You may have seen the social media storm that unfolded when the REPOSE study was published in March 2017. With this article we hope to give all relevant information and perhaps calm some fears.
Link to research article in BMJ
For many years some have been asking
- should insulin pumps be available to everyone on insulin including those who don’t meet the criteria set out in NICE TA151? and
- do pump users tend to get better outcomes than those on multiple daily injections (MDI) because of the pump or because of the extra education given to them?
REPOSE was designed to answer those questions.
The 2-year study involved 248 participants at its conclusion.
Participants had to meet all the following inclusion criteria:
- adults with type 1 diabetes for at least 12 months
- willing to undertake intensive insulin treatment with self monitoring of blood glucose levels, carbohydrate counting and insulin adjustment
- no preference for either pump or multiple daily injections
- with clinical indications for structured education in insulin treatment to optimise diabetes control who had not participated previously in structured training
The following were excluded from taking part:
- those who meet the NICE criteria for pump treatment
- those needing a pump in the opinion of the investigator
- those with a strong desire for pump treatment
- those with serious diabetic complications
- and those unable to communicate in English
Participants were randomised to the MDI or pump treatment group.
- attended standard DAFNE structured education course over five consecutive days in groups of 5-8 adults as outpatients
- they took Humalog or NovoRapid for meals and twice daily injections of Levemir
- they used the Accu-Chek Aviva Expert Bolus Advisor System as a bolus calculator
- attended a modified DAFNE course, previously validated in pump users, over five consecutive days. The course also incorporated the practical skills and learning outcomes needed to use pumps successfully delivered in an additional group session, one to three weeks before the main course.
- used a Minimed Paradigm Veo insulin pump with Humalog or NovoRapid
- the bolus wizard in the pumps was activated as part of the course
The study measured:
- change in HbA1c if it was 7.5% / 58mmols/mol or over at the start of the study;
- proportion of participants reaching NICE 2004 target HbA1c equal to or less than 7.5% / 58mmols/mol;
- episodes of moderate or severe hypoglycaemia;
- cholesterol levels; proteinuria; insulin dose; body weight.
Diabetic ketoacidosis was recorded through the assessment of serious adverse events throughout the trial.
It also looked at psychosocial outcomes including satisfaction with treatment, diabetes related quality of life, fear of hypoglycaemia and emotional wellbeing.
HbA1c: the pump group did slightly better but the difference between the groups was not clinically significant.
Proportion of participants reaching HbA1c ≤7.5% (58 mmol/mol): the pump group did slightly better (25.0% vs 23.3% of the MDI group).
Severe hypoglycaemia: no difference in rates of severe hypoglycaemia between the treatment groups. Across both treatment groups, the number of severe hypoglycaemic episodes was reduced.
Moderate hypoglycaemia: by 24 months, the MDI group did slightly better but there was no statistically significant difference between the groups.
Other biomedical outcomes
No statistically significant difference between the treatment groups at any time point.
The number or type of serious adverse events did not differ between the groups, with the exception of diabetic ketoacidosis, which was greater in the pump group compared with MDI group (17 v 5). In the first year, more patients using pumps than using MDI had several episodes (5 v 2). Most episodes of ketoacidosis were caused by infections and 18% by set failure in those using pumps. Only five episodes occurred when participants implemented all sick day rules.
No differences between the groups were found in the generic quality of life and health status instruments.
The overall diabetes specific quality of life showed that both groups improved, more in the pump group than the MDI group, although not always reaching statistical significance.
Regarding diet restrictions and daily hassle, the pump group had better outcomes.
The pump group also had better improvement in treatment satisfaction at all time points but the difference was statistically significant at 12 and 24 months only.
The authors concluded:”People with type 1 diabetes might be better served by ensuring far greater availability of high quality, structured self management training, which is currently only accessed by around 10% of adults in the UK. Participants might only recognise the limitations of insulin delivery by MDI if they start actively managing their diabetes after training. Those individuals could then be offered pump treatment to help them reach the stringent glucose targets necessary to achieve an HbA1c of 6.5% or to overcome problematic hypoglycaemia.”
Following some initial criticism to the BMJ article, the study authors response included the following:
“… our study by design meant we should exclude patients who had expressed a wish to use insulin pumps. … We also … excluded patients who met NICE criteria because the case for pumps (CSII) in that group is not in doubt. We have written to NICE to assure them that the results of REPOSE have no implications for the guidance in TA151. Our aim was to explore whether there was merit in extending indications for insulin pumps to a wider range of patients, including individuals whose HbA1c levels were far from target and who had yet to receive structured education to aid them in undertaking the complex skills of insulin self-management.
We believe that the priority of the diabetes community in the UK should be ensuring that individuals receive more effective structured training and ongoing support, issues we are addressing in ongoing research. In the meantime, as we conclude in our paper, pumps should be offered widely to individuals who are trained to manage their condition but find that the limitations of intermittent injections lead to hypoglycaemia or prevent them achieving tight glucose targets. The ambitious target of 6.5% HbA1c in the latest NICE guideline will increase their number.”
The Association of British Clinical Diabetologists (ABCD) Insulin Pump Network UK has also published a position statement on the results of REPOSE, including the following:
“The results of the REPOSE (Relative Effectiveness of Pumps Over Structured Education) trial were published recently in the BMJ. The ABCD Insulin Pump Network Committee have become aware of a number of cases where the findings have been misreported and/or misinterpreted. We thought it would be helpful for readers of British Journal of Diabetes if we clarify the main REPOSE findings and implications for clinical practice in the UK…
By design, the REPOSE study excluded patients who met the … TA151 criteria for CSII, examining whether CSII should be more widely available in T1D. Importantly, the results of REPOSE are thus not relevant to the patients currently covered by the evidence-based recommendations of TA151 and who would still be considered for CSII. REPOSE provided DAFNE education to both arms, finding sustained improvements in both arms in glycaemic control and measures of quality of life, reinforcing the use of structured education as an effective strategy in T1D.
In summary, the REPOSE findings support the current NICE T1D pathway, with structured education being offered first and CSII therapy then being considered where patients are still struggling to achieve glycaemic goals safely as set out in TA151. Sadly, most patients with T1D in the UK have not been offered evidence-based structured education. Similarly, access to CSII remains patchy, with the level of provision of CSII being lower than in other comparable countries. There is a danger that misrepresentation of the REPOSE data could worsen this inequality.”
Comment from INPUT
Essentially, REPOSE backed up the criteria set by NICE TA151 for pump therapy, ie, structured education first, and then pump therapy if treatment targets are still not met. It is a failure of the system when some patients are only offered structured education in preparation for starting on a pump.
NICE TA151 still stands, along with its mandate that CCGs MUST provide funding for pump therapy if a patient meets the criteria and has the consultant’s agreement that a pump is required.
When NICE TA151 is reviewed at some point in the future, REPOSE will not have a negative impact on access to pumps. It simply shows that “pumps for all” cannot be supported by evidence.
If you believe you meet the NICE criteria for pump therapy and have been denied pump treatment, please contact us.