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Abstract Background The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. Methods The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. Discussion This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

Abstract Background This paper reports on the cost-effectiveness evaluation of Link-me – a digitally supported, systematic approach to triaging care for depression and anxiety in primary care that uses a patient-completed Decision Support Tool (DST). Methods The economic evaluation was conducted alongside a parallel, stratified individually randomised controlled trial (RCT) comparing prognosis-matched care to usual care at six- and 12-month follow-up. Twenty-three general practices in three Australian Primary Health Networks recruited 1,671 adults (aged 18 – 75 years), predicted by the DST to have minimal/mild or severe depressive or anxiety symptoms in three months. The minimal/mild prognostic group was referred to low intensity services. Participants screened in the severe prognostic group were offered high intensity care navigation, a model of care coordination. The outcome measures included in this evaluation were health sector costs (including development and delivery of the DST, care navigation and other healthcare services used) and societal costs (health sector costs plus lost productivity), psychological distress [Kessler Psychological Distress Scale (K10)] and quality adjusted life years (QALYs) derived from the EuroQol 5-dimension quality of life questionnaire with Australian general population preference weights applied. Costs were valued in 2018–19 Australian dollars (A$). Results Across all participants, the health sector incremental cost-effectiveness ratio (ICER) of Link-me per point decrease in K10 at six months was estimated at $1,082 (95% CI $391 to $6,204) increasing to $2,371 (95% CI $191 to Dominated) at 12 months. From a societal perspective, the ICER was estimated at $1,257/K10 point decrease (95% CI Dominant to Dominated) at six months, decreasing to $1,217 (95% CI Dominant to Dominated) at 12 months. No significant differences in QALYs were detected between trial arms and the intervention was dominated (less effective, more costly) based on the cost/QALY ICER. Conclusions The Link-me approach to stepped mental health care would not be considered cost-effective utilising a cost/QALY outcome metric commonly adopted by health technology assessment agencies. Rather, Link-me showed a trend toward cost-effectiveness by providing improvement in mental health symptoms, measured by the K10, at an additional cost. Trial registration Australian and New Zealand Clinical Trials Registry, ANZCTRN 12617001333303.

Abstract Background The use of general practice electronic health records (EHRs) for research purposes is in its infancy in Australia. Given these data were collected for clinical purposes, questions remain around data quality and whether these data are suitable for use in prediction model development. In this study we assess the quality of data recorded in 201,462 patient EHRs from 483 Australian general practices to determine its usefulness in the development of a clinical prediction model for total knee replacement (TKR) surgery in patients with osteoarthritis (OA). Methods Variables to be used in model development were assessed for completeness and plausibility. Accuracy for the outcome and competing risk were assessed through record level linkage with two gold standard national registries, Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and National Death Index (NDI). The validity of the EHR data was tested using participant characteristics from the 2014–15 Australian National Health Survey (NHS). Results There were substantial missing data for body mass index and weight gain between early adulthood and middle age. TKR and death were recorded with good accuracy, however, year of TKR, year of death and side of TKR were poorly recorded. Patient characteristics recorded in the EHR were comparable to participant characteristics from the NHS, except for OA medication and metastatic solid tumour. Conclusions In this study, data relating to the outcome, competing risk and two predictors were unfit for prediction model development. This study highlights the need for more accurate and complete recording of patient data within EHRs if these data are to be used to develop clinical prediction models. Data linkage with other gold standard data sets/registries may in the meantime help overcome some of the current data quality challenges in general practice EHRs when developing prediction models.

