CCG application for funding for continuous glucose sensors (CGMS) paediatric diabetes patients
Background:
Glucose sensors accurately track and record interstitial glucose readings every 5 minutes for 288
times per 24 hour period for 6 days.* CGM technology enables the user and health care professional
to make precise diabetes management decisions based on a continuous trace rather than a single
fingertip blood glucose measurement. CGM technology provides a fuller picture of blood sugar
readings, giving patients confidence and a powerful tool to help them improve outcomes and quality
of life. When CGM sensors are used in combination with Sensor Augmented Insulin Pumps (SAP) preset blood glucose values can be set in the pump which informs the patient when their blood glucose
is declining and this allows them to take action in order to avoid a hypoglycaemic episode.
This business case outlines the rationale for it selective use of CGM in the paediatric diabetes service
to improve clinical outcomes.
The clinical evidence
We know from the Diabetes Control and Complications Trial (DCCT) 1: A large multinational study
from 1983-95. It showed that keeping blood glucose levels as close to normal as possible slows the
onset and progression of the eye, kidney, and nerve damage caused by diabetes. It has been the
gold standard evidence for intensification of insulin regime ever since. The DCCT trial showed that a
1% reduction in HbA1c can reduce the risk of Retinopathy (Eye disease) by 38%, Nephropathy
(Kidney damage) by 28%.Neuropathy (Nerve disease) by 60%.
Further evidence was then seen in the “Epidemiology of Diabetes Interventions and Complications
(EDIC)” trial an extension of the DCCT study .It showed significant reduction in cardiovascular risk
and that Intensive blood glucose control reduces risk of any cardiovascular disease event 42%
reduced risk Nonfatal heart attack, stroke, or death from cardiovascular causes 57%
The above remains the evidence for intensified insulin regimes, with the advent of insulin pumps
and CGM technology there has been a choice between a multiple injection regime for insulin or
insulin pumps.
Recent evidence now supports the use of insulin pumps for improved outcomes.
First is the ASPIRE Study-In home (Automation to Simulate Pancreatic Insulin Response)study this
was an RCT where 247 adults and teens were studied, comparing the MiniMed Veo sensor
augmented pump (SAP) therapy with low glucose suspend (LGS) feature ON, with SAP therapy alone.
It showed:
• Hypoglycaemic events were significantly reduced by 31.4%
• Nocturnal hypo events were significantly reduced by 31.8%
• The duration & severity of nocturnal hypos was reduced by 37.5% (as measured by AUC)
These results were achieved without compromising on HbA1c or significant rebound hypoglycaemia
Trial 2 “Ly et al Reduction of Severe Hypoglycaemia with Sensor Augmented Pump Therapy and
Automited Insulin Suspension in Patients with Type 1 diabetes- A RCT of 95 children and adults that
compared the rates of severe hypoglycaemia in patients with impaired hypo awareness when
randomised to CSII versus Sensor Augmented Pump (SAP) with the Low Glucose Suspend (LGS)
feature ON over a 6 month period. Severe hypoglycaemia was defined as coma or seizure associated
with hypoglycaemia.
Results
• Significant reduction in the number of severe hypoglycaemic events

Events were reduced from 21.9 to 0.0 events per 100 patient years in the LGS group versus
24.8 to 26.7 events per 100 patient years in the control group (p=0.017)
• Significant reduction exposure to hypoglycaemia.

Exposure to glucose values below 70mg/dl and 60mg/dl were significantly reduced in the
LGS group compared to control (p=0.006 and p=0.009 respectively)

Reduced fear of hypoglycaemia was shown in the LGS group.
Trial 3: Guard Control study: This 3 month Randomised Controlled Trial (RCT) was designed to see if
HbA1c can be reduced when using personal CGM. 162 patients were randomised equally to
Continuous use of CGM, 3 days use every other week or a control group using Self-Monitoring Blood
Glucose (SMBG) study showed that 50% of patients using full time CGM after 3 months had an
HbA1c of reduction of ≥1% and 26% had an HbA1c reduction of ≥ 2%
Trial 4: The Juvenile Diabetes Research Foundation study: This was a 2 x 26 week RCT designed to
evaluate the effect of CGM on HbA1c for patients with type 1 patients who had a HbA1c of between
7% -10%. 83% of patients were on insulin pumps. The primary objective was to measure the change
in HbA1c from baseline at 6 months.
The study found that for patients who wore CGM for 6 days or more reduced HbA1c by:
• Greater than 0.7% in the Paediatric group (Age 8-14
• Greater than 0.5% in the age 15-24 and greater than 25 age group. These outcomes were achieved
without increasing the risk of hypoglycaemia. It was also shown that patients within the CGM arm
spent 17% longer in target glucose range (3.9-10 mmol/l), 24% less time within the hyperglycaemic
range (>10mmol/l) and does not increase the time spent in the hypoglycaemic range.
