The cost-effectiveness of HCL in Ireland: closing the loop on a revolutionary new therapy

Type 1 Diabetes in Ireland: Diabetes Mellitus (DM) describes a group of metabolic diseases characterised by hyperglycemia. Once known as juvenile onset diabetes, type 1 diabetes mellitus (T1DM) involves an absolute insulin deficiency caused by the autoimmune destruction of beta cells in the pancreas. Type 2 diabetes mellitus (T2DM) involves a relative insulin deficiency caused by an acquired resistance to insulin, insufficient insulin production by beta cells or, both. While both T1DM and T2DM are characterised by hyperglycaemia, these diseases have different pathophysiology, risk factors and treatments.

T1DM affects about 20,000 people in Ireland, or 0.4% of the total Irish population. T1DM is a chronic condition that will affect an individual for the rest of their life. It typically develops during childhood or adolescence so the negative impact of hyperglycaemia can compound over one’s lifetime to produce severe complications such as heart disease, renal disease, blindness, and many more. This greatly affects a patient’s quality of life and can be very costly to treat (1).

Intervention in Type 1 Diabetes:

It is essential that people with T1DM maintain their blood glucose to reduce the risk of short and long-term complications. HbA1c and time in range are the current metrics by which clinicians monitor a patients glycaemic control. It is recommended that patients achieve a HbA1c of 53mmol/mol or lower and 70%, or higher, time in range (3.9mmol/L-10mmol/L). Many factors influence how much insulin a patient needs such as emotional stress, exercise, diet, how well they sleep, and many medications. As a result, many patients fail to meet their therapeutic targets (2).

T1DM is sometimes referred to as insulin-dependent diabetes because the only treatment is exogenous insulin. Before the preparation of recombinant DNA human insulin in 1978 by David Goeddel and his colleagues, insulin was obtained from cows and pigs. While animal insulins still exist in clinical practice today, the recombinant form is the dominant one in today’s market. While the types of insulin that clinicians have at their disposal has changed a lot over the years, the methods of delivery have remained relatively constant. Many patients with diabetes still rely on subcutaneous insulin infusions via needles or syringes. The modern option of a continuous subcutaneous insulin infusion (CSII) uses an insulin pump to constantly administer a preprogrammed dose of insulin which can be adapted to different doses depending on the time of day or activity of the patient. These have significantly improved glycaemic control in patients using the technology. However, these devices still require the patient to monitor many factors which can affect the amount of insulin they will require such as their blood glucose, food intake, exercise, sleep, any potential illness and more. The patient must then incorporate all this information to predict how much insulin they need to maintain blood glucose within range. Unsurprisingly, this system leads to hyperglycemia, hypoglycemia, mental stress, reduced sleep, and an overall reduction in quality of life. Hybrid closed-loop insulin pumps promise a breakthrough in diabetes care to address these issues and facilitate a reduction in the morbidity associated with T1DM.

A revolution in T1DM:

The hybrid closed-loop systems represent a paradigm shift in the management of T1DM. Often referred to as an artificial pancreas, such systems have an unprecedented ability to influence blood glucose levels based on real time blood glucose information. The hybrid closed loop systems involve three components: a CGM, an insulin pump and an algorithm within the pump. These work together to maintain normoglycaemia. The CGM monitors blood glucose and communicates this information to the algorithm. The algorithm notes the current blood glucose, whether it is trending upwards, downwards or remaining steady, and the target blood glucose. This informs the pump about how much insulin to deliver to the patient. These systems are referred to as “hybrid” because the patient must still count carbohydrate intake and manually enter this into the insulin pump. The closed loop system has allowed for improved glycemic control by reducing insulin infusion in anticipation of a hypoglycemic event and increasing insulin infusion to treat or prevent hyperglycemia.

The benefits of HCL

By responding to the individual patient’s insulin requirements in the moment, closed loop systems are improving glycemic control, preventing acute complications such as hypoglycemia and generating psychosocial benefits.

A meta-analysis which examined 32 studies showed that closed loop systems significantly improve time spent in the therapeutic range (3.9mmol/L to 10mmol/L) by 9.6%. This translated to an additional 140 minutes in range over a 24-hour period (3). Closed loop systems have also been shown to significantly reduce the amount of time spent hypoglycemic (<3.9mmol/L) by 1.5% (3). Importantly, most of these benefits came during the night, when patients are unable to respond to milder changes in their blood glucose. Average blood glucose overnight dropped by 0.81mmol/L and 0.48mmol/L during the day. This was reflective of the reduction in HbA1c improvement of 3mmol/mol. A recent study in England also found a benefit to HCL use on HbA1c, time in range, and the proportion of patients who achieved >70% time in range. Furthermore, 94.7% of the participants reported HCL had a positive impact on their quality of life.

Glycaemic variability has been suggested to predict diabetic complications, independent of HbA1c levels in patients with T2DM and may play a role in the development of microvascular complications in those with T1DM (4). Closed loop systems repeatedly lower glucose variability when compared to controls (5). Closed loop systems provide psychosocial benefits in the form of less anxiety, improved sleep, and less fear of hypoglycaemia, particularly in the context of exercise (6). Closed loop systems are improving the quality of life of those with T1DM and helping patients obtain blood glucose readings which should protect them from some of the complications of the disease.

