Adding a Gene Expression Profile Test to Aid Differential Diagnosis and Treatment in Aggressive Large B-Cell Lymphoma: An Early Exploratory Economic Evaluation.

BACKGROUND AND OBJECTIVE: Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies. METHODS: Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted. RESULTS: The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero. CONCLUSIONS: Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests.

How Least Developed to Lower-Middle Income Countries Use Health Technology Assessment: A Scoping Review.

Health Technology Assessment (HTA) is a multidisciplinary tool to inform healthcare decision-making. HTA has been implemented in high-income countries (HIC) for several decades but has only recently seen a growing investment in low- and middle-income countries. A scoping review was undertaken to define and compare the role of HTA in least developed and lower middle-income countries (LLMIC). MEDLINE and EMBASE databases were searched from January 2015 to August 2021. A matrix comprising categories on HTA objectives, methods, geographies, and partnerships was used for data extraction and synthesis to present our findings. The review identified 50 relevant articles. The matrix was populated and sub-divided into further categories as appropriate. We highlight topical aspects of HTA, including initiatives to overcome well-documented challenges around data and capacity development, and identify gaps in the research for consideration. Those areas we found to be under-studied or under-utilized included disinvestment, early HTA/implementation, system-level interventions, and cross-sectoral partnerships. We consider broad practical implications for decision-makers and researchers aiming to achieve greater interconnectedness between HTA and health systems and generate recommendations that LLMIC can use for HTA implementation. Whilst HIC may have led the way, LLMIC are increasingly beginning to develop HTA processes to assist in their healthcare decision-making. This review provides a forward-looking model that LLMIC can point to as a reference for their own implementation. We hope this can be seen as timely and useful contributions to optimize the impact of HTA in an era of investment and expansion and to encourage debate and implementation.

Economic evaluation of genomic/genetic tests: a review and future directions.

It has been suggested that health economists need to improve their methods in order to meet the challenges of evaluating genomic/genetic tests. In this article, we set out twelve challenges identified from a rapid review of the literature and suggest solutions to the challenges identified. Two challenges were common to all economic evaluations: choice of perspective and time-horizon. Five challenges were relevant for all diagnostic technologies: complexity of analysis; range of costs; under-developed evidence base; behavioral aspects; and choice of outcome metrics. The final five challenges were pertinent for genomic tests and only these may require methodological development: heterogeneity of tests and platforms, increasing stratification, capturing personal utility; incidental findings; and spillover effects. Current methods of economic evaluation are generally able to cope with genomic/genetic tests, although a renewed focus on specific decision-makers' needs and a willingness to move away from cost-utility analysis may be required. Certain analysts may be constrained by reference cases developed primarily for the assessment of pharmaceuticals. The combined impact of multiple challenges may require analysts to be particularly careful in setting the scope of their analysis in order to ensure that feasibility is balanced with usefulness to the decision maker. A key issue is the under-developed evidence-base and it may be necessary to rethink translation processes to ensure sufficient, relevant evidence is available to support economic evaluation and adoption of genomic/genetic tests.

Evaluation of Triage Tests When Existing Test Capacity Is Constrained: Application to Rapid Diagnostic Testing in COVID-19.

OBJECTIVES: A triage test is used to determine which patients will undergo an existing or "reference" test. This article explores the potential value of using triage tests before reference tests when the capacity of the reference test is constrained. METHODS: We developed a simple model with inputs: prevalence, sensitivity, specificity, and reference test capacity. We included a case study of rapid diagnostic tests for SARS-CoV-2 antigens used as triage tests before a reference polymerase chain reaction test. Performance data were obtained from an evaluation performed by an academic center on 425 samples from testing centers in the United Kingdom and Germany. RESULTS: When reference test capacity is constrained, the use of a triage test leads to a relative expansion of the population tested and cases identified; both are higher with a high-specificity triage test. When reference test capacity is not constrained, the potential advantages of introducing a triage test can be assessed using a standard cost-utility framework, balancing the utility of the reduction in the number of reference tests required against the disutility of missed cases associated with the use of a lower-sensitivity triage test. In the constrained case, the advantage of a triage testing strategy in terms of population covered and cases identified is reduced as the prevalence increases. In the unconstrained case, the reduction in reference tests required is reduced and the number of cases missed increase as the prevalence rises. CONCLUSION: When the availability of the reference test is constrained, tests added in a triage position do not need high levels of accuracy to increase the number of cases diagnosed. This has implications in many disease areas, including COVID-19.

