The Positive Choices trial: update to study protocol for a phase-III RCT trial of a whole-school social-marketing intervention to promote sexual health and reduce health inequalities.

BACKGROUND: Positive Choices is a whole-school social-marketing intervention to promote sexual health among secondary school students. Intervention comprises the following: school health promotion council involving staff and students coordinating delivery, student survey to inform local tailoring, teacher-delivered classroom curriculum, student-run campaigns, parent information and review of sexual/reproductive health services to inform improvements. This trial builds on an optimisation/pilot-RCT study which met progression criteria, plus findings from another pilot RCT of the Project Respect school-based intervention to prevent dating and relationship violence which concluded such work should be integrated within Positive Choices. Young people carry a disproportionate burden of adverse sexual health; most do not report competence at first sex. Relationships and sex education in schools can contribute to promoting sexual health but effects are small, inconsistent and not sustained. Such work needs to be supplemented by 'whole-school' (e.g. student campaigns, sexual health services) and 'social marketing' (harnessing commercial marketing to social ends) approaches for which there is good review-level evidence but not from the UK. METHODS: We will conduct a cluster RCT across 50 schools (minimum 6440, maximum 8500 students) allocated 1:1 to intervention/control assessing outcomes at 33 months. Our primary outcome is non-competent first sex. Secondary outcomes are non-competent last sex, age at sexual debut, non-use of contraception at first and last sex among those reporting heterosexual intercourse, number of sexual partners, dating and relationship violence, sexually transmitted infections and pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys. We will recruit 50 school and undertake baseline surveys by March 2022, implement the intervention over the 2022-2024 school years and conduct the economic and process evaluations by July 2024; undertake follow-up surveys by December 2024; complete analyses, all patient and policy involvement and draft the study report by March 2025 and engage in knowledge exchange from December 2024. DISCUSSION: This trial is one of a growing number focused on whole-school approaches to public health in schools. The key scientific output will be evidence about the effectiveness, costs and potential scalability and transferability of Positive Choices. TRIAL REGISTRATION: ISRCTN No: ISRCTN16723909 . Registered on 3 September 2021.

Achieving Quality and Effectiveness in Dementia Using Crisis Teams (AQUEDUCT): a study protocol for a randomised controlled trial of a Resource Kit.

BACKGROUND: Improving care at home for people with dementia is a core policy goal in the dementia strategies of many European countries. A challenge to effective home support is the occurrence of crises in the care of people with dementia which arise from changes in their health and social circumstances. Improving the management of these crises may prevent hospital admissions and facilitate better and longer care at home. This trial is part of a National Institute for Health Research funded programme, AQUEDUCT, which aims to improve the quality and effectiveness of teams working to manage crises in dementia. METHODS/DESIGN: It is a pragmatic randomised controlled trial of an online Resource Kit to enhance practice in teams managing crises in dementia care. Thirty teams managing mental health crises in dementia in community settings will be randomised between the Resource Kit intervention and treatment as usual. The primary outcome measure is psychiatric admissions to hospital for people with dementia in the teams' catchment area recorded 6 months after randomisation. Other outcomes include quality of life measures for people with dementia and their carers, practitioner impact measures, acute hospital admissions and costs. To enhance understanding of the Resource Kit intervention, qualitative work will explore staff, patient and carers' experience. DISCUSSION: The Resource Kit intervention reflects current policy to enable home-based care for people with dementia by addressing the management of crises which threaten the viability of care at home. It is based upon a model of best practice for managing crises in dementia designed to enhance the quality of care, developed in partnership with people with dementia, carers and practitioners. If the Resource Kit is shown to be clinically and cost-effective in this study, this will enhance the probability of its incorporation into mainstream practice. TRIAL REGISTRATION: ISRCTN 42855694 ; Registered on 04/03/2021; Protocol number: 127686/2020v9; Research Ethics Committee, 09/03/2021, Ref 21/WM/0004; IRAS ID: 289982.

A Board Level Intervention to Develop Organisation-Wide Quality Improvement Strategies: Cost-Consequences Analysis in 15 Healthcare Organisations.

