Cost-effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: An economic evaluation alongside a pragmatic cluster randomised trial.

BACKGROUND: Elimination targets for hepatitis C have been set across the world. In the UK almost 90% of infections are in people who inject drugs. Evidence shows community case-finding is effective at identifying and treating undiagnosed patients. The aim of this analysis was to assess, from a healthcare provider perspective, the cost-effectiveness of a new pharmacist-led test and treat pathway for hepatitis C in opioid agonist treatment (OAT) patients attending community pharmacies compared to conventional care. METHODS: In a cluster randomised controlled trial, pharmacies were randomised to the pharmacist-led or conventional care pathway. Mean cost per OAT patient and per patient initiating treatment was identified for each pathway. A Markov model tracking disease progression was developed, with a 50-year time horizon and 3·5% time discount rate, to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the probability of being cost-effective at a £30,000 per QALY willingness-to-pay threshold. Probabilistic sensitivity analysis was performed for a range of drug discounts, re-infection rates, and model assumptions. FINDINGS: Mean cost per OAT patient (£3,674 vs £1,965) and per patient initiating treatment (£863 vs £404) was higher in the pharmacist-led pathway, due to higher uptake of testing and pharmacist time requirements. Over a 50-year time horizon the ICER per QALY gained was £31,612 at NHS indicative price for treatment (£38,979 for 12 weeks) and 12·1/100 person-years re-infection rate, reducing to £21,027/£10,220/-£501 per QALY gained with 30%/60%/90% drug price discounts and £25,373/£21,738/£14,912 per QALY gained at re-infection rates of 8/5/2 per 100 person-years. At 30%/60%/90% drug discount rates, the pharmacist-led pathway has an 80%/98%/100% probability of being cost-effective. INTERPRETATION: The pharmacist-led pathway is effective at increasing testing and treatment uptake, with cost-effectiveness being highly dependent on drug price discounts. FUNDING: Trial funding provided by the Scottish Government, Gilead Sciences, and Bristol-Myers Squibb.

The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV.

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.

OBJECTIFS: L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD. CONCLUSIONS: Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.

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.

Respondent driven sampling and community structure in a population of injecting drug users, Bristol, UK.

BACKGROUND: A 2006 respondent driven sampling (RDS) survey of injecting drug users (IDUs) in Bristol, UK, estimated 40 per 100 person years HCV incidence but in 2009 another RDS survey estimated only 10 per 100 person years incidence amongst the same population. Estimated increases in intervention exposure do not fully explain the decrease in risk. We investigate whether the underlying contact network structure and differences in the structure of the RDS trees could have contributed to the apparent change in incidence. METHOD: We analyse the samples for evidence that individuals recruit participants who are like themselves (assortative recruiting). Using an assortativity measure, we develop a Monte Carlo approach to determine whether the RDS data exhibit significantly more assortativity than is expected for that sample. Motivated by these findings, a network model is used to investigate how much assortativity and the structure of the RDS tree impacts sample estimates of prevalence and incidence. RESULTS: The samples suggest there is some assortativity on injecting habits or markers of injecting risk. The 2009 sample has lower assortativity than 2006. Simulations of RDS confirm that assortativity influences the estimated incidence in a population and the structure of RDS samples can result in bias. Our simulations suggest that RDS incidence estimates have considerable variance, making them difficult to use for monitoring trends. CONCLUSIONS: We suggest there was likely to have been a decline in risk between 2006 and 2009 due to increased intervention coverage, but the bias and variance in the estimates prevents accurate estimation of the incidence.

The effects of scale on the costs of targeted HIV prevention interventions among female and male sex workers, men who have sex with men and transgenders in India.

