In this article, Paul Draper, Senior Sector Manager – Medical and Scientific at DCA, discusses the current state of connected injection pens and devices in the diabetes space, exploring the benefits that connectivity can bring to drug delivery devices and considering how to exemplify good design in a connected injection device for diabetes drug therapies.

Diabetes is a chronic condition in which the body does not produce sufficient insulin, or properly use it, potentially leading to severe health implications. To help prevent these problems many people rely on insulin therapy, which can require administration of multiple doses of different insulins every day. Frequent adjustments to insulin dosage are commonly needed to accommodate variations in diet or lifestyle. Keeping track of this can be challenging, particularly when trying to manage diabetes alongside all of the other complexities of daily life.

A chronic condition with a patient-adjusted treatment regimen will clearly carry significant challenges for adherence to treatment plans. Notwithstanding the challenge in accurately determining adherence rates in reality, studies indicate that adherence rates for insulin therapy could be as low as 44.3% in Type 2 diabetes patients (ref 1). Furthermore, studies have shown that only 20% of people starting a basal insulin treatment plan continued beyond the first year (ref 2). What’s more, these figures are unlikely to fully capture those patients who miss doses or take incorrect dose values. Whatever the true figures, there is, undoubtedly, a clear problem with patients lacking the control they need in order to avoid secondary health complications that inevitably come from inadequately managed diabetes.

The majority of patients deliver insulin therapy with pen injector devices (59% in the US and 93.6% in Europe; compared to the syringe and vial) (ref 3). The design of these pens has matured over the last 20 years, through continual optimisation. But now these classical mechanical pen injectors and the advances in pharmaceutical molecules are potentially reaching the top of their respective ‘s-curves’ of development, this leaves modest opportunity to improve outcomes without a change in the model. This is where connected insulin delivery devices can now make the difference. The aim is simple, to empower the patient and healthcare professionals with accurate data to improve their ability to achieve better glycaemic control, through increased adherence and persistence with insulin therapies.

The advantages for patients, payers, and insurance companies, alike, can be shown by examining the total cost associated with diabetes related treatments. Data from UK expenditure published in a study in 2011 is illustrated in Figure 1. This shows that £13 billion was spent on diabetes treatment in total. Of this, only £1 billion was on the cost of drugs for direct treatment (ref 4). The majority of the rest of the costs are associated with the treatment of complications. It can therefore be argued the opportunity exists already to reduce the burden on the healthcare and insurance systems.

The upside for the pharmaceutical companies can be expressed relatively simply as well. If patient adherence and persistence is low, then less insulin is being purchased. This is magnified if one considers that prescribers may be more likely to switch to an alternative insulin product that has a compliance-aiding connected device if a patient is not achieving good control of their condition.

Therefore, arguably the potential value of connected insulin delivery devices to patients, healthcare providers, payers and pharmaceutical companies is potentially compelling. Hence, the challenge remains to develop devices that are capable of taking maximum advantage of this value by addressing the needs of patients within a framework that considers overall cost burdens on healthcare systems.

A connected ecosystem

The increasing rates of adoption of Continuous Glucose Monitoring (CGM) could ultimately be considered to be paving the way for highly effective diabetes management with connected insulin injection devices (ref 5). CGMs give an illustration of why usability is a critical factor for patient adoption. One of the key reasons why CGMs are popular is the reduction from one finger ‘stick’ per reading to one ‘stick’ every 14 days. Note also that the latest generation CGMs seem to be tending towards fully seamless data synchronisation via Bluetooth, also demonstrating the importance of simplified user actions.

In the most part, the benefit of connecting pen injectors themselves comes down to management of information. The right information, well-presented, can inform decision making and more timely interventions – leading ultimately, to better outcomes, illustrated by the graphic in Figure 2.

For some people, it could be said that the panacea for diabetes treatment is a fully closed-loop system, with a body-worn insulin pump working in conjunction with a CGM to form a pseudo ‘artificial pancreas’. However, algorithm-controlled dosing may not be the perfect fit for everyone, and losing control of the therapeutic decisions may be of particular concern for some physicians. A fully wirelessly controlled delivery device, such as a pump, also carries the downsides of probably more upfront product cost and cybersecurity vulnerabilities. As a balanced option for growing patient populations, connected injection pens are a compelling alternative, and indeed studies have been published with some of the latest connected injection devices showing clinically measurable benefits (ref 6).

The adoption equation

The level of interest, and ultimately adoption, could be said to be shaped by a rather simple equation, see Figure 3.

