What does the term 'adherence' mean?
Adherence describes all aspects of how well or how poorly a patient follows a prescribed drug-dosing regimen or medical advice. Adherence is synonymous with the old term 'compliance', but is preferred as it is more patient centred (compliance implies following orders). Adherence to therapy remains a challenge regardless of the patient's age, illness and social background. Health care providers initiate therapeutic regimens on the assumption that patients will take all their pills at the right time. Adherence is better with acute than chronic medication and tends to wane over time in cases of chronic disease. Even in the ideal circumstances of a randomised clinical trial, adherence to chronic medication is seldom more than 80%.
Patterns of non-adherence
Three major patterns of non-adherence are recognised: non-acceptance (the patient never actually starts treatment), incomplete execution (extra or missed doses, including 'drug holidays'), and early discontinuation (early cessation of dosing that is not resumed). Adherence is not limited to the number of doses taken every day, but also includes taking the dose at the right time or dosing interval. The most commonly observed deviations are missed or delayed doses. Taking drug holidays--the sudden cessation and resumption of dosing--is a potentially hazardous adherence behaviour. Restarting medications such as anti-arrhythmics (e.g. encainide or flecainide) or peripheral vasodilators without re-titration has resulted in lethal pro-arrhythmia or hypotension, respectively.
The consequences of poor adherence range from personal disability (treatment failure, e.g. ineffective pain control) to a worldwide threat (e.g. emergence of multidrug-resistant tuberculosis), depending on the illness, pattern of non-adherence and acceptable limits of the dosing interval (the degree of 'forgiveness' in the dosing regimen).
Why are patients non-adherent?
Adherence is a complex human behaviour and is influenced by the patient's personal and social characteristics. Health care facilities and prescribers can be barriers to adherence. Some common barriers to adherence are listed in Table I. Note that socio-economic status (except homelessness) and level of education are not barriers to adherence.
In his book, Improving Medication Adherence--How to Talk With Patients About Their Medication, Shawn Shea suggests three considerations in the decision to take medication:
1. feeling that there is something wrong
2. feeling motivated to try to get help through the use of medication
3. believing that the advantages of taking the medication will, in the long run, outweigh the disadvantages.
In addition, he suggests that there are three different beliefs that determine if a patient will start or stay on a medication:
1. efficacy of the medication
2. cost of the medication
3. psychological meaning of the medication.
If the health care worker does not address the above issues, then it is unlikely that the patient will adhere to the prescribed treatment.
How can adherence be measured?
A major problem in assessing adherence, both for individual patient care and research, is that a gold standard for measuring adherence has not been identified. Direct and indirect methods are used to monitor adherence, each with advantages and disadvantages (Table II).
Directly observed therapy and measurement of drug concentrations (e.g. therapeutic drug monitoring) are considered direct methods of measuring adherence, but are expensive and provider intensive. Directly observed therapy has been promoted by national tuberculosis programmes, but recent studies indicate that more patient-centered approaches are more successful than traditional clinic-based directly observed therapy. 'White coat' adherence, the phenomenon whereby patients increase adherence a few days before or after a consultation, is common. If the patient is taking a drug that is suitable for therapeutic drug monitoring, white coat adherence can result in drug concentrations being in the therapeutic range, thus masking poor adherence. This is especially likely if the drug has a short half-life.
Methods to monitor adherence include self-report (asking patients about adherence or using questionnaires/medication diaries), caregiver/peer reports, assessing clinical response (e.g. correlating an outcome measure to adherence), pill counts, pharmacy refill rates, and electronic medication monitors (electronic monitors that record the date and time of opening pill bottles or actuating canisters).
How can adherence be improved?
One of the problems in addressing poor adherence is that it can be difficult to distinguish different types of adherence behaviour. For example, 50% adherence can mean either a patient who follows the dosing instructions meticulously but stops completely halfway into treatment because of intolerable side-effects, or a patient who only takes half the number of pills every day to try to save money. The interventions required to improve adherence will be completely different in these two examples.
Several adherence interventions and combinations of interventions have been studied. The type of intervention will depend on the barrier(s) to adherence. Informational interventions aim to increase the provision and retention of treatment-related information (e.g. structured individual or group counselling or education by physicians, health educators, and/or pharmacists). The most common and effective behavioural interventions are simplifying dose regimens, specialised packaging, and cognitive behaviour therapy. Informational and behavioural interventions are often combined.
Interventions that are simple and easy to implement in practice are:
* Always make a point of checking patients' adherence. Doctors often overestimate patients' reported medication use. Patients like to please health care providers, and will report what they expect the health care provider would like to hear.
* Asking patients in a reassuring and non-judgemental manner if it has been difficult for them to take all their medications, and asking what you can do to help them not to miss doses.