Trial 5 STAR 3: This randomised control multicentre trial over 12 months was designed to evaluate
the impact of Sensor Augmented Pump therapy on HbA1c compared to those who are using
Multiple Daily Injection (MDI). This study found that patients randomised to Sensor Augmented
Insulin Pump (SAP) therapy had a mean HbA1c reduction of 0.8% (7.5% from an 8.3% baseline)
compared with a reduction of 0.2% (8.1% from a baseline of 8.3%) in the MDI group. This was
achieved with no increase in episodes of hypoglycaemia.
Trial 6 SWITCH study: This randomized, controlled, cross-over multicentre study was designed to
investigate the efficacy of adding sensing to existing insulin pump treated patients, for a 6 month
period in type 1 patients aged between 6 years – 70 years, with inadequate metabolic control
(7.5%<HbA1c<9.5%) despite 1+ year on CSII. The Sensor On arm showed an overall 0.51% reduction
in HbA1c in patients that wore the sensor more than 70% of the time. Significantly less time was
spent within the hypoglycaemic range (<3.8 mmol/l) during the Sensor On vs. Sensor Off (19 vs. 31
minutes/day; P = 0.009). 15.3 fewer SMBG tests per month were performed in the Sensor ON arm
(P<0.001)
Trial 7 INTERPRET study: A 6 month pan European observational study assessing the effectiveness of
Sensor Augmented Insulin Pumps showed that patients with a HbA1c of >8% showed a reductions in
HbA1c of 0.43%.Subjects strongly agreed (mean 8.2 ± 2.4 on a 10-point Likert-scale) that SAP alarms
were helpful and help them improve control. There were significant reductions in the number of
diabetes-related hospital admissions/100 patients-years (P=0.0002) and the average length of stay
(P<0.001)
Trial 8 Eurhythmics Study: Multiple Daily Injections (MDI) vs. Sensor- augmented Pumps (Pumps with
personal CGM) This was a 6 month randomised control trial of 83 type 1 patients aged between 1865 using MDI that were uncontrolled (HbA1c ≥8.2%). Patients were either randomised to a
controlled group of MDI treatment with Self Monitored Blood Glucose (SMBG) or a treatment groupsensor-augmented pump therapy (SAP). After 6 months the SAP arm (Treatment arm) showed an
average HbA1c reduction of 1.23% vs. a 0.13% reduction for the MDI arm (Control group)
34% of patients in the SAP arm achieved a HbA1c of ≤7% without increasing the events of
hypoglycaemia
Trial 9 ASAP Study11: An open label, multicentre RCT 62 patients (13–40 years) with HbA1C ≤8.5%
were randomised 1:1 to determine the impact on glycaemic control of patient-led use of sensorguided pump management vs. standard insulin pump therapy.
A 0.43% reduction in mean HbA1c was shown in the intervention group compared with the control
group.
Post-hoc analysis showed there was a 0.6% HbA1C reduction (p=0.025) observed in the younger
subjects (13.0 -19.0 years)
Participants with 70% sensor use had 0.51% lower HbA1C (p=0.04)
These improvements in glycaemic control occurred despite no additional patient-clinician contact
over the study period or specific advice as to how to interpret the glucose trend information
Paper 9 Pickup Meta-analysis: This Meta-analysis was carried out on 6 Randomised Controlled
Trials: The aim of the study was to analyse the benefit of CGM vs. SMBG. There were a total of 449
patients within the CGM arm vs. 443 in the SMBG arm
If sensors used the majority of the time: If the starting HbA1c was 7% this resulted in a 0.5%
reduction where as if the starting HbA1c was 10% a 0.9% reduction was seen
The use of CGM with insulin pump therapy has been shown to significantly lower glycaemic
variability by MAGE vs. pump therapy alone13
Guidelines
Recommendations from the National Institute for Clinical and Health Excellence
National Institute of Clinical and Health Excellence (NICE) have recommended its use in their Clinical
Guidelines for Type 1 Diabetes Care (NICE 2003; CG1514). NICE recommends its use in the
management of adult patients with “consistent glucose control problems on insulin therapy,
notably;
• Repeated hyper- or hypoglycaemia at the same time of day
• Hypoglycaemia unawareness,
• Unresponsiveness to insulin dose adjustments”
The same guidance also recommended that “Continuous Glucose Monitoring systems should be
offered to children and young adults if they suffer from,
• Repeated hyper- or hypoglycaemia
• And/or hypo-unawareness”
Options appraisal
Option one
Do nothing, the outcome for this is that we will still have patient with recurrent hypoglycaemia with
hospital admission. The existing patients on the insulin pump won’t have the utility of CGMS to
improve their pump management and improve metabolic control. We wouldn’t have the facility for
diagnostic CMGS which is important to safeguarding reasons to identify poor patient compliance.