BACKGROUND: Hospital boards have statutory responsibility for upholding the quality of care in their organisations. International research on quality in hospitals resulted in a research-based guide to help senior hospital leaders develop and implement quality improvement (QI) strategies, the QUASER Guide. Previous research has established a link between board practices and quality of care; however, to our knowledge, no board-level intervention has been evaluated in relation to its costs and consequences. The aim of this research was to evaluate these impacts when the QUASER Guide was implemented in an organisational development intervention (iQUASER). METHODS: We conducted a 'before and after' cost-consequences analysis (CCA), as part of a mixed methods evaluation. The analysis combined qualitative data collected from 66 interviews, 60 hours of board meeting observations and documents from 15 healthcare organisations, of which 6 took part on iQUASER, and included direct and opportunity costs associated with the intervention. The consequences focused on the development of an organisation-wide QI strategy, progress on addressing 8 dimensions of QI (the QUASER challenges), how organisations compared to benchmarks, engagement with the intervention and progress in the implementation of a QI project. RESULTS: We found that participating organisations made greater progress in developing an organisation-wide QI strategy and became more similar to the high-performing benchmark than the comparators. However, progress in addressing all 8 QUASER challenges was only observed in one organisation. Stronger engagement with the intervention was associated with the implementation of a QI project. On average, iQUASER costed £23 496 per participating organisation, of which approximately 44% were staff time costs. Organisations that engaged less with the intervention had lower than average costs (£21 267 per organisation), but also failed to implement an organisation-wide QI project. CONCLUSION: We found a positive association between level of engagement with the intervention, development of an organisation-wide QI strategy and the implementation of an organisation-wide QI project. Support from the board, particularly the chair and chief executive, for participation in the intervention, is important for organisations to accrue most benefit. A board-level intervention for QI, such as iQUASER, is relatively inexpensive as a proportion of an organisation's budget.

The Positive Choices trial: study protocol for a Phase-III RCT trial of a whole-school social marketing intervention to promote sexual health and reduce health inequalities.

BACKGROUND: Positive Choices is a whole-school social marketing intervention to promote sexual health among secondary school students. Intervention comprises school health promotion council involving staff and students coordinating delivery; student survey to inform local tailoring; teacher-delivered classroom curriculum; student-run campaigns; parent information; and review of sexual/reproductive health services to inform improvements. This trial builds on an optimisation/pilot RCT study which met progression criteria, plus findings from another pilot RCT of the Project Respect school-based intervention to prevent dating and relationship violence which concluded such work should be integrated within Positive Choices. Young people carry a disproportionate burden of adverse sexual health; most do not report competence at first sex. Relationships and sex education in schools can contribute to promoting sexual health but effects are small, inconsistent and not sustained. Such work needs to be supplemented by 'whole-school' (e.g. student campaigns, sexual health services) and 'social marketing' (harnessing commercial marketing to social ends) approaches for which there is good review-level evidence but not from the UK. METHODS: We will conduct a cluster RCT across 50 schools (minimum 6440, maximum 8500 students) allocated 1:1 to intervention/control assessing outcomes at 33 months. Our primary outcome is non-competent first sex. Secondary outcomes are non-competent last sex, age at sexual debut, non-use of contraception at first and last sex among those reporting heterosexual intercourse, number of sexual partners, dating and relationship violence, sexually transmitted infections, and pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys. We will recruit 50 school and undertake baseline surveys by March 2022; implement the intervention over the 2022-2024 school years and conduct the economic and process evaluations by July 2024; undertake follow-up surveys by December 2024; complete analyses, all patient and policy involvement and draft the study report by March 2025; and engage in knowledge exchange from December 2024. DISCUSSION: This trial is one of a growing number focused on whole-school approaches to public health in schools. The key scientific output will be evidence about the effectiveness, costs and potential scalability and transferability of Positive Choices. TRIAL REGISTRATION: ISRCTN No: ISRCTN16723909 . Trial registration summary: Date:. Funded by: National Institute for Health Research Public Health Research Programme (NIHR131487). SPONSOR: LSHTM. Public/scientific contact: Chris Bonell. Public title: Positive Choices trial. Scientific title: Phase-III RCT of Positive Choices: a whole-school social marketing intervention to promote sexual health and reduce health inequalities. Countries of recruitment: UK. INTERVENTION: Positive Choices. INCLUSION CRITERIA: Students in year 8 (age 12-13 years) at baseline deemed competent by schools to participate in secondary schools excluding pupil referral units, schools for those with special educational needs and disabilities, and schools with 'inadequate' Ofsted inspections. STUDY TYPE: interventional study with superiority phase III cluster RCT design. Enrollment: 1/9/21-31/3/22. SAMPLE SIZE: 50 schools and 6440-8500 students. Recruitment status: pending. PRIMARY OUTCOME: binary measure of non-competent first sex. SECONDARY OUTCOMES: non-competent last sex; age at sexual debut; non-use of contraception at first and last sex; number of sexual partners; dating and relationship violence (DRV) victimisation; sexually transmitted infections; pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys using adapted versions of the RIPPLE measures. Ethics review: LSHTM research ethics committee (reference 26411). Completion data: 1/3/25. Sharing statement: Data will be made available after the main trial analyses have been completed on reasonable request from researchers with ethics approval and a clear protocol. Amendments to the protocol will be communicated to the investigators, sponsor, funder, research ethics committee, trial registration and the journal publishing the protocol. Amendments affecting participants' experience of the intervention or important amendments affecting the overall design and conduct of the trial will be communicated to participants.

