Medication adherence

What is medication adherence?

Medication adherence is recognised as the extent to which a patient’s behaviour coincides with medical or health advice¹. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) defines medication compliance, a synonym of adherence, as ‘the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen’².

One could interpret this as simply following ‘doctor’s orders’. However, medication adherence is a complex and multi-variable issue that requires a breadth of understanding if circumstances are to be improved. According to the UK’s National Institute for Health and Care Excellence (NICE), approximately one third to a half of all medicines prescribed for long-term conditions are not taken as recommended³. Similarly, the World Health Organisation (WHO) reports that adherence to long-term therapy for chronic illnesses in developed countries averages 50% with even lower figures expected in developing countries⁴.

What factors affect adherence behaviour?

There are, as one might expect, a wide array of recognised factors that impact on adherence behaviour. While a comprehensive list of recognised adherence barriers possibly extends into the hundreds, there are recurring themes that are seen across various patient groups ⁵. The WHO reports five different interacting factors and interventions that affect medication adherence including ⁴:

• social and economic (e.g. poor socioeconomic status, illiteracy or unemployment)
• health system/health care team related (e.g. poor medication distribution systems, inadequate or non-existent reimbursement or a lack of feedback on performance)
• therapeutic (e.g. complexity of medical regimens, duration of treatments or the immediacy of beneficial effects)
• condition related (e.g. severity of symptoms, rates of progression or level of disability)
• patient related (e.g. knowledge and beliefs, motivations to manage or confidence)

According to the Aston Medication Adherence Study (AMAS), the majority of factors affecting adherence are focused on social/economic and therapy-related factors 6. The report suggests that age and socioeconomic deprivation are significant, albeit complex, contributors to non-adherence, with younger and older age groups showing lower rates of adherence than the middle aged.

Therapy-related factors described in the AMAS study referred to the choice of agents, the number of regular medicines taken and the complexity of the dosing regimen⁶. According to the study there was consistent evidence to demonstrate an ‘inverse correlation between the number of daily doses prescribed and adherence rates’⁶.

I believe that defining both the nature of non-adherence, and understanding the ‘perceptual factors’ that influence a patient’s motivation to adhere to prescribed advice, is crucial in the design and development of medical devices.

What is the impact of non-adherence?

The consequences of low and non-adherence have widespread implications for patients, the healthcare system and society holistically. In fact, according to the WHO, there are a growing number of studies that claim that ‘increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments’⁴.

Poor adherence to medication regimens inhibits the benefits of medicines; this leads to a lack of health improvements for patients or, worse, a deterioration in health. Conversely, good adherence has been shown to lead to improvements in health and economic outcomes. In a study of 137,277 patients aged under 65, high levels of medication adherence were associated with lower disease related medical costs in patients with diabetes and hypercholesterolemia⁷. According to Sokol et al, the higher costs incurred by achieving good adherence are more than offset by the related reductions in medical and overall healthcare costs⁷. It has been estimated that the total cost to the US healthcare system of non-adherence is close to $300 billion annually in direct and indirect costs⁸.

The consequences of non-adherence also extend beyond initial loss of sales, representing longer term issues for pharmaceutical companies. The impact upon ‘brand equity’ through detrimental perceptions of medication inefficacy are difficult to measure, but the implications can be significant, and are compounded by the fact that acquisition of new patients is significantly more expensive than the retention of existing patients.

Current NICE guidance refers to two different, but overlapping, types of non-adherence behaviour: ‘intentional’ and ‘unintentional’³.

1. Intentional non-adherence refers to a patient’s decision to not follow treatment recommendations. This can include deliberately omitting prescriber advice, skipping or altering a dose or ceasing to take medication due to experienced side-effects.
2. Unintentional non-adherence occurs when the patient is prevented by specific barriers that are outside patient control. These may include failing to comprehend or understand instructions for use, an inability to pay for treatment, or simply forgetting to take medication.

The diversity and complexity of issues associated with medication non-adherence have long been researched and are well documented throughout the literature. In light of this, this article is focused specifically on how device design can influence patient behaviour and potentially lead to improved medication adherence and longer term health outcomes.

What are the possible design interventions and is there any evidence to suggest improved adherence?

Interventions to improve medication adherence for short and long term conditions can range from simpler instruction design to complex combination strategies. It should be said that many of the recognised approaches for improving medication adherence fall outside the scope of device design and development per se (e.g. pharmacist led interventions, counselling and close follow-ups). This does not mean to say that device design cannot influence a patient’s adherence behaviour. To the contrary, there is a growing body of evidence to suggest that certain design related interventions can offer enhancements in adherence:

• Changing the delivery route

The influence of delivery route can have a profound impact upon treatment satisfaction and consequently adherence rates. In an observational study comparing subcutaneous and oral treatments for iron chelation therapy, patient satisfaction was found to be greater in those receiving oral treatment and was typically associated with less treatment burden⁹. Rofail et al concluded that slow subcutaneous infusion negatively impacted upon treatment satisfaction which was shown to be a determinant of adherence⁹.
In another study of three treatments for patients with Rheumatoid Arthritis (RA), Hetland et al found that improvements in adherence ranged from 11–15% when patients were treated with Adalimumab (52%) or Etanercept (56%) as opposed to Infliximab (41%), which supports the theory that selecting the right delivery route for specific patient populations can influence adherence behaviour¹⁰.

