Estimating hepatitis B virus prevalence among key population groups for European Union and European Economic Area countries and the United Kingdom: a modelling study.

BACKGROUND: Hepatitis B virus (HBV) epidemiology in Europe differs by region and population risk group, and data are often incomplete. We estimated chronic HBV prevalence as measured by surface antigen (HBsAg) among general and key population groups for each country in the European Union, European Economic Area and the United Kingdom (EU/EEA/UK), including where data are currently unavailable. METHODS: We combined data from a 2018 systematic review (updated in 2021), data gathered directly by the European Centre for Disease Control (ECDC) from EU/EEA countries and the UK and further country-level data. We included data on adults from the general population, pregnant women, first time blood donors (FTBD), men who have sex with men (MSM), prisoners, people who inject drugs (PWID), and migrants from 2001 to 2021, with three exceptions made for pre-2001 estimates. Finite Mixture Models (FMM) and Beta regression were used to predict country and population group HBsAg prevalence. A separate multiplier method was used to estimate HBsAg prevalence among the migrant populations within each country, due to biases in the data available. RESULTS: There were 595 included studies from 31 countries (N = 41,955,969 people): 66 were among the general population (mean prevalence ([Formula: see text]) 1.3% [range: 0.0-7.6%]), 52 among pregnant women ([Formula: see text]1.1% [0.1-5.3%]), 315 among FTBD ([Formula: see text]0.3% [0.0-6.2%]), 20 among MSM ([Formula: see text]1.7% [0.0-11.2%]), 34 among PWID ([Formula: see text]3.9% [0.0-16.9%]), 24 among prisoners ([Formula: see text]2.9% [0.0-10.7%]), and 84 among migrants ([Formula: see text]7.0% [0.2-37.3%]). The FMM grouped countries into 3 classes. We estimated HBsAg prevalence among the general population to be < 1% in 24/31 countries, although it was higher in 7 Eastern/Southern European countries. HBsAg prevalence among each population group was higher in most Eastern/Southern European than Western/Northern European countries, whilst prevalence among PWID and prisoners was estimated at > 1% for most countries. Portugal had the highest estimated prevalence of HBsAg among migrants (5.0%), with the other highest prevalences mostly seen in Southern Europe. CONCLUSIONS: We estimated HBV prevalence for each population group within each EU/EAA country and the UK, with general population HBV prevalence to be < 1% in most countries. Further evidence is required on the HBsAg prevalence of high-risk populations for future evidence synthesis.

Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

Predicting reliability through structured expert elicitation with the repliCATS (Collaborative Assessments for Trustworthy Science) process.

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies.

An intensive model of care for hepatitis C virus screening and treatment with direct-acting antivirals in people who inject drugs in Nairobi, Kenya: a model-based cost-effectiveness analysis.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) treatment is essential for eliminating HCV in people who inject drugs (PWID), but has limited coverage in resource-limited settings. We measured the cost-effectiveness of a pilot HCV screening and treatment intervention using directly observed therapy among PWID attending harm reduction services in Nairobi, Kenya. DESIGN: We utilized an existing model of HIV and HCV transmission among current and former PWID in Nairobi to estimate the cost-effectiveness of screening and treatment for HCV, including prevention benefits versus no screening and treatment. The cure rate of treatment and costs for screening and treatment were estimated from intervention data, while other model parameters were derived from literature. Cost-effectiveness was evaluated over a life-time horizon from the health-care provider's perspective. One-way and probabilistic sensitivity analyses were performed. SETTING: Nairobi, Kenya. POPULATION: PWID. MEASUREMENTS: Treatment costs, incremental cost-effectiveness ratio (cost per disability-adjusted life year averted). FINDINGS: The cost per disability-adjusted life-year averted for the intervention was $975, with 92.1% of the probabilistic sensitivity analyses simulations falling below the per capita gross domestic product for Kenya ($1509; commonly used as a suitable threshold for determining whether an intervention is cost-effective). However, the intervention was not cost-effective at the opportunity cost-based cost-effectiveness threshold of $647 per disability-adjusted life-year averted. Sensitivity analyses showed that the intervention could provide more value for money by including modelled estimates for HCV disease care costs, assuming lower drug prices ($75 instead of $728 per course) and excluding directly-observed therapy costs. CONCLUSIONS: The current strategy of screening and treatment for hepatitis C virus (HCV) among people who inject drugs in Nairobi is likely to be highly cost-effective with currently available cheaper drug prices, if directly-observed therapy is not used and HCV disease care costs are accounted for.

Testing strategies for Lynch syndrome in people with endometrial cancer: systematic reviews and economic evaluation.

BACKGROUND: Lynch syndrome is an inherited genetic condition that is associated with an increased risk of certain cancers. The National Institute for Health and Care Excellence has recommended that people with colorectal cancer are tested for Lynch syndrome. Routine testing for Lynch syndrome among people with endometrial cancer is not currently conducted. OBJECTIVES: To systematically review the evidence on the test accuracy of immunohistochemistry- and microsatellite instability-based strategies to detect Lynch syndrome among people who have endometrial cancer, and the clinical effectiveness and the cost-effectiveness of testing for Lynch syndrome among people who have been diagnosed with endometrial cancer. DATA SOURCES: Searches were conducted in the following databases, from inception to August 2019 - MEDLINE ALL, EMBASE (both via Ovid), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (both via Wiley Online Library), Database of Abstracts of Reviews of Effects, Health Technology Assessment Database (both via the Centre for Reviews and Dissemination), Science Citation Index, Conference Proceedings Citation Index - Science (both via Web of Science), PROSPERO international prospective register of systematic reviews (via the Centre for Reviews and Dissemination), NHS Economic Evaluation Database, Cost-Effectiveness Analysis Registry, EconPapers (Research Papers in Economics) and School of Health and Related Research Health Utilities Database. The references of included studies and relevant systematic reviews were also checked and experts on the team were consulted. REVIEW METHODS: Eligible studies included people with endometrial cancer who were tested for Lynch syndrome using immunohistochemistry- and/or microsatellite instability-based testing [with or without mutL homologue 1 (MLH1) promoter hypermethylation testing], with Lynch syndrome diagnosis being established though germline testing of normal (non-tumour) tissue for constitutional mutations in mismatch repair. The risk of bias in studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, the Consolidated Health Economic Reporting Standards and the Philips' checklist. Two reviewers independently conducted each stage of the review. A meta-analysis of test accuracy was not possible because of the number and heterogeneity of studies. A narrative summary of test accuracy results was provided, reporting test accuracy estimates and presenting forest plots. The economic model constituted a decision tree followed by Markov models for the impact of colorectal and endometrial surveillance, and aspirin prophylaxis with a lifetime time horizon. RESULTS: The clinical effectiveness search identified 3308 studies; 38 studies of test accuracy were included. (No studies of clinical effectiveness of endometrial cancer surveillance met the inclusion criteria.) Four test accuracy studies compared microsatellite instability with immunohistochemistry. No clear difference in accuracy between immunohistochemistry and microsatellite instability was observed. There was some evidence that specificity of immunohistochemistry could be improved with the addition of methylation testing. There was high concordance between immunohistochemistry and microsatellite instability. The economic model indicated that all testing strategies, compared with no testing, were cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Immunohistochemistry with MLH1 promoter hypermethylation testing was the most cost-effective strategy, with an incremental cost-effectiveness ratio of £9420 per quality-adjusted life-year. The second most cost-effective strategy was immunohistochemistry testing alone, but incremental analysis produced an incremental cost-effectiveness ratio exceeding £130,000. Results were robust across all scenario analyses. Incremental cost-effectiveness ratios ranged from £5690 to £20,740; only removing the benefits of colorectal cancer surveillance produced an incremental cost-effectiveness ratio in excess of the £20,000 willingness-to-pay threshold. A sensitivity analysis identified the main cost drivers of the incremental cost-effectiveness ratio as percentage of relatives accepting counselling and prevalence of Lynch syndrome in the population. A probabilistic sensitivity analysis showed, at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year, a 0.93 probability that immunohistochemistry with MLH1 promoter hypermethylation testing is cost-effective, compared with no testing. LIMITATIONS: The systematic review excluded grey literature, studies written in non-English languages and studies for which the reference standard could not be established. Studies were included when Lynch syndrome was diagnosed by genetic confirmation of constitutional variants in the four mismatch repair genes (i.e. MLH1, mutS homologue 2, mutS homologue 6 and postmeiotic segregation increased 2). Variants of uncertain significance were reported as per the studies. There were limitations in the economic model around uncertainty in the model parameters and a lack of modelling of the potential harms of gynaecological surveillance and specific pathway modelling of genetic testing for somatic mismatch repair mutations. CONCLUSION: The economic model suggests that testing women with endometrial cancer for Lynch syndrome is cost-effective, but that results should be treated with caution because of uncertain model inputs. FUTURE WORK: Randomised controlled trials could provide evidence on the effect of earlier intervention on outcomes and the balance of benefits and harms of gynaecological cancer surveillance. Follow-up of negative cases through disease registers could be used to determine false negative cases. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019147185. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 42. See the NIHR Journals Library website for further project information.