The costs of HCL:

The costs associated with HCL are undeniably higher than multiple insulin injections or even continuous subcutaneous insulin infusion. The pump is costly and requires associated consumables and training, while the lifetime of between four to eight years necessitates relatively frequent replacement over the disease’s time horizon. However, such initial costs may be partially or wholly offset by significant cost savings in the long run due to reduced insulin requirements, improved clinical outcomes and the reduced diabetes-related complications – such as hypoglycaemia and long-term disease – that come with improved glycaemic control.

The Cost-Effectiveness of HCL in Ireland:

Health care is more than the provision of medical services to those who need them. In a system with finite resources, it is necessary to make decisions on which services to provide, who to provide these services to, and how to pay for them. Such choices have implications for the health of all users of the healthcare system. Funding one area of care will necessarily provide fewer resources for another because healthcare systems must allocate resources across a broad range of needs. For example, introducing a new treatment that reduces the disease burden of diabetes in adults could inadvertently lead to higher rates of mortality and morbidity in newborns as fewer funds are available for neonatal services. Health economics provides national decision-makers with the tools to make informed choices that maximise the well-being of all users of a healthcare system in the population. Particularly, health economics recognises the opportunity cost of a choice. As described above, for health care resources, this is the value of the best alternative that is necessarily forgone when finite resources require a funding decision between several mutually exclusive options. Simply put, allocating the health budget to hiring neonatal nurses is impossible when it has already been spent on a new diabetes medication. Reflecting this, decisions on national investments in new healthcare technologies are typically guided by a costeffectiveness analysis in Ireland.

Cost-effectiveness analysis compares the costs and benefits of competing healthcare interventions which aim to achieve the same outcome. In the context of constrained healthcare budgets, such an analysis allows decision-makers to prioritise and trade-off across competing needs, allocating resources to maximise the expected overall benefits from the health system and, thus, the health gain for the population. Notionally, the Irish healthcare service offers insulin pumps and consumable products through the HSE’s Community Funded Schemes and the long-term illness scheme. Public hospitals also provide free training on the usage of such pumps. However, the qualifying criteria for meeting access to such pumps are not transparent, and waitlists are long. This may explain why uptakes are so low, almost 77% less than the international average, according to Diabetes Ireland. Additionally, the National Clinical Guidelines (NCG) for Adults with T1DM recently reported that more than two-thirds of the Irish population does not have access to pump therapy as a treatment option.

The allocation of healthcare resources must be fair, efficient and transparent. While HCL therapy suggests significant potential for improving health outcomes, it is also costly, and the healthcare system can only reduce health inequalities by investing in interventions that deliver value for money while enhancing the quality of care. By applying a cost-effectiveness analysis to the widespread and transparent uptake of HCL therapy in T1DM, the system can ensure that it achieves the best possible health outcomes for the people of Ireland.

To evaluate the long-term costeffectiveness in Ireland, an analysis must be performed over a lifetime horizon and from the healthcare payer’s perspective (the HSE). Clinical input data should be sourced from the critical trials that resulted in the introduction of such pumps to Ireland. Disutilities associated with diabetes-related complications can be sourced from the published literature. Costs can be based on list prices and include direct costs and consumables, such as the pump, cannula, reservoir, sensors, insulin, blood glucose monitoring, diabetes complications, hospital visits, and pump training. Where necessary, national demographics and characteristics can be drawn from Irish patient cohort studies. Improvements in quality-adjusted life years (QALYs) relative to the current standard of care and total lifetime costs can be assessed.

An incremental cost-effectiveness ratio (ICER) per QALY gained can be calculated and compared to standard of care. Sensitivity analysis can demonstrate the robustness of any such ICER values to various ranges of clinical effectiveness (glycemic control) and the quality-of-life benefit and costs associated with this new technology.

Such analysis has already been conducted in the UK and Europe. For example, HCL versus continuous subcutaneous insulin infusion yielded an ICER of ¤14,000 per QALY gained in Sweden. In the UK, a comparison to continuous subcutaneous insulin infusion yielded an ICER of ¤25,000 per QALY gained. In the Netherlands, HCL versus multiple daily injections with intermittently scanned glucose monitoring resulted in an ICER of EUR 6,133 per QALY gained. These are well below the threshold of ¤45,000 per QALY gained, at which an intervention is usually considered cost-effective in Ireland and recommended for reimbursement. However, these estimates are based on assumptions and data from other settings and do not reflect Ireland’s actual costs and outcomes. Therefore, a national analysis is necessary to answer the question once and for all: is HCL therapy a cost-effective use of Irish healthcare resources?

References available on request

Written by Dr Jonathan Briody, Health Economist & Liam Manning, Medical Student, RCSI University of Medicine and Health Sciences

Dr Jonathan Briody is a health economist conducting an economic evaluation of intervention in, and prevention of, diabetes at RCSI University of Medicine and Health Sciences. With Professor Seamus Sreenan, he was awarded the Irish Endocrine Society Student Research Bursary to encourage promising students to pursue careers in endocrinology. He is supporting Liam Manning as part of this award.

Liam Manning is a medical student in RCSI. He is also collecting and analysing information on patients with diabetes. As the Irish Endocrine Society student award recipient Liam is participating in a research project at Connolly Hospital under the guidance of Professor Seamus Sreenan and Dr Jonathan Briody. He would like to thank the Irish Endocrine Society for their support.

Acknowledgement:

This research is funded by the Irish Research Council and Diabetes Ireland under the Enterprise Partnership Scheme – Postdoctoral Fellowships Project ID: EPSPD/2022/165

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