Julia Fox-Rushby

Introduction: High-Flow Nasal Therapy (HFNT) is an innovative non-invasive form of respiratory support. Compared to standard oxygen therapy (SOT), there is an equipoise regarding the effect of HFNT on patient-centred outcomes among those at high risk of developing postoperative pulmonary complications after undergoing cardiac surgery. The NOTACS trial aims to determine the clinical and cost-effectiveness of HFNT compared to SOT within 90 days of surgery in the United Kingdom, Australia, and New Zealand. This protocol describes the methods and analyses planned for economic evaluation embedded within the ongoing NOTACS trial. Methods and analysis: The economic evaluation will identify, measure and value resources and health outcomes in both trial arms and compare changes in costs with ‘days alive and at home’ and EQ-5D-5L quality adjusted life years (QALYs) from the perspective most relevant to the decision-making country. Results from pooling data across the trial will use health and social care sector perspective. All patient-specific data including hospital/community care and health outcomes will be collected prospectively. Unit costs will be sourced from national, published or local data. Missing data will be assessed, with values replaced depending on assumed mechanism of missingness, and impact of replacement on cost-effectiveness assessed. Costs and outcomes by trial arm will be presented as components and totals per patient using a range of descriptive statistics. Regression models for costs and effects will account for patient characteristics, quality of life and health service utilization at baseline. Uncertainty in parameters, sampling and heterogeneity will be addressed through deterministic, probabilistic and subgroup analyses to assess the impact of varying methods and assumptions for costs, outcomes and approaches used in base-case analysis. Results will be interpreted using recommended national cost-effectiveness thresholds. Registration details: The study is registered with ISRCTN (ISRCTN14092678) on 13/05/2020. ISRCTN is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set.

Introduction: High-Flow Nasal Therapy (HFNT) is an innovative non-invasive form of respiratory support. Compared to standard oxygen therapy (SOT), there is an equipoise regarding the effect of HFNT on patient-centred outcomes among those at high risk of developing postoperative pulmonary complications after undergoing cardiac surgery. The NOTACS trial aims to determine the clinical and cost-effectiveness of HFNT compared to SOT within 90 days of surgery in the United Kingdom, Australia, and New Zealand. This protocol describes the methods and analyses planned for economic evaluation embedded within the ongoing NOTACS trial. Methods and analysis: The economic evaluation will identify, measure and value resources and health outcomes in both trial arms and compare changes in costs with ‘days alive and at home’ and EQ-5D-5L quality adjusted life years (QALYs) from the perspective most relevant to the decision-making country. Results from pooling data across the trial will use health and social care sector perspective. All patient-specific data including hospital/community care and health outcomes will be collected prospectively. Unit costs will be sourced interpreted using recommended national cost-effectiveness thresholds. Registration details: The study is registered with ISRCTN ( ISRCTN14092678 ) on 13/05/2020. ISRCTN is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set.

Background: Digital health interventions (DHIs) have shown promising results in enhancing the management of heart failure (HF). Although health care interventions are increasingly being delivered digitally, with growing evidence on the potential cost-effectiveness of adopting them, there has been little effort to collate and synthesize the findings. Objective: This study’s objective was to systematically review the economic evaluations that assess the adoption of DHIs in the management and treatment of HF. Methods: A systematic review was conducted using 3 electronic databases: PubMed, EBSCOhost, and Scopus. Articles reporting full economic evaluations of DHIs for patients with HF published up to July 2023 were eligible for inclusion. Study characteristics, design (both trial based and model based), input parameters, and main results were extracted from full-text articles. Data synthesis was conducted based on the technologies used for delivering DHIs in the management of patients with HF, and the findings were analyzed narratively. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for this systematic review. The reporting quality of the included studies was evaluated using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. Results: Overall, 27 economic evaluations were included in the review. The economic evaluations were based on models (13/27, 48%), trials (13/27, 48%), or a combination approach (1/27, 4%). The devices evaluated included noninvasive remote monitoring devices (eg, home telemonitoring using digital tablets or specific medical devices that enable transmission of physiological data), telephone support, mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems. Most of the studies (24/27, 89%) used cost-utility analysis. The majority of the studies (25/27, 93%) were conducted in high-income countries, particularly European countries (16/27, 59%) such as the United Kingdom and the Netherlands. Mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems yielded cost-effective results or even emerged as dominant strategies. However, conflicting results were observed, particularly in noninvasive remote monitoring devices and telephone support. In 15% (4/27) of the studies, these DHIs were found to be less costly and more effective than the comparators (ie, dominant), while 33% (9/27) reported them to be more costly but more effective with incremental cost-effectiveness ratios below the respective willingness-to-pay thresholds (ie, cost-effective). Furthermore, in 11% (3/27) of the studies, noninvasive remote monitoring devices and telephone support were either above the willingness-to-pay thresholds or more costly than, yet as effective as, the comparators (ie, not cost-effective). In terms of reporting quality, the studies were classified as good (20/27, 74%), moderate (6/27, 22%), or excellent (1/27, 4%). Conclusions: Despite the conflicting results, the main findings indicated that, overall, DHIs were more cost-effective than non-DHI alternatives. Trial Registration: PROSPERO CRD42023388241; https://tinyurl.com/2p9axpmc

Background: Genetic‐guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost‐effectiveness. Methods and Results: From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model‐based cost‐utility analyses alone, or alongside cost‐effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin‐converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non‐PGx), PGx was more effective and more costly than non‐PGx clopidogrel (28/43) but less costly than non‐PGx prasugrel (10/15) and less costly and less effective than non‐PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions. Conclusions: Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost‐effective, but findings varied based on the non‐PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx.

