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.

Uncovering the emotional aspects of working on a clinical trial: a qualitative study of the experiences and views of staff involved in a type 1 diabetes trial.

BACKGROUND: The perspectives and experiences of trial staff are increasingly being investigated as these can be used to improve recruitment, adherence to trial protocols and support given to future staff. We interviewed staff working on a type 1 diabetes trial in order to aid interpretation of trial findings, inform recommendations for the rollout of the treatments investigated and provide recommendations for the conduct of future trials. However, our interviews uncovered aspects of trial work erstwhile unrecognised or underreported in the trials literature, and it is these which form the focus of this paper. METHODS: In-depth interviews were conducted with (n = 18) staff, recruited from seven centres, who were involved in recruitment and trial delivery. Data were analysed thematically. RESULTS: Alongside logistical and practical issues which made trial work challenging, staff often talked spontaneously and at length about how trial work had affected them emotionally. Staff not only described the emotional stresses arising from having to meet recruitment targets and from balancing research roles with clinical responsibilities, they also discussed having to emotionally manage patients and their colleagues. The emotional aspects of trial work particularly came to the fore when staff notified patients about their treatment allocation. On such occasions, staff described having to employ emotional strategies to pre-empt and manage potential patient disappointment and anger. Staff also described having to manage their own emotions when patients withdrew from the trial or were not randomised to the treatment arm which, in their clinical judgment, would have been in their best interests. To help address the emotional challenges they encountered, staff highlighted a need for more practical, emotional and specialist psychological support. CONCLUSIONS: More attention should be paid to the emotional aspects of trial work to help ensure trial staff are adequately supported. Such support could comprise: increased training for staff to improve their own and patients' understandings of randomization, role-play to develop techniques to manage patient anger and disappointment, sharing of good practice, formalised team support with psychological input and access to specialist psychological support to troubleshoot complex emotional and ethical issues.