Cost impact of introducing a treatment escalation/limitation plan during patients' last hospital admission before death.

OBJECTIVE: A recent study found that the use of a treatment escalation/limitation plan (TELP) was associated with a significant reduction in non-beneficial interventions (NBIs) and harms in patients admitted acutely who subsequently died. We quantify the economic benefit of the use of a TELP. DESIGN: NBIs were micro-costed. Mean costs for patients with a TELP were compared to patients without a TELP using generalized linear model regression, and results were extrapolated to the Scottish population. SETTING: Medical, surgical and intensive care units of district general hospital in Scotland, UK. PARTICIPANTS: Two hundred and eighty-seven consecutive patients who died over 3 months in 2017. Of these, death was 'expected' in 245 (85.4%) using Gold Standards Framework criteria. INTERVENTION: Treatment escalation/limitation plan. MAIN OUTCOME MEASURE: Between-group difference in estimated mean cost of NBIs. RESULTS: The group with a TELP (n = 152) had a mean reduction in hospital costs due to NBIs of GB £220.29 (US $;281.97) compared to those without a TELP (n = 132) (95% confidence intervals GB £323.31 (US $413.84) to GB £117.27 (US $150.11), P = <0.001). Assuming that a TELP could be put in place for all expected deaths in Scottish hospitals, the potential annual saving would be GB £2.4 million (US $3.1 million) from having a TELP in place for all 'expected' deaths in hospital. CONCLUSIONS: The use of a TELP in an acute hospital setting may result in a reduction in costs attributable to NBIs.

A different animal? Identifying the features of health technology assessment for developers of medical technologies.

Health technology assessment (HTA) conducted to inform developers of health technologies (development-focused HTA, DF-HTA) has a number of distinct features when compared to HTA conducted to inform usage decisions (use-focused HTA). To conduct effective DF-HTA, it is important that analysts are aware of its distinct features as analyses are often not published. We set out a framework of ten features, drawn from the literature and our own experience: a target audience of developers and investors; an underlying user objective to maximize return on investment; a broad range of decisions to inform; wide decision space; reduced evidence available; earlier timing of analysis; fluid business model; constrained resources for analysis; a positive stance of analysis; and a "consumer"-specific burden of proof. This paper presents a framework of ten features of DF-HTA intended to initiate debate as well as provide an introduction for analysts unfamiliar with the field.

A case-controlled study of relatives' complaints concerning patients who died in hospital: The role of treatment escalation/limitation planning.

OBJECTIVES: To independently assess quality of care among patients who died in hospital and whose next-of-kin submitted a letter of complaint and make comparisons with matched controls. To identify whether use of a treatment escalation limitation plan (TELP) during the terminal illness was a relevant background factor. DESIGN: The study was an investigator-blinded retrospective case-note review of 42 complaints cases and 72 controls matched for age, sex, ward location and time of death. SETTING: The acute medical and surgical wards of three District General Hospitals administered by NHS Lanarkshire, Scotland. PARTICIPANTS: None. INTERVENTION: None. OUTCOME MEASURES: Quality of care: clinical 'problems', non-beneficial interventions (NBIs) and harms were evaluated using the Structured Judgment Review Method. Complaints were categorized using the Healthcare Complaints Analysis Tool. RESULTS: The event frequencies and rate ratios for clinical 'problems', NBIs and harms were consistently higher in complaint cases compared to controls. The difference was only significant for NBIs (P = 0.05). TELPs were used less frequently in complaint cases compared to controls (23.8 versus 47.2%, P = 0.013). The relationship between TELP use and the three key clinical outcomes was nonsignificant. CONCLUSIONS: Care delivered to patients at end-of-life whose next-of-kin submitted a complaint was poorer overall than among control patients when assessed independently by blinded reviewers. Regular use of a TELP in acute clinical settings has the potential to influence complaints relating to end-of-life care, but this requires further prospective study.

