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Background\ud \ud Falls impose significant health and economic burdens on community-dwelling older persons. Decision modelling can inform commissioning of alternative falls prevention strategies. Several methodological challenges arise when modelling public health interventions including community-based falls prevention. This study aims to conduct a systematic review (SR) to: systematically identify community-based falls prevention economic models; synthesise and critically appraise how the models handled key methodological challenges associated with public health modelling; and suggest areas for further methodological research.\ud \ud \ud \ud Methods\ud \ud The SR followed the 2021 PRISMA reporting guideline and covered the period 2003–2020 and 12 academic databases and grey literature. The extracted methodological features of included models were synthesised by their relevance to the following challenges: (1) capturing non-health outcomes and societal intervention costs; (2) considering heterogeneity and dynamic complexity; (3) considering theories of human behaviour and implementation; and (4) considering equity issues. The critical appraisal assessed the prevalence of each feature across models, then appraised the methods used to incorporate the feature. The methodological strengths and limitations stated by the modellers were used as indicators of desirable modelling practice and scope for improvement, respectively. The methods were also compared against those suggested in the broader empirical and methodological literature. Areas of further methodological research were suggested based on appraisal results.\ud \ud \ud \ud Results\ud \ud 46 models were identified. Comprehensive incorporation of non-health outcomes and societal intervention costs was infrequent. The assessments of heterogeneity and dynamic complexity were limited; subgroup delineation was confined primarily to demographics and binary disease/physical status. Few models incorporated heterogeneity in intervention implementation level, efficacy and cost. Few dynamic variables other than age and falls history were incorporated to characterise the trajectories of falls risk and general health/frailty. Intervention sustainability was frequently based on assumptions; few models estimated the economic/health returns from improved implementation. Seven models incorporated ethnicity- and severity-based subgroups but did not estimate the equity-efficiency trade-offs. Sixteen methodological research suggestions were made.\ud \ud \ud \ud Conclusion\ud \ud Existing community-based falls prevention models contain methodological limitations spanning four challenge areas relevant for public health modelling. There is scope for further methodological research to inform the development of falls prevention and other public health models.

Background\ud \ud Falls impose significant health and economic burdens on older people. The volume of falls prevention economic evaluations has increased, the findings from which have been synthesised by systematic reviews (SRs). Such SRs can inform commissioning and design of future evaluations; however, their findings can be misleading and incomplete, dependent on their pre-specified criteria. This study aims to conduct a systematic overview (SO) to: (1) systematically identify SRs of community-based falls prevention economic evaluations; (2) describe the methodology and findings of SRs; (3) critically appraise the methodology of SRs; and (4) suggest commissioning recommendations based on SO findings.\ud \ud \ud \ud Methods\ud \ud The SO followed the PRISMA guideline and the Cochrane guideline on SO, covering 12 databases and grey literature for the period 2003–2020. Eligible studies were SRs with 50% or more included studies that were economic evaluations of community-based falls prevention (against any comparator) for older persons (aged 60 +) or high-risk individuals aged 50–59. Identified SRs’ aims, search strategies and results, extracted data fields, quality assessment methods/results, and commissioning and research recommendations were synthesised. The comprehensiveness of previous SRs’ data synthesis was judged against criteria drawn from literature on falls prevention/public health economic evaluation. Outcomes of general population, lifetime decision models were re-analysed to inform commissioning recommendations. The SO protocol is registered in the Prospective Register of Systematic Reviews (CRD42021234379).\ud \ud \ud \ud Results\ud \ud Seven SRs were identified, which extracted 8 to 33 data fields from 44 economic evaluations. Four economic evaluation methodological/reporting quality checklists were used; three SRs narratively synthesised methodological features to varying extent and focus. SRs generally did not appraise decision modelling features, including methods for characterising dynamic complexity of falls risk and intervention need. Their commissioning recommendations were based mainly on cost-per-unit ratios (e.g., incremental cost-effectiveness ratios) and neglected aggregate impact. There is model-based evidence of multifactorial and environmental interventions, home assessment and modification and Tai Chi being cost-effective but also the risk that they exacerbate social inequities of health.\ud \ud \ud \ud Conclusions\ud \ud Current SRs of falls prevention economic evaluations do not holistically inform commissioning and evaluation. Accounting for broader decisional factors and methodological nuances of economic evaluations, particularly decision models, is needed.