Emotional support from family members may have an important effect on adolescent health outcomes, and has been identified as a target for policy to protect against the impacts of poverty and other early life adversities. However, few studies have assessed the extent to which poverty and adversity themselves influence the nature of emotional support that parents can provide to adolescents. We, therefore, aimed to investigate the impact of trajectories of income poverty and family adversities, including parental mental ill health, alcohol misuse and domestic violence across childhood developmental stages on young people’s relationships with their families and perceived emotional support received. We analysed longitudinal data on 10,976 children from the nationally representative UK Millennium Cohort study. Exposure trajectories of poverty and family adversities were characterised using group-based multi-trajectory models (age 9 months–14 years). The outcomes were perceived emotional support and quality of family relationships, measured by the three-item Short Social Provisions Scale (SPS-3) and levels of parent–adolescent closeness and conflict, measured at age 14. ORs and 95% CIs were estimated using multivariable logistic regression models, adjusting for potential confounding factors. At age 14, the overall prevalence of low perceived emotional support was 13% (95% CI: 12, 14). Children of mothers with lower socioeconomic status (SES) were more likely to report low emotional support, with a clear social gradient (education—degree plus: 10.3% vs. no qualifications: 15.4%). Compared with children exposed to low levels of poverty and adversity, children in the persistent adversity trajectory groups experienced higher odds of low emotional support and low-quality parent–adolescent relationship; those exposed to both persistent poverty and poor parental mental health were particularly at increased risk of experiencing poor family relationships and low perceived emotional support (adjusted odds ratio 2·2; 95% CI 1·7–2·9). Low perceived emotional support and poor family relationships in adolescence are more prevalent among socially disadvantaged children and adolescents and those experiencing social adversity. Policies to improve levels of family support for UK adolescents should focus on improving modifiable determinants such as child poverty and family mental health.

Background: ‘High-cost’ individuals with multimorbidity account for a disproportionately large share of healthcare costs and are at most risk of poor quality of care and health outcomes.Aim: To compare high-cost with lower-cost individuals with multimorbidity and assess whether these populations can be clustered based on similar disease patterns.Design and setting: A cross-sectional study based on 2019/2020 electronic medical records from adults registered to primary care practices (n= 41) in a London borough.Method: Multimorbidity is defined as having ≥2 long-term conditions (LTCs). Primary care costs reflected consultations, which were costed based on provider and consultation types. High cost was defined as the top 20% of individuals in the cost distribution. Descriptive analyses identified combinations of 32 LTCs and their contribution to costs. Latent class analysis explored clustering patterns.Results: Of 386 238 individuals, 101 498 (26%) had multimorbidity. The high-cost group (n= 20 304) incurred 53% of total costs and had 6833 unique disease combinations, about three times the diversity of the lower-cost group (n= 81 194). The trio of anxiety, chronic pain, and depression represented the highest share of costs (5%). High-cost individuals were best grouped into five clusters, but no cluster was dominated by a single LTC combination. In three of five clusters, mental health conditions were the most prevalent.Conclusion: High-cost individuals with multimorbidity have extensive heterogeneity in LTCs, with no single LTC combination dominating their primary care costs. The frequent presence of mental health conditions in this population supports the need to enhance coordination of mental and physical health care to improve outcomes and reduce costs.

