A lifelong approach to promote effective self-management in adults with type 1 diabetes: the DAFNEplus research programme including a cluster RCT

Background Dose Adjustment For Normal Eating is a 5-day, group-based clinical education programme for adults with type 1 diabetes, training them in the complex self-management skills, enabling them to optimise both their glycaemic management and quality of life. Although Dose Adjustment For Normal Eating is associated with improvements in many aspects of diabetes management, including psychological outcomes, it has been challenging to maintain the biomedical improvements for longer term, which have remained well above the glucose levels recommended by National Institute for Health and Care Excellence. Objectives We aimed to develop and evaluate Dose Adjustment For Normal Eating plus, an enhanced version of Dose Adjustment For Normal Eating, to enable improvements in glycaemic management (glycated haemoglobin) without compromising the quality of life. The objectives of the programme were to modify the existing Dose Adjustment For Normal Eating curriculum and evaluate it in a cluster randomised controlled trial. Design This programme comprised four workstreams. The first three workstreams focused on redevelopment of the Dose Adjustment For Normal Eating intervention to become ‘Dose Adjustment For Normal Eating plus’: involving revision of the curriculum for a 5-day, group-based programme, including relevant behaviour change techniques (workstream 1); development of a new structured, pro-active, follow-up programme to be delivered by Dose Adjustment For Normal Eating plus facilitators post course to support ongoing diabetes self-management (workstream 2); and development of a new technology interface to help glucose pattern recognition to inform improved self-management (workstream 3). We used mixed methods to review, develop and refine the Dose Adjustment For Normal Eating plus intervention (course, individual support and technological aspects). The intervention was piloted in three National Health Service specialist diabetes centres and was reviewed via two iterative waves before finalisation. Workstream 4 was a cluster randomised controlled trial using a pragmatic, parallel group (1 : 1) allocation design (Dose Adjustment For Normal Eating vs. Dose Adjustment For Normal Eating plus), with concurrent process and health economic evaluations. The primary biomedical outcome was the between-group difference in glycated haemoglobin at 12 months. The primary psychological outcome was the between-group difference in the impact of type 1 diabetes on quality of life (using Audit of Diabetes-Dependent Quality of Life-15) at 12 months. Setting The workstreams and the randomised controlled trial were undertaken in university and National Health Service specialist centres in England and Scotland. Participants Four hundred and seventy-one adults aged ≥ 18 years with confirmed diagnosis of type 1 diabetes participated in the cluster randomised controlled trial, which was 144 fewer than planned and approximately 77% of the planned sample size. Intervention Dose Adjustment For Normal Eating plus is a standardised 5-day educational course (described above), delivered 1 day per week over 5 weeks in groups, meeting face to face, followed by five individual support sessions over 12 months. An online platform supports the upload, visualisation, pattern recognition and review of glycaemic data for participants and clinicians. Trial outcome measures In the cluster randomised controlled trial, the primary biomedical outcome was glycaemia, defined as glycated haemoglobin, at 12 months. The primary psychological outcome was the impact of diabetes on quality of life (assessed using the widely recognised scale, Audit of Diabetes-Dependent Quality of Life-15). Key secondary biomedical outcomes included rates and proportions of severe hypoglycaemia and diabetic ketoacidosis. Key secondary psychological outcomes included diabetes-specific distress, diabetes-specific positive well-being and fear of hypoglycaemia. Results In the primary intention-to-treat population (309), mean glycated haemoglobin reduced from 9.1% to 8.2% (75.9–66.5 mmol/mol) in the Dose Adjustment For Normal Eating group and from 9.1% to 8.1% (75.6–65.1 mmol/mol) in the Dose Adjustment For Normal Eating plus group. The cluster randomised controlled trial showed no evidence of a between-group difference at 12 months in glycated haemoglobin {point estimate [95% confidence interval −0.014 (−0.284 to 0.255); p = 0.915]}, or diabetes-specific quality of life {point estimate [95% confidence interval 0.2 (−0.1 to 0.5); p = 0.21]}. At 12 months, significant between-group differences were observed, favouring Dose Adjustment For Normal Eating plus, in secondary psychological outcomes (diabetes-specific distress, diabetes-specific positive well-being and actions taken to avoid hypoglycaemia). Limitations Due to trial-suspension during coronavirus disease, we recruited 471 adults to the cluster randomised controlled trial, 144 fewer than planned. Although this reduced overall statistical power, we showed that the difference in glycated haemoglobin between the groups was far below that we considered a meaningful clinical difference (0.5%). Recruitment also meant that more participants were using continuous glucose monitoring, both before and during