Abstract Background Hypertensive disorders of pregnancy (HDP) are the leading cause of maternal mortality in Indonesia. Focused HDP management pathways for Indonesian primary care practice have been developed from a consensus development process. However, the acceptability and feasibility of the pathways in practice have not been explored. This study reports on the implementation process of the pathways to determine their acceptability and feasibility in Indonesian practice. Methods The pathways were implemented in three public primary care clinics (Puskesmas) in Yogyakarta province for a month, guided by implementation science frameworks of Medical Research Council (MRC) and the Practical Robust Implementation and Sustainability Model (PRISM). The participating providers (general practitioners (GPs), midwives, and nurses) were asked to use recommendations in the pathways for a month. The pathway implementation evaluations were then conducted using clinical audits and a triangulation of observations, focus groups (FGs), and interviews with all of the participants. Clinical audit data were analysed descriptively, and qualitative data were analysed using a mix of the inductive-deductive approach of thematic analysis. Results A total of 50 primary care providers, four obstetricians, a maternal division officer in the local health office and 61 patients agreed to participate, and 48 of the recruited participants participated in evaluation FGs or interviews. All of the providers in the Puskesmas attempted to apply recommendations from the pathways to various degrees, mainly adopting preeclampsia risk factor screenings and HDP monitoring. The participants expressed that the recommendations empowered their practice when it came to HDP management. However, their practices were challenged by professional boundaries and hierarchical barriers among health care professionals, limited clinical resources, and regulations from the local health office. Suggestions for future scale-up studies were also mentioned, such as involving champion obstetricians and providing more patient education toolkits. Conclusion The HDP management pathways are acceptable and feasible in Indonesian primary care. A further scale-up study is desired and can be initiated with investigations to minimise the implementation challenges and enhance the pathways’ value in primary care practice.

Abstract Background Hypertensive disorders of pregnancy (HDP) are a significant contributor to the high maternal mortality rate in Indonesia. At the moment, limited guidelines are available to assist primary care providers in managing HDP cases. A previous review of 16 international HDP guidelines has identified opportunities for improving HDP management in Indonesian primary care, but it has not determined the suitability of the recommendations in practice. This study aims to achieve consensus among the experts regarding the recommendations suitability and to develop HDP pathways in Indonesian primary care. Methods Maternal health experts, including GPs, midwives, nurses, medical specialists and health policy researchers from Indonesia and overseas were recruited for the study. They participated in a consensus development process that applied a mix of quantitative and qualitative questions in three Delphi survey rounds. At the first and second-round survey, the participants were asked to rate their agreement on whether each of 125 statements about HDP and HDP management is appropriate for use in Indonesian primary care settings. The third-round survey presented the drafts of HDP pathways and sought participants’ agreement and further suggestions. The participants’ agreement scores were calculated with a statement needing a minimum of 70% agreement to be included in the HDP pathways. The participants’ responses and suggestions to the free text questions were analysed thematically. Results A total of 52 participants were included, with 48, 45 and 37 of them completing the first, second and third round of the survey respectively. Consensus was reached for 115 of the 125 statements on HDP definition, screening, management and long-term follow-up. Agreement scores for the statements ranged from 70.8–100.0%, and potential implementation barriers of the pathways were identified. Drafts of HDP management pathways were also agreed upon and received suggestions from the participants. Conclusions Most evidence-based management recommendations achieved consensus and were included in the developed HDP management pathways, which can potentially be implemented in Indonesian settings. Further investigations are needed to explore the acceptability and feasibility of the developed HDP pathways in primary care practice.

