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.

INTRODUCTION: The successful treatment of type 1 diabetes (T1D) requires those affected to employ insulin therapy to maintain their blood glucose levels as close to normal to avoid complications in the long-term. The Dose Adjustment For Normal Eating (DAFNE) intervention is a group education course designed to help adults with T1D develop and sustain the complex self-management skills needed to adjust insulin in everyday life. It leads to improved glucose levels in the short term (manifest by falls in glycated haemoglobin, HbA1c), reduced rates of hypoglycaemia and sustained improvements in quality of life but overall glucose levels remain well above national targets. The DAFNEplus intervention is a development of DAFNE designed to incorporate behavioural change techniques, technology and longer-term structured support from healthcare professionals (HCPs). METHODS AND ANALYSIS: A pragmatic cluster randomised controlled trial in adults with T1D, delivered in diabetes centres in National Health Service secondary care hospitals in the UK. Centres will be randomised on a 1:1 basis to standard DAFNE or DAFNEplus. Primary clinical outcome is the change in HbA1c and the primary endpoint is HbA1c at 12 months, in those entering the trial with HbA1c >7.5% (58 mmol/mol), and HbA1c at 6 months is the secondary endpoint. Sample size is 662 participants (approximately 47 per centre); 92% power to detect a 0.5% difference in the primary outcome of HbA1c between treatment groups. The trial also measures rates of hypoglycaemia, psychological outcomes, an economic evaluation and process evaluation. ETHICS AND DISSEMINATION: Ethics approval was granted by South West-Exeter Research Ethics Committee (REC ref: 18/SW/0100) on 14 May 2018. The results of the trial will be published in a National Institute for Health Research monograph and relevant high-impact journals. TRIAL REGISTRATION NUMBER: ISRCTN42908016.

A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.

BACKGROUND: Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy. DESIGN: Pragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI. SETTING: Eight secondary care diabetes centres in the UK. PARTICIPANTS: Adults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps. INTERVENTIONS: Pump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm® VeoTM (Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK). MAIN OUTCOME MEASURES: Primary outcome - change in glycated haemoglobin (HbA1c) at 2 years in participants whose baseline HbA1c was ≥ 7.5% (58 mmol/mol). Key secondary outcome - proportion of participants with HbA1c ≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months - moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness. RESULTS: We randomised 46 courses comprising 317 participants: 267 attended a Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline HbA1c of ≥ 7.5%. HbA1c and severe hypoglycaemia improved in both groups. The drop in HbA1c% at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference (MD) in HbA1c change at 2 years, at which the baseline HbA1c was ≥ 7.5%, was -0.24% [95% confidence interval (CI) -0.53% to 0.05%] in favour of the pump (p = 0.098). The per-protocol analysis showed a MD in change of -0.36% (95% CI -0.64% to -0.07%) favouring pumps (p = 0.015). Pumps were not cost-effective in the base case and all of the sensitivity analyses. The pump group had greater improvement in diabetes-specific QoL diet restrictions, daily hassle plus treatment satisfaction, statistically significant at 12 and 24 months and supported by qualitative interviews. LIMITATION: Blinding of pump therapy was not possible, although an objective primary outcome was used. CONCLUSION: Adding pump therapy to structured training in flexible insulin therapy did not significantly enhance glycaemic control or psychosocial outcomes in adults with T1DM. RESEARCH PRIORITY: To understand why few patients achieve a HbA1c of < 7.5%, particularly as glycaemic control is worse in the UK than in other European countries. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61215213. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 20. See the NIHR Journals Library website for further project information.

Staff experiences of closing out a clinical trial involving withdrawal of treatment: qualitative study.