• Fixed-dose combinations (FDCs)

FDCs refer to switching patients from individual agents to a combined single dose regimen. This form of dosing simplification has been shown to improve adherence rates in antidiabetics, lipid-lowering agents and hypertension medication6. In another study, conducted by Dezii, it was reported that patients prescribed with FDCs of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Hydrochlorothiazide (HCTZ) were 20% more likely to persist with therapy for one year than patients taking equivalent agents individually¹¹.

• Packaging design

Medication packaging has been shown to affect adherence rates. In a randomised controlled trial of 85 elderly patients, Schneider et al reported that patients receiving Lisinopril for hypertension in daily dose blister packaging were more adherent to therapy than patients receiving their medication loose in bottles¹². Previous studies have also shown unit-of-use packaging to improve adherence rates over standard or conventional packaging in patients with type 2 diabetes¹³. However, a systematic review conducted by Zedler et al states that while calendar packaging may appear ‘intuitively attractive’ as a single strategy, the evidence suggesting it leads to improved adherence is inconclusive due to methodological limitations in the data¹⁴.

• Patient reminder systems

Reminder systems have been widely associated with a positive influence on adherence. In a study of 110 asthma patients using Metered Dose Inhalers (MDIs), an audio-visual reminder function reportedly enhanced adherence rates by 18% over a 12 week timeframe when compared with a standard MDI device¹⁵. Similarly, a randomised controlled trial of 398 patients, held over a six month period, revealed a 6% increase in patient adherence to Telmisartan among newly diagnosed hypertensive patients using a reminder device¹⁶.

• Simplify the dosing regimen

In a systematic review of 20 studies of adherence of medications for chronic conditions, all studies reported enhanced adherence rates in patients using less frequently dosed medications6. Saini et al reported that adherence rates were 22–41% better in patients receiving once daily dosing as opposed to two or three doses per day¹⁷. In another review conducted by Schroeder et al, simplification of the dosing regimen for antihypertensive medication was found to increase adherence by 8–20% across seven of nine studies¹⁸.

One must consider, however, that guaranteeing improved medication adherence through any single or combined strategy cannot be assured. With this in mind, I believe it is more appropriate to identify the potential problems experienced by patients in the non-adherence of a dosing regimen than to explore ways in which device design can offer improvements to such issues.

Summary

Medication non-adherence is an on-going, complex issue for the pharmaceutical industry and one that will continue into the foreseeable future. The evidence on interventions to improve medication adherence currently suggests a lack of consistently effective strategies, with no single optimal strategy recognised within the literature^4,6,19.

If improvements in medication adherence are to be made, it is believed that more emphasis must be placed upon the characteristics of patients, disease conditions and treatment regimens¹. Realistic assessments of patient knowledge, understanding of dosing regimens, and of beliefs will then enable more effective targeting of potential adherence problems¹⁹.

My personal view is that the complexity of medication adherence requires an empathic understanding of patient needs, expectations and lifestyles. After all, non-adherence is often regarded as a hidden problem, one that

NICE states requires honest and open discussion amongst the healthcare community to develop better strategies for improvement³. Through collaboration with our multi-disciplinary teams, such discussions occur early in the design and development process with our clients to understand the specific difficulties that patients may experience with adherence. If the wider industry and supply chain can work closely on this topic, I believe we can enhance medication adherence through design and continuously look for new opportunities and research to build on our expertise in this area.

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What does ‘thinking about adherence’ mean for device developers?

– By Julian Dixon, Director of Human Factors

If one thing is clear from Thomas’ literature review, adherence is a complex human phenomenon. As device developers, we can’t expect to be adherence experts, but we do expect to have sufficient awareness of its complexity. Awareness enables clarity of thought about what we can and should do about adherence – and about what limits our ability to influence it.

Of course, we can’t have much impact on the socio-economic circumstances or age of our intended users, on the nature of their disease condition or on drug side-effects. And influencing the healthcare systems within which our products exist is a task beyond the scope of any individual company.

But working in partnership with drug and formulation development teams we can influence dosing frequency, the nature of dosage administration (e.g. IV vs SC) and, through the design of user experiences we can also influence patients’ feelings about their treatment. On an increasing basis we are working with our pharmaceutical clients to improve patients’ experiences often in small, but practical and significant ways, and with a focus on two basic questions:

• How can we reduce the demands we make of patients?
• How can we support patients to help them adhere?

We presented some initial thoughts on this topic at the PDA Europe Pre-Filled Syringes interest group meeting in Berlin, March 2011.