Evaluating the effectiveness and cost effectiveness of the 'strengthening families, strengthening communities' group-based parenting programme: study protocol and initial insights.

BACKGROUND: Up to 20% of UK children experience socio-emotional difficulties which can have serious implications for themselves, their families and society. Stark socioeconomic and ethnic inequalities in children's well-being exist. Supporting parents to develop effective parenting skills is an important preventive strategy in reducing inequalities. Parenting interventions have been developed, which aim to reduce the severity and impact of these difficulties. However, most parenting interventions in the UK focus on early childhood (0-10 years) and often fail to engage families from ethnic minority groups and those living in poverty. Strengthening Families, Strengthening Communities (SFSC) is a parenting programme designed by the Race Equality Foundation, which aims to address this gap. Evidence from preliminary studies is encouraging, but no randomised controlled trials have been undertaken so far. METHODS/DESIGN: The TOGETHER study is a multi-centre, waiting list controlled, randomised trial, which aims to test the effectiveness of SFSC in families with children aged 3-18 across seven urban areas in England with ethnically and socially diverse populations. The primary outcome is parental mental well-being (assessed by the Warwick-Edinburgh Mental Well-Being Scale). Secondary outcomes include child socio-emotional well-being, parenting practices, family relationships, self-efficacy, quality of life, and community engagement. Outcomes are assessed at baseline, post intervention, three- and six-months post intervention. Cost effectiveness will be estimated using a cost-utility analysis and cost-consequences analysis. The study is conducted in two stages. Stage 1 comprised a 6-month internal pilot to determine the feasibility of the trial. A set of progression criteria were developed to determine whether the stage 2 main trial should proceed. An embedded process evaluation will assess the fidelity and acceptability of the intervention. DISCUSSION: In this paper we provide details of the study protocol for this trial. We also describe challenges to implementing the protocol and how these were addressed. Once completed, if beneficial effects on both parental and child outcomes are found, the impact, both immediate and longer term, are potentially significant. As the intervention focuses on supporting families living in poverty and those from minority ethnic communities, the intervention should also ultimately have a beneficial impact on reducing health inequalities. TRIAL REGISTRATION: Prospectively registered Randomised Controlled Trial ISRCTN15194500 .

How to Cost the Implementation of Major System Change for Economic Evaluations: Case Study Using Reconfigurations of Specialist Cancer Surgery in Part of London, England.