BACKGROUND: The ending of a clinical trial may be challenging, particularly if staff are required to withdraw the investigated treatment(s); however, this aspect of trial work is surprisingly under-researched. To address this gap, we explored the experiences of staff involved in closing out a trial that entailed withdrawal of treatment (insulin pumps) from some patients. METHODS: Interviews were conducted with n = 22 staff, recruited from seven trial sites. Data were analysed thematically. RESULTS: Staff described a myriad of ethical and emotional challenges at closeout, many of which had been unforeseen when the trial began. A key challenge for staff was that, while patients gave their agreement to participate on the understanding that pump treatment could be withdrawn, they often found themselves benefitting from this regimen in ways they could not have foreseen. Hence, as the trial progressed, patients became increasingly anxious about withdrawal of treatment. This situation forced staff to consider whether the consent patients had given at the outset remained valid; it also presented them with a dilemma at closeout because many of those who had wanted to remain on a pump did not meet the clinical criteria required for post-trial funding. When deciding whether to withdraw treatment, staff not only had to take funding pressures and patient distress into account, but they also found themselves caught between an ethic of Hippocratic individualism and one of utilitarianism. These conflicting pressures and ethical considerations resulted in staff decision-making varying across the sites, an issue that some described as a further source of ethical unease. Staff concluded that, had there been more advanced planning and discussion, and greater accountability to an ethics committee, some of the challenges they had confronted at closeout could have been lessened or even prevented. CONCLUSIONS: The same kinds of ethical issues that may vex staff at the beginning of a trial (e.g. patients having unrealistic expectations of trial participation; staff experiencing conflicts between research and clinical roles) may re-present themselves at the end. To safeguard the wellbeing of staff and patients, greater planning, coordination and ethical oversight should go into the closeout of trials involving withdrawal of treatment(s). TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ISRCTN61215213 . Registered on 11 May 2011.

Type 1 diabetes patients' experiences of, and need for, social support after attending a structured education programme: a qualitative longitudinal investigation.

AIMS AND OBJECTIVES: To explore patients' experiences of, views about and need for, social support after attending a structured education programme for type 1 diabetes. BACKGROUND: Patients who attend structured education programmes attain short-term improvements in biomedical and quality-of-life measures but require support to sustain self-management principles over the longer term. Social support can influence patients' self-management practices; however, little is known about how programme graduates use other people's help. DESIGN: This study was informed by the principles of grounded theory and involved concurrent data collection and analysis. Data were analysed using an inductive, thematic approach. METHODS: In-depth interviews were undertaken postcourse, six and 12 months later, with 30 adult patients with type 1 diabetes recruited from Dose Adjustment for Normal Eating courses in the United Kingdom. RESULTS: Patients' preferences for social support from other people ranged from wanting minimal involvement, to benefiting from auxiliary forms of assistance, to regular monitoring and policing. New self-management skills learnt on their courses prompted and facilitated patients to seek and obtain more social support. Support received/expected from parents varied according to when patients were diagnosed, but parents' use of outdated knowledge could act as a barrier to effective support. Support sought from others, including friends/colleagues, was informed by patients' domestic/employment circumstances. CONCLUSION: This study responds to calls for deeper understanding of the social context in which chronic illness self-management occurs. It highlights how patients can solicit and receive more social support from family members and friends after implementing self-care practices taught on education programmes. RELEVANCE TO CLINICAL PRACTICE: Health professionals including diabetes specialist nurses and dietitians should explore: patients' access to and preferences for social support; how patients might be encouraged to capitalise on social support postcourse; and new ways to inform/educate people within patients' social networks.

A randomised trial of insulin on well-being and carer strain in elderly type 2 diabetic subjects.

INTRODUCTION: Selected tablet-treated elderly type 2 subjects with very poor glycaemic control may experience improvements in well-being after starting twice-daily insulin. In this study, the health status, mood, and treatment satisfaction of diabetic subjects with poor control on oral medication were assessed before and after being randomised to one of two insulin regimens. METHODOLOGY: Fifty-seven type 2 subjects with poor glycaemic control (HBA(1c) 9.7%) were randomised to continue tablets (Group l), twice-daily isophane insulin (Group 2), or basal/bolus isophane/lispro insulin (Group 3). Health status, treatment satisfaction, and mood were measured at baseline, 1, 3, and 6 months. RESULTS: Mean HBA(1c) levels were lower in Groups 1 and 3 at 6 months (P<.02 and.03, respectively) but not Group 2 (P=.2). Mean health status scores did not differ between the groups at any time point. In Group 3, significant within-subject improvements occurred in six domains of the SF-36 at 1 month, four domains at 3 months, and six domains at 6 months. There were no significant within-subject changes in health status scores in the other groups. Mean anxiety scores improved in both Groups 1 and 3 over 6 months, and mean depression scores also improved in Group 3 during the study. CONCLUSIONS: Small improvements in health status and mood may be associated with basal/bolus, but not twice-daily, insulin in elderly type 2 subjects. These effects may be independent of glycaemic control.