Huajie Jin

Background: Depression trials typically use symptom-based outcomes to determine treatment efficacy. Qualitative work with service users and clinicians indicates that other outcomes may be equally or more important. Quantitative investigations are needed to assess the relative importance of outcomes to key stakeholders. Aims: To examine how stakeholders (service users with minimal symptoms (Beck Depression Inventory Second Edition (BDI-II) score ≤18), those who were currently symptomatic (BDI-II score ≥19) and clinicians working with people with depression) prioritise outcome domains drawn from two completed trials of cognitive behavioural therapy (CBT) for depression. This was from a new sample of stakeholders in order to explore similarities, differences and predictors of domain importance. Method: An online survey using a novel point-allocation method examined stakeholder priorities for outcome domains from two completed UK trials of CBT for depression. Stakeholder free-text responses explaining point allocations were thematically analysed. Multivariate analysis of covariance explored differences in domain importance across groups, and exploratory multivariate general linear models investigated predictive variables. Results: In total, 229 participants completed the survey (57 with minimal symptoms, 108 who were currently symptomatic and 64 clinicians). Median point allocations suggest that all three participant groups assigned similar importance to depression symptoms, quality of life, anxiety symptoms and impact on activities. Sociodemographic factors significantly predicted domain importance within the currently symptomatic group, and age was a predictor both across and within this subgroup. Conclusions: Stakeholders valued several outcome domains with similar importance. While depression symptoms are not unimportant to stakeholders, they are balanced with other outcomes, such as quality of life, that are rarely measured in depression trials. These findings demonstrate the need to incorporate stakeholder-important outcomes into trial design, with stakeholder-weighted composite outcomes offering a potential method to capture this broader judgement of benefit.

Introduction Diabetes distress describes the psychological and emotional burden of living with diabetes and is associated with reduced self-management and adverse diabetes outcomes. Clinical guidelines recommend routine assessment and management of diabetes distress, but this is not always implemented. Therefore, there is a need to develop approaches to deliver emotional health support in routine clinical care more effectively. We describe here the protocol for a study to I) assess the feasibility of implementation of the D-stress Pathway, comprising Enhanced Usual Care (EUC) and an online, group-based, psychological diabetes distress reduction intervention called REDUCE, ii) evaluate the feasibility of the study protocol iii) detect an effect signal of diabetes distress score and Interstitial Glucose Time in Range and iv) refine initial programme theories of how both interventions (EUC and REDUCE) work, for whom, and under what circumstances. Methods This feasibility study includes a multicentre trial within a cohort design (TWICs) where sites have a staggered exposure to the interventions alongside a realist process evaluation. Four UK NHS diabetes services will recruit 80 adults with type 1 diabetes (≥1 year) using continuous glucose monitoring (CGM) (≥3 months). All participants will receive EUC and provide monthly data over 7 months on diabetes distress (measured by the Type 1 Diabetes Distress Assessment System (T1DDAS) and interstitial glucose measured by using continuous glucose monitoring. Participants with elevated diabetes distress, will be offered the six-week, group-based, online REDUCE intervention plus EUC, compared to EUC alone. Up to twenty participants with type 1 diabetes, ten family members/friends, sixteen healthcare professionals delivering EUC and five REDUCE facilitators will be interviewed to explore their experience of receiving training and delivering the D-stress Pathway. Up to 20 EUC consultations and REDUCE sessions will be observed. Analysis Feasibility will be assessed against pre-specified progression criteria and analysed descriptively using summary statistics. Primary outcomes include baseline level of diabetes distress, recruitment rate, intervention uptake, and data completeness, which will be analysed descriptively. Qualitative data will be analysed using framework analysis guided by realist programme theories developed for this study. Ethics Ethics approval has been granted by NHS Research Ethics Committee (REC) (Bromley REC: 25/LO/0469) and Health Research Authority obtained. All participants will provide informed consent. Trial registration no: Registered at ClinicalTrials.gov number NCT07193446 on 26/11/2025. Protocol and statistical analysis plan: The trial protocol and statistical analysis plan can be accessed at ClinicalTrials.gov.

