Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with Juvenile Idiopathic Arthritis

Purpose To investigate the cost effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with juvenile idiopathic arthritis (JIA). Design A cost-utility analysis based on a clinical trial and decision analytic model. Participants Children and adolescents 2 to 18 years of age with persistently active uveitis associated with JIA, despite optimized methotrexate treatment for at least 12 weeks. Methods The SYCAMORE (Randomised controlled trial of the clinical effectiveness, SafetY and Cost effectiveness of Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis) trial (identifier, ISRCTN10065623) of methotrexate (up to 25 mg weekly) with or without fortnightly administered adalimumab (20 or 40 mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. Main Outcome Measures Medical costs to the National Health Service in the United Kingdom, utility of defined health states, quality-adjusted life-years (QALYs), and incremental cost per QALY. Results Adalimumab in combination with methotrexate resulted in additional costs of £39 316, with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129 025 per QALY gained. The probability of cost effectiveness at a threshold of £30 000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost effective. Conclusions Adalimumab is clinically effective in uveitis associated with JIA; however, its cost effectiveness is not demonstrated compared with methotrexate alone in the United Kingdom setting

Reactions of industry and associated organisations to the announcement of the UK Soft Drinks Industry Levy: longitudinal thematic analysis of UK media articles, 2016-18

BACKGROUND: The UK Soft Drinks Industry Levy (SDIL) was announced in March 2016, became law in April 2017, and was implemented in April 2018. Empirical analyses of commercial responses have not been undertaken to establish the scale, direction or nuance of industry media messaging around fiscal policies. We aimed to develop a detailed understanding of industry reactions to the SDIL in publicly available media, including whether and how these changed from announcement to implementation. METHODS: We searched Factiva to identify articles related to sugar, soft-drinks, and the SDIL, between 16th March 2016-5th April 2018. Articles included were UK publications written in English and reporting a quotation from an industry actor in response to the SDIL. We used a longitudinal thematic analysis of public statements by the soft-drinks industry that covered their reactions in relation to key policy milestones. RESULTS: Two hundred and ninety-eight articles were included. After the announcement in March 2016, there was strong opposition to the SDIL. After the public consultation, evolving opposition narratives were seen. After the SDIL became law, reactions reflected a shift to adapting to the SDIL. Following the publication of the final regulations, statements sought to emphasise industry opportunities and ensure the perceived profitability of the soft drinks sector. The most significant change in message (from opposition to adapting to the SDIL) occurred when the SDIL was implemented (6th April 2018). CONCLUSION: Reactions to the SDIL changed over time. Industry modified its media responses from a position of strong opposition to one that appeared to focus on adaptation and maximising perceived profitability after the SDIL became law. This shift suggests that the forces that shape industry media responses to fiscal policies do not remain constant but evolve in response to policy characteristics and the stage of the policy process to maximise beneficial framing

Models for Access to Maternal Smoking cessation Support (MAMSS): a study protocol of a quasi-experiment to increase the engagement of pregnant women who smoke in NHS Stop Smoking Services

Background: Maternal smoking is a key cause of poor outcomes for mothers, babies and children and Wales has higher rates of smoking in pregnancy than any other UK country. Despite various improvements within the NHS Stop Smoking Service to strengthen the intervention for pregnant women, referrals and successful quit attempts for this group have continued to remain extremely low. A key element of UK national guidance for smoking cessation during pregnancy is to provide a flexible and tailored service to help increase levels of engagement. This study aims to test the effectiveness of three different models of service delivery to address the gap in the evidence base about how to deliver a flexible, tailored smoking cessation service to pregnant women. Methods: This study will adopt a quasi-experimental design over a 12 month period. The setting is four of Wales’ seven Health Boards using an integrated approach between maternity services, local public health teams and the NHS Stop Smoking Service. Core recommendations from UK public health guidance are being implemented across intervention and usual care sites. Stop smoking support for pregnant women in intervention sites is being delivered more flexibly than in usual care sites. Both qualitative and quantitative approaches will be adopted to capture important contextual information and consider multiple perspectives. A health economic analysis will be undertaken using a cost-consequences analysis approach. The primary outcome measure is engagement with stop smoking services (defined as having at least one face-to-face therapeutic contact with a clinician). Discussion: Supporting pregnant women to stop smoking is a challenging area of public health. The proposed study will address several areas where there are key evidence gaps relating to smoking cessation interventions for pregnant women. Specifically, how best to encourage pregnant women to attend a specialist stop smoking support service, how to deliver the service and who should provide it

Industry views of the UK soft drinks industry levy: a thematic analysis of elite interviews with food and drink industry professionals, 2018-2020

