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Advancing adherence

This article first appeared in Innovations in Pharmaceutical Technology.

It is well-understood in the healthcare industry that over half of patients do not adhere to medication prescriptions, and this is responsible for over $290 billion of additional healthcare costs in the US alone. Numerous initiatives and research studies have sought to address this issue.  It is generally accepted that good patient adherence is achieved through a combination of cultural understanding, human-physiology, motivation and behavioural change.

Smart packaging is a key development that can support the improvement of patient adherence, and ‘smart’ products have been around for almost a decade. However, the technologies developed so far have only been used in clinical trials, with very little adoption in real world healthcare.

Production cost, patient inconvenience, the proprietary nature of solutions and lack of physician interest are the key barriers to wider integration. However, the rapid global rise of advanced consumer technologies and sensors could facilitate a new generation of lower costing and smarter drugs. They could be integrated into patients’ digital lives through smart phones and personal health records, resulting in mainstream adoption, directly addressing the cultural and behavioural changes that will drive real improvements in adherence.

What is the Problem?

Dr C Everett Koop once said “drugs don’t work in patients who don’t take them” (1). A significant number of patients do not take their drugs as prescribed; 30-50% of patients suffer from chronic diseases in developed countries, which is a serious issue. Patients who do not correctly take their medication have poor health outcomes and a reduced quality of life (2). The Center for Disease Control released data in 2013 stating that in the US nonadherence causes approximately 30-50% of treatment failures and 125,000 deaths annually (3). Additionally, it leads to significant costs to the healthcare system – in the US, an estimated $100-290 billion and in the UK it reaches £300 million a year for wasted medication (3,4). That does not take into account the downstream costs of further treatment, re-admittance and so on (5).

Considering the huge savings and improved health and quality of living that can be achieved through better medication adherence, why are health systems and governments not investing more to tackle the problem? Answering that is not easy. The WHO define adherence as “the extent to which a person’s behaviour – taking medication, following a diet, and or executing lifestyle changes – corresponds with the agreed recommendations from a provider” (6). This definition incorporates a key factor of nonadherence: the fact that people struggle to change their lifestyles even when it is to improve their own health. However, it is important to recognise that it is not just about lifestyle – research has shown the reasons for nonadherence are multi-faceted and certainly not easily addressed (7).

A study by the Boston Consulting Group in 2003 estimated that only 24% of patients forget to use or refill their drugs, suggesting most nonadherence behaviour is intentional. For example, patients are unwilling to pay the price, believe they do not need the drugs or are not prepared to accept the side effects (8).

Internal and external factors are behind this behaviour. Internal factors reflect a patient’s intentional and unintentional beliefs, such as religious beliefs or a belief that they are already ‘cured’ before completing the prescription (7). External factors can include socioeconomic factors, family/community support, healthcare systems/ insurance and more (7).  The WHO groups these into five dimensions: social and economic, health system-related, therapy- related, condition-related and patient-related (6). Another way to consider these complexities is to look at perpetual factors, including beliefs, preferences and incentives, and practical factors, such as capacity and resources (1).

Many different approaches have tried to address adherence, such as behavioural, educational, integrated care interventions and technological packaging- based solutions.

The more successful programmes have integrated aspects of these different types of interventions, though they still have had mixed results and have not fully addressed the scale of the problem. In 2014, Nieuwlaat R performed an extensive review evaluating adherence interventions in 182 randomised clinical trials and concluded that even the most effective interventions did not lead to large improvements in adherence (10).

One issue has been that, historically, adherence programmes took a population- based approach in the belief that the answer was a single approach across the population (for example, more physician and patient face-to-face time). This then steadily became more disease-orientated as the significance of the condition to the level of adherence became evident (eg chronic vs acute).

More recently, advances in technology have led to claims that the problem of adherence can now be solved. New solutions are being developed to track the action of taking a pill more closely. It is possible for patients to receive a text reminding them to take their pill, open their smart pill box that tracks the pill’s removal, video themselves taking the pill and, once it reaches their stomach, it will  signal a device worn on their skin that the right amount of medication has been digested (11-13).

A Successful Solution

However, it is clear that these kinds of packaging technology solutions – such as radio-frequency identification (RFID), smart pillboxes or printed electronics – will not move the dial on patient adherence on their own, even if the cost and inconvenience aspects were to be addressed. All the tools needed to create a great adherence package are in our hands, but smarter packaging to integrate all the technologies available should be utilised.

Evidence suggests that the most successful attempts to improve adherence outcomes are those strategies that integrate multiple interventions (behavioural, education, integrated with care and technology). These include:

Addressing Behavioural Change: Using smart phones has already proven to be effective. WellDoc’s BlueStar – an FDA-approved prescribable diabetes management tool – is an example of what can be achieved. It balances motivation, education and result tracking with an algorithmic solution to deliver evidence-based benefits to diabetes patients.

Education: Educational material has long been delivered in multimedia and online, and many programmes have apps to support content and assess progress in understanding. Over 500 apps on the Apple Store provide healthcare and medical information to patients on specific conditions.