Background: International evidence suggests that Early Intervention for Psychosis (EIP) services are both effective and cost-effective. Such evidence, however, comes almost exclusively from high-income countries. Aims: Our aim was to estimate the cost-effectiveness of EIP services in a Latin American setting. Method: We compared EIP services against community mental health teams (CMHT) from the Chilean health system perspective. We developed a six-state Markov model to estimate the costs, benefits (measured as quality-adjusted life-years (QALYs)) and incremental cost-effectiveness ratio (ICER) for a 10-year time horizon. The model was populated with data from a Chilean EIP cohort, published literature and expert opinion. We characterised uncertainty through probabilistic sensitivity analysis and calculated the value of information to reduce such uncertainty. Results: In the base case analysis, EIP was cost-effective compared with CMHT, with an ICER of 5 550 044 Chilean pesos per QALY (USD 13 742 adjusted for purchasing power parity). Uncertainty analysis revealed an 80% probability of EIP services being the most cost-effective option at a willingness-to-pay threshold of one gross domestic product per capita (USD 15 923). Sensitivity analysis showed that the results were sensitive to parameters such as intervention effectiveness and cost, suggesting that a new trial might be worthwhile to reduce uncertainty. Conclusions: This model suggests that implementing EIP services in Chile may cost more, but it is likely to be cost-effective. Nonetheless, more evidence about affordability, equity and broader perspectives is needed to improve the economic case of implementing EIP services in less-resourced settings, such as in Latin America.

Background and Hypothesis: Trials rarely include outcomes co-developed with stakeholders, which creates uncertainty about whether trial endpoints reflect the benefits valued by patients and clinicians. There is therefore a need to explore how stakeholder perspectives might influence the interpretation of trial results. Study Design: In a 2-phase study, we first engaged service users and staff to rank outcomes from a recently completed randomized controlled trial of cognitive remediation therapy (CRT). We then used multi-criteria decision modelling to generate value-weighted composite scores and reanalyzed the trial data from three arms: individual CRT, group CRT, and treatment as usual (TAU). This approach allowed us to examine how weighting outcomes differently, according to stakeholder perspectives, might affect the conclusions drawn from the trial. Study Results: Both stakeholder groups prioritized the Global Assessment Scale (primary outcome) and quality of life, but disagreed on the importance of cognition. Reanalyses using weighted composite scores produced the same robust finding as the original trial: CRT delivered in group or one-to-one formats provides significant benefit compared with TAU. Sensitivity analyses applying different stakeholder weights showed the same pattern. However, exploratory analyses revealed that group treatment for the service user weighted composite was not significant. Conclusions: This study shows how stakeholder values can identify nuances in outcomes depending on the value placed on treatment benefits. Embedding this approach into trial design can strengthen the alignment of outcomes with patient and service priorities and help close the gap between randomized trials and service implementation.

Background: People of Black African and Black Caribbean ethnicity experience higher rates and poorer outcomes of type 2 diabetes (T2D) than people of White European ethnicity; these inequalities are compounded by poor healthcare access. Cultural tailoring of diabetes self-management education and support (DSMES) programs has the potential to improve healthcare engagement and clinical outcomes for ethnic minority groups. Healthy Eating & Active Lifestyles for Diabetes (HEAL-D) is a co-designed, culturally tailored group-based DSMES program for adults of Black African and Black Caribbean ethnicity. Objective: This trial aims to evaluate the clinical and cost effectiveness of the HEAL-D intervention, compared to standard DSMES programs, in Black African and Black Caribbean adults living with T2D. Methods: A 24-month, multicenter, pragmatic, open-label, 2-arm, parallel-group, individually randomized group treatment trial will be conducted, with primary end point (glycated hemoglobin [HbA1c]) assessment at 12 months. Black African and Black Caribbean adults with T2D (n=300), recruited from 3 to 5 centers in the United Kingdom (including London, West Midlands, and Greater Manchester), will be randomized in a 1:1 ratio to HEAL-D (intervention) or a standard DSMES program (control). HbA1c, blood lipids, anthropometric outcomes, blood pressure, physical activity, and patient-reported outcome measures relating to psychological well-being and self-management support, lifestyle behaviors, and health economics will be collected at baseline and follow-up visits (6, 12, and 24 months). Cost-effectiveness will be assessed through a cost-utility analysis conducted from a health and social care perspective. A mixed methods process evaluation will provide a formative evaluation of delivery, intervention fidelity, and implementation of HEAL-D, and an embedded study within a project will assess the impact of multiple long-term conditions on uptake of, and engagement with HEAL-D, and the impact of HEAL-D on multiple long-term conditions. The trial received Research Authority and Research Ethics Council approval on April 22, 2024. Results: Funding began in August 2023. Site “green light” was received on August 15, 2024, for London; November 29, 2024, for Manchester; and January 31, 2025, for the West Midlands. Recruitment commenced in August 2024 and is due to run for 11 months. As of March 26, 2025, a total of 76 participants have consented. Last patient, last visit is expected in June 2027; primary data analysis is expected to begin in July 2027. Final results are anticipated to be available in September 2027, and publication is expected by the end of 2027. Conclusions: The HEAL-D trial will address whether a culturally tailored DSMES program, provided in-person or via videoconferencing, is clinically and cost-effective compared to standard DSMES at improving diabetes management in Black African and Black Caribbean adults. If effective, this would provide an evidence-based model of equitable DSMES services and improve the implementation of healthcare programs for ethnic minority groups. Trial Registration: ISRCTN 1434448; https://www.isrctn.com/ISRCTN14344948 International Registered Report Identifier (IRRID): DERR1-10.2196/71861

