Description of the proposed service

This systematic review examines the clinical and cost-effectiveness of continuous subcutaneous insulin infusion (CSII) using insulin pumps compared with multiple daily injections (MDI) for diabetes.

Epidemiology and background

There are two main types of diabetes. Type 1 diabetes involves a process of destruction of the beta cells of the pancreas, leading to severe insulin deficiency, so that insulin treatment is required for survival. It represents about 10-15% of all diabetes in England and Wales. Type 2 diabetes is much more common, and is characterised by insulin resistance and relative insulin deficiency. Type 2 diabetes is linked to overweight and obesity and to physical inactivity. The number of people with insulin-treated diabetes has increased owing to the marked increase in the incidence of Type 1 diabetes and also to a greater number of people with Type 2 diabetes being treated with insulin to improve diabetic control. There has also been an increase in the prevalence of Type 2 diabetes, particularly among the Asian community. Poor control of diabetes, reflected in high blood glucose levels, can in the short term result in diabetic ketoacidosis, a serious and potentially fatal condition, and in the long term increase the risk of complications such as diabetic retinopathy and nephropathy. However, studies have shown that good diabetic control is associated with a reduced risk of these complications.

If insulin levels are too high and blood glucose falls, hypoglycaemic episodes occur. The effects of a hypoglycaemic episode depend on how low the blood glucose level falls, varying from mild and rapidly corrected by food or sugary drinks, to severe where help is required. Severe hypoglycaemia can lead to unconsciousness, convulsions or death.

There are several problems with current treatment. In the non-diabetic state, the body needs a little insulin all the time (basal insulin) boosted by increased output after meals. This is difficult to achieve with conventional insulin injections, and in particular good control of blood glucose during the night is difficult. Intensive insulin regimens such as CSII aim to resemble more closely the output of a normal pancreas by providing basal insulin for fasting periods and additional short-acting supplements to cover meals.

Methods

A systematic review of the literature and an economic evaluation were undertaken.

Number and quality of studies

Searching identified 20 studies comparing CSII with MDI. These included eight parallel RCTs, nine randomised crossover studies and three non-random crossover studies. Fourteen studies included adults with Type 1 diabetes, four studies included pregnant women and two studies included adolescents. The quality of reporting and methodology of the studies, many of which dated from many years ago, were often poor by today's standards, with just two studies having adequate randomisation and none reporting adequate allocation concealment.

No RCTs or crossover studies were identified in children, on overnight use of CSII, in patients with poorly controlled Type 2 diabetes or on discontinuation rates; therefore, selected observational studies were discussed in these sections.

Six studies (one parallel RCT and five random crossover studies) were identified comparing analogue with soluble insulin in CSII. Randomisation and allocation concealment were adequate in the parallel RCT but not reported in the crossover studies.

No economic evaluations comparing CSII with optimised MDI were found.

Summary of benefits

Costs

The additional cost of CSII compared with MDI varies according to the make of pump and the estimated life of the device, from £1091 per annum using the cheapest pump and assuming an 8-year life of the pump to £1680 per annum with the most expensive model and assuming a life of only 4 years. These estimates include costs for consumables and the initial education required when patients switch from MDI to CSII. The largest component of cost is the consumable items, such as infusion sets (tubing, etc.), with the capital cost of the pump secondary. Initial education for those switching to CSII is very important, and we estimated an additional cost per patient switching from MDI to CSII to be in the region of £150.

Costs per life year gained

There are definite benefits of CSII over MDI, including improved control of diabetes, not just as reflected in glycated haemoglobin and in a slightly reduced incidence of severe hypoglycaemic events, but also in flexibility of lifestyle and hence quality of life. However, evidence on quality of life is reported in only one trial, and comes mainly from testimonies of pump users.

One would expect the improvement in HbA_1c to be reflected in reduced long-term complications and for that to be accompanied by reduced costs to the NHS. However, we have not found a satisfactory method of converting the observed benefits into a cost per quality-adjusted life-year.

The main problem with the current evidence is that it does not fully reflect the selection of patients for CSII. Most people on insulin therapy would not have much to gain from CSII, but those with particular problems such as recurrent severe hypoglycaemia would. Their benefits would include not only fewer hypoglycaemic episodes, but also a reduction in fear of them. However, the utility effect of the reduction in fear of hypoglycaemic episodes has not been quantified. The cost-effectiveness of CSII is likely to be much better for certain subgroups.

Sensitivity analysis

The main costs are of consumables and pumps. The price of pumps might come down with bulk purchase, but this is speculative. This would not have much impact on the cost per annum.

Conclusions

Control of diabetes consists of more than just control of blood glucose as reflected in glycated haemoglobin. Compared with optimised multiple injection insulin therapy, CSII results in a modest but worthwhile improvement in glycated haemoglobin, but its main value may be in reducing other problems such as hypoglycaemia and the dawn phenomenon, and in improving quality of life by allowing greater flexibility of lifestyle. Pumps appear to be a useful advance for patients having particular problems, rather than a dramatic breakthrough in therapy, and would probably be used by only a small percentage of patients.

Implications of approval of an increased use of CSII

Many health authorities are not funding insulin pumps, and some of those that are have restricted the number. Many patients are funding their own pumps. According to clinical consensus, it is unlikely that CSII would be used by more than a small proportion of people with Type 1 diabetes, but the exact proportion is not known. We would not expect any use in true Type 2 diabetes in the foreseeable future. The cost to the NHS per year would be around £3.5 million in England and Wales if 1% of people with Type 1 diabetes used CSII, £10.5 million for 3% and £17.5 million for 5%. The educational needs of patients starting CSII are significant, and it would usually be diabetes specialist nurses who would provide this. However, there are many other demands on their time.

Need for further research

The trials to date have focused on easily measurable outcomes such as glycated haemoglobin. The main benefits may be in terms of flexibility of lifestyle and quality of life, and data on those would help with cost-effectiveness analysis. Some of the implications for patients such as the psychological impact of wearing a device for 24 hours every day have not been quantified.

There appears to be no wholly satisfactory economic model for diabetes, which would allow improvements in diabetes control to be converted into a cost per quality-adjusted life-year. Research is also needed into the use of CSII in children of different ages.

Publication

• Colquitt JL, Green C, Sidhu MK, Hartwell D, Waugh N. Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes. Health Technol Assess 2004;8(43). [PubMed: 15488165]

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