Introduction\ud \ud The WHO-Europe’s Health Economic Assessment Tool is a tool used to estimate the costs and benefits of changes in walking and cycling. Due to data limitations the tool’s physical activity module assumes a linear dose response relationship be-tween physical activity and mortality.\ud \ud \ud \ud Methods\ud \ud This study estimates baseline population physical activity distributions for 44 countries included in the HEAT. It then compares, for three different scenarios, the results generated by the current method, using a linear dose-response relationship, with results generated using a non-linear dose-response relationship.\ud \ud \ud \ud Results\ud \ud The study finds that estimated deaths averted are relatively higher (lower) using the non-linear effect in countries with less (more) active populations. This difference is largest for interventions which affect the activity levels of the least active the most. Since more active populations, e.g. in Eastern Europe, also tend to have lower Value of a Statistical Life estimates the net monetary benefit estimated by the scenarios are much higher in western-Europe than eastern-Europe.\ud \ud \ud \ud Conclusions\ud \ud Using a non-linear dose response function results in materially different estimates where populations are particularly inactive or particularly active. Estimating base-line distributions is possible with limited additional data requirements, although the method has yet to be validated. Given the significant role of the physical activity module within the HEAT tool it is likely that in the evaluation of many interventions the monetary benefit estimates will be sensitive to the choice of the physical activity dose response function.

AIM: To analyse the cost-effectiveness of different interventions for Type 2 diabetes prevention. within a common framework METHODS: A micro-simulation model was developed to evaluate the cost-effectiveness of a range of diabetes prevention interventions including: (1) soft drinks taxation; (2) retail policy in socially deprived areas; (3) workplace intervention; (4) community-based intervention; and (5) screening and intensive lifestyle intervention in individuals with high diabetes risk. Within the model, individuals follow metabolic trajectories (for BMI, cholesterol, systolic blood pressure and glycaemia); individuals may develop diabetes, and some may exhibit complications of diabetes and related disorders, including cardiovascular disease, and eventually die. Lifetime healthcare costs, employment costs and quality-adjusted life-years are collected for each person. RESULTS: All interventions generate more life-years and lifetime quality-adjusted life-years and reduce healthcare spending compared with doing nothing. Screening and intensive lifestyle intervention generates greatest lifetime net benefit (£37) but is costly to implement. In comparison, soft drinks taxation or retail policy generate lower net benefit (£11 and £11) but are cost-saving in a shorter time period, preferentially benefit individuals from deprived backgrounds and reduce employer costs. CONCLUSION: The model enables a wide range of diabetes prevention interventions to be evaluated according to cost-effectiveness, employment and equity impacts over the short and long term, allowing decision-makers to prioritize policies that maximize the expected benefits, as well as fulfilling other policy targets, such as addressing social inequalities. This article is protected by copyright. All rights reserved.

AIMS: To develop a cost-effectiveness model to compare Type 2 diabetes prevention programmes targeting different at-risk population subgroups with a lifestyle intervention of varying intensity. METHODS: An individual patient simulation model was constructed to simulate the development of diabetes in a representative sample of adults without diabetes from the UK population. The model incorporates trajectories for HbA1c , 2-h glucose, fasting plasma glucose, BMI, systolic blood pressure, total cholesterol and HDL cholesterol. Patients can be diagnosed with diabetes, cardiovascular disease, microvascular complications of diabetes, cancer, osteoarthritis and depression, or can die. The model collects costs and utilities over a lifetime horizon. The perspective is the UK National Health Service and personal social services. We used the model to evaluate the population-wide impact of targeting a lifestyle intervention of varying intensity to six population subgroups defined as high risk for diabetes. RESULTS: The intervention produces 0.0003 to 0.0009 incremental quality-adjusted life years and saves up to £1.04 per person in the general population, depending upon the subgroup targeted. Cost-effectiveness increases with intervention intensity. The most cost-effective options are to target individuals with HbA1c > 42 mmol/mol (6%) or with a high Finnish Diabetes Risk (FINDRISC) probability score (> 0.1). CONCLUSION: The model indicates that diabetes prevention interventions are likely to be cost-effective and may be cost-saving over a lifetime. In the model, the criteria for selecting at-risk individuals differentially impact upon diabetes and cardiovascular disease outcomes, and on the timing of benefits. These findings have implications for deciding who should be targeted for diabetes prevention interventions.

Type-2 diabetes is a complex disease with multiple risk factors and health consequences whose prevention is a major public health priority. We have developed a microsimulation model written in the R programming language that can evaluate the effectiveness and cost-effectiveness of a comprehensive range of different diabetes prevention interventions, either in the general population or in subgroups at high risk of diabetes. Within the model individual patients with different risk factors for diabetes follow metabolic trajectories (for body mass index, cholesterol, systolic blood pressure and glycaemia), develop diabetes, complications of diabetes and related disorders including cardiovascular disease and cancer, and eventually die. Lifetime costs and quality-adjusted life-years are collected for each patient. The model allows assessment of the wider social impact on employment and the equity impact of different interventions. Interventions may be population-based, community-based or individually targeted, and administered singly or layered together. The model is fully enabled for probabilistic sensitivity analysis (PSA) to provide an estimate of decision uncertainty. This discussion paper provides a detailed description of the model background, methods and assumptions, together with details of all parameters used in the model, their sources and distributions for PSA.