Download here: http://te-am.co/pdaeu2011

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References
1. McDonald, HP, Garg, AX, Haynes, RB,
Interventions to enhance patient adherence to medication prescriptions: scientific review, JAMA: the Journal of the American Medical Association 2002, 288(22), pp2868–2879.
2. Cramer, JA, Roy, A, Burrell, A, Fairchild, CJ, Fuldeore, MJ, Ollendorf, DA, Wong, PK, Medication compliance and persistence: Terminology and definitions, Value Health 2008,11, pp44–47.
3. National Institute for Health and Care Excellence (NICE), Medicines adherence: Involving patients in decisions about prescribed medicines and supporting adherence. NICE Clinical Guideline 76, January 2009.
4. World Health Organisation (WHO), Adherence to long-term therapies: Evidence for action, 2003.
5. Zeber, JE, Manias, E, Williams, AF, Hutchins, D, Udezi, WA, Roberts, CS, Peterson, AM, A systematic literature review of psychosocial and behavioural factors associated with initial medication adherence: a report of the ISPOR medication adherence & persistence special interest group. Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research, 2003, 16(5), pp891–900.
6. Langley, CA, Bush, J, Marriott, JF, Wilson, KA, Establishing the extent of patient non- adherence to prescribed medication in the Heart of Birmingham teaching Primary Care Trust (HoBtPCT), The Aston Medication Adherence Study (AMAS), Final Report, 2012.
7. Sokol, MC, McGuigan, KA, Verbrugge, RR, Epstein, RS, Impact of medication adherence on hospitalization risk and healthcare cost, Medical Care, 2005, 43(6), pp521–530.
8. New England Healthcare Institute, Thinking Outside the Pillbox: A System-wide Approach to Improving Patient Medication Adherence for Chronic Disease, 2009, pp1–21.
9. Rofail, D, Abetz, L, Viala, M, Gait, C, Baladi, JF, Payne, K, Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument, Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research, 2009, 12 (1), pp109–117.
10. Hetland, ML, Christensen, IJ, Tarp, U, Dreyer, L, Hansen, A, Hansen, IT, Kollerup, G, Linde, L, Lindegaard, HM, Poulsen, UE, Schlemmer, A, Jensen, DV, Jensen, S, Hostenkamp, G, Ostergaard, M, Direct comparison of treatment responses, remission rates and drug adherence in patients with rheumatoid arthritis treated with Adalimumab, Etanercept or Infliximab, Arthritis & Rheumatism, 2010, Vol 62, No 1, pp22–32, DOI 10.1002/art.27227, American College of Rheumatology.
11. Dezii, CM, A retrospective study of persistence
with single-pill combination therapy vs. concurrent two-pill therapy in patients with hypertension, Managed Care (Langhorne, Pa.) 2000, 9(9 Suppl), pp2–6.
12. Schneider, PJ, Murphy, JE, Pedersen, CA, Impact of medication packaging on adherence and treatment outcomes in older ambulatory patients, JAPhA: Journal of the American Pharmacists Association, 2008, 48, pp58–63.
13. Skaer, TL, Sclar, DA, Markowski, DJ, Won, JK, Effect of value-added utilities on prescription refill compliance and Medicaid health care expenditures — a study of patients with non- insulin-dependent diabetes mellitus, Journal of Clinical Pharmacy and Therapeutics, 1993, 18(4), pp295–299.
14. Zedler, BK, Kakad, P, Colilla, S, Murrelle, L, Shah, NR, Does packaging with a calendar feature improve adherence to self-administered medication for long-term use? A systematic review, Clinical Therapeutics, 2011, 33(1), pp62–73.
15. Charles, T, Quinn, D, Weatherall, M, Aldington, S, Beasley, R, Holt, S, An audiovisual reminder function improves adherence with inhaled corticosteroid therapy in asthma, The Journal of Allergy and Clinical Immunology, 2007, 119(4), pp811–816.
16. Christensen, A, Christrup, LL, Fabricius, PE, Chrostowska, M, Wronka, M, Narkiewicz, K, Hansen, EH, The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial, Journal of Hypertension, 2010, 28(1), pp194–200.
17. Saini, SD, Schoenfeld, P, Kaulback, K, Dubinsky, M, Effect of medication dosing frequency on adherence in chronic diseases, The American Journal of Managed Care, 2009, 15(6), ppe22–e33.
18. Schroeder, K, Fahey, T, Ebrahim, S, How can we improve adherence to blood pressure- lowering medication in ambulatory care? Systematic review of randomized controlled trials, Archives of Internal Medicine, 2004, 164(7), pp722–732.
19. Martin, LR, Williams, SL, Haskard, KB, DiMatteo, MR, 2005, The challenge of patient adherence, Therapeutics and Clinical Risk Management, 2005, 1(3), pp189–199.

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About Tom
Thomas is a human factors engineer at Team. He is integral to the planning and conducting of formative and summative human factors studies all over the world. Thomas has a PhD in home use medical device design.
thomas.grant@team-consulting.com