Lynch syndrome is an inherited condition that is caused by a problem in the genes. People who have Lynch syndrome have a higher risk of some types of cancer (such as bowel and womb cancers) than people who do not have it. Identifying Lynch syndrome could stop cancers developing, lead to earlier treatment for cancers and help to find other family members who might have it. Currently, the National Institute for Health and Care Excellence guidance recommends testing for Lynch syndrome in people who have bowel cancer. Our aim was to investigate whether or not we should test for Lynch syndrome in women with womb cancer, and their relatives. We investigated two main tests: immunohistochemistry and microsatellite instability. There was no clear evidence that one of these tests is better than the other. There is some evidence that both tests are reasonably accurate. There was no good-quality evidence about whether or not treating women with Lynch syndrome with extra cancer screening and aspirin improves their outcomes. We used the best evidence available in our economic model, but it was at high risk of bias. The economic model suggested that testing women with endometrial cancer for Lynch syndrome is cost-effective. The best test in the model was immunohistochemistry followed by methylation testing. We are unsure of these results because of the low quality of evidence available.

Rapid antigen detection and molecular tests for group A streptococcal infections for acute sore throat: systematic reviews and economic evaluation.

BACKGROUND: Sore throat is a common condition caused by an infection of the airway. Most cases are of a viral nature; however, a number of these infections may be caused by the group A Streptococcus bacterium. Most viral and bacterial sore throat infections resolve spontaneously within a few weeks. Point-of-care testing in primary care has been recognised as an emerging technology for aiding targeted antibiotic prescribing for sore throat in cases that do not spontaneously resolve. OBJECTIVE: Systematically review the evidence for 21 point-of-care tests for detecting group A Streptococcus bacteria and develop a de novo economic model to compare the cost-effectiveness of point-of-care tests alongside clinical scoring tools with the cost-effectiveness of clinical scoring tools alone for patients managed in primary care and hospital settings. DATA SOURCES: Multiple electronic databases were searched from inception to March 2019. The following databases were searched in November and December 2018 and searches were updated in March 2019: MEDLINE [via OvidSP (Health First, Rockledge, FL, USA)], MEDLINE In-Process & Other Non-Indexed Citations (via OvidSP), MEDLINE Epub Ahead of Print (via OvidSP), MEDLINE Daily Update (via OvidSP), EMBASE (via OvidSP), Cochrane Database of Systematic Reviews [via Wiley Online Library (John Wiley & Sons, Inc., Hoboken, NJ, USA)], Cochrane Central Register of Controlled Trials (CENTRAL) (via Wiley Online Library), Database of Abstracts of Reviews of Effects (DARE) (via Centre for Reviews and Dissemination), Health Technology Assessment database (via the Centre for Reviews and Dissemination), Science Citation Index and Conference Proceedings [via the Web of Science™ (Clarivate Analytics, Philadelphia, PA, USA)] and the PROSPERO International Prospective Register of Systematic Reviews (via the Centre for Reviews and Dissemination). REVIEW METHODS: Eligible studies included those of people aged ≥ 5 years presenting with sore throat symptoms, studies comparing point-of-care testing with antibiotic-prescribing decisions, studies of test accuracy and studies of cost-effectiveness. Quality assessment of eligible studies was undertaken. Meta-analysis of sensitivity and specificity was carried out for tests with sufficient data. A decision tree model estimated costs and quality-adjusted life-years from an NHS and Personal Social Services perspective. RESULTS: The searches identified 38 studies of clinical effectiveness and three studies of cost-effectiveness. Twenty-six full-text articles and abstracts reported on the test accuracy of point-of-care tests and/or clinical scores with biological culture as a reference standard. In the population of interest (patients with Centor/McIsaac scores of ≥ 3 points or FeverPAIN scores of ≥ 4 points), point estimates