Short summary

Aim: To investigate the effects of conducting the visits in the outpatient clinic remotely by a telemedicine solution, for people living with an insulin pump.

Method: RCT

Rationale

Introduction

Diabetes Mellitus (DM) has doubled over the last three decades (1). It is estimated that this escalation continues over the next decades resulting in an enormous prevalence of 628.9 million people affected with DM in 2045 (2).

The most common forms of DM are type 1 and 2, other types, and gestational diabetes (3). DM is associated with both micro and macro vascular complications. Long-term intensive blood glucose control significantly delays onset and slows the progression of microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy (4-6). Among macrovascular complications, coronary heart disease has been associated with DM in numerous studies beginning with the Framingham study (7). More recent studies have shown that the risk of myocardial infarction is significantly higher DM patients (8). DM increases the risk for stroke more than five times (9). Furthermore, studies have shown that the cerebrovascular mortality rate is elevated at all ages in patients with DM (10).

Risk of cerebrovascular disease mortality has been shown to be associated with serum cholesterol levels, systolic blood pressure, and cigarette smoking, for both DM patients and non- DM patients (11). However higher values increased the risk more for DM patients than non- DM patients(11).

A large study demonstrated that during 17 years of prospective analysis, intensive treatment of DM1 patients, including lower A1C, is associated with a 42% risk reduction in all cardiovascular events and a 57% reduction in the risk of nonfatal Myocardia infarct, stroke, or death from cardio vascular diseases (12). Microalbuminuria is often viewed upon as an early sign of macrovascular disease. In line with this the Steno-2 Study Showed that intensive treatment for DM2 with microalbuminuria targeted hyperglycaemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin could reduce the risk of cardiovascular and microvascular events by about 50 percent(13).

In a meta-analysis of 12 randomized controlled trials (RCT) including a total of 600 people treated in period of 2,5 - 24 months the authors concluded that insulin pump treatment lead to significantly better glycaemia control, measured by Hba1c (14). This is estimated to result in a reduction in retinopathy of 25%, which corresponds to 5% fewer developing diabetic retinopathy after 10 years of insulin pump treatment compared to basal-bolus-treatment (14).

In Denmark the indications for receiving an insulin pump for adults are(15)

- DM1 and HbA1c > 7.0% with multiple injection therapy.

Provided one or more of the following conditions apply:

- the patient, despite optimized treatment, including a dose increase in insulin, experience many and unpredictable hypoglycaemia cases

- the patient has a lack of recognition of insulin sensation

- the patient cannot control the blood glucose level during the night in conventional therapy

And provided that the unsatisfactory control of multiple insulin injections is not due to:

- the patient does not want to measure home blood glucose adequately (≥ 4 times daily,) or

- that the patient has generally impaired compliance and / or understanding problems with the interaction between insulin, diet and physical activity

- the patient suffers from diseases or disabilities that make it impossible to use the pump safely (e.g. blindness, consequences of apoplexy, alcohol abuse etc.).

American studies suggest that centres with a large volume of insulin pump patients have a lower complication rate and achieve better metabolic control (lower HbA1c levels) than smaller centres (16). There is no set number, but it is estimated that a minimum of 25-30 patients is required. Larger centres would benefit from greater experience and knowledge and would also economically ensure a more rational operation of the unit.

Sygehus Sønderjylland (SHS) covers the municipalities of Haderslev, Tønder, Åbenrå and Sønderborg. There are DM clinics in Tønder, Åbenrå and Sønderbog, however all adult insulin pump patients are gathered at the department of endocrinology in Sønderborg.

From Tønder to Sønderborg there is approximately 70 km, a distance which takes a little under 1 hour, by car and can take several hours using public transportation, depending on date and time (17, 18).

Accordingly, patients will have larger distance to their centre, more traveling time, and more inconvenience. Hence some patients may not even want to start insulin pump treatment due to distance or may not even get the offer by the HCP even if the indications are present. The Longer travel times might lead some patients to opt out of an insulin pump treatment, or make patients wait longer before contacting staff in case of technical problems or medical issues.

The Danish society of endocrinology recommends that patients in treatment with insulin pump should, like any other affiliated with a diabetes ambulatory have access to a 24-hour telephone service. Furthermore, due to the potential problems with the insulin pump treatment, among others technical issues, it is essential that patients can have their problems solved quickly and competently.

A solution to overcome distances centre and make the healthcare service provide even better could be by use of telemedicine.

Telemedicine was defined in 1997 by the World Health Organization, as "The delivery of health care services, where distance is a critical factor, by all health care professionals using information and communication technologies for the exchange of valid information for diagnosis, treatment and prevention of disease and injuries, research and evaluation, and for the continuing education of health care providers, all in the interests of advancing the health of individuals and their communities" (19).

