity factor concentrate to high-purity products was £8614 per PY. When clotting factor concentrate and expenditure on haemophilia-related inpatient admissions were excluded, the mean cost of treating HIV infection per PY was £6065, varying with CD4+ count (≤50×106/l, £13093; 51–200×106/1, £6521; 201–500×106/l, £2848; >501×106/l, £1497). ConclusionsCD4+ count may be used as a marker of costs of HIV infection. The HIV-related cost estimates can be used for the planning of current and future hospital-based care in the National Health Service in the United Kingdom. The switch from intermediate-purity factor concentrate to high-purity products has increased the mean HIV-related cost per PY of treating haemophilic patients infected with HIV.

The influence of socioeconomic status on health service utilisation by patients with AIDS in North Italy

AbstractObjective: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. Design and Setting: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. Main Outcome Measures and Results: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from £4695 (95% CI: £3769 to £5648) for asymptomatic patients, to £7605 (95% CI: £6273 to £8909) for symptomatic non-AIDS patients to £20 358 (95% CI: £17 681 to £23 206) for patients with AIDS. Conclusions: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatientrelated activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.