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)BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j1285 (Published 30 March 2017) Cite this as: BMJ 2017;356:j1285
- The REPOSE Study Group
- Correspondence to: S Heller Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
- Accepted 8 February 2017
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.
We thank those with diabetes who participated in the trial and members of the trial steering committee and data monitoring and ethics committee for their contribution. The research governance sponsor was Sheffield Teaching Hospitals NHS Foundation Trust. The clinical sites taking part were: Cambridge University Hospitals NHS Foundation Trust, Dumfries and Galloway Royal Infirmary, NHS Greater Glasgow and Clyde, Harrogate and District NHS Foundation Trust, King’s College Hospital NHS Foundation Trust, NHS Lothian, Nottingham University Hospitals NHS Trust, and Sheffield Teaching Hospitals NHS Foundation Trust.
Writing committee on behalf of the REPOSE Study Group
Simon Heller (Department of Oncology and Metabolism, University of Sheffield), Stephanie Amiel (Kings College, University of London), Michael Campbell (School of Health and Related Research, ScHARR, University of Sheffield), Pratik Choudhary (Kings College, University of London), Cindy Cooper (Sheffield Clinical Trials Research Unit, University of Sheffield), Munya Dimairo (Sheffield Clinical Trials Research Unit, University of Sheffield), Jackie Elliott (Department of Oncology and Metabolism, University of Sheffield), Peter Hammond (Harrogate and District Foundation Trust), Ellen Lee (Sheffield Clinical Trials Research Unit, University of Sheffield), Robert Lindsay (University of Glasgow), Peter Mansell (Nottingham University Hospitals NHS Trust), Norman Waugh (Warwick Medical School, University of Warwick) and David White (Sheffield Clinical Trials Research Unit, University of Sheffield).
Members of the REPOSE Study Group
Simon Heller was the chief investigator. Norman Waugh was the deputy chief investigator. Stephanie Amiel, Mark Evans, Fiona Green, Peter Hammond, Alan Jaap, Brian Kennon, Robert Lindsay, and Peter Mansell were site principal investigators and contributed to the study design and data interpretation.
The following contributed at sites to participant recruitment, intervention delivery, and data collection: Jane Baillie, Anita Beckwith, Helen Brown, Karen Callaby, Katy Davenport, Sarah Donald, Jackie Elliott, Leila Faghahati, Sara Hartnell, Allison Housden, Kalbir Kaur Pabla, Nicola Croxon, Sheena Macdonald, Muna Mohammed, Vicky Steel, Katy Valentine, Pamela Young, Ann Boal, Patsy Clerkin, Lynn Doran, Joanne Flynn, Emma Gibb, Hilary Peddie, Bernie Quinn, Helen Rogers, Janice Shephard, Janet Carling, Ann Collins, Laura Dinning, Christine Hare, Joyce Lodge, Sutapa Ray, Debora Brown, Jenny Farmer, Alison Cox, Chris Cheyette, Pratik Choudhary, Linda East, June Ellul, Katherine Hunt, Kimberley Shaw, Ben Stothard, Lucy Diamond, Lindsay Aniello, Debbie Anderson, Kathy Cockerell, Vida Heaney, Alison Hutchison, Nicola Zammitt, Gayna Babington, Gail Bird, Janet Evans, Tasso Gazis, Nicola Maude, Karen Nunnick, Dawn Spick, Laura Fenn, Carla Gianfrancesco, Valerie Gordon, Linda Greaves, Susan Hudson, Valerie Naylor, Chloe Nisbet, Carolin Taylor, Karen Towse, and Candice Ward.
Cindy Cooper, Gemma Hackney, Diana Papaioannou, Emma Whatley, and David White provided central trial management, oversight, and monitoring. Mike Bradburn, Michael Campbell, Munya Dimairo, and Ellen Lee contributed to the statistics. Hasan Basarir, Alan Brennan, Simon Dixon, and Daniel Pollard contributed to the health economics. Nina Hallowell, Jackie Kirkham, Julia Lawton, and David Rankin designed and undertook the qualitative work. Katharine Barnard led the quantitative psychosocial work. Timothy Chater and Kirsty Pemberton provided data management. Fiona Allsop and Lucy Carr provided central administration. Pamela Royle conducted literature searches and exploratory analyses. Gill Thompson and Sharon Walker provided central DAFNE support. Pauline Cowling conducted the fidelity assessment. Henry Smithson provided user representation on the management group.
Contributors: Simon Heller, Stephanie Amiel, Michael Campbell, Pratik Choudhary, Cindy Cooper, Munya Dimairo, Jackie Elliott, Peter Hammond, Ellen Lee, Robert Lindsay, Peter Mansell, Norman Waugh, and David White provided input into the study design, data interpretation, and drafting the final paper. All had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. SH is the guarantor.
Funding: This research was funded by the UK Health Technology Assessment Programme (project No 08/107/01) and will be published in full in Health Technology Assessment. See the HTA programme website for further project information. (http://www.nets.nihr.ac.uk/). This report presents independent research commissioned by the National Institute for Health Research (NIHR). We also acknowledge financial support from the Research and Development Programmes of the Department of Health for England and the Scottish Health and Social Care Directorates who supported the costs of consumables, and of Medtronic UK, which provided the insulin pumps for the trial. These funders had no involvement in the design of the protocol; the collection, analysis, and interpretation of the data; the writing of this paper; or the decision to submit this article for publication. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the HTA, NIHR, NHS, the Department of Health, or Medtronic UK.
Competing interests: All members of the writing committee have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: grant funding from the UK Health Technology Assessment Programme and financial support from Medtronic UK, for the submitted work; PC reports personal fees and non-financial support from Medtronic UK and personal fees from Roche, outside the submitted work. JE reports personal fees from Astra Zeneca, Eli Lily, Merck Sharpe Dohme, Novo Nordisk, Sanofi Aventis, and Takeda, and non-financial support from Eli Lilly, Novo Nordisk, and Sanofi, outside the submitted work. PH reports personal fees from Medtronic UK, Johnson and Johnson, Roche, Novo Nordisk, and Lilly, outside the submitted work. RL reports personal fees from Eli Lilly and Novo Nordisk, outside the submitted work. SH reports grants from Medtronic UK during the conduct of the study, and personal fees from Sanofi Aventis, Eli Lilly, Takeda, NovoNordisk, and Astra Zeneca, outside of the submitted work. His institution has received remuneration from Eli Lilly, Boeringher Ingelheim, NovoNordisk, Eli Lilly, and Takeda, outside the submitted work; he is currently chief investigator on an NIHR programme grant for applied research: RP-PG-0514-20013, the purpose of which is to develop more effective training programmes to improve self management of type 1 diabetes; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The protocol was approved by the Research Ethics Committee North West, Liverpool East (11/H1002/10). Each participating centre gave NHS Research and Development approval. The protocol received MHRA clinical trials authorisation. All participants provided written informed consent before taking part in the study.
Data sharing: Requests for patient level data and statistical code should be made to the corresponding author and will be considered by the REPOSE trial management group who, although specific consent for data sharing was not obtained, will release data on a case by case basis following the principles for sharing patient level data as described by Smith et al. 23 The presented data do not contain any direct identifiers, we will minimise indirect identifiers and remove free text data, to minimise the risk of identification.
Transparency: The guarantor (SH) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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