Since then the world has experienced a new digital revolution, with approximately 56% of the world population with internet access today, compared to only 5.8 % in 2000 (20). Denmark is estimated to have an internet user penetration of 96.5% of the population (21).

Likewise the number of smartphones sold to end users worldwide from 2007 (when the first iPhone was released in the United States(22)), to 2018 has grown from 122.32 million to 1.56 billion (23). The same pattern applies in Denmark. In 2011 40% of the Danish population owned a smartphone, while the number had increased to 88.6% in 2017 (24).

Telemedicine also has the potential to be a cost effective solution, due to reductions in traveling costs and saved working days, as well as increase patient satisfaction, mainly by reducing the transportation time, which The Svendborg Telemedicine Diabetes Project showed already in 2013 (25).

A recent review, including 19 studies, of the effect of telemedicine on glycaemia control, for DM in general, found that there was insufficient evidence to support telemedicine use for glycaemic control and other clinically relevant outcome among adult patients with type 1 DM (26). However, the effect varied among subgroups, and the majority of the studies included patients using an insulin pen (26). Several Studies have evaluated telemedicine for use in DM patients with an insulin pump (27-29). In all of these studies the telemedicine group had scheduled more contacts with the health care professionals (HCP) than in the standard care group. To our knowledge no one has investigated telemedicine, compared to standard care with the same number of scheduled contacts. We believe telemedicine should be a solution to help both patients and HCPs. Hence, we want to increase the healthcare service provide by the HCPs and not add on more work to their limited resources. From the patient's point of view, we want the telemedical solution to give them a more flexible way of visiting their HCP rather than a burden on top of regular treatment.

In this PhD we aim to compare telemedicine to regular outpatient clinic visits, if the number of scheduled contacts is the same. We believe telemedicine should be a solution to help both patients and HCPs in a healthcare system with limited resources, rather than a burden on top of regular treatment. In our case the frequency of scheduled contacts will be determined by the clinician at each contact. However, we hypothesis that we will have more unplanned contacts, e.g. helping with technical problems with the insulin pump, which might in the long term reduce the need for scheduled contacts. In this PhD we aim to investigate three different aspects of conducting an outpatient clinic visit remotely using telemedicine. The areas investigated will be: Medical perspective, patient and HCP perception of the solution, and number of contacts to the outpatient clinic and socio-economic gain.

Purpose

In this PhD we aim to investigate the effects of conducting the visits in the outpatient clinic remotely by a telemedicine solution, for people living with an insulin pump.

Outcomes

Medical perspective

The main outcome will be change in Hba1c.

Secondary outcomes will be effects on glycaemic control, shown by hypoglycaemia events, measured, by the sensor, felt by the patient or an event where help was required. Changes in time: in, over or below an individual set range measured by continuous blood glucose monitoring, compared to before starting the tele medical period.

Prevalence of insulin pump patients taking medication for hypercholesterolemia or hypertension, discontinuation by Q&A.

Patients, relatives & health care professionals' perception of the solution

This question will be answered by use of semi-structed interviews. A qualitative research strategy has been chosen, in order to understand the perception of both the patients, relatives and HCPs. Rather than knowing if they liked the solution or not, we want to investigate WHY they liked it or didn't like it. The Semi-structed interview also provides the potential for exploring unknown factors. This might prove helpful not only to DM patients but for development of tele medical solutions in general in the future.

Number of contacts to the outpatient clinic & socio-economic gain

Primary outcome will be number of scheduled and unscheduled contacts

Secondary outcomes: travel time for patient, absence from work/study and expenses (transport cost vs. telemedicine solution).

Participants will be asked to fill out Diabetes Treatment Satisfaction Questionnaire (Status) (DTSQs), Diabetes Treatment Satisfaction Questionnaire (Change) (DTSQc) and the Audit of Diabetes Dependent Quality of Life (ADDQoL19), in order to make a utility analysis. The DTSQs, DTSQc and ADDQoL19 are validated questionnaires.

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Description of the cohort

Participants will be included from the Diabetes ambulatory at Hospital of Southern Jutland Adult patients, diagnosed with DM1 and use of insulin pump for at least 6 months. Exclusion criteria: No internet access or unable to adhere to protocol. Unable to speak or read Danish.

Data and biological material

Data Collection

- Semi-Structed interviews with participants and Health care professionals.

- Biochemical data

( Standard blood samples according to yearly control: Hba1c, creatinine, eGFR, sodium, potassium, albumin/creatinine (urine sample), total cholesterol, HDL, LDL, triglycerides, Hb.).

- Hypoglycemia events

-Number of Contacts

-Absence from work/study and expenses

- ADDQoL19

- DTSQs

- DTSQc

- Travel time saved

- Data on medication

Collaborating researchers and departments

Center of health economics research, Syddansk Universitet/University of Southern Denmark

• Kjeld Møller Pedersen