BACKGROUND: Studies have been published regarding the impact of major system change (MSC) on care quality and outcomes, but few evaluate implementation costs or include them in cost-effectiveness analysis (CEA). This is despite large potential costs of MSC: change planning, purchasing or repurposing assets, and staff time. Implementation costs can influence implementation decisions. We describe our framework and principles for costing MSC implementation and illustrate them using a case study. METHODS: We outlined MSC implementation stages and identified components, using a framework conceived during our work on MSC in stroke services. We present a case study of MSC of specialist surgery services for prostate, bladder, renal and oesophagogastric cancers, focusing on North Central and North East London and West Essex. Health economists collaborated with qualitative researchers, clinicians and managers, identifying key reconfiguration stages and expenditures. Data sources (n = approximately 100) included meeting minutes, interviews, and business cases. National Health Service (NHS) finance and service managers and clinicians were consulted. Using bottom-up costing, items were identified, and unit costs based on salaries, asset costs and consultancy fees assigned. Itemised costs were adjusted and summed. RESULTS: Cost components included options appraisal, bidding process, external review; stakeholder engagement events; planning/monitoring boards/meetings; and making the change: new assets, facilities, posts. Other considerations included hospital tariff changes; costs to patients; patient population; and lifetime of changes. Using the framework facilitated data identification and collection. The total adjusted implementation cost was estimated at £7.2 million, broken down as replacing robots (£4.0 million), consultancy fees (£1.9 million), staff time costs (£1.1 million) and other costs (£0.2 million). CONCLUSIONS: These principles can be used by funders, service providers and commissioners planning MSC and researchers evaluating MSC. Health economists should be involved early, alongside qualitative and health-service colleagues, as retrospective capture risks information loss. These analyses are challenging; many cost factors are difficult to identify, access and measure, and assumptions regarding lifetime of the changes are important. Including implementation costs in CEA might make MSC appear less cost effective, influencing future decisions. Future work will incorporate this implementation cost into the full CEAs of the London Cancer MSC. TRIAL REGISTRATION: Not applicable.

Dental attendance and behavioural pathways to adult oral health inequalities.

BACKGROUND: While inequalities in oral health are documented, little is known about the extent to which they are attributable to potentially modifiable factors. We examined the role of behavioural and dental attendance pathways in explaining oral health inequalities among adults in England, Wales and Northern Ireland. METHODS: Using nationally representative data, we analysed inequalities in self-rated oral health and number of natural teeth. Highest educational attainment, equivalised household income and occupational social class were used to derive a latent socioeconomic position (SEP) variable. Pathways were dental attendance and behaviours (smoking and oral hygiene). We used structural equation modelling to test the hypothesis that SEP influences oral health directly and also indirectly via dental attendance and behavioural pathways. RESULTS: Lower SEP was directly associated with fewer natural teeth and worse self-rated oral health (standardised path coefficients, -0.21 (SE=0.01) and -0.10 (SE=0.01), respectively). We also found significant indirect effects via behavioural factors for both outcomes and via dental attendance primarily for self-rated oral health. While the standardised parameters of total effects were similar between the two outcomes, for number of teeth, the estimated effect of SEP was mostly direct while for self-rated oral health, it was almost equally split between direct and indirect effects. CONCLUSION: Reducing inequalities in dental attendance and health behaviours is necessary but not sufficient to tackle socioeconomic inequalities in oral health.

A model-based cost-utility analysis of multi-professional simulation training in obstetric emergencies.

OBJECTIVE: To determine the cost-utility of a multi-professional simulation training programme for obstetric emergencies-Practical Obstetric Multi-Professional Training (PROMPT)-with a particular focus on its impact on permanent obstetric brachial plexus injuries (OBPIs). DESIGN: A model-based cost-utility analysis. SETTING: Maternity units in England. POPULATION: Simulated cohorts of individuals affected by permanent OBPIs. METHODS: A decision tree model was developed to estimate the cost-utility of adopting annual, PROMPT training (scenario 1a) or standalone shoulder dystocia training (scenario 1b) in all maternity units in England compared to current practice, where only a proportion of English units use the training programme (scenario 2). The time horizon was 30 years and the analysis was conducted from an English National Health Service (NHS) and Personal Social Services perspective. A probabilistic sensitivity analysis was performed to account for uncertainties in the model parameters. MAIN OUTCOME MEASURES: Outcomes for the entire simulated period included the following: total costs for PROMPT or shoulder dystocia training (including costs of OBPIs), number of OBPIs averted, number of affected adult/parental/dyadic quality adjusted life years (QALYs) gained and the incremental cost per QALY gained. RESULTS: Nationwide PROMPT or shoulder dystocia training conferred significant savings (in excess of £1 billion ($1.5 billion)) compared to current practice, resulting in cost-savings of at least £1 million ($1.5 million) per any type of QALY gained. The probabilistic sensitivity analysis demonstrated similar findings. CONCLUSION: In this model, national implementation of multi-professional simulation training for obstetric emergencies (or standalone shoulder dystocia training) in England appeared to both be cost-saving when evaluating their impact on permanent OBPIs.