Do age, period or cohort effects explain circulatory disease mortality trends, Scotland 1974-2015?

OBJECTIVE: We aimed to explore whether age, period or cohort effects explain the trends and inequalities in ischaemic heart disease (IHD) and cerebrovascular disease (CeVD) mortality in Scotland. METHODS: We analysed IHD and CeVD deaths for 1974-2015 by sex, age and area deprivation, visually explored the data using heatmaps and dotplots and built regression models. RESULTS: CeVD mortality improved steadily over time while IHD mortality improved more rapidly from the late 1980s. Age effects were evident; both outcomes showed an exponential relationship with age for all except males for IHD in the 1980s and 1990s. The mortality profiles by age became older, although improvement was slower for those aged <50 years for IHD, especially for males, and faster for CeVD in females aged <65 years. Rates were higher, and inequalities greater, among males, especially for IHD. For IHD, increased risk for males over females reduced with age (incidence rate ratio for 41-50 year old males=4.28 (95% CI 4.12 to 4.44) and 1.17 (95% CI 1.16 to 1.18) for 71-80 year olds). Inequalities in IHD mortality by area deprivation persisted over time, increasing from around 10% to around 25% higher risk in the most deprived areas between 1974 and 1986 before declining in absolute terms from around 2000. Inequalities for CeVD increased after the late 1980s. CONCLUSIONS: IHD and CeVD mortality in Scotland exhibit age but not recent distinct period or cohort effects. The improvements in mortality rates have been more sustained for CeVD and inequalities greater for IHD.

Context-Specific Economic Evaluation for Molecular Pathology Tests: An Application in Colorectal Cancer in the West of Scotland.

OBJECTIVES: The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources. METHODS: We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment. RESULTS: A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population. CONCLUSIONS: The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented.

Economic evaluation of the introduction of the Prostate Health Index as a rule-out test to avoid unnecessary biopsies in men with prostate specific antigen levels of 4-10 in Hong Kong.

A recent study showed that the Prostate Health Index may avoid unnecessary biopsies in men with prostate specific antigen 4-10ng/ml and normal digital rectal examination in the diagnosis of prostate cancer in Hong Kong. This study aimed to conduct an economic evaluation of the impact of adopting this commercially-available test in the Hong Kong public health service to determine whether further research is justified. A cost-consequence analysis was undertaken comparing the current diagnostic pathway with a proposed diagnostic pathway using the Prostate Health Index. Data for the model was taken from a prospective cohort study recruited at a single-institution and micro-costing studies. Using a cut off PHI score of 35 to avoid biopsy would cost HK$3,000 and save HK$7,988 per patient in biopsy costs and HK$511 from a reduction in biopsy-related adverse events. The net cost impact of the change was estimated to be HK$5,500 under base case assumptions. At the base case sensitivity and specificity for all grades of cancer (61.3% and 77.5% respectively) all grade cancer could be missed in 4.22% of the population and high grade cancer in 0.53%. The introduction of the prostate health index into the diagnostic pathway for prostate cancer in Hong Kong has the potential to reduce biopsies, biopsy costs and biopsy-related adverse events. Policy makers should consider the clinical and economic impact of this proposal.

Synthetic control methodology as a tool for evaluating population-level health interventions.

BACKGROUND: Many public health interventions cannot be evaluated using randomised controlled trials so they rely on the assessment of observational data. Techniques for evaluating public health interventions using observational data include interrupted time series analysis, panel data regression-based approaches, regression discontinuity and instrumental variable approaches. The inclusion of a counterfactual improves causal inference for approaches based on time series analysis, but the selection of a suitable counterfactual or control area can be problematic. The synthetic control method builds a counterfactual using a weighted combination of potential control units. METHODS: We explain the synthetic control method, summarise its use in health research to date, set out its advantages, assumptions and limitations and describe its implementation through a case study of life expectancy following German reunification. RESULTS: Advantages of the synthetic control method are that it offers an approach suitable when there is a small number of treated units and control units and it does not rely on parallel preimplementation trends like difference in difference methods. The credibility of the result relies on achieving a good preimplementation fit for the outcome of interest between treated unit and synthetic control. If a good preimplementation fit is established over an extended period of time, a discrepancy in the outcome variable following the intervention can be interpreted as an intervention effect. It is critical that the synthetic control is built from a pool of potential controls that are similar to the treated unit. There is currently no consensus on what constitutes a 'good fit' or how to judge similarity. Traditional statistical inference is not appropriate with this approach, although alternatives are available. From our review, we noted that the synthetic control method has been underused in public health. CONCLUSIONS: Synthetic control methods are a valuable addition to the range of approaches for evaluating public health interventions when randomisation is impractical. They deserve to be more widely applied, ideally in combination with other methods so that the dependence of findings on particular assumptions can be assessed.

