1ISSN 2041-599010.4155/TDE.12.57 © 2012 Future Science Ltd Therapeutic Delivery (2012) 3(7), 1–xxx

Keywords: adherence/compliance n drug-delivery devices n electronics n self management

Editorial

Since the turn of the 20th century, electronics and pharmaceuticals have developed in parallel and at pace (albeit at different speeds). Electronics are now omnipresent and advances in device-based drug delivery – such as inhalers and auto-injectors – are commonplace, and while these two sectors have developed separately, electronics as an enabling technology in drug delivery has been evolving quietly since the 1980s. Various drivers, such as regulatory pressure on usability, healthcare economics, the availability of low-cost components and a patient appetite for greater functionality, means that electronically enabled delivery devices (EEDDs) will be more important in the coming years.

The improvement of patient adherence is of significant interest to prescribers, payers, regulators and, ultimately, to patients. In fact it is fair to say that of all the drivers pushing the electronic agenda, it may be the most significant, and it is not difficult to see why. Poor adherence has become a major problem for individuals, for society and for national economies. US surveys have shown that even patients with chronic conditions achieve an average of only 50% adherence when using prescribed medication [1]; nonadherence is estimated to result in approximately 125,000 deaths per year [2], and cause 10% of hospital admissions and 23% of nursing home admissions [3]. In terms of healthcare costs, this equates to an estimated US$100 billion per year [4] and a loss of productivity (a direct loss to GDP) of around $50 billion per year [4].

Electronics can reduce the cognitive, emotional and physica l burdens that can compromise patient adherence, and consequently compliance, by supporting users and helping them deal with factors including forgetfulness, incomprehension and anxiety. Those of the ‘iPod generation’ may consider

that if electronic functionality can be added, it should be. But are the potential benefits always accessible, or indeed justifiable given the implications of increased cost and ‘disruption’ involved? Or are other less complex design strategies possibly more relevant in different patient contexts and, therefore, potentially more effective? Just because we can, it does not mean that we should.

EEDDs first entered the market in the late 1970s, largely made possible by the invention of the microprocessor. Their potential was first recognized by those involved in the management of diabetes, leading to the development of the first commercial EEDD, the AutoSyringe AS6C (DEKA R&D Corporation, NH, USA), a continuous subcutaneous insulin infusion pump (CSII). EEDDs used in diabetes management have increased in sophistication over the past 30 years and now offer touchscreen handsets, near-field communication to a portable monitor unit and much more. Even insulin pens – well established, mature mechanical devices – are now being offered with electronic memory features to help users keep track of dosage time and size, both as built-in features (e.g., the NovoPen Echo® from NovoNordisk) or aftermarket devices (e.g., the Timesulin™ smart cap). Diabetes management has a long history, stretching back over 60 years and experience gained in insulin-delivery devices has been a stimulus to device evolution in other therapeutic areas. The easypod® from Merck Serono is a ‘full featured’ electromechanically operated and electronically controlled injection device. The first of its kind, the easypod was launched in 2007 and is used to deliver hGH. At the simpler end of the spectrum, electronic dose counters for inhalers have been available for a number of years as an aftermarket product and more recently, as an integrated feature of some inhalers and nasal delivery devices.

Electronically enabled drug-delivery devices: are they part of the future?

“Ideally, the future will see well-designed electronically enabled delivery devices and non-electronically enabled delivery devices both entering the market and providing greater patient choice and improved compliance.”

Andy FryTeam Consulting Ltd., Abbey Barns, Duxford Road Ickleton, Cambridge CB10 1SX, UK Tel.: +44 1799 532 739 E-mail: andy.fry@ team-consulting.com

Editorial | Fry

Therapeutic Delivery (2012) 3(7)2 future science group

It is fair to say that just a few years ago electronic device features were largely considered complicated and challenging by many pharmaceutical companies, both from a technical and a regulatory point of view. Now, electronic enhancements have the potential to significantly improve compliance, although ‘traditional’ nonelectronic devices, with a sound design basis in human factors engineering, can also help eliminate some of the negatives that compromise adherence, from accommodating the full range of grip styles to minimizing pain or anxiety caused when the device is in use. However, adherence is not all about usability. Even the best designed, most ‘user-friendly’ device still cannot address the ‘self-management burden’ – ensuring the patient or caregiver remembers to administer the therapy correctly in the first place.

EEDDs can help reduce this self-management burden by building in functions, such as electronic alarms or instruction screens, designed to prevent user forgetfulness, incomprehension or fear. Wearable, ‘fit and forget’ EEDDs – for example, the OmniPod® from Insulet Corporation – can ensure consistent drug delivery is maintained over the longer term. ‘On-board’ features can also deliver relevant updates for users, caregivers and healthcare practitioners on dosage times, say, or dosage patterns.