were 0.829 to 0.946 for sensitivity and 0.849 to 0.991 for specificity. There was considerable heterogeneity, even for studies using the same point-of-care test, suggesting that is unlikely that any single study will have accurately captured a test's true performance. There is some randomised controlled trial evidence to suggest that the use of rapid antigen detection tests may help to reduce antibiotic-prescribing rates. Sensitivity and specificity estimates for each test in each age group and care setting combination were obtained using meta-analyses where appropriate. Any apparent differences in test accuracy may not be attributable to the tests, and may have been caused by known differences in the studies, latent characteristics or chance. Fourteen of the 21 tests reviewed were included in the economic modelling, and these tests were not cost-effective within the current National Institute for Health and Care Excellence's cost-effectiveness thresholds. Uncertainties in the cost-effectiveness estimates included model parameter inputs and assumptions that increase the cost of testing, and the penalty for antibiotic overprescriptions. LIMITATIONS: No information was identified for the elderly population or pharmacy setting. It was not possible to identify which test is the most accurate owing to the paucity of evidence. CONCLUSIONS: The systematic review and the cost-effectiveness models identified uncertainties around the adoption of point-of-care tests in primary and secondary care settings. Although sensitivity and specificity estimates are promising, we have little information to establish the most accurate point-of-care test. Further research is needed to understand the test accuracy of point-of-care tests in the proposed NHS pathway and in comparable settings and patient groups. STUDY REGISTRATION: The protocol of the review is registered as PROSPERO CRD42018118653. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 31. See the NIHR Journals Library website for further project information.

Sore throat is a common condition caused by an infection of the airway. Most cases are viral; however, a small number may be caused by the group A Streptococcus bacterium. Most viral and bacterial sore throat infections resolve spontaneously within a few weeks; however, some may be more serious and require antibiotics. Currently, National Institute for Health and Care Excellence guidance recommends the use of clinical scoring tools to identify patients for whom antibiotic treatment is appropriate. Ideally, a throat swab culture should be obtained to identify the organism causing the infection in cases in which diagnosis is uncertain. However, this takes time, causing potential delays in administering the correct treatment. Point-of-care tests can be administered at or near the site of the patient; therefore, they are much faster. Our review considered evidence for the test accuracy and cost-effectiveness of 21 point-of-care tests for detecting group A Streptococcus bacteria. We built an economic model, predicting costs and benefits for adults and children in a primary care or hospital setting. The findings will support the National Institute for Health and Care Excellence to make recommendations about the use of these point-of-care tests for detecting group A Streptococcus bacteria in the NHS in England and Wales. The clinical effectiveness review found 38 relevant studies; of these, 26 reported on the accuracy of point-of-care tests. These studies found wide variation in the accuracy of the tests. The quality of the evidence was weak and there was little information on some of the 21 tests. As the studies were all so different, it was not possible to identify which test is the most accurate. The economic model found considerable uncertainty about how costs and benefits would change if point-of-care tests were introduced in different care settings. Further research is needed to see whether or not point-of-care testing provides value for money.

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis.

BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID.

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol).

INTRODUCTION: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

Cost-effectiveness of scaling-up HCV prevention and treatment in the United States for people who inject drugs.