Integrated Care: Connecting patients with professional care-givers will play an important role in the future of healthcare and adherence. 

Technology Barriers

Technology that can facilitate patient adherence is increasingly available and accessible on a number of levels that cross both the pharmaceutical supply chain and treatment pathways. Specifically, this is the use of technology:

  • In the users’ environment, in the form of connected mobile devices
  • On the packaging, in the form of smart packaging
  • In the manufacturing process and supply chain, in the form of industry 4.0
  • Cloud data storage and analysis, which links the above systems together

Mobile devices that are already in the hands of patients offer a wealth of options for user interfaces to engage the patient, such as connectivity to the cloud and a range of sensors. The latter provides a wide range of creative options to detect how and when the patient uses the packaging. Examples include:

  • User interfaces to enable the patient to record and monitor usage
  • Using the camera to take photos of printed QR codes and blisters before or after use, coupled with image processing and cloud connectivity to log corresponding usage
  • Using the microphone and audio signal processing to detect usage
  • Wireless connectivity to connect to both smart packaging and cloud databases

Smart packaging ranges from storage of unique data on each package through to integrated electronic sensors that detect when and how the drug is taken, which inform user feedback. Typically, this is a trade-off between the level of function and connectivity and the cost of putting potentially electronic functions onto otherwise very low-cost packaging. Already, QR codes – digitally printed during manufacture – offer a mature solution that can uniquely link a package to a patient and treatment-specific dataset in the cloud.

New technologies are also emerging fast that could enable much more sophisticated functions to be placed in the package. RFID tags are a commodity technology sold for less than $0.10 and can be read and written through the supply chain and by consumers using NFC on smart phones. More sophisticated NFC labels with a simple usage sensor are also becoming commercially available. This is just the beginning of what is possible through using printed electronics technology to enable more sophisticated electronic systems to be produced in a thin, flexible form that is compatible with existing packaging solutions.

It also offers the advantage of doing this at lower cost than conventional electronic systems. For example, multiple sensors and longer range wireless connectivity solutions could be added to packaging by this means.

The development of intelligent and flexible manufacturing processes, through the adoption of industry 4.0, can link the packaging to the rest of the supply chain. Opportunities range from production improvement through sensing and tracking all units through the supply chain to delivering customised production and packaging of different drugs to match a patient’s individual prescription, thus making compliance easy and simple.

Cloud data storage and analytics will link these different components, with increasingly sophisticated algorithms and artificial intelligence techniques able to better engage with the consumer and optimise treatment.

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Cultural and Behavioural Changes

The technologies described above are enabling and, as they reach appropriate price points and become more prevalent, it will be possible to build adherence ecosystems. These will combine different pieces of technology in alternate configurations that directly address the cultural barriers to compliance.

This will help us to think about system solutions, not just one technology solution that has a small number of core properties. These include addressing the psychology of nonadherence using gamification, nudges and subtle cues to encourage patients to stick to their prescription. They also need to be personalised – patients are nonadherent for their own reasons, and we need to build personalised responses to address these. That is likely to involve a combination of services and technologies that is right just for that patient.

We should also be looking to provide a standardised ecosystem – a ‘walled garden’ that will encourage third parties to build on enabling technologies to create ever better adherence platforms, such as the adherence equivalent of an iTunes store. Finally, we should build on the enabling technologies, but not be a slave to them and use the existing infrastructure in novel and exciting ways to engage with patients.

The elements needed to create this future are around us; they just have not been integrated together. The problem of drug nonadherence is not a new one and the technologies that will be used to solve the problem will not be new either – just combined and interpreted in a new way.

It was the mantra of Steve Jobs at Apple that simplification and integration of products and services into consumer-oriented offerings was what drove the greatest innovations. The same approach could now drive the development of the smarter drug packaging solutions that will make the difference in adherence to the benefit of patients and healthcare systems.


  1. Academy of Medical Sciences and Faculty of Pharmaceutical Medicine, Patient adherence to medicines, Forum: December 2014
  2. Costa E et al, Interventional tools to improve medication adherence: Review of literature, Patient Prefer Adherence 9: pp1,303-14, 2015
  3. Centers for Disease Control and Prevention, Medication adherence, CDC Noon Conference: p13, 2013
  4. Visit:
  5. Trueman P et al, Evaluation of the scale, causes and costs of waste medicines: Final report, York Health Economics Consortium and The School of Pharmacy, University of London: 2010
  6. WHO, Adherence to long-term therapies: Evidence for action, WHO: 2003
  7. Srivatsan N et al, Medication adherence in the real world, Cognizant 20-20 Insights: October 2014
  8. Visit
  9. Granger BB and Bosworth HB, Medication adherence: Emerging use of technology, Curr Opin Cardiol 26(4): pp279-87, 2011
  10. Nieuwlaat R et al, Interventions for enhancing medication adherence, Cochrane Database Syst Rev (11): CD000011, 2014
  11. Visit:
  12. Visit:
  13. Visit:

Simon Hall is a life sciences expert at PA Consulting Group

This article is taken from Innovations in Pharmaceutical Technology January 2018, pages 10-13. © Samedan Ltd

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