“Even the best designed, most ‘user-friendly’ device still cannot address the ‘self-management

burden’ – ensuring the patient or caregiver remembers to administer the therapy correctly

in the first place.”EEDDs can prove their worth when used

to deliver therapies required regularly but infrequently (again, often high-value biologics such as treatments for rheumatoid arthritis). In such contexts, patients do not gain sufficient skills from repeated device use to ensure the procedure remains consistent and compliance is achieved. An EEDD could provide the support and feedback required to ensure the user remains confident when using the device.

The US FDA, previously very cautious regarding EEDDs, is now prepared to consider supporting their use when it can be shown that they can significantly improve compliance, giving a significant boost to future investment in this area. However, there clearly remains a place for non-EEDD products.

‘Traditional’, non-electronic devices will be the positive choice for certain patient populations;

whereas younger patients may possibly be happier to use an EEDD, someone older or less physically capable may prefer a simpler device. Lower cost therapies, especially those in single-use disposable format, may also be less likely EEDD candidates.

When considering whether to opt for an EEDD, stakeholders should focus first on the key fundamentals of good compliance: robust, reliable and accurate drug delivery; clear device interaction cues and feedback; a ‘positive’ operating force that meets the capability of diverse users; and good ergonomics, making the device easy and safe to manipulate. However, if a purely mechanical design is the most effective option, that is the right answer.

Currently, the issues of user adherence and self-management are key drivers in EEDD design, but trends currently emerging across the pharmaceutical industry will certainly influence future device development. For example, counterfeiting is a major issue for pharmaceutical companies and healthcare providers, with the WHO estimating that counterfeit drugs now account for 10% of worldwide pharmaceuticals [101]. EEDDs have the potential to provide therapy verification and traceability if they can incorporate similar technologies to those used by the finance sector to ensure the security of banking transactions. In my opinion, EEDDs could potentially strike a serious blow at counterfeiters, prompting the incorporation of more anti-counterfeiting features in future devices.

Another issue is how to accommodate the needs of the sustainability agenda and the growing raft of legislation related to disposal, recycling and the management of hazardous waste. For any battery-powered device, end-of-life device disposal is an issue that needs to be properly addressed, especially if longer term goals include more single-use, disposable EEDDs.

One solution is to design reusable EEDDs; one example from SwissMedDev Sàrl (Switzerland) is a reusable autoinjector that accepts prefilled syringes and automates the entire injection operation. Another solution is to retain only the most basic electronic functionality in the disposable device, perhaps in the form of an radiofrequency identification tag, while the more sophisticated support, control and monitoring systems are stored elsewhere, possibly within an application running on a mobile device or smartphone. Passive, near-field communication is a well-proven technology, used in applications ranging from cattle tags to transport payment

Electronically enabled drug-delivery devices: are they part of the future? | Editorial

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cards and even ‘smart’ trainers. If used within an EEDD, patients could use a smartphone to check device authenticity, provide dosage alerts, log dosage records and check when a dose is complete. When the delivery device itself is thrown away, valuable data and support is retained within the smartphone, making device disposal much simpler and more sustainable, and reducing the cost of goods.

“Only those features and attributes that contribute towards an intuitive and reassuring device, designed for ease-of-use and minimal

risk of error, should be part of any design remit. As a result, the best solution may not always be

an electronically enabled delivery device.” It seems likely that EEDDs will exert a

growing inf luence on drug delivery as our body of experience grows, and technology advances and patient expectations evolve. But the fundamental objective – and the essence of regulatory guidelines – is that every device

should help patients comply with their therapy and thereby manage their condition. Only those features and attributes that contribute towards an intuitive and reassuring device, designed for ease-of-use and minimal risk of error, should be part of any design remit. As a result, the best solution may not always be an EEDD. Technology can certainly encourage compliance, but not all patients and caregivers will engage successfully with technology. Ideally, the future will see well-designed EEDDs and non-EEDDs both entering the market and provide a greater patient choice and improved compliance.

Financial & competing interests disclosureThe author is employed by Team Consulting Ltd. The author has no other relevant affiliations or financial involvement with any organization or entity with a finan-cial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

References1 Haynes RB, McDonald H, Garg AX,

Montague P. Interventions for helping patients to follow prescriptions for medications. Cochrane Database Syst. Rev. 2, CD000011 (2002).

2 Burrell CD, Levy RA. Therapeutic consequences of noncompliance. Improving medication compliance. Proceedings of a Symposium: National Pharmaceutical Council. Washington, DC, USA, 7–16 (1984).

3 Noncompliance with Medication Regimens. An Economic Tragedy. Emerging Issues in Pharmaceutical Cost Containing. National Pharmaceutical Council, Washington, DC, USA, 1–16 (1992).

4 Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence. Am. J. Health Syst. Pharm. 60(7), 657–665, (2003).

�� Website101 Berkrot B. Fake Avastin shows very little

protects drug supply. Reuters, NY, USA (2012). www.reuters.com/article/2012/03/12/us-drugs-counterfeits-idUSBRE82B00120120312