the trial than we anticipated. This may have reduced additional benefit of the Dose Adjustment For Normal Eating plus intervention on glycated haemoglobin. The pandemic probably influenced diabetes self-management during the trial in both groups. Conclusions Dose Adjustment For Normal Eating plus did not lead to greater falls in glycated haemoglobin at 12 months compared to Dose Adjustment For Normal Eating, but these falls were double those reported in previous Dose Adjustment For Normal Eating randomised controlled trials. Sixty-eight per cent of participants showed clinically relevant improved glucose levels. Those in Dose Adjustment For Normal Eating plus reported significant falls in diabetes distress, positive well-being and qualitative research reported positive experiences of Dose Adjustment For Normal Eating plus among participants and health professionals. Future work In view of major improvements in diabetes distress and positive experiences in both participants and health professionals, the Dose Adjustment For Normal Eating executives, who co-ordinate the delivery of Dose Adjustment For Normal Eating courses, are planning to include key elements of Dose Adjustment For Normal Eating plus in future courses, particularly structured support to participants following the course and key elements of the curriculum. Study registration This study is registered as IRAS: 235621 and ISRCTN: 42908016. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20013) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 21. See the NIHR Funding and Awards website for further award information. Plain language summary Researchers from hospitals and universities in the United Kingdom and psychologists from Australia received money from the National Institute for Health Research to undertake research to improve an education programme. It helps adults with type 1 diabetes to self-treat their condition and improve their health and quality of life. We built on the existing (DAFNE) course by including key steps in self-treating diabetes, new technology and support after the course, calling it DAFNEplus. Adults with diabetes helped in all areas of the research. Between 2018 and 2022, 471 adults with type 1 diabetes from 13 diabetes centres across the United Kingdom took part in a trial. Centres were chosen by chance to teach either DAFNE or the new DAFNEplus course. All those involved, attended a 5-day course, but DAFNEplus added five follow-up sessions and used technology to feedback results and glucose patterns. Those taking part provided blood to measure glucose and other lab tests and questionnaires. We talked to both participants receiving and staff providing DAFNEplus and recorded their experiences. Results were collected before the course and 12 months later. The trial was badly affected by COVID-19, but enough people took part for us to collect reliable results. At 12 months, glucose levels and quality of life had improved, but there were no differences between those on the standard DAFNE and those on DAFNEplus. Glucose levels actually improved by twice the amount we had previously found in DAFNE trials in both groups. The people doing DAFNEplus also had improved levels of diabetes distress and other quality-of-life measures. The people and staff who took part in the research programme were particularly positive about the DAFNEplus approach, and we are working out how to include some parts of DAFNEplus in future DAFNE courses. Scientific summary Background Successful long-term management of type 1 diabetes (T1D) requires sustained individual engagement in complex self-management behaviours to maintain blood glucose [glycated haemoglobin (HbA1c)] levels within an optimal range. In 2002, we published a randomised controlled trial (RCT) reporting results of a 5-day training course, showing significantly improved levels of glucose and quality of life (QoL) at 12 months with no change in the control group. Although structured education programmes lead to clinically significant decreases in HbA1c, increased hypoglycaemia awareness and improved QoL, these benefits are not always sustained and glucose levels rarely reach recommended targets. The work of the Dose Adjustment For Normal Eating (DAFNE) collaborative and its associated research programmes have provided important understanding, including qualitative work, which has suggested roles in therapeutic interventions for: ongoing structured long-term support, including behaviour change science to support initial and ongoing learning and technology, facilitating links between professionals and a person with diabetes. Objectives The overall aim of Dose Adjustment For Normal Eating plus (DAFNEplus) was to refine the existing DAFNE curriculum, embedding behavioural science frameworks in all aspects of the intervention, addressing ‘ongoing support’, and including technological support, to aid long-term maintenance of HbA1c within an acceptable clinical range with no negative effects on participant’s QoL. Methods and results Workstream 1 The specific aims of this workstream (WS) were to: specify behaviours involved in T1D self-management and barriers and enablers to sustaining these behaviours specify behaviour change techniques (BCTs) included in the existing DAFNE intervention and examine whether they target the identified barriers/enablers identify additional BCTs with the potential to