The REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) Trial

• The change in HbA1c after 2 years in those participants whose baseline HbA1c was at or above 7.5% (58mmol/mol). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

  The change in HbA1c after 2 years in those participants whose baseline HbA1c was at or above 7.5% (58mmol/mol).

  (Change will be calculated from baseline at 24 months)

  
  

• The proportion of participants reaching the NICE target of an HbA1c level of 7.5% (58mmol/mol) or less [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  HbA1c is a measurement of glycosylated haemoglobin which reflects overall blood glucose values over the previous 6-8 weeks(24). This is regarded as the gold standard measure of glycaemic control. There is a strong relationship between HbA1c and the risk of developing long term diabetic complications and it is accepted as a surrogate for long term outcomes in individuals with diabetes.

  Since HbA1c can be measured by different techniques we will ensure standardisation by measuring HbA1c in blood samples at a central laboratory.

  (Change will be calculated from baseline at 24 months)

  
  
• Diabetes specific quality of life [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  DSQOL Diabetes-specific quality of life (QoL) will be assessed using the scale DSQOL.

  (Change will be calculated from baseline at 24 months)

  
  
• Hypoglycaemia (severe & moderate) [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  The investigators will record both severe and moderate episodes of hypoglycaemia in participants. This should increase power and identify the ability of CSII to reduce rates of hypoglycaemia. It will also be possible to assess the effects of both, by comparing quality of life measures in those with only moderate hypos, versus those with moderate and severe.

  (Change will be calculated from baseline at 24 months)

  
  
• Insulin dose [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Some studies have indicated that CSII results in the use of less insulin. We will therefore record participants' self-reported insulin dose at each time point and calculate units/kg body weight.

  (Change will be calculated from baseline at 24 months)

  
  
• Body weight [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  If CSII treatment results in the use of less insulin, it may have a favourable effect on weight since with less insulin there is a propensity for the body to store fewer nutrients. We will therefore record weight at each time point of the trial.

  (Change will be calculated from baseline at 24 months)

  
  
• Blood lipids & proteinuria [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Blood samples will be taken using local labs and lipids (including HDL cholesterol). Albumin- creatinine ratio (a sensitive measure of proteinuria) will be measured from urine samples.

  (Change will be calculated from baseline at 24 months)

  
  
• Diabetic Ketoacidosis [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  This outcome will be measured through the assessment of any SAE's and AEs.

  (Change will be calculated from baseline at 24 months)

  
  
• Fear of hypoglycaemia [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  The Hypoglycaemia Fear Scale (HFS) is a well validated psychometric tool assessing participants fear of hypoglycaemia both overall and in terms of behaviour and worry. It has been used to assess the impacts of different hypoglycaemic events such as severe, moderate and mild hypoglycaemic episodes on fear of hypoglycaemia (33). A specific benefit to the HFS is that it may be able to identify participants who are likely to maintain high blood glucose levels, thus aiding understanding of potential reasons for poor glycaemic control.

  (Change will be calculated from baseline at 24 months)

  
  
• Diabetes Treatment Satisfaction [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  The Diabetes Treatment Satisfaction Questionnaire (DTSQ measures treatment satisfaction which refers to an individual's subjective appraisal of their experience of treatment, including ease of use, side effects and efficacy. Improvements in satisfaction are not necessarily accompanied by improvements in QoL; treatment satisfaction can be high despite diabetes having a negative impact on QoL, which is why it is important to measure both separately.

  (Change will be calculated from baseline at 24 months)

  
  
• Emotional Wellbeing [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  The Hospital Anxiety and Depression Scale (HADS) measures anxiety on one subscale and depression on another through the use of 7 questions for each characteristic. It is important to measure emotional wellbeing in the trial as participants may find it easier to manage their condition after DAFNE education or with one of the treatments. This might have a substantial effect on their emotional wellbeing that the QoL measures are not sensitive enough to pick up.

  (Change will be calculated from baseline at 24 months)

  
  
• Participant views regarding the pump/multiple injection course & treatment [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Participant post course interviews

  Participants will be interviewed regarding:

  1. Understandings of the trial and motivation for participation.
  2. Views about outcome of randomisation.
  3. Expectations/concerns about trial participation and (if relevant) change to CSII.
  4. Experience of/views about the course and (if relevant) change to CSII.
  5. Changes they have made to diabetes management since the course and short/long terms goals set.
  6. Likes/dislikes of CSII or MDI treatment. (Change will be calculated from baseline at 24 months)
  
  
• Educator views regarding the pump/multiple injection course & treatment [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Educator post course interviews

  Educators will be interviewed regarding:

  a) Insight and experience of what took place on the course. b) Recommendations for future course development.

  c) Recommendations for support that should be offered to patients who move onto pumps.

  (Change will be calculated from baseline at 24 months)

  
  
• Costs and Outcomes [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Costs and quality adjusted life years will be estimated for each individual recruited to the trial. Mean values for each arm will be calculated.

  (Change will be calculated from baseline at 24 months)

  
  
• Incremental cost-effectiveness ratio [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Cost-effectiveness will be described using plots of incremental costs and QALYs on the cost-effectiveness plane, together with their associated cost-effectiveness acceptability curves and frontiers. The incremental cost-effectiveness ratio and the probability that CSII will be cost-effective in the range of £20,000-£30,000 per QALY will be the main focus.

  (Change will be calculated from baseline at 24 months)

  
  
• Costs [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  Mean values of cost wll be estimated and the value will be calculated for each individual

  (Change will be calculated from baseline at 24 months)

  
  
• General Quality of Life [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]

  This will be measured by 3 different measures, the WHOQOL bref, SF12 and EQ5D.

  (Change will be calculated from baseline at 24 months)

  
  
• Quality of adjusted life years [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]
  Mean values will be estimated and value will be calculated for each individual (Change will be calculated from baseline at 24 months)
  
  

The trial is a multi-centre randomised controlled trial whereby between 40 and 49 type-1 diabetic, adult volunteers, aged 18 and above, will be recruited per site from 7 secondary care centres (Sheffield, Kings College Hospital London, Harrogate District Hospital, Addenbrookes Hospital Cambridge, Glasgow Royal Infirmary, Dumfries and Galloway Royal Infirmary and Edinburgh Royal Infirmary). The sites will be required to recruit participants to at least 3 CSII DAFNE (Dose Adjustment for Normal Eating)courses and 3 MDI DAFNE courses. This will mean that in total on the trial, 140 participants are randomised to CSII and 140 to MDI. Participants will be recruited through direct approach if already on the waiting list for a DAFNE course or through advertisement in various clinics.