AIMS: To examine the cost-effectiveness of hepatitis C virus (HCV) treatment of people who inject drugs (PWID), combined with medication-assisted treatment (MAT) and syringe-service programs (SSP), to tackle the increasing HCV epidemic in the United States. DESIGN: HCV transmission and disease progression models with cost-effectiveness analysis using a health-care perspective. SETTING: Rural Perry County, KY (PC) and urban San Francisco, CA (SF), USA. Compared with PC, SF has a greater proportion of PWID with access to MAT or SSP. HCV treatment of PWID is negligible in both settings. PARTICIPANTS: PWID data were collected between 1998 and 2015 from Social Networks Among Appalachian People, U Find Out, Urban Health Study and National HIV Behavioral Surveillance System studies. INTERVENTIONS AND COMPARATOR: Three intervention scenarios modeled: baseline-existing SSP and MAT coverage with HCV screening and treatment with direct-acting antiviral for ex-injectors only as per standard of care; intervention 1-scale-up of SSP and MAT without changes to treatment; and intervention 2-scale-up as intervention 1 combined with HCV screening and treatment for current PWID. MEASUREMENTS: Incremental cost-effectiveness ratios (ICERs) and uncertainty using cost-effectiveness acceptability curves. Benefits were measured in quality-adjusted life-years (QALYs). FINDINGS: For both settings, intervention 2 is preferred to intervention 1 and the appropriate comparator for intervention 2 is the baseline scenario. Relative to baseline, for PC intervention 2 averts 1852 more HCV infections, increases QALYS by 3095, costs $21.6 million more and has an ICER of $6975/QALY. For SF, intervention 2 averts 36 473 more HCV infections, increases QALYs by 7893, costs $872 million more and has an ICER of $11 044/QALY. The cost-effectiveness of intervention 2 was robust to several sensitivity analysis. CONCLUSIONS: Hepatitis C screening and treatment for people who inject drugs, combined with medication-assisted treatment and syringe-service programs, is a cost-effective strategy for reducing hepatitis C burden in the United States.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation.

BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-ß) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-ß and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. REVIEW METHODS: Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. RESULTS: In total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-ß-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained). LIMITATIONS: Although we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria. CONCLUSIONS: DMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016043278. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Comparison of a full systematic review versus rapid review approaches to assess a newborn screening test for tyrosinemia type 1.

BACKGROUND: Rapid reviews are increasingly used to replace/complement systematic reviews to support evidence-based decision-making. Little is known about how this expedited process affects results. OBJECTIVES: To assess differences between rapid and systematic review approaches for a case study of test accuracy of succinylacetone for detecting tyrosinemia type 1. METHODS: Two reviewers conducted an "enhanced" rapid review then a systematic review. The enhanced rapid review involved narrower searches, a single reviewer checking 20% of titles/abstracts and data extraction, and quality assessment using an unadjusted QUADAS-2. Two reviewers performed the systematic review with a tailored QUADAS-2. Post hoc analysis examined rapid reviewing with a single reviewer (basic rapid review). RESULTS: Ten papers were included. Basic rapid reviews would have missed 1 or 4 of these (dependent on which reviewer). Enhanced rapid and systematic reviews identified all 10 papers; one paper was only identified in the rapid review through reference checking. Two thousand one hundred seventy-six fewer title/abstracts and 129 fewer full texts were screened during the enhanced rapid review than the systematic review. The unadjusted QUADAS-2 generated more "unclear" ratings than the adjusted QUADAS-2 [29/70 (41.4%) versus 16/70 (22.9%)], and fewer "high" ratings [22/70 (31.4%) versus 42/70 (60.0%)]. Basic rapid reviews contained important inaccuracies in data extraction, which were detected by a second reviewer in the enhanced rapid and systematic reviews. CONCLUSIONS: Enhanced rapid reviews with 20% checking by a second reviewer may be an appropriate tool for policymakers to expeditiously assess evidence. Basic rapid reviews (single reviewer) have higher risks of important inaccuracies and omissions.