Katharine A Smith’s research while affiliated with University of Oxford and other places

Objective We summarize the key steps to develop and assess an innovative online, evidence-based tool that supports shared decision-making in routine care to personalize antidepressant treatment in adults with depression. This PETRUSHKA tool is part of the PETRUSHKA trial (Personalize antidEpressant Treatment foR Unipolar depreSsion combining individual cHoices, risKs, and big datA). Methods The PETRUSHKA tool: (a) is based on prediction models, which use a combination of advanced analytics, i.e., traditional statistics, and machine learning methods; (b) utilizes electronic health records from primary care patients with depressive disorder in England and data from randomized controlled trials on antidepressants in depression, both at aggregate and individual patient level; (c) incorporates preferences from patients and clinicians (especially about adverse events); (d) generates a ranked list of personalized treatment recommendations to inform the discussion between clinicians and patients, and facilitates the final treatment choice. The PETRUSHKA tool is implemented as a web-based application, accessible from any computer, smartphone or tablet. Results We employed a bespoke algorithm to identify the best antidepressant for each individual patient, using patients’ clinical and demographic characteristics and harnessing the power of innovations in digital technology, large datasets and machine learning. We established a dedicated group of patient representatives that were involved in the co-production of the tool, to maximize its impact in real-world clinical practice across the world. To test the tool, we designed an international multi-site, randomized trial (target sample: 504 participants), comparing the PETRUSHKA tool with usual care to personalize pharmacological treatment in patients with depressive disorder across Brazil, Canada and the UK. Conclusions Using evidence-based patient decision aids has been recommended to support shared decision-making when quality is assured. Future studies in precision mental health should develop multimodal web tools, incorporating patients’ preferences and their individual demographic, cultural, clinical, and genetic characteristics.

Background Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis. Aims To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation. Method This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists. Results The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms. Conclusions This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.

Background Adverse events (AEs) are commonly reported in clinical studies using the Medical Dictionary for Regulatory Activities (MedDRA), an international standard for drug safety monitoring. However, the technical language of MedDRA makes it challenging for patients and clinicians to share understanding and therefore to make shared decisions about medical interventions. In this project, people with lived experience of depression and antidepressant treatment worked with clinicians and researchers to co-design an online dictionary of AEs associated with antidepressants, taking into account its ease of use and applicability to real-world settings. Methods Through a pre-defined literature search, we identified MedDRA-coded AEs from randomised controlled trials of antidepressants used in the treatment of depression. In collaboration with the McPin Foundation, four co-design workshops with a lived experience advisory panel (LEAP) and one independent focus group (FG) were conducted to produce user-friendly translations of AE terms. Guiding principles for translation were co-designed with McPin/LEAP members and defined before the finalisation of Clinical Codes (CCs, or non-technical terms to represent specific AE concepts). FG results were thematically analysed using the Framework Method. Results Starting from 522 trials identified by the search, 736 MedDRA-coded AE terms were translated into 187 CCs, which balanced key factors identified as important to the LEAP and FG (namely, breadth, specificity, generalisability, patient-understandability and acceptability). Work with the LEAP showed that a user-friendly language of AEs should aim to mitigate stigma, acknowledge the multiple levels of comprehension in ‘lay’ language and balance the need for semantic accuracy with user-friendliness. Guided by these principles, an online dictionary of AEs was co-designed and made freely available (https://thesymptomglossary.com). The digital tool was perceived by the LEAP and FG as a resource which could feasibly improve antidepressant treatment by facilitating the accurate, meaningful expression of preferences about potential harms through a shared decision-making process. Conclusions This dictionary was developed in English around AEs from antidepressants in depression but it can be adapted to different languages and cultural contexts, and can also become a model for other interventions and disorders (i.e., antipsychotics in schizophrenia). Co-designed digital resources may improve the patient experience by helping to deliver personalised information on potential benefits and harms in an evidence-based, preference-sensitive way.