Drug-related deaths in Scotland 1979-2013: evidence of a vulnerable cohort of young men living in deprived areas.

BACKGROUND: Even after accounting for deprivation, mortality rates are higher in Scotland relative to the rest of Western Europe. Higher mortality from alcohol- and drug-related deaths (DRDs), violence and suicide (particularly in young adults) contribute to this 'excess' mortality. Age-period and cohort effects help explain the trends in alcohol-related deaths and suicide, respectively. This study investigated whether age, period or cohort effects might explain recent trends in DRDs in Scotland and relate to exposure to the changing political context from the 1980s. METHODS: We analysed data on DRDs from 1979 to 2013 by sex and deprivation using shaded contour plots and intrinsic estimator regression modelling to identify and quantify relative age, period and cohort effects. RESULTS: The peak age for DRDs fell around 1990, especially for males as rates increased for those aged 18 to 45 years. There was evidence of a cohort effect, especially among males living in the most deprived areas; those born between 1960 and 1980 had an increased risk of DRD, highest for those born 1970 to 1975. The cohort effect started around a decade earlier in the most deprived areas compared to the rest of the population. CONCLUSION: Age-standardised rates for DRDs among young adults rose during the 1990s in Scotland due to an increased risk of DRD for the cohort born between 1960 and 1980, especially for males living in the most deprived areas. This cohort effect is consistent with the hypothesis that exposure to the changing social, economic and political contexts of the 1980s created a delayed negative health impact.

The short-term impact of the alcohol act on alcohol-related deaths and hospital admissions in Scotland: a natural experiment.

BACKGROUND AND AIM: The introduction of the Alcohol Act in Scotland on 1 October 2011, which included a ban on multi-buy promotions, was probably associated with a fall in off-trade alcohol sales in the year after its implementation. The aim of this study was to test if the same legislation was associated with reduced levels of alcohol-related deaths and hospital admissions in the 3-year period after its introduction. DESIGN: A natural experiment design using time-series data to assess the impact of the Alcohol Act legislation in Scotland. Comparisons were made with unexposed populations in the rest of Great Britain. SETTING: Scotland with comparable data obtained for geographical control groups in other parts of Great Britain. PARTICIPANTS: For alcohol-related deaths, a total of 17 732 in Scotland and 88 001 in England and Wales throughout 169 4-week periods between January 2001 and December 2013 and for alcohol-related hospital admissions, a total of 121 314 in Scotland and 696 892 in England throughout 182 4-week periods between January 2001 and December 2014. MEASUREMENTS: Deaths and hospital admissions in Scotland and control groups that were wholly attributable to alcohol for consecutive 4-week periods between January 2001 and December 2014. Data were obtained by age, sex and area-based socio-economic position. FINDINGS: There was no evidence to suggest that the Alcohol Act was associated with changes in the overall rate of alcohol-related deaths [incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI) = 0.91-1.07)] or hospital admissions (IRR = 0.98, 95% CI = 0.95-1.02) in Scotland. In control group analyses, the pseudo intervention variable was not associated with a change in alcohol-related death rates in England/Wales (IRR = 0.99, 95% CI = 0.95-1.02), but was associated with an increase in alcohol-related hospital admission rates in England (IRR = 1.05, 95% CI = 1.03-1.07). In combined models, the interaction analysis did not provide support for a 'net effect' of the legislation on alcohol-related deaths in Scotland compared with England/Wales (IRR 0.99, 95% CI = 0.95-1.04), but suggested a net reduction in hospital admissions for Scotland compared with England (IRR = 0.93, 95% CI = 0.87-0.98). CONCLUSION: The implementation of the Alcohol Act in Scotland has not been associated clearly with a reduction in alcohol-related deaths or hospital admissions in the 3-year period after it was implemented in October 2011.