BACKGROUND: The India AIDS Initiative (Avahan) project is involved in rapid scale-up of HIV-prevention interventions in high-risk populations. This study examines the cost variation of 107 non-governmental organisations (NGOs) implementing targeted interventions, over the start up (defined as period from project inception until services to the key population commenced) and first 2 years of intervention. METHODS: The Avahan interventions for female and male sex workers and their clients, in 62 districts of four southern states were costed for the financial years 2004/2005 and 2005/2006 using standard costing techniques. Data sources include financial and economic costs from the lead implementing partners (LPs) and subcontracted local implementing NGOs retrospectively and prospectively collected from a provider perspective. Ingredients and step-down allocation processes were used. Outcomes were measured using routinely collected project data. The average costs were estimated and a regression analysis carried out to explore causes of cost variation. Costs were calculated in US$ 2006. RESULTS: The total number of registered people was 134,391 at the end of 2 years, and 124,669 had used STI services during that period. The median average cost of Avahan programme for this period was $76 per person registered with the project. Sixty-one per cent of the cost variation could be explained by scale (positive association), number of NGOs per district (negative), number of LPs in the state (negative) and project maturity (positive) (p<0.0001). CONCLUSIONS: During rapid scale-up in the initial phase of the Avahan programme, a significant reduction in average costs was observed. As full scale-up had not yet been achieved, the average cost at scale is yet to be realised and the extent of the impact of scale on costs yet to be captured. Scale effects are important to quantify for planning resource requirements of large-scale interventions. The average cost after 2 years is within the range of global scale-up costs estimates and other studies in India.

Modelling the cost per ulcer treated of incorporating episodic treatment for HSV-2 into the syndromic algorithm for genital ulcer disease.

BACKGROUND: The proportion of genital ulcer disease (GUD) due to herpes simplex virus type-2 (HSV-2) has increased in sub-Saharan Africa. The most recent 2003 WHO syndromic GUD algorithm includes antiviral treatment for HSV-2 for anyone with "typical" symptoms/signs, and suggests that all GUD patients receive treatment for HSV-2 in settings where HSV-2 GUD aetiology is greater than 30%. The previous algorithm (1994) only targeted Haemophilus ducreyi (HD) and Treponema pallidum (TP). METHODS: A static deterministic model was used to compare the cost per ulcer treated of using the 1994 and 2003 algorithms amongst individuals presenting with GUD, with sensitivity analyses for different economic and epidemiological scenarios. RESULTS: Except when the proportion of ulcers due to HD/TP (defined as ulcer prevalence) is high (>40%), and HSV-2 ulcer prevalence is low (<30%), the 2003 algorithm should result in more patients receiving the correct treatment (correct drugs for the syndrome) than the 1994 algorithm, and it will cost less per ulcer treated if HSV-2 treatment costs less than US$2. Greatest impact in terms of ulcers treated is achieved with the 2003 algorithm if HSV-2 treatment is given to all GUD patients. The incremental and/or relative cost per ulcer treated of doing this, compared to only treating those with typical symptoms/signs, is reduced if the HSV-2 ulcer prevalence is high and/or the HSV-2 treatment cost or sensitivity of HSV-2 ulcer diagnosis (using symptoms/signs) is low. CONCLUSIONS: In certain scenarios, including HSV-2 treatment can increase the number of ulcers treated and reduce the cost per ulcer treated of GUD syndromic management.

Evaluating large-scale HIV prevention interventions: study design for an integrated mathematical modelling approach.

BACKGROUND: There is an urgent need to evaluate HIV prevention interventions, thereby improving our understanding of what works, under what circumstances and what is cost effective. OBJECTIVES: To describe an integrated mathematical evaluation framework designed to assess the population-level impact of large-scale HIV interventions and applied in the context of Avahan, the Indian AIDS Initiative, in southern India. The Avahan Initiative is a large-scale HIV prevention intervention, funded by the Bill & Melinda Gates Foundation, which targets high-risk groups in selected districts of the six states most affected by the HIV/AIDS epidemic (Maharashtra, Karnataka, Tamil Nadu, Andhra Pradesh, Nagaland and Manipur) and along the national highways. METHODS: One important component of the monitoring and evaluation of Avahan relies on an integrated mathematical framework that combines empirical biological and behavioural data from different subpopulations in the intervention areas, with the use of tailor-made transmission dynamics models embedded within a Bayesian framework. RESULTS: An overview of the Avahan Initiative and the objectives of the monitoring and evaluation of the intervention is given. The rationale for choosing this evaluation design compared with other possible designs is presented, and the different components of the evaluation framework are described and its advantages and challenges are discussed, with illustrated examples. CONCLUSIONS: This is the first time such an approach has been applied on such a large scale. Lessons learnt from the CHARME project could help in the design of future evaluations of large-scale interventions in other settings, whereas the results of the evaluation will be of programmatic and public health relevance.

Modelling the cost effectiveness of rapid point of care diagnostic tests for the control of HIV and other sexually transmitted infections among female sex workers.

BACKGROUND: In sub-Saharan Africa, gonococcal and chlamydial infections are usually managed using the syndromic approach. However, many infections are asymptomatic in women, and the syndromic algorithm has poor sensitivity and specificity for infections caused by Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct). Because of this, rapid point of care (POC) tests for Ct/Ng could improve sexually transmitted infection (STI) management in women. This study uses mathematical modelling to estimate the incremental cost effectiveness of using POC tests to diagnose Ng/Ct instead of the current syndromic approach used by the SIDA2 HIV/STI prevention project for female sex workers in Cotonou, Benin. METHODS: A dynamic mathematical model was used with data from Cotonou to estimate the HIV impact of the existing SIDA2 project (1995-8), and to project how impact would change if POC tests had been used. As observed in test evaluations, the POC tests were assumed to have high specificity, but a range of sensitivities. The incremental economic cost effectiveness of using POC tests was modelled using data on intervention costs and an evaluation of an Ng POC test in Cotonou in 2004. All costs were in 2004 US dollars. RESULTS: The model estimated the STI treatment aspect of the intervention averted 18 553 Ng/Ct and 359 HIV infections over 4 years when the syndromic approach was used. In contrast, if Ng/Ct had been diagnosed with a 70-80% sensitive and 95% specific POC test then 24-31% fewer clinic attenders would have been treated, 40-60% more Ng/Ct and HIV infections would have been averted, and the incremental cost effectiveness of using them would have been 107-151 dollars per HIV infection averted if the POC tests cost 2 dollars and 58-81 dollars if they cost 1 dollar. CONCLUSIONS: POC tests can be a cost effective strategy for substantially increasing the impact on HIV transmission, and decreasing the degree of inappropriate treatment of STI treatment interventions that use syndromic management to diagnose Ng/Ct.

Modelling the cost-effectiveness of introducing rapid syphilis tests into an antenatal syphilis screening programme in Mwanza, Tanzania.

OBJECTIVES: A study found screening (with rapid plasma reagin (RPR)) pregnant women for maternal syphilis was cost-effective in Mwanza, Tanzania. Recently, four rapid point-of-care (POC) syphilis tests were evaluated in Mwanza, and found to have reasonable sensitivity/specificity. This analysis estimates the relative cost-effectiveness of using these POC tests in the Mwanza syphilis screening intervention. METHODS: Empirical cost and epidemiological data were used to model the potential benefit of using POC tests instead of RPR. Reductions in costs relating to training, supplies, and equipment were estimated, and any changes in impact due to test sensitivity were included. Additional modelling explored how the results vary with prevalence of past infection, misclassified RPR results, and if not all women return for treatment. RESULTS: The cost-effectiveness of using POC tests is mainly dependent on their cost and sensitivity for high titre active syphilis (HTAS). Savings due to reductions in training and equipment are small. Current POC tests may save more disability-adjusted life years (DALYs) than the RPR test in Mwanza, but the test cost needs to be <0.63 US dollars to be as cost-effective as RPR. However, the cost-effectiveness of the RPR test worsens by 15% if its HTAS sensitivity had been 75% instead of 86%, and by 25-65% if 20-40% of women had not returned for treatment. In such settings, POC tests could improve cost-effectiveness. Lastly, the cost-effectiveness of POC tests is affected little by the prevalence of syphilis, false RPR-positives, and past infections. DISCUSSION: Although the price of most POC tests needs to be reduced to make them as cost-effective as RPR, their simplicity and limited requirements for electricity/equipment suggest their use could improve the coverage of antenatal syphilis screening in developing countries.