Medication adherence is not only the mantra of modern medicine, but also the catalyst to achieve prevention, cure, and wellbeing. Patients require medications, and the majority understand that adherence is paramount. Physicians ‘prescribe’ the medications, yet medication adherence remains a major challenge. What if the physician’s role extended beyond ‘prescribing’ to include a seemingly simple but critical part of medical practice: patient education? What if the patient’s role extended beyond ‘collecting’ those pills to taking the initiative and asking their physician for clarification or simplified explanations? After all, it takes two to tango.
Health and financial ramifications of non-adherence in England and the United States
Non-adherence is common and, therefore, might be seen by some as “a fact of life”, but it should not remain a “fact of healthcare”. The consequences are severe, ranging from a negative impact on the quality of life, poor management of symptoms to even death. Not only does non-adherence touch the patient, but it also affects the healthcare system and the economy. A 2015 report revealed that one billion medicines are wasted every year in the UK
. The report also revealed that one in five patients in the UK does not complete their prescribed course of medication. Almost 200,000 people in the European Union die each year because of non-adherence, with two-thirds of those patients having simply forgotten to take their medicine; a quarter fearing side-effects; and almost 20% feeling they did not need the medication at the time. More than 30% of patients admit to disposing of their unused drugs rather than returning them, according to the survey.
Non-adherence costs the NHS £500m each year. This naturally leads to a reduction in the cost-effectiveness of medications that have been approved by the National Institute for Health and Care Excellence. Almost 45% of British adults were given medicines through the NHS in the month immediately preceding the study.
This £500m net loss could play a positive role in taking a significant burden off the NHS — it is estimated to cost the same amount to employ 21,000 qualified nurses or pay for 30,000 kidney transplants,
The New York Times described non-adherence in the US as an “out of control epidemic” costing the US more than any other disease entity
. A recent systematic review showed that suboptimum medication adherence is costing the US 125,000 deaths per year, and its healthcare systems US$100–289bn annually. Around 30% of prescriptions are never filled and almost half of prescriptions given for chronic illnesses are not taken properly, according to the review
. The study also highlights pharmacists’ essential role in establishing adherence, showing that face-to-face pharmacist support improved adherence and patient satisfaction, decreased hypertension and reduced emergency visits associated with heart failure.
Health literacy: concept, past and present
Health literacy is defined as the extent to which individuals can obtain, process and communicate health information, and how this will subsequently influence their capacity to make appropriate health decisions. Health education has emerged as a powerful tool; it has been used effectively for disease prevention, and for teenage substance abuse prevention in schools and other settings
During the 1980s, health education matured further to include theories of behavioural change and social marketing,,
. Those theories were the stepping stone to understanding the complex interplay between perceived social norms, personal beliefs, the influence of social, economic and environmental factors, and behavioural changes towards health decisions,
. On the other hand, social marketing contributed to creating relevant approaches and educational programmes to target individuals in our society
In the late 20th century, public health practitioners started to catch up with their influential role in positively deciding the determinants of health for their patients. Today, health literacy is a multi-faceted model
. It is functional, which reflects the outcomes of traditional education on health risk and how to use health systems. It is interactive, which focuses on creating a supportive environment to patients and how they can acquire social skills towards a healthier life. It is critical, which means patients can now analyse health information more efficiently and have a better control over their health.
Compliance, concordance and adherence: what is the difference?
Previously, the term compliance was widely used to describe how patients comply with their physician’s wishes regarding a remedy. It was criticised because of its paternalistic nature, directed from the physician towards the patient
. As a result, concordance arose advocating that the physician and patient reach a mutual agreement on the medication regimen or treatment plan
. This was also criticised because of its undefined aspects: is this agreement beneficial to the patient, and do the patients like to take on a greater responsibility and be part of such a process? Eventually, adherence was born. Simply stated, adherence indicates how persistent patients are in taking their medications 
. The rate of adherence is defined as the percentage of doses of the prescribed medication taken by patients over a specific period of time
Non-adherence can be categorised into:
a) Non-adherence: patients never fill or initiate their medications and this is divided into intentional, which is determined by the patient’s beliefs, expectations and attitudes; and unintentional, which is determined by limitations of resources and personal constraints;
b) Non-persistence: patients stop taking the medication after starting it;
c) Non-conforming: patients do not take the medication properly as described, whether it is the dose or time etc
Factors influencing adherence vary from social and economic-related, such as poverty, medication costs and insufficient insurance coverage, to patient-related factors including forgetfulness and health misconceptions, medication-related factors like the number of medications, medication dosage and frequency,
. For example, polypharmacy, which is a medication regime of more than three drugs a day, was shown to be a notable barrier to adherence. The last and most significant factors that influence adherence are healthcare system-related, such as differences in physician’s approaches towards patients.