Recent cohort effects in suicide in Scotland: a legacy of the 1980s?

BACKGROUND: Mortality rates are higher in Scotland relative to England and Wales, even after accounting for deprivation. This 'excess' mortality is partly due to higher mortality from alcohol-related and drug-related deaths, violence and suicide (particularly in young adults). This study investigated whether cohort effects from exposure to neoliberal politics from the 1980s might explain the recent trends in suicide in Scotland. METHODS: We analysed suicide deaths data from 1974 to 2013 by sex and deprivation using shaded contour plots and intrinsic estimator regression modelling to identify and quantify relative age, period and cohort effects. RESULTS: Suicide was most common in young adults (aged around 25-40 years) living in deprived areas, with a younger peak in men. The peak age for suicide fell around 1990, especially for men for whom it dropped quickly from around 50 to 30 years. There was evidence of an increased risk of suicide for the cohort born between 1960 and 1980, especially among men living in the most deprived areas (of around 30%). The cohort at highest risk occurred earlier in the most deprived areas, 1965-1969 compared with 1970-1974. CONCLUSIONS: The risk of suicide increased in Scotland for those born between 1960 and 1980, especially for men living in the most deprived areas, which resulted in a rise in age-standardised rates for suicide among young adults during the 1990s. This is consistent with the hypothesis that exposure to neoliberal politics created a delayed negative health impact.

Evaluating the impact of a national naloxone programme on ambulance attendance at overdose incidents: a controlled time-series analysis.

BACKGROUND AND AIMS: It has been suggested that distributing naloxone to people who inject drugs (PWID) will lead to fewer attendances by emergency medical services at opioid-related overdose incidents if peer administration of naloxone was perceived to have resuscitated the overdose victim successfully. This study evaluated the impact of a national naloxone programme (NNP) on ambulance attendance at opioid-related overdose incidents throughout Scotland. Specifically, we aimed to answer the following research questions: is there evidence of an association between ambulance call-outs to opioid-related overdose incidents and the cumulative number of 'take-home naloxone' (THN) kits in issue; and is there evidence of an association between ambulance call-outs to opioid-related overdose incidents in early adopter (pilot) or later adopting (non-pilot) regions and the cumulative number of THN kits issued in those areas? DESIGN: Controlled time-series analysis. SETTING: Scotland, UK, 2008-15. PARTICIPANTS: Pre-NNP implementation period for the evaluation was defined as 1 April 2008 to 31 March 2011 and the post-implementation period as 1 April 2011 to 31 March 2015. In total, 3721 ambulance attendances at opioid-related overdose were recorded for the pre-NNP implementation period across 158 weeks (mean 23.6 attendances per week) and 5258 attendances across 212 weeks in the post-implementation period (mean 24.8 attendances per week). INTERVENTION: Scotland's NNP; formally implemented on 1 April 2011. MEASUREMENTS: Primary outcome measure was weekly incidence (counts) of call-outs to opioid-related overdoses at national and regional Health Board level. Data were acquired from the Scottish Ambulance Service (SAS). Models were adjusted for opioid replacement therapy using data acquired from the Information Services Division on monthly sums of all dispensed methadone and buprenorphine in the study period. Models were adjusted further for a control group: weekly incidence (counts) of call-outs to heroin-related overdose in the London Borough area acquired from the London Ambulance Service. FINDINGS: There was no significant association between SAS call-outs to opioid-related overdose incidents and THN kits in issue for Scotland as a whole (coefficient 0.009, 95% confidence intervals = -0.01, 0.03, P = 0.39). In addition, the magnitude of association between THN kits and SAS call-outs did not differ significantly between pilot and non-pilot regions (interaction test, P = 0.62). CONCLUSIONS: The supply of take-home naloxone kits through a National Naloxone Programme in Scotland was not associated clearly with a decrease in ambulance attendance at opioid-related overdose incidents in the 4-year period after it was implemented in April 2011.

The SCottish Alcoholic Liver disease Evaluation: A Population-Level Matched Cohort Study of Hospital-Based Costs, 1991-2011.

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses.