Carolin Taylor

Long-term biomedical and psychosocial outcomes following DAFNE (Dose Adjustment For Normal Eating) structured education to promote intensive insulin therapy in adults with sub-optimally controlled Type 1 diabetes

AIMS To explore long-term outcomes of participation in a Dose Adjustment For Normal Eating (DAFNE) training course, which provided one-off exposure to structured education in intensive insulin therapy to people with established Type 1 diabetes. METHODS A cohort design follow-up of original trial participants at a mean of 44 months (range: 37-51 months) in hospital diabetes clinics in three English health districts. 104 (74%) original participants provided biomedical data; 88 (63%) completed questionnaires including the ADDQoL, measuring impact of diabetes on quality of life (QoL). RESULTS At 44 months, mean improvement in HbA(1c) from baseline was 0.36% (9.32+/-1.1% to 8.96+/-1.2%, p<0.01) remaining significant but deteriorated from 12 months (p<0.05). Improvements in QoL seen at 12 months were sustained at 44 (e.g. impact of diabetes on dietary freedom: -1.78+/-2.33 at 44 months versus -4.27+/-2.94, baseline, p<0.0001; versus 1.80+/-2.32 at 12 months, ns). Similar results were obtained using last observation carried forward for patients not supplying follow-up data. CONCLUSIONS The impact of a single DAFNE course on glycaemic control remains apparent in the long term, although further interventions will be required to achieve recommended HbA(1c). In contrast, improvements in QoL and other patient-reported outcomes are well maintained over approximately 4 years.

Perceptions and experiences of using automated bolus advisors amongst people with type 1 diabetes: A longitudinal qualitative investigation

Aims We explored peoples reasons for, and experiences of, using bolus advisors to determine insulin doses; and, their likes/dislikes of this technology. Subjects and methods 42 people with type 1 diabetes who had received instruction in use of bolus advisors during a structured education course were interviewed post-course and 6 months later. Data were analysed thematically. Results Participants who considered themselves to have poor mathematical skills highlighted a gratitude for, and heavy reliance on, advisors. Others liked and chose to use advisors because they saved time and effort calculating doses and/or had a data storage facility. Follow-up interviews highlighted that, by virtue of no longer calculating their doses, participants could become deskilled and increasingly dependent on advisors. Some forgot what their mealtime ratios were; others reported a misperception that, because they were pre-programmed during courses, these parameters never needed changing. Use of data storage facilities could hinder effective review of blood glucose data and some participants reported an adverse impact on glycaemic control. Discussion While participants liked and perceived benefits to using advisors, there may be unintended consequences to giving people access to this technology. To promote effective use, on-going input and education from trained health professionals may be necessary.

Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)

Objective To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment. Design Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial). Setting Eight secondary care centres in England and Scotland. Participants Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment (“dose adjustment for normal eating,” DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections. Interventions Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years. Main outcome measures The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction. Results 317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was −0.85% with pump treatment and −0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was −0.24% (−2.7 mmol/mol) in favour of pump users (95% confidence interval −0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24 months. Conclusions Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. Adding pump treatment to structured training in flexible intensive insulin treatment did not substantially enhance educational benefits on glycaemic control, hypoglycaemia, or psychosocial outcomes in adults with type 1 diabetes. These results do not support a policy of providing insulin pumps to adults with poor glycaemic control until the effects of training on participants’ level of engagement in intensive self management have been determined. Trial registration Current Controlled Trials ISRCTN61215213.

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.

BackgroundThe 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.MethodsInterviews were conducted with n = 22 staff, recruited from seven trial sites. Data were analysed thematically.ResultsStaff 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.ConclusionsThe 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 registrationInternational Standard Randomised Controlled Trials Number (ISRCTN) Registry, ISRCTN61215213. Registered on 11 May 2011