Background and Objective Inflammatory arthritis is a common condition treated in rheumatology clinics, contributing significantly to healthcare costs and societal burden. Understanding the economic impact of inflammatory arthritis requires a comprehensive analysis through cost-of-illness studies. This systematic review aims to gather up-to-date cost-of-illness data on inflammatory arthritis from various countries, identify the primary cost drivers, describe shifts in cost components and appraise the quality of cost-of-illness study reporting in this field. Methods An electronic search was performed across four databases, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews and the Health Management Information Consortium, to identify cost-of-illness studies on inflammatory arthritis published over the past two decades. The primary outcome was the annual cost per patient with inflammatory arthritis, categorised by cost components. All costs were standardised to 2024 US dollar values. The quality of the included studies was evaluated using the Larg and Moss checklist and the modified Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results From an initial 12,264 publications, 82 studies were included in this review, covering axial spondyloarthritis (n = 49), psoriatic arthritis (n = 30), reactive arthritis (n = 2), rheumatoid arthritis (n = 13; 2019 onwards) and seronegative/seropositive rheumatoid arthritis (n = 8). Annual total societal costs varied considerably across inflammatory arthritis subtypes and countries. Medication expenditures consistently emerged as the primary direct healthcare cost driver, while productivity losses due to morbidity constituted the major component of indirect costs. Carer productivity loss represented a substantial proportion of indirect costs (up to 60.9%), yet was infrequently reported. Over time, we observed an increasing proportion of medication-related costs and a decreasing proportion of productivity losses for axial spondyloarthritis, alongside a reduction in inpatient care costs for psoriatic arthritis. These evolving cost distributions mirror patterns previously reported in rheumatoid arthritis. Methodological gaps were evident, with most studies lacking sensitivity analyses and comprehensive cost perspectives. Conclusions A substantial economic impact of inflammatory arthritis across different regions and subtypes was identified. This review emphasises the importance of including comprehensive cost components to fully assess the economic burden of inflammatory arthritis and provides methodological recommendations for future studies.

Investigating the use and impact of community Care (Education) and Treatment Reviews (C(E)TRs) in people with intellectual disability and autistic people: protocol for a cohort study using electronic health records Introduction: Care (Education) and Treatment Reviews (C(E)TRs) are intended to reduce unnecessary psychiatric hospital admission and length of stay for people with intellectual disability and autistic people. The use and impact of C(E)TRs has not been systematically evaluated since their introduction in England in 2015. The aims of this study are to describe the demographic and clinical profiles of people who receive a community C(E)TR and to investigate their effects on admission, length of hospital stay, and clinical and functional change. Methods and analysis: We will conduct a retrospective cohort study using de-identified data from electronic health records derived from two large National Health Service mental health providers in London, England, including one replication site. Data will be extracted using the Clinical Record Interactive Search (CRIS) tool for all people with recorded intellectual disability and/or autism who received mental healthcare from 2015. We will identify community C(E)TR events using keyword searches. Community C(E)TRs will be examined in two ways: 1) in a community cohort, we will capture data in the 6-month periods before and after a community C(E)TR and compare this to a matched control group, and 2) in a hospital cohort, we will compare groups who did and did not receive a community C(E)TR prior to their admission. We will describe the socio-demographic and clinical profiles of each group and their health service use and compare C(E)TR and no C(E)TR groups using t-tests (or a non-parametric equivalent). The primary outcomes are admission to psychiatric hospital (community cohort) and length of psychiatric hospital admission and clinical change (hospital cohort), which will be estimated using propensity score weighting and difference-in-differences methods for psychiatric hospitalization, and Cox’s proportional hazard model for length of hospital admission, and repeated-measures ANOVA for clinical change. Ethics and dissemination: Use of CRIS to examine de-identified clinical data for research purposes has overarching ethical approval. This study has been granted local approval by the South London and Maudsley CRIS Oversight Committee. Findings will be disseminated in an open access peer-reviewed academic publication, at conference presentations, and to service users and carers in accessible formats. Strengths and limitations of this study: This study will provide a much-needed evidence base to guide the provision of community C(E)TRs their effectiveness in the care pathway of people with intellectual disability and autistic people. Routinely collected health data represent real-world clinical practice and enable us to generate a relatively large cohort not biased by participant selection. The study will be undertaken in a large NHS Trust with a diverse catchment area. We will replicate the study in a second NHS Trust to provide evidence for the generalizability of the initial findings across a different population. The number of people in the dataset who have received a community C(E)TRs is unknown; if there are relatively few events, our dataset may be under-powered to demonstrate differences between those who do and do not receive the intervention (type 2 error). Electronic health record data are generated as part of routine clinical practice. There may be a high level of missing data which could limit our analysis.