Background Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe mental illness (SMI). Objective An international multidisciplinary group was convened to reach a consensus on the challenges and potential solutions regarding collecting data, delivering treatment, and the ethical challenges in digital mental health approaches for schizophrenia and SMI. Methods The consensus development panel method was used, with an in-person meeting of 2 groups: the expert group and the panel. Membership was multidisciplinary including those with lived experience, with equal participation at all stages and coproduction of the consensus outputs and summary. Relevant literature was shared in advance of the meeting, and a systematic search of the recent literature on digital mental health interventions for schizophrenia and psychosis was completed to ensure that the panel was informed before the meeting with the expert group. Results Four broad areas of challenge and proposed solutions were identified: (1) user involvement for real coproduction; (2) new approaches to methodology in digital mental health, including agreed standards, data sharing, measuring harms, prevention strategies, and mechanistic research; (3) regulation and funding issues; and (4) implementation in real-world settings (including multidisciplinary collaboration, training, augmenting existing service provision, and social and population-focused approaches). Examples are provided with more detail on human-centered research design, lived experience perspectives, and biomedical ethics in digital mental health approaches for SMI. Conclusions The group agreed by consensus on a number of recommendations: (1) a new and improved approach to digital mental health research (with agreed reporting standards, data sharing, and shared protocols), (2) equal emphasis on social and population research as well as biological and psychological approaches, (3) meaningful collaborations across varied disciplines that have previously not worked closely together, (4) increased focus on the business model and product with planning and new funding structures across the whole development pathway, (5) increased focus and reporting on ethical issues and potential harms, and (6) organizational changes to allow for true communication and coproduction with those with lived experience of SMI. This study approach, combining an international expert meeting with patient and public involvement and engagement throughout the process, consensus methodology, discussion, and publication, is a helpful way to identify directions for future research and clinical implementation in rapidly evolving areas and can be combined with measurements of real-world clinical impact over time. Similar initiatives will be helpful in other areas of digital mental health and similarly fast-evolving fields to focus research and organizational change and effect improved real-world clinical implementation.

BACKGROUND Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe mental illness (SMI). OBJECTIVE An international multidisciplinary group was convened to reach a consensus on the challenges and potential solutions regarding collecting data, delivering treatment, and the ethical challenges in digital mental health approaches for schizophrenia and SMI. METHODS The consensus development panel method was used, with an in-person meeting of 2 groups: the expert group and the panel. Membership was multidisciplinary including those with lived experience, with equal participation at all stages and coproduction of the consensus outputs and summary. Relevant literature was shared in advance of the meeting, and a systematic search of the recent literature on digital mental health interventions for schizophrenia and psychosis was completed to ensure that the panel was informed before the meeting with the expert group. RESULTS Four broad areas of challenge and proposed solutions were identified: (1) user involvement for real coproduction; (2) new approaches to methodology in digital mental health, including agreed standards, data sharing, measuring harms, prevention strategies, and mechanistic research; (3) regulation and funding issues; and (4) implementation in real-world settings (including multidisciplinary collaboration, training, augmenting existing service provision, and social and population-focused approaches). Examples are provided with more detail on human-centered research design, lived experience perspectives, and biomedical ethics in digital mental health approaches for SMI. CONCLUSIONS The group agreed by consensus on a number of recommendations: (1) a new and improved approach to digital mental health research (with agreed reporting standards, data sharing, and shared protocols), (2) equal emphasis on social and population research as well as biological and psychological approaches, (3) meaningful collaborations across varied disciplines that have previously not worked closely together, (4) increased focus on the business model and product with planning and new funding structures across the whole development pathway, (5) increased focus and reporting on ethical issues and potential harms, and (6) organizational changes to allow for true communication and coproduction with those with lived experience of SMI. This study approach, combining an international expert meeting with patient and public involvement and engagement throughout the process, consensus methodology, discussion, and publication, is a helpful way to identify directions for future research and clinical implementation in rapidly evolving areas and can be combined with measurements of real-world clinical impact over time. Similar initiatives will be helpful in other areas of digital mental health and similarly fast-evolving fields to focus research and organizational change and effect improved real-world clinical implementation.