Mathes and colleagues conducted a systematic literature evaluation of seven systematic reviews
. They observed that employment status and higher education exerted a positive effect on adherence. Whereas co-payments, higher medication cost, medication regimen complexity, and the status of ethnic minorities exerted a negative effect.
Lehmann and colleagues demonstrated that 87% of patients felt comfortable with bedside presentations provided by the physicians, and almost half felt this helped them to better understand their illness
. Despite this, time spent in bedside presentations remains minimal. However, half of the patients found the terminology during bedside presentations confusing, and a majority thought it was intended not for them but for the residents. This means, physicians have yet to polish their skills and better utilise this method of health literacy.
Another study showed that 40–60% of patients could not correctly report what their physicians expected of them between 10 and 80 minutes after being provided with the information, and 60% misunderstood their physician’s directions,
. This means physicians still have a long way to go in communicating better with their patients.
Proposed approaches to better help patients adhere
Zullig and Bosworth described three phases of medication adherence: initiation, implementation and discontinuation
. To avoid discontinuation, there are multiple options to identify those at high risk of non-adherence. Integrated data systems have been utilised, as have electronic medical records data, and predictive analytics ,,
. These databases document previous patient behaviours and their personal characteristics. This, in essence, is a preemptive approach to avoid non-adherence in high-risk patients. Patient-reported outcomes emerged as another useful tool. It is based on the patient’s delivered status of health without any interpretation by another party
Overall, it is best to develop a patient-centered model to aid adherence,
. This takes into consideration their beliefs, misconceptions, preferences, aims and obstacles in taking medications, and can also better help them to generate health behaviours.
At the level of prescribing, physicians are advised to simplify the medication taking, and involve patients in the treatment plan
. At the level of communication, physicians are advised to explain key information when dispensing the medications, utilise aids to improve their patients’ adherence, such as drug cards or calendars, and provide behavioural support. At the level of follow-ups, it is advised to schedule appropriate follow-ups and try to asses medication adherence, identify barriers to adherence and address them directly with the patient
Where do we go from here?
Patients cannot take the sole blame for medication wastage and the subsequent financial losses to healthcare systems; especially if their physicians failed to educate them in the first place. Everyone understands that medicine, as a career, is hectic and physicians seek a high turnover of patients to treat as many as they can, but this should not be by sacrificing the quality of healthcare delivery. Physicians should not turn over their patients like shuffling cards in a game. This eventually becomes counterproductive and contradicts their Hippocratic Oath that has the motto: “First do no harm”. Not educating our patients is, in fact, a euphemism for indirect harm. One part of the oath reads: “I will prevent disease whenever I can but I will always look for a path to a cure for all diseases”. Patient education is one path to a cure for all diseases.
Patients should take the initiative if their physicians do not, and try to acquire basic or advanced health literacy to avoid misconceptions, and aid their treatment course and progress. Pharmacists and well-informed nurses can also become part of this multi-component adherence intervention.
In the case of tamoxifen, women cannot have it all. Discomfort with postmenopausal symptoms associated with tamoxifen administration versus a proven adjuvant protection from breast cancer recurrence, could be viewed as a worthy investment. Craig Jordan recounts a sad story concerning a 31-year-old patient with breast cancer, who had initial courses of chemotherapy for two years and long-term adjuvant tamoxifen therapy
. In year five, the patient had a recurrence that showed oestrogen receptor (ER) positivity, but she was on tamoxifen and the ER would therefore have been blocked. Jordan’s laboratory had done the ER assay and he was confident of the result. Fortunately, at Wisconsin Clinical Cancer Center in the 1980s, blood was routinely drawn from patients and stored for research. Blood levels of tamoxifen and metabolites demonstrated that the patient was non-compliant during year four. She explained she was newly married and the adverse effects of tamoxifen had been unacceptable to her and her husband. Sadly, she died five months later.
Adherence packs for medications were initiated in the UK 30 years ago
. In these packs, multiple medications were organised together with an easy-to-follow format to take the right dose at the right time, and these were given to patients or their caregivers. One million patients in the UK have benefited from this positive healthcare strategy, which exemplified that patient education can improve medication adherence.
I thank V Craig Jordan, OBE, FMedSci, Dallas/Ft. Worth Living Legend, professor of cancer research, for his mentorship and support during my fellowship training at MD Anderson Cancer Center. He turned 70 years old this year, and my paper is dedicated to him. This work was supported by Cancer Center Support Grant CA016672 awarded to the MD Anderson Cancer Center. Professor Jordan is one of only two honorary members of the Royal Pharmaceutical Society of Great Britain, who is not a practising pharmacist. He also created the group of medicines called Selective oEstrogen Receptor Modulators (SERMs), most notably tamoxifen and raloxifene.
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