Implementing and Evaluating a National Integrated Digital Registry and Clinical Decision Support System in Early Intervention in Psychosis Services (Early Psychosis Informatics Into Care): Co-Designed Protocol

BACKGROUND: Early intervention in psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems (CDSSs) have revolutionized the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. OBJECTIVE: This paper reports the protocol for the program development phase of this study, in which we aimed to co-design and produce an evidence-based, stakeholder-informed framework for the building, implementation, piloting, and evaluation of a national integrated digital registry and CDSS for psychosis, known as EPICare (Early Psychosis Informatics into Care). METHODS: We conducted 3 concurrent work packages, with reciprocal knowledge exchange between each. In work package 1, using a participatory co-design framework, key stakeholders (clinicians, academics, policy makers, and patient and public contributors) engaged in 4 workshops to review, refine, and identify a core set of essential and desirable measures and features of the EPICare registry and CDSS. Using a modified Delphi approach, we then developed a consensus of data priorities. In work package 2, we collaborated with National Health Service (NHS) informatics teams to identify relevant data currently captured in electronic health records, understand data retrieval methods, and design the software architecture and data model to inform future implementation. In work package 3, observations of stakeholder workshops and individual interviews with representative stakeholders (n=10) were subject to interpretative qualitative analysis, guided by normalization process theory, to identify factors likely to influence the adoption and implementation of EPICare into routine practice. RESULTS: Stage 1 of the EPICare study took place between December 2021 and September 2022. The next steps include stage 2 building, piloting, implementation, and evaluation of EPICare in 5 demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England. CONCLUSIONS: By establishing a multistakeholder network and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare registry and CDSS; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to proceed with the building, piloting, implementation, and evaluation of EPICare. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50177

Antidepressants for the prevention of depression following first-episode psychosis (ADEPP): study protocol for a multi-centre, double-blind, randomised controlled trial

Background: Depressive episodes are common after first-episode psychosis (FEP), affecting more than 40% of people, adding to individual burden, poor outcomes, and healthcare costs. If the risks of developing depression were lower, this could have a beneficial effect on morbidity and mortality, as well as improving outcomes. Sertraline is a selective serotonin reuptake inhibitor and a common first-line medication for the treatment of depression in adults. It has been shown to be safe when co-prescribed with antipsychotic medication, and there is evidence that it is an effective treatment for depression in established schizophrenia. We present a protocol for a multi-centre, double-blind, randomised, placebo-controlled clinical trial called ADEPP that aims to investigate the efficacy and cost-effectiveness of sertraline in preventing depression after FEP. Methods: The recruitment target is 452 participants between the ages of 18 and 65 years who are within 12 months of treatment initiation for FEP. Having provided informed consent, participants will be randomised to receive either 50 mg of sertraline daily or matched placebo for 6 months, in addition to treatment as usual. The primary outcome measure will be a comparison of the number of new cases of depression between the treatment and placebo arms over the 6-month intervention phase. Secondary outcomes include suicidal behaviour, anxiety, rates of relapse, functional outcome, quality of life, and resource use. Discussion: The ADEPP trial will test whether the addition of sertraline following FEP is a clinically useful, acceptable, and cost-effective way of improving outcomes following FEP. Trial registration: ISRCTN12682719 registration date 24/11/2020

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Implementing and Evaluating a National Integrated Digital Registry and Clinical Decision Support System in Early Intervention in Psychosis Services (Early Psychosis Informatics into Care):A Co-Designed Protocol

Background: Early Intervention in Psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems have revolutionised the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. Objectives: This paper reports the protocol for the programme development phase of this study, in which we aimed to co-design and produce an evidence-based, stakeholder-informed framework for the build, implementation, piloting, and evaluation of a national integrated digital registry and clinical decision support system (CDSS) for psychosis, known as EPICare (Early Psychosis Informatics into Care).Methods: We conducted three concurrent work packages, with reciprocal knowledge exchange between each. In Work Package 1, using a participatory co-design framework, key stakeholders (clinicians, academics, policymakers, and patient and public contributors) engaged in four workshops to review, refine, and identify a core set of essential and desirable measures and features of the EPICare registry and CDSS. Using a modified Delphi approach, we then developed a consensus of data priorities. In Work Package 2, we collaborated with National Health Service (NHS) informatics teams to identify relevant data currently captured in electronic health records, understand data retrieval methods, and design the software architecture and data model to inform future implementation. In Work Package 3, observations of stakeholder workshops and individual interviews with representative stakeholders (n=10) were subject to interpretative qualitative analysis, guided by Normalisation Process Theory, to identify factors likely to influence adoption and implementation of EPICare into routine practice. Results: Stage 1 of the EPICare study took place between December 2021 and September 2022. Next steps include Stage 2 building, piloting, implementation, and evaluation of EPICare in five demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by Stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England.Conclusions: By establishing a multi-stakeholder network and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare registry and CDSS; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to proceed with the building, piloting, implementation, and evaluation of EPICare.<br/