Also for the diagnosis if nocturnal hypoglycaemia.
The economic impact would need an audit for this information to be available.
Option 2
A selective use of CGMS based on the following 6 criteria.
1.
2.
3.
4.
To diagnose the cause extreme glucose variability in type 1 diabetes on insulin therapy
To diagnose the cause of unexplained hypoglycaemia type 1 diabetes on insulin therapy
For safeguarding concern relating to patients whom we suspect of deliberate insulin misuse.
Improve the outcomes of pump therapy as part of the annual review process including the
HbA1c. ( 1 sensor per patient per year )
5. On-going management of children on insulin pump therapy with recurrent hypoglycaemia at
least 3 months post commencement on an insulin pump.
6. Reduce hospital admissions and risk of DKA, severe hypoglycaemia for patients on insulin
pumps with severe insulin sensitivity. Improving long term outcomes
Number 1-3 are diagnostic and by definition are for a fixed period of time. Typically 6-12 day or use
of 1-2 sensors.
Number 4 is part of routine pump management CGM would be run on each patient for 6 days prior
to annual review with the aim of optimisation of the pump setting to improve glycaemic outcomes.
Numbers 5-6 are long term and would only be considered in existing pump patients if the following
steps have been tried and failed
1. Intensive education to improve kaufman competency to 5/8 or above
2. Optimisation of pump settings via diagnostic CGMS and the use of carelink software.
3. Demonstration of full compliance with routine pump management.
In those patients who continue to have the following a CGMS trial would be undertaken for 1 year.
1.
Recurrent hypoglycaemia
2. Recurrent DKA or hospitalisation
Patients would be mandated to wear the CGMS for 6 days a week, as the evidence show that no
benefit is seen in children if CGM is worn with less frequency. At the end of this time they would be
assessed to see if there had been a significant improvement in outcomes:
1. <90% compliance with the regime
2. Patients with HbA1c >8.5%
Will have CGM discontinued and pump management reviewed with the option to return to basal
bolus therapy.
The funding to date has been on an individual ad hoc patient basis. There has not been a formal
process for day to day management of patients who require CGMS monitoring. (E.g. recurrent
sensor use). Through the IFR process we have applied CGMS for 4 patients. There has been a request
by commissioners that the IFR process is not appropriate and that a bid is required for funding
sensors. Hospital admissions and additional cost for this patient (See section 4 for full description
Admission costs
Number of admissions within the last year for
pump remediable conditions
20
Cost of admission (£)
ITU bed day
£1,935
3 bed days
£1,935
Subtotal
£
- 3150
patient 1 diagnosed at 13 days of age
5 days ITU
9,675
37 days inpatient with CGM
14985
182 inpatient without CGM
73710
patient 2 diagnosed at 10 months of age
2 days ITU
3870
21 days inpatient with CGM
8505
91 days inpatient without CGM
36855
patient 3 with 21 admissions for DKA at £3,150 per
admission
66,150
after CGM no admissions for 3 years
Current finger stick costing's for this patient
The average number of finger stick test per day
10
Cost per strip
31p
Cost per day
£ 3.10
Cost per week
£
21.57
-
Cost per month
£ 92.42
-
Cost per year
£ 1109
-
Anticipated cost of CGM over one and two years for continuous use
Initial Costs
Enlite sensor starter kit (Includes 5 sensors)
£
687.00
On-going costs
Number of glucose sensors required per month (1-4)
Number of Enlite sensors required per year
Cost per Enlite sensor
4
52
£ 52.50
Annual costs each year
Year 1*
£3607
Year 2**
£ 2703
*(The number of Enlite sensors required per year – 5 Enlite sensors which are included within the Enlite starter kit)
x (The cost of the Enlite sensor) + (The cost of the Enlite starter kit)
** Cost of sensor(s) x Number of Enlite sensors required per year
Anticipated overall savings (Admissions, fingerstick, additional clinical team hours)
4 finger stick tests are required as a minimum per day for effective pump calibration
Bayer Contour Strips
Cost of glucose strips (per 50)
Cost per glucose strip
Cost of 4 tests per day with pump to calibrate the CGM
Cost of strips per week
Cost of strips per month
Estimated total yearly cost of finger stick testing with a pump
Total cost of CGM + finger testing strips
£
15.11
£
0.30
£
1.20
£
8.40
£
33.60
£
403.20
£3133
Total costing for diagnostic sensors per patient based on use of sensor 6 days
On-going costs
Number of glucose sensors required
Cost per Enlite sensor
1
£
52.50
Anticipated overall savings (Admissions, fingerstick, additional clinical team hours)
4 finger stick tests are required as a minimum per day for effective pump calibration
Bayer Contour Strips
Cost of glucose strips (per 50)
Cost per glucose strip
Cost of 4 tests per day with pump to calibrate the CGM
Cost of strips in 6 days
Total cost of CGM + finger testing strips
£
15.11
£
0.30
£
1.20
£
7.20
£59.70
Therefore total costing of CGM service Number of patients that will meet these criteria per annum
1. Insulin pump patients = 70 for annual review
2. Insulin pump patients on-going sensor management = 5
3. Diagnostic investigation = 12
4. Total = 344 sensors
Total cost for continuous use ( 5 patients ) £3133 x 5
Total cost of diagnostic sensors (82 sensors)
Total cost for CGMs business case per annum
£15666
£4895
£20561.40
References
1) Diabetes Control and Complications Trial Research Group. (1993). "The effect of intensive
treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus". N Engl J Med. 329 (14): 977–86.