Precision medical test is the cornerstone of personalized medicine and targeted therapies, play a crucial role in tailoring treatment plans to individual patients and optimizing medical resource utilization. This paper establishes a quantitative model to systematically analyze the relationship between the accuracy of a precision medical test and its cost-effectiveness. It is proven that the accuracy of a precision medical test must exceed two lower bounds to be considered cost-effective. The first lower bound requires that the test accuracy exceed the lower limit of matching requirements to match each patient's most appropriate individualized intervention plan, thereby achieving the local optimal decision-making. The second lower bound requires that the test accuracy must exceed the overall lower limit of medical testing for maximizing the net monetary benefit of the entire group of patients, that is, to achieve the global optimum. The special case of sensitivity and specificity on binary test results gives a more intuitive proof of the theorems. In addition, the theorems also provide an economic explanation for the underdiagnosis of rare diseases and the challenge of implementing precision medicine in small groups of patients. Numerical simulations support these findings.

Background: Lithium and several atypical antipsychotics are the recommended first-line augmentation options for treatment-resistant depression; however, few studies have compared them directly, and none for longer than 8 weeks. Consequently, there is little evidence-based guidance for clinicians when choosing an augmentation option for patients with treatment-resistant depression. Objectives: This trial examined whether it is more clinically and cost-effective to prescribe lithium or quetiapine augmentation therapy for patients with treatment-resistant depression over 12 months. Design: This was a parallel group, multicentre, pragmatic, open-label superiority trial comparing the clinical and cost-effectiveness of lithium versus quetiapine augmentation of antidepressant medication in treatment-resistant depression. Participants were randomised 1 : 1 at baseline to the decision to prescribe either lithium or quetiapine. Setting: Six National Health Service trusts in England. Participants: Eligible participants were aged ≥ 18 years, met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for major depressive disorder, scored ≥ 14 on the 17-item Hamilton Depression Rating Scale and whose depression had had an inadequate response to at least two therapeutic antidepressant treatment trials in the current episode, with a current antidepressant treatment at or above the therapeutic dose for ≥ 6 weeks. Patients with a history of psychosis or bipolar disorder were excluded. Patients were judged suitable for either treatment. Interventions: After randomisation, pre-prescribing safety checks were undertaken as per standard care and trial clinicians decided whether to proceed with prescribing the allocated medication. Trial clinicians received recommendations for titration and dosing in line with current clinical guidelines; however, dosing regimens could be altered according to tolerability and response. Participants were followed up using weekly self-report questionnaires and 8-, 26- and 52-week research visits. Main outcome measures: The co-primary outcome measures were depressive symptom severity over 52 weeks, measured weekly using the self-rated Quick Inventory of Depressive Symptomatology, and time to all-cause treatment discontinuation of the trial medication. Economic analyses compared costs between the two treatment arms over 52 weeks, from a National Health Service and Personal Social Services perspective, and a societal perspective. Results: Two hundred and twelve participants were randomised, 107 to quetiapine and 105 to lithium. The quetiapine arm showed a significantly greater reduction in depressive symptoms than the lithium arm over 52 weeks (quetiapine vs. lithium area under the differences curve = −68.36, 95% confidence interval: −129.95 to −6.76, p = 0.0296). Median days to discontinuation did not significantly differ between the two arms (quetiapine = 365.0, interquartile range = 57.0–365.0, lithium = 212.0, interquartile range = 21.0–365.0), p = 0.1196. Quetiapine was more cost effective than lithium. Thirty-two serious adverse events were recorded, only one of which was deemed possibly related to the intervention (lithium). Limitations: The trial was unblinded, therefore expectancies regarding the trial medications may have influenced the results. Further, there was substantial missing data for some of the secondary outcome measures. Conclusions: As well as being more cost-effective, quetiapine may be a more clinically effective augmentation option for treatment-resistant depression. Future work: Examining predictors of treatment response, including clinical, sociodemographic and biological factors, will help establish whether there are additional factors to consider when choosing an augmentation treatment for treatment-resistant depression. Trial registration: This trial is registered as ISRCTN16387615. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/222/02) and is published in full in Health Technology Assessment; Vol. 29, No. 12. See the NIHR Funding and Awards website for further award information.