* Asking patients about side-effects; this can also often unmask poor adherence.
* It is important to make the patient feel part of the therapeutic decision-making process.
* Always follow-up adherence interventions and reassess the patient's commitment/interest in the treatment plan.
What is the take-home message?
Patients' adherence to a prescribed regimen or medical advice is a complex behaviour. A patient's engagement with his/her illness, the prescribed drug regimen, the health care providers and health care facilities can all act as barriers to acceptable levels of adherence. Health care providers usually overestimate patients' reported medication use. Monitor for poor adherence in asymptomatic diseases and when patients fail therapy despite an optimal dosing regimen.
C. Everett Koop, former Surgeon General of the USA, is accredited with the following excellent advice: 'Drug's don't work in patients who don't take them'.
Diiorio C, McCarty F, Depadilla L, et al. Adherence to antiretroviral medication regimens: A test of a psychosocial model. AIDS Behaviour 3 November 2007 (Epub ahead of print).
Osterberg L, Blaschke, T. Adherence to medication. N Engl J Med 2005; 353: 487-497.
Shea SC. Improving Medication Adherence: How to Talk With Patients About Their Medications. Philadelphia: Lippincott Williams & Wilkins, 2006.
Simoni JM, Montgomery A, Martin E, New M, Demas AD, Rana S. Adherence to antiretroviral therapy for pediatric HIV infection: a qualitative systematic review with recommendations for research and clinical management. Pediatrics 2007; 119(6): e1371-e1383. (Epub 28 May 2007, Review.)
Urquhart J, Vrijens B. Introduction to pharmionics: the vagaries in ambulatory patients' adherence to prescribed drug dosing regimens, and some of their clinical and economic consequences. In: Mann RD, Andrews EB, eds. Pharmacovigilance. Chichester: John Wiley & Sons Ltd, 2007: 603-618.
JAN-STEFAN VAN DER WALT, MB ChB
GARY MAARTENS, MB ChB, MMed, FCP
Division of Clinical Pharmacology, Department
of Medicine, University of Cape Town
Table I. Common barriers to adherence to treatment for chronic conditions Patient characteristics Adolescence Forgetfulness Running out of pills Missed clinic appointments Travelling Poor access to pharmacy Other priorities (including financial commitments) Lack of information Lack of belief in benefit of treatment Lack of insight into the illness Not counselled in home language Psychological problems Active depression Substance abuse Cognitive impairment Lack of self-efficacy (the belief that a patient can execute a behaviour required to produce a certain outcome successfully) Treatment/disease characteristics Treatment of asymptomatic diseases Side-effects of medication Complexity of treatment (e.g. dosing frequency, number of pills, food restrictions) Treatment regimen incompatible with patient's lifestyle/routine Prescriber characteristics Poor knowledge of drug costs/medical-aid coverage Low level of job dissatisfaction Prescribing complex regimen Prescribing a regimen incompatible with the patient's lifestyle Poor therapeutic relationship Health care system Missed appointments High health care costs (costs of drugs, co-payments, or both) Inability of patient to access the pharmacy Switching to a different formulary Table II. Advantages and disadvantages of direct and indirect adherence methods Method Advantages Disadvantages Self-report Inexpensive Considerably Caregiver report Allows discussion overestimates (questioning of reasons for low adherence patients adherence directly, and completing questionnaires) Clinical outcome Inexpensive Confounded by (measuring drug Allows discussion factors other effect, e.g. of reasons for low than non-adherence [HbA.sub.1c] adherence in diabetics, lipid profiles for patients on statins, viral loads for patients on HAART) Pharmacy refill Suitable for Moderately (rates of individual patients overestimates refilling as well as adherence prescriptions) programmes (more sensitive than pill counts) Pill count Inexpensive Patients rapidly (counting the number Useful to detect learn to provide of pills remaining misconceptions about the correct number in the patient's dosing, especially of pills medication bottles early on in therapy (discarding unused or vials) doses/not returning unused medication) Time consuming Moderately overestimates adherence Therapeutic Direct measure Expensive drug monitoring Detection/prevention (measuring drug of drug toxicity, Subject to 'white and metabolite especially in coat' adherence concentrations in populations at and may reflect blood or urine) risk (e.g. elderly, only that the children, pregnancy, last dose renal or liver was taken impairment) Confounded by other causes of low concentrations May overestimate adherence Electronic Provides data on Expensive medication monitoring timing and (electronic monitor patterns of Unable to detect that records the date missed doses if patient and time of opening takes wrong dose, pill bottles, or takes multiple actuating canisters, doses out of etc.) container at the same time (e.g. taking morning and evening doses out simultaneously and putting the evening dose into a small pill box) May underestimate adherence