address barriers/enablers not currently targeted generate recommendations for revising the existing DAFNE curricula via stakeholder consultation and consensus integrate recommendations into a coproduced DAFNEplus intervention, pilot and refine the intervention ahead of the trial. This WS applied behavioural science to refine the existing DAFNE structured education programme into DAFNEplus. We identified underlying behaviours and influencing factors contributing to T1D self-management, and we identified 51 unique BCTs to address these. This enabled co-design of the DAFNEplus intervention which was piloted and refined in three centres and then taken forward for the evaluation of effectiveness and cost-effectiveness in a cluster RCT (cRCT) (WS4), and a parallel process evaluation was performed to explore the mechanisms of action, acceptability and fidelity (WS4). Workstream 2 The aims were to explore participants’ self-management after attending structured T1D education and their unmet need(s) for support to sustain improvements in glycaemic management and then to develop an evidence-informed model to guide effective follow-up support following DAFNEplus. To inform the design of effective follow-up support, we undertook a meta-ethnography of qualitative studies focusing on self-management of T1D, following structured education. We expressed the synthesis as a logic model: Follow-Up Support for Effective T1D Self-management (FUSED). The FUSED model provided an explanation of why people find it difficult to maintain T1D self-management following structured education, and it outlined the elements required for effective follow-up support. Following on from this activity, we undertook a further systematic review to identify the most effective type of education programme to support sustained improvements in glycaemia. Workstream 3 Workstream 3 aimed to develop technological resources to support learning and understanding of individual glycaemic control. The Glucollector web-based platform is supported by the WithCare+ device for data acquisition and by developed bespoke tools for modelling, decision support and visual representation and interpretation. It incorporates functionalities to support shared visualisation for patients and clinicians based on collected data from various monitoring devices, automated feedback, goal setting and self-care facilitation. The WithCare+ device transmits data securely on self-care behaviours like blood glucose measurements [including both capillary glucose readings and continuous glucose monitoring (CGM) from Libre flash monitoring], carbohydrate intake and insulin doses. It supports linking to activity tracking devices and prompts users to contextualise abnormal readings. Clinician versions are available for in-clinic use. Pilot and feasibility trial We undertook a pilot study to assess the feasibility and best approach to developing the logistics of the cRCT. We considered recruitment, intervention delivery, participant engagement and data collection methods, with the intention of refining the prototype DAFNEplus programme to optimise the intervention prior to the trial. The prototype DAFNEplus programme was piloted in two waves, at three DAFNE centres, at: Sheffield Teaching Hospitals NHS Foundation Trust King’s College Hospital NHS Foundation Trust Norfolk and Norwich University Hospitals NHS Foundation Trust This was a non-randomised feasibility pilot where all participants received the intervention. The pilot intervention was delivered by practising DAFNE educators (diabetes specialist nurses, dietitians and physicians) at each participating site, who had undertaken training in DAFNEplus. We anticipated that the DAFNEplus programme could be optimised with participants from eight courses across the three centres. The number of courses was selected to enable all centres to complete at least two DAFNEplus courses during the pilot. Eight DAFNEplus courses involving 54 patient participants were completed. The collaborative working group We developed a novel structured collaborative working group (CWG) process to use findings from the embedded qualitative work and feedback from other stakeholders (e.g. individuals involved in designing and delivering the intervention) to make iterative refinements to the intervention prior to the RCT. Pilot study components Pilot study process evaluation Glucollector/Withcare+ user testing Collection of outcome measures Pilot study key outcomes We piloted and iteratively amended the DAFNEplus curriculum via two waves of pilot courses. All eight DAFNEplus cohorts in the pilot study were given access to the technology and structured follow-up support as part of the intervention. In line with the work developing and refining the curriculum, the CWG used the same approach to optimising the structured support and technology. The qualitative research with DAFNEplus participants and facilitators enabled the identification of key barriers and facilitators to delivery and receipt of the intervention in real time. In addition, we were able, through the CWG, to mobilise the knowledge generated through both the pilot study and patient and public involvement feedback, to iteratively develop the intervention and address any identified shortcomings. The Your Self-management And You study advised on the primary and other psychological-related, patient-reported outcome