Promoting Independence in Dementia (PRIDE): protocol for a feasibility randomised controlled trial.

BACKGROUND: Memory services often see people with early stage dementia who are largely independent and able to participate in community activities but who run the risk of reducing activities and social networks. PRIDE is a self-management intervention designed to promote living well and enhance independence for people with mild dementia. This study aims to examine the feasibility of conducting a definitive randomised trial comparing the clinical and cost-effectiveness of the PRIDE intervention offered in addition to usual care or with usual care alone. METHODS/DESIGN: PRIDE is a parallel, two-arm, multicentre, feasibility, randomised controlled trial (RCT). Eligible participants aged 18 or over who have mild dementia (defined as a score of 0.5 or 1 on the Clinical Dementia Rating Scale) who can participate in the intervention and provide informed consent will be randomised (1:1) to treatment with the PRIDE intervention delivered in addition to usual care, or usual care only. Participants will be followed-up at 3 and 6 month's post-randomisation. There will be an option for a supporter to join each participant. Each supporter will be provided with questionnaires at baseline and follow-ups at 3 to 6 months. Embedded qualitative research with both participants and supporters will explore their perspectives on the intervention investigating a range of themes including acceptability and barriers and facilitators to delivery and participation. The feasibility of conducting a full RCT associated with participant recruitment and follow-up of both conditions, intervention delivery including the recruitment, training, retention of PRIDE trained facilitators, clinical outcomes, intervention and resource use costs and the acceptability of the intervention and study related procedures will be examined. DISCUSSION: This study will assess whether a definitive randomised trial comparing the clinical and cost-effectiveness of whether the PRIDE intervention offered in addition to usual care is feasible in comparison to usual care alone, and if so, will provide data to inform the design and conduct of a future trial. TRIAL REGISTRATION: ISRCTN, ISRCTN11288961, registered on 23 October 2019, http://www.isrctn.com/ISRCTN12345678 Protocol V2.1 dated 19 June 2019.

Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.

BACKGROUND: The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening. METHODS AND FINDINGS: A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose. CONCLUSIONS: Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness.

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer.

BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

Protocol for pilot cluster RCT of project respect: a school-based intervention to prevent dating and relationship violence and address health inequalities among young people.

BACKGROUND: Dating and relationship violence (DRV)-intimate partner violence during adolescence-encompasses physical, sexual and emotional abuse. DRV is associated with a range of adverse health outcomes including injuries, sexually transmitted infections, adolescent pregnancy and mental health issues. Experiencing DRV also predicts both victimisation and perpetration of partner violence in adulthood.Prevention targeting early adolescence is important because this is when dating behaviours begin, behavioural norms become established and DRV starts to manifest. Despite high rates of DRV victimisation in England, from 22 to 48% among girls and 12 to 27% among boys ages 14-17 who report intimate relationships, no RCTs of DRV prevention programmes have taken place in the UK. Informed by two school-based interventions that have shown promising results in RCTs in the USA-Safe Dates and Shifting Boundaries-Project Respect aims to optimise and pilot a DRV prevention programme for secondary schools in England. METHODS: Design: optimisation and pilot cluster RCT. Trial will include a process evaluation and assess the feasibility of conducting a phase III RCT with embedded economic evaluation. Cognitive interviewing will inform survey development.Participants: optimisation involves four schools and pilot RCT involves six (four intervention, two control). All are secondary schools in England. Baseline surveys conducted with students in years 8 and 9 (ages 12-14). Follow-up surveys conducted with the same cohort, 16 months post-baseline. Optimisation sessions to inform intervention and research methods will involve consultations with stakeholders, including young people.Intervention: school staff training, including guidance on reviewing school policies and addressing 'hotspots' for DRV and gender-based harassment; information for parents; informing students of a help-seeking app; and a classroom curriculum for students in years 9 and 10, including a student-led campaign.Primary outcome: the primary outcome of the pilot RCT will be whether progression to a phase III RCT is justified. Testing within the pilot will also determine which of two existing scales is optimal for assessing DRV victimisation and perpetration in a phase III RCT. DISCUSSION: This will be the first RCT of an intervention to prevent DRV in the UK. If findings indicate feasibility and acceptability, we will undertake planning for a phase III RCT of effectiveness. TRIAL REGISTRATION: ISRCTN, ISRCTN 65324176. Registered 8 June 2017.