The UK Soft Drinks Industry Levy (SDIL), implemented in 2018, has been successful in reducing the sugar content and purchasing of soft drinks, with limited financial impact on industry. Understanding the views of food and drink industry professionals involved in reacting to the SDIL is important for policymaking. However, their perceptions of the challenges of implementation and strategic responses are unknown. The aim of this study, therefore, was to explore how senior food and drink industry professionals viewed the SDIL. We undertook a qualitative descriptive study using elite interviews. Data were analysed using Braun and Clarke's thematic analysis, taking an inductive exploratory and descriptive approach not informed by prior theory or frameworks. Interviews were conducted via telephone with 14 senior professionals working in the food and drink industry. Five main themes were identified: ; industry accepted the SDIL as an attempt to create a level playing field but due to the exclusion of milk-based drinks, this was viewed as inadequate, ; the SDIL was complex, expensive and time consuming to implement, with industry responses dependent on leadership buy-in, ; soft drinks are an unfair target when other categories also contain high sugar, ; consumers were a key focus of the industry response to this policy and ; there appeared to be a wider ripple effect, which primed industry to prepare for future regulation in support of health and environmental sustainability. Insights from senior food and drink industry professionals illustrate how sugar-sweetened beverage taxes might be successfully implemented and improve understanding of industry responses to taxes and other food and drink policies

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT

Abstract Background Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting The setting was tertiary care centres throughout the UK. Participants Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified

Parliamentary reaction to the announcement and implementation of the UK Soft Drinks Industry Levy: Applied thematic analysis of 2016-2020 parliamentary debates

Objective: The UK Soft Drinks Industry Levy (SDIL) (announced March 2016; implemented April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order understand how health policy can become established and resilient to opposition. Design: Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus. Setting: The United Kingdom Parliament Participants: N/A Results: Between the announcement (16/03/2016) - royal assent (26/04/2017) two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent - implementation (5/04/2018) one theme was identified 3: The SDIL worked - what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL. Conclusions: After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Development and application of the DePtH framework for categorising the agentic demands of population health interventions [Pre-print]

The ‘agentic demand’ of population health interventions may influence intervention effectiveness and equity, yet the absence of an adequate framework to classify agentic demands limits the fields’ advancement. We systematically developed the DEmands for PopulaTion Health Interventions (DePtH) framework identifying three constructs influencing agentic demand - exposure (initial contact with intervention), mechanism of action (how the intervention enables or discourages behaviour), and engagement (recipient response), combined into twenty classifications. We conducted expert qualitative feedback and reliability testing, revised the framework and applied it in a proof-of-concept review, combining it with data on overall effectiveness and equity of dietary and physical activity interventions. Intervention components were concentrated in a small number of classifications; DePtH classification appeared to be related to intervention equity but not effectiveness. This framework holds potential for future research, policy and practice, facilitating the design, selection, evaluation and synthesis of evidence

Development and application of the Demands for Population Health Interventions (Depth) framework for categorising the agentic demands of population health interventions

Background: The ‘agentic demand’ of population health interventions (PHIs) refers to the capacity, resources and freedom to act that interventions demand of their recipients to benefit, which have a socio-economical pattern. Highly agentic interventions, e.g. information campaigns, rely on recipients noticing and responding to the intervention and thus might affect intervention effectiveness and equity. The absence of an adequate framework to classify agentic demands limits the fields’ ability to systematically explore these associations. Methods: We systematically developed the Demands for Population Health Interventions (Depth) framework using an iterative approach: (1) Developing the Depth framework by systematically identifying examples of PHIs aiming to promote healthier diets and physical activity, coding of intervention actors and actions and synthesising the data to develop the framework; (2) Testing the Depth framework in online workshops with academic and policy experts and a quantitative reliability assessment. We applied the final framework in a proof-of-concept review, extracting studies from three existing equity focused systematic reviews on framework category, overall effectiveness and differential socioeconomic effects and visualised the findings in Harvest Plots. Results: The Depth framework identifies three constructs influencing agentic demand: exposure - initial contact with intervention (2 levels), mechanism of action - how the intervention enables or discourages behaviour (5 levels), and engagement - recipient response (2 levels). When combined, these constructs form a matrix of twenty possible classifications. In the proof-of-concept review, we classified all components of 31 interventions according to the Depth framework. Intervention components were concentrated in a small number of Depth classifications; Depth classification appeared to be related to intervention equity but not effectiveness. Conclusions: This framework holds potential for future research, policy and practice, facilitating the design, selection and evaluation of interventions and evidence synthesis

Research protocol: general practice organ donation intervention-a feasibility study (GPOD)

BACKGROUND: New interventions are required to increase the number of people donating their organs after death. In the United States of America (USA), general practice has proved to be a successful location to increase organ donor registration. However, a dearth of research exists examining this in the United Kingdom (UK). due to the unique challenges presented by the National Health Service (NHS). This protocol outlines a feasibility study to assess whether UK general practice is a feasible and acceptable location for organ donation intervention targeting NHS Organ Donor Register (NHS ODR) membership. METHODS: The primary intervention element, prompted choice, requires general practice to ask patients in consultations if they wish to join the NHS ODR. Two additional intervention techniques will be used to support prompted choice: staff training and leaflets and posters. The intervention will run for 3 months (April-July 2018) followed by a period of data collection. The following methods will be used to assess feasibility, acceptability and fidelity: registration data, a training evaluation survey, focus groups with staff and online surveys for staff and patients. DISCUSSION: By examining the feasibility, acceptability and fidelity of a prompted choice intervention in UK general practice, important knowledge can be gathered on whether it is a suitable location to conduct this. Additional learning can also be gained generally for implementing interventions in general practice. This could contribute to the knowledge base concerning the feasibility of NHS general practice to host interventions