BACKGROUND Digital health interventions (DHIs) have shown promising results in enhancing the management of heart failure (HF). Although health care interventions are increasingly being delivered digitally, with growing evidence on the potential cost-effectiveness of adopting them, there has been little effort to collate and synthesize the findings. OBJECTIVE This study’s objective was to systematically review the economic evaluations that assess the adoption of DHIs in the management and treatment of HF. METHODS A systematic review was conducted using 3 electronic databases: PubMed, EBSCOhost, and Scopus. Articles reporting full economic evaluations of DHIs for patients with HF published up to July 2023 were eligible for inclusion. Study characteristics, design (both trial based and model based), input parameters, and main results were extracted from full-text articles. Data synthesis was conducted based on the technologies used for delivering DHIs in the management of patients with HF, and the findings were analyzed narratively. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for this systematic review. The reporting quality of the included studies was evaluated using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. RESULTS Overall, 27 economic evaluations were included in the review. The economic evaluations were based on models (13/27, 48%), trials (13/27, 48%), or a combination approach (1/27, 4%). The devices evaluated included noninvasive remote monitoring devices (eg, home telemonitoring using digital tablets or specific medical devices that enable transmission of physiological data), telephone support, mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems. Most of the studies (24/27, 89%) used cost-utility analysis. The majority of the studies (25/27, 93%) were conducted in high-income countries, particularly European countries (16/27, 59%) such as the United Kingdom and the Netherlands. Mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems yielded cost-effective results or even emerged as dominant strategies. However, conflicting results were observed, particularly in noninvasive remote monitoring devices and telephone support. In 15% (4/27) of the studies, these DHIs were found to be less costly and more effective than the comparators (ie, dominant), while 33% (9/27) reported them to be more costly but more effective with incremental cost-effectiveness ratios below the respective willingness-to-pay thresholds (ie, cost-effective). Furthermore, in 11% (3/27) of the studies, noninvasive remote monitoring devices and telephone support were either above the willingness-to-pay thresholds or more costly than, yet as effective as, the comparators (ie, not cost-effective). In terms of reporting quality, the studies were classified as good (20/27, 74%), moderate (6/27, 22%), or excellent (1/27, 4%). CONCLUSIONS Despite the conflicting results, the main findings indicated that, overall, DHIs were more cost-effective than non-DHI alternatives. CLINICALTRIAL PROSPERO CRD42023388241; https://tinyurl.com/2p9axpmc

Background: Obstructive sleep apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other health impacts. Continuous positive airway pressure (CPAP) therapy is effective first line treatment for moderate to severe OSA. Unfortunately, many patients have difficulty tolerating CPAP and pressure intolerance is probably an important contributing factor. Mandibular advancement devices (MAD) are an alternative to CPAP. They are worn in the mouth during sleep to reduce airway obstruction. There is some evidence that, when used in combination with CPAP, MADs improve airway anatomy enough to reduce the CPAP pressure required to treat OSA and that this combination therapy could improve CPAP adherence. Methods: Consecutive patients starting on CPAP for moderate to severe OSA will be recruited at a regional NHS sleep service. Patients with high CPAP pressure requirements after initial titration, who satisfy all entry criteria and consent to participate, will undertake a 2-arm randomised crossover trial. The arms will be (i) standalone CPAP and (ii) CPAP + MAD therapy. Each arm will last 12 weeks, including 2 weeks acclimatisation. CPAP machines will be auto-titrating and with facility for data download, so the impact of MAD on CPAP pressure requirements and CPAP adherence can be easily measured. The primary outcome will be CPAP adherence. Secondary outcomes will include measures of OSA severity, patient-reported outcome measures including subjective daytime sleepiness, quality of life, and treatment preference at the trial exit and health service use. Cost-effectiveness analyses will be undertaken. Discussion: If the intervention is shown to be effective and cost-effective in improving adherence in this standard CPAP-eligible OSA patient population it would be relatively straightforward to introduce into existing OSA treatment pathways, within the wider NHS and more widely. Both MAD and CPAP are already used by sleep services so their combination would require only minor adjustments to existing clinical pathways. It would be straightforward to disseminate the results of the study through regional, national, and international respiratory meetings. The health economics analysis would provide cost-effectiveness data to inform service planning and clinical guidelines through policy briefing papers, including those by NICE and SIGN. Trial registration: PAPMAT was registered with ISRCTN prior to recruitment beginning (ISRCTN Registry 2021): https://www.isrctn.com/ISRCTN33966032 . Registered on 17th November 2021.

Objectives The aim of this study was to examine whether and how the content of six checklists (Caro, Consensus on Health Economic Criteria [CHEC]-Extended, European Network of Health Economic Databases [EURONHEED], National Institute for Health and Care Excellence [NICE], Philips, Welte) affect the consistency in findings on methodological quality and transferability, using 10 model-based economic evaluations of genetic-guided pharmacotherapy for venous thromboembolism. Methods Each checklist was categorised by domain (structure, data, consistency, etc.) and type of assessment (presence vs. appropriateness) and was applied to each study by two independent reviewers who agreed on ratings via consensus, and discussion with a third reviewer when necessary. Methodological quality scores and rankings were examined using Spearman correlation tests, with subgroup analyses for domains and types of assessment. We compared overall ratings of transferability qualitatively, including how content may affect what is considered ‘transferable’. Results The checklists had similar proportions of items judging presence and appropriateness, but varying proportions of items across domains. For methodological quality, ranking consistencies were the highest between CHEC-Extended-Philips, Philips-NICE and NICE-Caro, with similar consistencies for domains and type of assessment. For transferability, NICE and Caro identified the same study, which scored high on EURONHEED, as transferable to the UK, while Welte, which considered methodological quality, identified none as transferable. Conclusions We found that the choice of checklist can affect findings on study quality and decisions about whether study results are transferable, indicating that different checklists may shortlist different sets of studies in formulating policy recommendations, leading to different policy decisions. Our systematic approach for evaluating the content of methodological quality and transferability checklists of economic evaluations can be extended to other checklists.