Cost-effectiveness of a domestic violence and abuse training and support programme in primary care in the real world: updated modelling based on an MRC phase IV observational pragmatic implementation study.

OBJECTIVES: To evaluate the cost-effectiveness of the implementation of the Identification and Referral to Improve Safety (IRIS) programme using up-to-date real-world information on costs and effectiveness from routine clinical practice. A Markov model was constructed to estimate mean costs and quality-adjusted life-years (QALYs) of IRIS versus usual care per woman registered at a general practice from a societal and health service perspective with a 10-year time horizon. DESIGN AND SETTING: Cost-utility analysis in UK general practices, including data from six sites which have been running IRIS for at least 2 years across England. PARTICIPANTS: Based on the Markov model, which uses health states to represent possible outcomes of the intervention, we stipulated a hypothetical cohort of 10 000 women aged 16 years or older. INTERVENTIONS: The IRIS trial was a randomised controlled trial that tested the effectiveness of a primary care training and support intervention to improve the response to women experiencing domestic violence and abuse, and found it to be cost-effective. As a result, the IRIS programme has been implemented across the UK, generating data on costs and effectiveness outside a trial context. RESULTS: The IRIS programme saved £14 per woman aged 16 years or older registered in general practice (95% uncertainty interval -£151 to £37) and produced QALY gains of 0.001 per woman (95% uncertainty interval -0.005 to 0.006). The incremental net monetary benefit was positive both from a societal and National Health Service perspective (£42 and £22, respectively) and the IRIS programme was cost-effective in 61% of simulations using real-life data when the cost-effectiveness threshold was £20 000 per QALY gained as advised by National Institute for Health and Care Excellence. CONCLUSION: The IRIS programme is likely to be cost-effective and cost-saving from a societal perspective in the UK and cost-effective from a health service perspective, although there is considerable uncertainty surrounding these results, reflected in the large uncertainty intervals.

Cost-effectiveness and Benefit-to-Harm Ratio of Risk-Stratified Screening for Breast Cancer: A Life-Table Model.

Importance: The age-based or "one-size-fits-all" breast screening approach does not take into account the individual variation in risk. Mammography screening reduces death from breast cancer at the cost of overdiagnosis. Identifying risk-stratified screening strategies with a more favorable ratio of overdiagnoses to breast cancer deaths prevented would improve the quality of life of women and save resources. Objective: To assess the benefit-to-harm ratio and the cost-effectiveness of risk-stratified breast screening programs compared with a standard age-based screening program and no screening. Design, Setting, and Population: A life-table model was created of a hypothetical cohort of 364 500 women in the United Kingdom, aged 50 years, with follow-up to age 85 years, using (1) findings of the Independent UK Panel on Breast Cancer Screening and (2) risk distribution based on polygenic risk profile. The analysis was undertaken from the National Health Service perspective. Interventions: The modeled interventions were (1) no screening, (2) age-based screening (mammography screening every 3 years from age 50 to 69 years), and (3) risk-stratified screening (a proportion of women aged 50 years with a risk score greater than a threshold risk were offered screening every 3 years until age 69 years) considering each percentile of the risk distribution. All analyses took place between July 2016 and September 2017. Main Outcomes and Measures: Overdiagnoses, breast cancer deaths averted, quality-adjusted life-years (QALYs) gained, costs in British pounds, and net monetary benefit (NMB). Probabilistic sensitivity analyses were used to assess uncertainty around parameter estimates. Future costs and benefits were discounted at 3.5% per year. Results: The risk-stratified analysis of this life-table model included a hypothetical cohort of 364 500 women followed up from age 50 to 85 years. As the risk threshold was lowered, the incremental cost of the program increased linearly, compared with no screening, with no additional QALYs gained below 35th percentile risk threshold. Of the 3 screening scenarios, the risk-stratified scenario with risk threshold at the 70th percentile had the highest NMB, at a willingness to pay of £20 000 (US $26 800) per QALY gained, with a 72% probability of being cost-effective. Compared with age-based screening, risk-stratified screening at the 32nd percentile vs 70th percentile risk threshold would cost £20 066 (US $26 888) vs £537 985 (US $720 900) less, would have 26.7% vs 71.4% fewer overdiagnoses, and would avert 2.9% vs 9.6% fewer breast cancer deaths, respectively. Conclusions and Relevance: Not offering breast cancer screening to women at lower risk could improve the cost-effectiveness of the screening program, reduce overdiagnosis, and maintain the benefits of screening.