Here we are talking about the value to the individual, which will differ from person to person. However, it is likely to include metrics such as convenience and peace of mind, as well as the health outcomes that provide value to the patient as well as the healthcare providers and payers.

Similarly, the ‘burden’ will also change from person to person and is likely to include aspects such as the full-life fiscal cost to the patient or payer, environmental impact, number of task steps required, the complexity of the tasks, the time overhead per patient for the healthcare professional, etc.

For connected, or smart, devices to succeed the equation must be balanced such that the value proposition outweighs the overall burden.

The seven pillars of connected drug delivery development

It can be very helpful to categorise the aspects of device development into seven topics to illustrate the key things to consider to both maximise the value and reduce the burden, see Figure 4. This article will reference just a few of the key topics, from the seven, in order to highlight some important considerations.

It is important to make Usability the central factor when considering the level of adoption, and ultimately the success, of an injection device. It is often all too easy to allow compromise to usability when seeking to design connected injection devices or device accessories. A few examples of the problems associated with these compromises are discussed below.

Insulin pen injectors are often optimised during design to balance the thumb extension, for single-handed operation, with the dispense force (note that increased mechanical advantage brings lower dispense forces but larger travel distances). It is often simplest to integrate the connectivity hardware into the button of the insulin pen, to conveniently encode the mechanism for dispense recording for example. Figure 5 illustrates how this can be very detrimental to the ergonomics and can start to exclude some user groups from dispensing how they want to and have been able to historically.

When considering adding electronics to an injection device this will realistically require the incorporation of a battery and therefore design decisions are necessary for battery technology choices and charging and replaceability approaches. There is significant user overhead associated with charging, in both the physical actions of connecting cables or docks and the cognitive aspects of interpreting signals from the device and/or remembering to charge at the appropriate times. The alternative approach of making the battery replaceable by the user leads to all sorts of usability challenges for accessing and handling small batteries and casework covers. However, with leading-edge engineering development and innovation in low-power solutions, it is, in our experience, possible to implement a battery that lasts the lifetime of the injection device, thereby requiring no specific intervention from the user above and beyond the normal use of the device.

Another topic is data communication technology. It is inherent in a connected solution that data connectivity is required. This is again where seamlessness is incredibly powerful. But communication is heavily linked to power as well as usability and cannot be considered in isolation. The lowest power and easiest technologies to implement inherently carry additional user burdens. A wired or optical data download will require the user to take steps to connect cables or docks and to initiate the data transfer from either side, or both sides, of the communication link. Similarly, the use of Near Field Communication (NFC) technology may require slightly fewer user steps, but it still requires a deliberate and conscious action to be taken. A longer-range wireless technology, such as Bluetooth, can be made to operate seamlessly in the background. This comes with a greater power requirement and adds therefore to the development challenge. The reward for overcoming this challenge, in our view, is likely to ultimately be measurable in the adoption rates for the product in market.

Conclusion

Designing connected drug delivery devices that can succeed is a complex and multi-faceted challenge. It is a key strategic requirement to understand the business case, as well as the value proposition to the patient. It is then even harder to be able to design and develop a connected device to preserve the strategic goals, without accepting compromise at some point in the process. Success in this area requires a truly integrated approach, for all skills from strategy, human factors, mechanical engineering, electronic engineering, software engineering, and industrial design, to manufacturing, and industrialisation. All of these aspects need to be led by decision makers with the vision and experience to forge a path to success.

References

1. Perez-Nieves M, Kabul S, Desai U, et al. “Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US”. Curr Med Res Opin. 2016;32:669-680.

2. Yavuz DG, Ozcan S, Deyneli O. “Adherence to insulin treatment in insulin-naïve type 2 diabetic patients initiated on different insulin regimens”. Patient Prefer Adherence. 2015;9:1225-1231.

3. Masierek M, Nabrdalik K, et all. “The Review of Insulin Pens—Past, Present, and Look to the Future”. Frontiers in Endocrinology 2022.

4. Kanavos P, van den Aardweg S and Schurer W. “Diabetes expenditure, burden of disease and management in 5 EU countries”. LSE (Jan 2012).

5. Abbott. “2021 annual report”.Adolfsson P, Hartvig NV, Kaas A, Møller JB, Hellman J. “Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen”. Diabetes Technol Ther. 2020 Oct;22(10):709-718. doi: 10.1089/dia.2019.0411. Epub 2020 Mar 11.