Implementing and Evaluating a National Integrated Digital Registry and Clinical Decision Support System in Early Intervention in Psychosis Services (Early Psychosis Informatics into Care):A Co-Designed Protocol

Background: Early Intervention in Psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems have revolutionised the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. Objectives: This paper reports the protocol for the programme development phase of this study, in which we aimed to co-design and produce an evidence-based, stakeholder-informed framework for the build, implementation, piloting, and evaluation of a national integrated digital registry and clinical decision support system (CDSS) for psychosis, known as EPICare (Early Psychosis Informatics into Care).Methods: We conducted three concurrent work packages, with reciprocal knowledge exchange between each. In Work Package 1, using a participatory co-design framework, key stakeholders (clinicians, academics, policymakers, and patient and public contributors) engaged in four workshops to review, refine, and identify a core set of essential and desirable measures and features of the EPICare registry and CDSS. Using a modified Delphi approach, we then developed a consensus of data priorities. In Work Package 2, we collaborated with National Health Service (NHS) informatics teams to identify relevant data currently captured in electronic health records, understand data retrieval methods, and design the software architecture and data model to inform future implementation. In Work Package 3, observations of stakeholder workshops and individual interviews with representative stakeholders (n=10) were subject to interpretative qualitative analysis, guided by Normalisation Process Theory, to identify factors likely to influence adoption and implementation of EPICare into routine practice. Results: Stage 1 of the EPICare study took place between December 2021 and September 2022. Next steps include Stage 2 building, piloting, implementation, and evaluation of EPICare in five demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by Stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England.Conclusions: By establishing a multi-stakeholder network and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare registry and CDSS; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to proceed with the building, piloting, implementation, and evaluation of EPICare.<br/

Early Psychosis Informatics into Care [EPICare]: A co-designed protocol for implementing and evaluating a national integrated digital registry and clinical decision support system within early intervention in psychosis services

Early Intervention in Psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems have revolutionised delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care and prognosis. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. Objectives: Here, we provide details of a co-designed protocol to produce an evidence-based, stakeholder-informed framework for the build, implementation, and evaluation of a national integrated digital registry and clinical decision support system for psychosis, known as EPICare (Early Psychosis Informatics into Care). Here, we provide details of a co-designed protocol to produce an evidence-based, stakeholder-informed framework for the build, implementation, and evaluation of a national integrated digital registry and clinical decision support system for psychosis, known as EPICare (Early Psychosis Informatics into Care). Using a participatory co-design framework, we engaged key stakeholders across four meetings to establish the parameters and essential features of EPICare and identify factors likely to influence adoption and implementation into routine practice. Stakeholders consisted of organisational, clinical, academic, and patient and public contributors. In collaboration with National Health Service (NHS) informatics teams, we identified how to retrieve key data items from Electronic Health Records and subsequently design the software architecture and data model to create an infrastructure plan for future implementation. Guided by Normalisation Process Theory, data synthesised from observations of stakeholder meetings and individual interviews (n=10) were subject to interpretative qualitative analysis. Finally, a co-designed set of guides were produced to allow for the build, implementation, and evaluation of EPICare in a larger, future study. An inclusive, representative stakeholder group, fully engaged with the future co-development of EPICare, was also established. Stage 1 of the EPICare study is now complete. Next steps include Stage 2 building, piloting, implementation, and evaluation of the EPICare platform in five demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by Stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England. By establishing a multi-stakeholder network comprising organisational, clinical, academic, and patient and public contributors and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare platform; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to move forward with the building, piloting, implementation, and evaluation of the EPICare platform in the next stage of the study

Implementing and evaluating a national integrated digital registry and clinical decision support system in early intervention in psychosis services (Early Psychosis Informatics Into Care): Co-designed protocol