Study protocol for the optimisation, feasibility testing and pilot cluster randomised trial of Positive Choices: a school-based social marketing intervention to promote sexual health, prevent unintended teenage pregnancies and address health inequalities in England.

BACKGROUND: Since the introduction of the Teenage Pregnancy Strategy (TPS), England's under-18 conception rate has fallen by 55%, but a continued focus on prevention is needed to maintain and accelerate progress. The teenage birth rate remains higher in the UK than comparable Western European countries. Previous trials indicate that school-based social marketing interventions are a promising approach to addressing teenage pregnancy and improving sexual health. Such interventions are yet to be trialled in the UK. This study aims to optimise and establish the feasibility and acceptability of one such intervention: Positive Choices. METHODS: Design: Optimisation, feasibility testing and pilot cluster randomised trial.Interventions: The Positive Choices intervention comprises a student needs survey, a student/staff led School Health Promotion Council (SHPC), a classroom curriculum for year nine students covering social and emotional skills and sex education, student-led social marketing activities, parent information and a review of school sexual health services.Systematic optimisation of Positive Choices will be carried out with the National Children's Bureau Sex Education Forum (NCB SEF), one state secondary school in England and other youth and policy stakeholders.Feasibility testing will involve the same state secondary school and will assess progression criteria to advance to the pilot cluster RCT.Pilot cluster RCT with integral process evaluation will involve six different state secondary schools (four interventions and two controls) and will assess the feasibility and utility of progressing to a full effectiveness trial.The following outcome measures will be trialled as part of the pilot:Self-reported pregnancy and unintended pregnancy (initiation of pregnancy for boys) and sexually transmitted infections,Age of sexual debut, number of sexual partners, use of contraception at first and last sex and non-volitional sexEducational attainmentThe feasibility of linking administrative data on births and termination to self-report survey data to measure our primary outcome (unintended teenage pregnancy) will also be tested. DISCUSSION: This will be the first UK-based pilot trial of a school-wide social marketing intervention to reduce unintended teenage pregnancy and improve sexual health. If this study indicates feasibility and acceptability of the optimised Positive Choices intervention in English secondary schools, plans will be initiated for a phase III trial and economic evaluation of the intervention. TRIAL REGISTRATION: ISRCTN registry (ISCTN12524938. Registered 03/07/2017).

Clinical and cost-effectiveness of an intervention for reducing cholesterol and cardiovascular risk for people with severe mental illness in English primary care: a cluster randomised controlled trial.