measures. The health economists completed an evaluation of the potential cost-effectiveness of DAFNEplus compared to standard DAFNE in an NHS setting. This is detailed within the health economic evaluation. Workstream 4 cluster randomised trial Introduction A cRCT was conducted to examine the effectiveness of the intervention (DAFNEplus) compared with standard DAFNE. Concurrent health economic and process evaluations were undertaken. The aim of this superiority cRCT was to investigate whether DAFNEplus enabled improved and sustained diabetes self-management behaviours, leading to better glucose management (i.e. reduced mean HbA1c by minimum clinically significant difference of 0.5%) at 12 months than achieved with standard DAFNE, without compromising QoL [Coates E, Amiel S, Baird W, Benaissa M, Brennan A, Campbell MJ, et al.; DAFNEplus group. Protocol for a cluster randomised controlled trial of the DAFNEplus (Dose Adjustment For Normal Eating) intervention compared with 5x1 DAFNE: a lifelong approach to promote effective self-management in adults with type 1 diabetes. BMJ Open 2021;11:e040438]. Objectives The primary objective was to compare the effect of DAFNEplus to standard DAFNE on glycaemia (HbA1c) at 12 months (primary biomedical outcome). The secondary objectives were: to compare the effects of DAFNEplus to standard DAFNE on: diabetes-specific QoL at 12 months (primary psychological outcome) glycaemia (HbA1c) at 6 months (medium-term outcome) other biomedical outcomes, including severe hypoglycaemic episodes, diabetic ketoacidosis (DKA), weight, body mass index, blood pressure and lipids secondary psychological outcomes, including diabetes distress, diabetes-specific positive well-being and fear of hypoglycaemia to undertake a mixed-methods process evaluation to aid understanding of the cRCT findings and inform decision-making about the implementation of DAFNEplus in clinical care post trial to assess the fidelity of delivery of DAFNEplus to undertake a health economic analysis to determine the cost-effectiveness of DAFNEplus versus standard DAFNE. Design The trial used a pragmatic, parallel group, superiority cluster randomised (1 : 1 allocation) controlled design involving 14 NHS specialist diabetes centres. Centre randomisation was implemented rather than individual participants, as contamination of the control arm may have occurred if educators were trained in DAFNEplus (intervention) and still were required to deliver standard DAFNE (control). Cluster randomised controlled trial methods Participants Participants were considered eligible if they were ≥ 18 years of age, had a diagnosis of T1D for at least 6 months (or post honeymoon), were prepared to undertake multiple daily injection therapy and frequent self-monitoring of blood glucose, could attend all sessions as part of the intervention and the principal investigator was confident that they could adhere to the protocol requirements. Those currently using continuous subcutaneous insulin infusion pump therapy or who had attended a DAFNE course within the last 5 years were ineligible. Intervention DAFNEplus was facilitated by practising DAFNE educators (diabetes nurses, dietitians and physicians) in the NHS, all of whom had previous experience in DAFNE training. An extensive training package was undertaken by all intervention staff. Randomisation All participating centres were randomised on a 1 : 1 basis to control (standard DAFNE course) or the intervention arm (DAFNEplus programme). End points The primary biomedical outcome was HbA1c at 12 months. The study was powered for this single, primary end point. All additional analyses were performed to further inform this primary end point and should be interpreted accordingly. The number of participants achieving glycaemic control [defined as either a HbA1c 7.5%, analysed as per their randomisation allocation, regardless of treatment adherence and protocol non-compliances. Full ITT population composed of consented participants, analysed as per their randomisation allocation, regardless of treatment adherence and protocol non-compliances. Per-protocol population composed of the subset of the primary ITT population who adhered to their assigned intervention. For all analysis populations, participants recruited in 2020, who did not attend at least one session of the initial DAFNE course, were excluded. This was due to courses not running during the COVID-19 pandemic. Cluster randomised controlled trial results Key findings: biomedical outcomes Four hundred and seventy-one people were recruited from 13 sites over 4 years, which was 144 fewer than planned (approximately, 77% of the planned sample size, which was planned to recruit over 3 years). In the primary ITT population, mean HbA1c reduced from 9.1% to 8.2% (75.9–66.5 mmol/mol) in the DAFNE group and from 9.1% to 8.1% (75.6–65.1 mmol/mol) in the DAFNEplus group. There was no evidence of a between-arm difference in HbA1c at 12 months {point estimate [95% confidence interval (CI) −0.014 (−0.284 to 0.255); p = 0.915]} in the primary ITT population. This was consistent with sensitivity analyses, including those adjusting for adherence, and varying assumptions about missing data. In the full ITT population (245 DAFNE, 178 DAFNEplus) of those we have baseline and 12-month HbA1c paired measurements, around 70% improved their glucose levels during the trial; either HbA1c