Background During the COVID-19 pandemic, the Oxford Precision Psychiatry Lab (OxPPL) developed open-access web-based summaries of mental health care guidelines (OxPPL guidance) in key areas such as digital approaches and telepsychiatry, suicide and self-harm, domestic violence and abuse, perinatal care, and vaccine hesitancy and prioritization in the context of mental illness, to inform timely clinical decision-making. Objective This study aimed to evaluate the practice of creating evidence-based health guidelines during health emergencies using the OxPPL guidance as an example. An international network of clinical sites and colleagues (in Australia, New Zealand, and the United Kingdom) including clinicians, researchers, and experts by experience aimed to (1) evaluate the clinical impact of the OxPPL guidance, as an example of an evidence-based summary of guidelines; (2) review the literature for other evidence-based summaries of COVID-19 guidelines regarding mental health care; and (3) produce a framework for response to future global health emergencies. Methods The impact and clinical utility of the OxPPL guidance were assessed using clinicians’ feedback via an international survey and focus groups. A systematic review (protocol registered on Open Science Framework) identified summaries or syntheses of guidelines for mental health care during and after the COVID-19 pandemic and assessed the accuracy of the methods used in the OxPPL guidance by identifying any resources that the guidance had not included. Results Overall, 80.2% (146/182) of the clinicians agreed or strongly agreed that the OxPPL guidance answered important clinical questions, 73.1% (133/182) stated that the guidance was relevant to their service, 59.3% (108/182) said that the guidelines had or would have a positive impact on their clinical practice, 42.9% (78/182) that they had shared or would share the guidance, and 80.2% (146/182) stated that the methodology could be used during future health crises. The focus groups found that the combination of evidence-based knowledge, clinical viewpoint, and visibility was crucial for clinical implementation. The systematic review identified 2543 records, of which 2 syntheses of guidelines met all the inclusion criteria, but only 1 (the OxPPL guidance) used evidence-based methodology. The review showed that the OxPPL guidance had included the majority of eligible guidelines, but 6 were identified that had not been included. Conclusions The study identified an unmet need for web-based, evidence-based mental health care guidance during the COVID-19 pandemic. The OxPPL guidance was evaluated by clinicians as having a real-world clinical impact. Robust evidence-based methodology and expertise in mental health are necessary, but easy accessibility is also needed, and digital technology can materially help. Further health emergencies are inevitable and now is the ideal time to prepare, including addressing the training needs of clinicians, patients, and carers, especially in areas such as telepsychiatry and digital mental health. For future planning, guidance should be widely disseminated on an international platform, with allocated resources to support adaptive updates.

BACKGROUND Globally, the needs of those with mental health illness were particularly acute during the COVID-19 pandemic, and pre-existing disparities in health care were also highlighted. However, guidelines specifically for mental health were often limited or difficult to find, particularly in the early phases. During the COVID-19 pandemic, the Oxford Precision Psychiatry Lab developed open access online summaries of mental health guidelines (OxPPL guidance) in key areas such as digital approaches and telepsychiatry, suicide and self-harm, domestic violence and abuse, perinatal care, vaccine hesitancy and prioritisation, to inform timely clinical decision-making. The current study aimed to examine the practice of developing evidence-based health guidelines during a health emergency in general and by using the example of the OxPPL guidance in particular. OBJECTIVE An international network of clinical sites and colleagues (in Australia, New Zealand and the UK) including clinicians, researchers and experts by experience aimed to (i) review the literature for evidence-based summaries of COVID-19 guidelines in mental health, (ii) evaluate the clinical impact of the OxPPL guidance, as an example of an evidence-based summary of guidelines, and (iii) produce a framework for response to future global health emergencies. METHODS We carried out a systematic review (protocol registered on OSF: https://osf.io/amsbj/) to identify published summaries/syntheses of guidelines for mental health care which were available during and after the COVID-19 pandemic. The impact and clinical utility of the OxPPL guidance were also assessed using clinicians’ feedback via an international survey and focus groups. RESULTS The systematic review identified 2543 records. Of these, two syntheses of guidelines met all inclusion criteria, but only one (the OxPPL guidance) used evidence-based methodology. In the survey, 81% of clinicians agreed/strongly agreed that the OxPPL guidance answered important clinical questions, 73% that the guidance was relevant to their service, 59% that the guidelines had/would have a positive impact on their clinical practice, 43% that they had shared or would share the guidance, 80% that the methodology could be used in future health crises. The focus groups found that the combination of evidence-based knowledge, clinical viewpoint and visibility was crucial for clinical implementation. CONCLUSIONS The survey, focus groups and systematic review identified a clear unmet need for online evidence-based guidance in mental health during the COVID-19 pandemic. The OxPPL guidance was evaluated by clinicians as having a real-world clinical impact. Robust evidence-based methodology and expertise in mental health are necessary, but easy accessibility is also needed and digital technology can materially help. Further health emergencies are inevitable and now is the ideal time to prepare for the next health crisis, including addressing the training needs of clinicians, patients and carers especially in areas such as telepsychiatry and digital mental health. For future planning, guidance should be widely disseminated on an international platform, with allocated resources to support adaptive updates. CLINICALTRIAL N/A