doi:10.1056/NEJM199309303291401. PMID 8366922.
2) DCCT and EDIC: The Diabetes Control and Complications Trial and Follow-up Study". National
Diabetes Information Clearinghouse (NDIC). National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health. 2008-05. Archived from the original on 2007-10-18.
3) Bergenstal RM, Klonoff DC, Garg SK. E t al. N Engl J Med. June 22, 2013DOI: 10.1056 /
NEJMoa1303576
4) Ly, T., Nicolas, J., Retterath, A. et al. Reduction of Severe Hypoglycaemia with Sensor Augmented
Pump Therapy and Automited Insulin Suspension in Patients with Type 1 diabetes. 2013 ADA
Abstract 228-OR .
5) Guard Control study: Deiss D, Bolinder J, Riveline JP, et al. Improved glycemic control in poorly
controlled patients with type 1 diabetes using real-time continuous glucose monitoring. Diabetes
Care 2006; 29: 2730–2732.
6) The Juvenile Diabetes Research Foundation CGM Study Group, N Engl J Med 2008: 359:14, 14641467
7) STAR 3: Bergenstal RM, Tamborlane WV, Ahmann A, et al. Effectiveness of sensor-augmented
insulin pump therapy in type 1 diabetes. N Engl J Med 2010;363:311-320.
8) SWITCH study: Diabetologia DOI 10.1007/s00125‐012‐2708‐9 Epub ahead of print.
9) Routine Sensor-Augmented Pump Therapy in Type 1 Diabetes: INTERPRET Study. Norgaard, K. et
al. Diab Tech & Therap. 2013. 15(4). epub ahead of print DOI: 10.1089/dia.2012.0288
10) Eurhythmics: Hermanides J, Norgaard K, Bruttomesso D, et al. Sensor augmented pump
therapy substantially lowers HbA1c; a randomized controlled trial. [EASD abstract 90]. Diabetologia.
2009;52 (Suppl 1): S43.
11) ASAP study: O’Connell MA et al. Glycaemic impact of patient-led use of sensor-guided pump
therapy in type 1 diabetes: a randomised control trial. Diabetologia 2009;52:1250–1257
12) Pickup JC, Freeman SC, Sutton AJ. Glycaemic control in type 1diabetes during real time
continuous glucose monitoring compared with self-monitoring of blood glucose: meta-analysis of
randomised controlled trials using individual patient data. BMJ 2011; 343: d3805
doi:10.1136/bmj.d3805.
13) Kordonouri O, et al. Sensor-augmented pump therapy from the diagnosis of childhood type 1
diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment. Diabetologia
2010; 53: 2487-2495
14) NICE. Clinical Guidelines 15. Type 1 diabetes: diagnosis and management of type 1 diabetes in
children, young people and adults. 2004-Update June 2009. Available at:
http://www.nice.org.uk/nicemedia/live/10944/29390/29390.pdf [Accessed 14th June 2011]
15) Hammond PJ, Amiel SA, Dayan CM, Kerr D, Pickup JC, Shaw JAM, Campbell FM, Greene SA,
Hindmarsh PC, on behalf of the Association of British Clinical Diabetologists (ABCD) and endorsed
by the British Society for Paediatric Endocrinology and Diabetes (BSPED). ABCD Position Statement
on continuous glucose monitoring: use of glucose sensing in outpatient clinical diabetes care.
Practical Diabetes International 2010, March; 27(2)
For consideration happy to discuss further with evidence base and clinical outcomes.
Yours sincerely Dr James Greening, Tina Clegg Linda dales