BACKGROUND: People with severe mental illnesses, including psychosis, have an increased risk of cardiovascular disease. We aimed to evaluate the effects of a primary care intervention on decreasing total cholesterol concentrations and cardiovascular disease risk in people with severe mental illnesses. METHODS: We did this cluster randomised trial in general practices across England, with general practices as the cluster unit. We randomly assigned general practices (1:1) with 40 or more patients with severe mental illnesses using a computer-generated random sequence with a block size of four. Researchers were masked to allocation, but patients and general practice staff were not. We included participants aged 30-75 years with severe mental illnesses (schizophrenia, bipolar disorder, or psychosis), who had raised cholesterol concentrations (5·0 mmol/L) or a total:HDL cholesterol ratio of 4·0 mmol/L or more and one or more modifiable cardiovascular disease risk factors. Eligible participants were recruited within each practice before randomisation. The Primrose intervention consisted of appointments (≤12) with a trained primary care professional involving manualised interventions for cardiovascular disease prevention (ie, adhering to statins, improving diet or physical activity levels, reducing alcohol, or quitting smoking). Treatment as usual involved feedback of screening results only. The primary outcome was total cholesterol at 12 months and the primary economic analysis outcome was health-care costs. We used intention-to-treat analysis. The trial is registered with Current Controlled Trials, number ISRCTN13762819. FINDINGS: Between Dec 10, 2013, and Sept 30, 2015, we recruited general practices and between May 9, 2014, and Feb 10, 2016, we recruited participants and randomly assigned 76 general practices with 327 participants to the Primrose intervention (n=38 with 155 patients) or treatment as usual (n=38 with 172 patients). Total cholesterol concentration data were available at 12 months for 137 (88%) participants in the Primrose intervention group and 152 (88%) participants in the treatment-as-usual group. The mean total cholesterol concentration did not differ at 12 months between the two groups (5·4 mmol/L [SD 1·1] for Primrose vs 5·5 mmol/L [1·1] for treatment as usual; mean difference estimate 0·03, 95% CI -0·22 to 0·29; p=0·788). This result was unchanged by pre-agreed supportive analyses. Mean cholesterol decreased over 12 months (-0·22 mmol/L [1·1] for Primrose vs -0·36 mmol/L [1·1] for treatment as usual). Total health-care costs (£1286 [SE 178] in the Primrose intervention group vs £2182 [328] in the treatment-as-usual group; mean difference -£895, 95% CI -1631 to -160; p=0·012) and psychiatric inpatient costs (£157 [135] vs £956 [313]; -£799, -1480 to -117; p=0·018) were lower in the Primrose intervention group than the treatment-as-usual group. Six serious adverse events of hospital admission and one death occurred in the Primrose group (n=7) and 23, including three deaths, occurred in the treatment-as-usual group (n=18). INTERPRETATION: Total cholesterol concentration at 12 months did not differ between the Primrose and treatment-as-usual groups, possibly because of the cluster design, good care in the treatment-as-usual group, short duration of the intervention, or suboptimal focus on statin prescribing. The association between the Primrose intervention and fewer psychiatric admissions, with potential cost-effectiveness, might be important. FUNDING: National Institute of Health Research Programme Grants for Applied Research.

Estimating preferences for modes of drug administration: The case of US healthcare professionals.

BACKGROUND: There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. OBJECTIVES: This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. METHODS: A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. RESULTS: The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. CONCLUSIONS: An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general.

Cost-effectiveness of laparoscopic versus open distal pancreatectomy for pancreatic cancer.

BACKGROUND: A recent Cochrane review compared laparoscopic versus open distal pancreatectomy for people with for cancers of the body and tail of the pancreas and found that laparoscopic distal pancreatectomy may reduce the length of hospital stay. We compared the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy for pancreatic cancer. METHOD: Model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service. A decision tree model was constructed using probabilities, outcomes and cost data from published sources. A time horizon of 5 years was used. One-way and probabilistic sensitivity analyses were undertaken. RESULTS: The probabilistic sensitivity analysis showed that the incremental net monetary benefit was positive (£3,708.58 (95% confidence intervals (CI) -£9,473.62 to £16,115.69) but the 95% CI includes zero, indicating that there is significant uncertainty about the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy. The probability laparoscopic distal pancreatectomy was cost-effective compared to open distal pancreatectomy for pancreatic cancer was between 70% and 80% at the willingness-to-pay thresholds generally used in England (£20,000 to £30,000 per QALY gained). Results were sensitive to the survival proportions and the operating time. CONCLUSIONS: There is considerable uncertainty about whether laparoscopic distal pancreatectomy is cost-effective compared to open distal pancreatectomy for pancreatic cancer in the NHS setting.