Background Worldwide uptake of telepsychiatry accelerated during the COVID-19 pandemic. Objective To conduct an evaluation of the opinions, preferences and attitudes to telepsychiatry from service users, carers and clinicians in order to understand how telepsychiatry can be best used in the peri/post-COVID-19 era. Methods This mixed-methods, multicentre, international study of telepsychiatry was set in two sites in England and two in Italy. Survey questionnaires and focus group topic guides were co-produced for each participant group (service users, carers and clinicians). Findings In the UK, 906 service users, 117 carers and 483 clinicians, and in Italy, 164 service users, 56 carers and 72 clinicians completed the surveys. In all, 17 service users/carers and 14 clinicians participated in focus groups. Overall, telepsychiatry was seen as convenient in follow-ups with a specific purpose such as medication reviews; however, it was perceived as less effective for establishing a therapeutic relationship or for assessing acutely disturbed mental states. In contrast to clinicians, most service users and carers indicated that telepsychiatry had not improved during the COVID-19 pandemic. Most service users and carers reported that the choice of appointment modality was most often determined by the service or clinician. Conclusion and relevance There were circumstances in which telepsychiatry was seen as more suitable than others and clear differences in clinician, carer and service user perspectives on telepsychiatry. Clinical implications All stakeholders should be actively engaged in determining a hybrid model of care according to clinical features and service user and carer preferences. Clinicians should be engaged in training programmes on telepsychiatry.

Digital innovations in mental health offer great potential, but present unique challenges. Using a consensus development panel approach, an expert, international, cross-disciplinary panel met to provide a framework to conceptualise digital mental health innovations, research into mechanisms and effectiveness and approaches for clinical implementation. Key questions and outputs from the group were agreed by consensus, and are presented and discussed in the text and supported by case examples in an accompanying appendix. A number of key themes emerged. (1) Digital approaches may work best across traditional diagnostic systems: we do not have effective ontologies of mental illness and transdiagnostic/symptom-based approaches may be more fruitful. (2) Approaches in clinical implementation of digital tools/interventions need to be creative and require organisational change: not only do clinicians and patients need training and education to be more confident and skilled in using digital technologies to support shared care decision-making, but traditional roles need to be extended, with clinicians working alongside digital navigators and non-clinicians who are delivering protocolised treatments. (3) Designing appropriate studies to measure the effectiveness of implementation is also key: including digital data raises unique ethical issues, and measurement of potential harms is only just beginning. (4) Accessibility and codesign are needed to ensure innovations are long lasting. (5) Standardised guidelines for reporting would ensure effective synthesis of the evidence to inform clinical implementation. COVID-19 and the transition to virtual consultations have shown us the potential for digital innovations to improve access and quality of care in mental health: now is the ideal time to act.