In pharmacotherapy, the terms “compliance” and “adherence” are often used interchangeably, although the latter term is preferred by some as it acknowledges the patient’s role in the decision-making process. Adherence has been defined as “the extent to which a person’s behavior— taking medication, following a diet, and/or executing lifestyle changes—corresponds with agreed recommendations from a healthcare provider” (1).

Deviations from medical advice on the part of the patient (such as using the wrong route of administration, taking too low or too high a dose, or taking the medication at the wrong times or for an inappropriate length of time) is defined as noncompliance. Besides these types of noncompliance, other factors, such as comedication or the intake of certain foods or nutritional supplements, can affect the pharmacokinetics (absorption, distribution, metabolism, or elimination) or pharmacodynamics (drug effect on the body) of the prescribed drug and can result in either a suboptimal effect or unforeseen side effects, both of which can be serious. Once it is known that a particular drug should not be taken with another drug or food (e.g., grapefruit juice*), avoidance of this other drug or food becomes a part of the therapy, and lack of adherence to this recommendation can be considered a form of noncompliance as well. Compliance issues have been well studied in adults, but comparatively little data exist about pediatric compliance.

Despite the best efforts on the part of the physician to diagnose and appropriately treat a condition, treatment failure can still occur if the patient fails to follow medical advice. Adherence is therefore an extremely vulnerable step in the therapeutic process, and one that often receives little consideration. However, attention to matters of adherence can have a very real and beneficial effect on the overall outcome. In this chapter, we describe the impact of compliance on patient care, how to measure it, the types of noncompliance, the factors that contribute to noncompliance in pharmacotherapy, and means of reducing this behavior.

Noncompliance is a significant problem in all areas of medicine. Studies show that noncompliance for medications ranges from 13% to 93% in adults and from 25% to 82% in children (3). Noncompliance should therefore be viewed more as the rule than the exception. As a result of noncompliance, misjudgment of the efficacy of therapy on the part of the physician who assumes compliance with the medication regimen may result in additional consultations and investigations, alterations of dose or drug, hospitalization, loss of productivity (lost work or school days), and increased risk of adverse effects related to prolonged therapy.

When assessing the prevalence of noncompliance, it is also important to take into account the way in which compliance is determined. Patient self-report, pill count, biological assays, and electronic monitoring devices may vary significantly from each other in terms of the data obtained. Difficulties also arise from the lack of truly objective definitions for compliance, as the dividing line between adherence and nonadherence is not uniformly agreed upon.

The question of whether a patient will comply with the prescribed medication regimen introduces an element of uncertainty into the decision-making process of the physician. When a patient’s condition improves, compliance is usually assumed on the part of the physician. However, when things do not go as planned, questions arise and the physician must decide whether the poor response represents a failure at the stages of diagnosis or treatment or in adherence to medical advice. Exploration of issues of compliance can make physicians and patients uncomfortable and is therefore often deferred or avoided. As a result,
extra and potentially unnecessary therapies may be used on the noncompliant patient, when an honest discussion may have proved sufficient.

Because there is an overall noncompliance rate of about 50% for the millions of prescriptions written annually, this issue becomes a general public health problem. Noncompliance translates into additional expenditures in terms of wasted medication, repeated or changed courses of medications due to a perceived treatment failure, and extra physician visits. The cost of noncompliance to society is not solely a financial one. The spread of infections such as tuberculosis is an important public health problem and must be treated appropriately (4,5). Untreated or inadequate therapy may result in epidemics or resistance to drugs leading to potentially serious consequences.

Our knowledge of any phenomenon is dependent on the reliability of the data provided and thus on the means of assessing it. The accuracy and reliability of measurements of compliance vary with the method used. This determination is further complicated by the lack of a clear consensus as to what defines compliance and noncompliance. The simplest way to get information about adherence to therapy is to ask the patient, but the nature of compliance is complex and does not always allow easy accurate assessment. A significant amount of noncompliance happens without the awareness of the patient; as a result, other techniques must be employed to get an accurate assessment of patient compliance.

There are several types of noncompliance, which can be subclassified and ranked in terms of the disease, the status of the patient, and the characteristics of the therapeutic regimen. It should be understood that compliance is a dynamic process, and that the degree of compliance will change over time. Compliance is also not a binary process. Some children or families will be quite compliant with some aspects of therapy and completely noncompliant with others.

The reasons for a patient not following his or her treatment regimen can be divided into two groups: conscious and unconscious noncompliance. In general, most noncompliance is not a conscious deliberate act. Willingness to be treated is accepted as normal behavior, and patients believe they are following the description of the treatment. However, many factors (to be discussed) related to the disease or the age of the patient may affect the compliance rate. For example, others must care for a small child who is unable to take his or her medicine. In this case, the compliance is not primarily related to the patient but more to other people, often the parents who are caring for the child. Noncompliance in such a case is considered a form of unconscious noncompliance. Unfortunately, there does not appear to be a difference between the parent’s behavior in terms of their compliance and compliance with their children’s therapy. Kleinteich reported the results of an anonymous questionnaire given to mothers (24). He showed that only half of the prescribed drug had been administered to the children according to the instructions. In a subanalysis, compliance was found to vary with the type of drug as well (24).

Psychological factors affecting compliance with therapy may fall under unconscious noncompliance as well. These complicated factors have been investigated in many studies, especially in adolescents (25). Other factors, such as poor explanation of the therapy on the part of the physician or pharmacist, may result in decreased compliance with therapy and should not be classified as conscious noncompliance.

Unconscious noncompliance may relate to environmental and economic issues. Despite the development of therapeutic alternatives, in many parts of the world, appropriate therapies are not available. A patient may not be able to afford the therapy or may not have access to it in his or her neighborhood. Physicians should take time to ask questions to screen for the availability of the therapy and to check whether there are financial barriers to obtaining the medication.

Because of the many multifactorial interactions that affect and determine compliance, it is almost impossible to broadly identify which factors are the more involved. Among those factors that have been found to have some association with compliance, none has been found to be either necessary or sufficient to produce noncompliance. At their best, these factors are useful clues to the astute clinician but are not reliable measures or predictors of compliance. A summary of factors affecting compliance is given in Table 6.1. It has been shown that initial compliance is the best predictor of subsequent compliance with therapy, but compliance is a dynamic process and may change over time within the same patient (17,24,25,26).

Forgetfulness is often the most commonly cited reason for not taking one’s medication or for parent’s not administering their children’s medication (9,27,28,29).