Abstract Background Indonesia has the highest maternal mortality rate in South East Asia, that a third of the mortality is caused by hypertensive disorders of pregnancy (HDP), including preeclampsia and eclampsia. Research suggests that maternal deaths from HDP are avoidable with appropriate initial management in primary care. However, little is known regarding the exact way HDP management is conducted in Indonesian primary care. This research aims to explore the way HDP management is provided, including its barriers and facilitators in Indonesian primary care settings. Methods This research applied a practical qualitative methodology using interviews with a topic guide. It is guided by the implementation science framework of the Medical Research Council (MRC) framework and Practical Robust Implementation and Sustainability Model (PRISM) to design and evaluate complex healthcare interventions. Primary care key stakeholders from Yogyakarta province were recruited from May–December 2018. The interviews were conducted in face-to-face, telephone, and teleconference interviews. Data from the interviews were analysed thematically using a mix of inductive and deductive approaches. Results A total of 24 participants were interviewed, consisting of four general practitioners, five midwives, three nurses, three obstetricians, a cardiologist, five policymakers and three women with a previous history of HDP. Referrals are the usual management performed for HDP women in primary care and the primary care providers’ practice is challenged by three identified themes: (i) providers’ limited confidence to perform HDP management, (ii) fragmented continuity of care, and (iii) community beliefs. Many participants also desired to have more focused guidance to improve HDP management in primary care practice. Conclusion Even though Indonesian antenatal care and referrals are generally accessible, there are many challenges and fragmentation of HDP management. The most prominent challenge is the primary care providers’ lack of confidence in performing the management and the ‘elephant’ of an urgent need of practice guidelines in primary care that has never been appropriately described in the literature. Further development of an evidence-based primary care-focused guidance will potentially improve primary care providers’ skills to perform optimal HDP management and provide appropriate education to their patients.

Abstract Background National and international guidelines for the management of hypertensive disorders of pregnancy (HDP) are available in developing countries. However, more detailed clinical pathways for primary care settings are limited. This study focuses on Indonesia, where 72% of women who died from HDP and its complications had received less appropriate treatment according to international guidelines. There is an urgent need to develop primary care focused pathways that enable general practitioners (GPs), midwives and other relevant providers to manage HDP better. Objectives This paper describes a study protocol for the development of HDP management pathways for Indonesian primary care settings. Methods This study design is informed by Implementation Science theories and consists of three phases. The exploratory phase will involve conducting semi-structured interviews with key Indonesian primary care stakeholders to explore their experiences and views on HDP management. The development phase will apply evidence from the literature review and results of the exploratory phase to develop HDP management pathways contextualised to Indonesian primary care settings. Consensus will be sought from approximately 50 experts, consist of general practitioners (GPs), midwives, obstetricians, nurses and policy makers using Delphi technique survey. The evaluation phase will involve a pilot study to evaluate the pathways’ acceptability and feasibility in a sample of Indonesian primary care practices using mixed methods. Discussion The implementation science frameworks inform and guide the phases in this study. Qualitative interviews in the exploratory phase are conducive to eliciting opinions from key stakeholders. Using Delphi technique at the development phase is suitable to seek participants’ consensus on HDP management in primary care. Observations, focus group discussions, interviews as well as analysis of patients’ medical records at the evaluation phase are expected to provide a comprehensive investigation of the implementation of the pathways in practice settings.

Abstract Background Depression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months’ time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care. Methods The Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group. Discussion To our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data.

Abstract Background Engagement is essential in trials research but is rarely embedded across all stages of the research continuum. The development, use, effectiveness and value of engagement in trials research is poorly researched and understood, and models of engagement are rarely informed by theory. This article describes an innovative methodological approach for the development and application of a relational model of engagement in a stepped wedge designed cluster randomised controlled trial (RCT), the CORE study. The purpose of the model is to embed engagement across the continuum of the trial which will test if an experience-based co-design intervention improves psychosocial recovery for people affected by severe mental illness. Methods The model was developed in three stages and used a structured iterative approach. A context mapping assessment of trial sites was followed by a literature review on recruitment and retention of hard-to-reach groups in complex interventions and RCTs. Relevant theoretical and philosophical underpinnings were identified by an additional review of literature to inform model development and enactment of engagement activities. Results Policy, organisational and service user data combined with evidence from the literature on barriers to recruitment provided contextual information. Four perspectives support the theoretical framework of the relational model of engagement and this is organised around two facets: the relational and continuous. The relational facet is underpinned by relational ethical theories and participatory action research principles. The continuous facet is supported by systems thinking and translation theories. These combine to enact an ethics of engagement and evoke knowledge mobilisation to reach the higher order goals of the model. Conclusions Engagement models are invaluable for trials research, but there are opportunities to advance their theoretical development and application, particularly within stepped wedge designed studies where there may be a significant waiting period between enrolment in a study and receipt of an intervention.