Background: Early intervention in psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems (CDSSs) have revolutionized the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. Objective: This paper reports the protocol for the program development phase of this study, in which we aimed to co-design and produce an evidence-based, stakeholder-informed framework for the building, implementation, piloting, and evaluation of a national integrated digital registry and CDSS for psychosis, known as EPICare (Early Psychosis Informatics into Care). Methods: We conducted 3 concurrent work packages, with reciprocal knowledge exchange between each. In work package 1, using a participatory co-design framework, key stakeholders (clinicians, academics, policy makers, and patient and public contributors) engaged in 4 workshops to review, refine, and identify a core set of essential and desirable measures and features of the EPICare registry and CDSS. Using a modified Delphi approach, we then developed a consensus of data priorities. In work package 2, we collaborated with National Health Service (NHS) informatics teams to identify relevant data currently captured in electronic health records, understand data retrieval methods, and design the software architecture and data model to inform future implementation. In work package 3, observations of stakeholder workshops and individual interviews with representative stakeholders (n=10) were subject to interpretative qualitative analysis, guided by normalization process theory, to identify factors likely to influence the adoption and implementation of EPICare into routine practice. Results: Stage 1 of the EPICare study took place between December 2021 and September 2022. The next steps include stage 2 building, piloting, implementation, and evaluation of EPICare in 5 demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England. Conclusions: By establishing a multistakeholder network and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare registry and CDSS; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to proceed with the building, piloting, implementation, and evaluation of EPICare

Exploring the research needs, barriers and facilitators to the collection of biological data in adolescence for mental health research:a scoping review protocol paper

Introduction: While research into adolescent mental health has developed a considerable understanding of environmental and psychosocial risk factors, equivalent biological evidence is lacking and is not representative of economic, social and ethnic diversity in the adolescent population. It is important to understand the possible barriers and facilitators to conduct this research. This will then allow us to improve our understanding of how biology interacts with environmental and psychosocial risk factors during adolescence. The objective of this scoping review is to identify and understand the needs, barriers and facilitators related to the collection of biological data in adolescent mental health research. Methods and analysis: Reviewers will conduct a systematic search of PubMed, Medline, Scopus, Cochrane, ERIC, EMBASE, ProQuest, EBSCO Global Health electronic databases, relevant publications and reference lists to identify studies published in the English language at any time. This scoping review will identify published studies exploring mental health/psychopathology outcomes, with biological measures, in participants between the ages of 11 and 18 and examine the reported methodology used for data collection. Data will be summarised in tabular form with narrative synthesis and will use the methodology of Levac et al, supplemented by subsequent recommendations from the Joanna Briggs Institute Scoping Review Methodology. Ethics and dissemination: Ethical approval is not required for this scoping review. The scoping review will be conducted with input from patient and public involvement, specifically including young people involved in our study (‘Co-producing a framework of guiding principles for Engaging representative and diverse cohorts of young peopLE in Biological ReseArch in menTal hEalth’—www.celebrateproject.co.uk) Youth Expert Working Group. Dissemination will include publication in peer-reviewed journals, academic presentations and on the project website

Exploring the research needs, barriers and facilitators to the collection of biological data in adolescence for mental health research:a scoping review protocol paper

Introduction: While research into adolescent mental health has developed a considerable understanding of environmental and psychosocial risk factors, equivalent biological evidence is lacking and is not representative of economic, social and ethnic diversity in the adolescent population. It is important to understand the possible barriers and facilitators to conduct this research. This will then allow us to improve our understanding of how biology interacts with environmental and psychosocial risk factors during adolescence. The objective of this scoping review is to identify and understand the needs, barriers and facilitators related to the collection of biological data in adolescent mental health research. Methods and analysis: Reviewers will conduct a systematic search of PubMed, Medline, Scopus, Cochrane, ERIC, EMBASE, ProQuest, EBSCO Global Health electronic databases, relevant publications and reference lists to identify studies published in the English language at any time. This scoping review will identify published studies exploring mental health/psychopathology outcomes, with biological measures, in participants between the ages of 11 and 18 and examine the reported methodology used for data collection. Data will be summarised in tabular form with narrative synthesis and will use the methodology of Levac et al, supplemented by subsequent recommendations from the Joanna Briggs Institute Scoping Review Methodology. Ethics and dissemination: Ethical approval is not required for this scoping review. The scoping review will be conducted with input from patient and public involvement, specifically including young people involved in our study (‘Co-producing a framework of guiding principles for Engaging representative and diverse cohorts of young peopLE in Biological ReseArch in menTal hEalth’—www.celebrateproject.co.uk) Youth Expert Working Group. Dissemination will include publication in peer-reviewed journals, academic presentations and on the project website