Background: Nilotinib is a tyrosine kinase inhibitor (TKI) for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML) in chronic phase. The ENESTnd phase III trial demonstrated that nilotinib has clinical superiority over current standard treatment of first-line imatinib in patients with chronic phase Ph+ CML, on the basis that fewer patients progressed to accelerated phase/blast crisis. Whilst the clinical benefits of nilotinib have been demonstrated, the cost-effectiveness of first-line nilotinib has not been explored.\ud \ud Aim: To evaluate the cost-effectiveness of first-line nilotinib followed by second-line dasatinib compared to first-line imatinib followed by second-line dasatinib for patients newly diagnosed with chronic phase Ph+ CML.\ud \ud Methods: A Markov state-transition model based on the 24 month follow-up from the ENESTnd randomised controlled trial was developed to simulate the transitions of a hypothetical cohort of patients over a lifetime. The model estimates when one treatment will fail and hence the patient is switched to an alternative treatment. Patients who discontinue first-line treatment go on to second-line dasatinib. Patients who fail on second-line dasatinib receive stem cell transplantation or HU therapy. Patients transition from chronic phase, to accelerated phase, to blast crisis, to CML-related mortality. Patients may die from other causes at any time. EQ-5D utilities were applied to patients in each health state and utility decrements were estimated for patients experiencing severe (grade 3 and 4) adverse events (AEs) on TKI therapy. Costs (2010/11 Sterling) were estimated from the perspective of the UK National Health Service (NHS) and Personal Social Services (PSS). These include the costs associated with the different drug therapies, stem cell transplantation, routine hospital appointments for administration and monitoring, and treatment for severe AEs. A patient access scheme is available for first-line nilotinib therapy and is included in the analysis. All costs and QALYs were discounted by 3.5% as recommended by NICE. Probabilistic sensitivity analysis (PSA) was conducted to explore the impact of the joint uncertainty of all model parameters on the cost-effectiveness results. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life-years (QALYs) gained. Cost-effectiveness acceptability curves (CEACs) were also generated.\ud \ud Results: The mean undiscounted survival in the nilotinib arm was estimated to be 13.96 years compared to 13.32 years in the imatinib arm. Over a lifetime horizon patients are estimated to gain an additional 0.64 life-years (LYs) and 0.49 quality-adjusted life-years (QALYs) in the nilotinib arm compared to the imatinib arm. Using a discount rate of 3.5% patients are estimated to accrue an additional 0.35 LYs and 0.28 QALYs in the nilotinib arm compared to the imatinib arm. Expected lifetime (discounted) costs in the nilotinib arm were £220,416 compared to £232,941 in the imatinib arm. The nilotinib arm dominates the imatinib arm as it is more effective and less costly.\ud \ud Conclusions: The results suggest that nilotinib produces improvements in survival and QALYs compared to standard treatment of first-line imatinib and it is likely to offer a cost-effective use of NHS resources.

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Background: The rates of teenage pregnancy in the UK are relatively high. Although early entry to parenthood can be a positive experience, most studies find large adverse effects on long term outcomes for the mother, child and father, in addition to being costly for the NHS. This is why the government launched its Teenage Pregnancy Strategy in 1999. However, there is growing evidence that teenage pregnancy might be mainly an indicator of disadvantage which is the underlying cause of the negative outcomes.\ud \ud Methods: A systematic literature review was undertaken of studies which used a UK dataset to quantify any long term outcomes of a teenage birth upon the mother, father or child. Studies were included if they used appropriate methods to isolate the causal effect of early parenthood. The databases searched included Medline, Cochrane, EconLit and Web of Science.\ud \ud Results: Six studies were identified by the review; five studies considered the mother’s socioeconomic outcomes, one study reported the child’s outcomes, and no studies met the inclusion criteria for the father’s outcomes. The studies suggested that early motherhood accounts for relatively few of the negative long term socioeconomic outcomes and it is predominantly an indicator of a disadvantaged family background.\ud \ud Conclusion: Limited evidence is available to understand the long term outcomes associated with teenage birth within the UK for the mother, father and child. Current econometric studies suggest that effective interventions to prevent teenage pregnancies will not eradicate the poorer long term socioeconomic outcomes often associated with early motherhood. Thus policy should focus on reducing initial disadvantage in addition to preventing teenage pregnancy. Additional econometric analyses around the mothers’, fathers’ and children’s long term socioeconomic and health-related outcomes would be\ud valuable.