Are your patients taking their medication?

September 2005

Many Pharmacology Consult columns over the past several years have discussed medications most likely to be effective for children with specific diagnoses. For many of these conditions, clinicians are able to choose from at least several specific drugs, and these drugs are likely to be highly effective if used properly by the patient. Unfortunately, many patients do not take the prescribed medication properly. When assessing a patient’s response to therapy, clinicians then must determine if the patient did indeed take the medication as prescribed, and if so, how much was taken. If the clinician believes that an adequate amount of the medication was not taken, a strategy for increasing the amount of medication to be taken must be employed. These issues will be discussed in this month’s column.

Definitions and determinants

“Compliance” is a term commonly used to describe a patient’s behavior or likelihood of taking a prescribed medication or following a clinician’s suggested therapy or advice. However, the term “adherence” is favored by many clinicians and is more commonly used in the recently published literature, as this term implies a less authoritarian concept (ie, a noncompliant patient may be viewed as a “bad” patient), and is less nonjudgmental. An accepted definition of adherence is this: the extent to which a patient’s behavior (in terms of taking medication, following a diet, modifying habits or attending clinics) coincides with medical or health advice. “Concordance” is a similar term that may be found in some published studies, as concordance denotes an agreed plan between the patient and clinician. For the remainder of this column, the term adherence will be used.

Missed doses or lack of completion of an acute medication course is a common form of nonadherence. There is no agreement as to how many missed doses define nonadherence. Is one missed dose of 10 total treatment course doses nonadherence? Some advocate the use of therapeutic outcome as a measure of adherence (ie, if the patient is meeting therapeutic goals, then adherence must be adequate). Research studies often use an adherence rate of 70% to 80% or more to define a patient as adherent to the medication. Other than missed doses, other forms of medication nonadherence include not obtaining the original prescription or taking more doses than the prescribed regimen.

Do factors exist that clinicians may use to predict adherence?

Socioeconomic status, race, level of education or sex do not seem to be adequate predictors. Age may be important, as it has been shown that adolescents are less likely to be adherent. The patient’s or caregiver’s perception of the illness treated, ie, his health beliefs, may be important. Those who believe the illness is serious with the potential for significant adverse effects if not treated are more likely to be adherent to therapy. Clinicians should discuss the patient’s or caregiver’s beliefs about his illness prior to and throughout therapy. Previous history of nonadherence with medications or attending scheduled office visits may be other predictors of nonadherence. Lack of social support or a dysfunctional family environment is an additional risk factor for nonadherence. Adherence is likely to be decreased as treatment regimen complexity increases.

Determining adherence

Unfortunately, although there are several means that can be used to determine adherence, an ideal method, or gold standard, does not exist. An adherence rate of 50% is used in the literature as a general approximation of adherence likely for prescribed medications. Different methods are used to determine adherence. The methods most commonly employed in clinical practice are patient and caregiver reports and estimation by the clinician. Unfortunately, these methods are not accurate, as have been suggested by some published data. These data have shown than self-reports of nonadherence are more reliable than self-reports of adherence. By one report, a self-report of missing any medication is indicative of an adherence rate of less than 60%. One published study of adherence with penicillin prophylaxis for sickle cell disease reported a parental report of adherence of 60% for obtaining medication refills, as compared to a rate of 12% by pharmacy refill documentation.

When attempting to assess a patient’s medication adherence, it is important to present a nonjudgmental manner.

Published data suggest that physicians’ estimation of their patients’ adherence is not accurate, and it has been compared with the accuracy of flipping a coin (ie, no better than chance accuracy in predicting adherence).

Methods more commonly used in research studies include medication counts, bioassays or measurement of drug blood levels. While these methods may provide more accuracy than self-reporting or clinician estimates, they have inherent problems. Some patients may increase medication adherence prior to an office visit, yielding therapeutic blood levels or bioassays. As well, it is possible that a low blood level is only an indication of several missed doses prior to the office visit, when the patient’s adherence at other times is relatively good. Blood levels may also be affected by other factors not related to adherence, including drug-drug interactions or unique pharmacokinetics of the patient. If patients are asked to bring in their medication bottles to each clinic visit, some may purposefully discard medication not taken to give the impression of good adherence. Liquid medication that is accidentally spilled or difficulties with administration (eg, spitting out or vomiting of medication) may also yield false estimations of adherence. Pharmacy refill records may also be used to estimate medication adherence, although verification of the use of one pharmacy by the patient to obtain medication refills should be made. Because a gold standard of determining adherence does not exist, a strategy of using multiple methods of assessment, with an appreciation for the limitations of each method, may be the best approach.

Studies

Few studies have specifically evaluated adherence to medication regimens in the pediatric population. In 2002, Heather P. McDonald BSc, reviewed the literature for randomized controlled trials of methods to improve medication adherence (adult and pediatric population) with measurement of treatment outcome. Thirty-three studies of 39 interventions were evaluated in disorders requiring acute (eg, streptococcal pharyngitis) or chronic (eg, asthma, hypertension) treatment regimens. Forty-nine percent of these interventions produced a significant increase in adherence. Interventions employed varied, and included enhanced patient instruction, increased communication and counseling, telephone follow-up, dose reminders and others. Counseling on the importance of adherence together with written instructions was found to effectively increase adherence for streptococcal pharyngitis.

Several trials evaluated methods to increase adherence for asthma therapy. These methods were generally complex, including enhanced counseling, support groups or scheduled individual consultations with clinicians (eg, nurses, pharmacists). Adherence was not consistently improved in these studies, with several trials reporting no positive effects upon adherence, while two trials found adherence to improve.

Published studies reporting medication adherence for infectious disease disorders in children suggest the potential for significant nonadherence. Studies of otitis media reveal rates of medication nonadherence of 7.3%-56% for the complete regimen. Similarly, only 44% and 18% of children were adherent with all doses of a streptococcal pharyngitis penicillin regimen at day 3 and 9, respectively, in one study.

Methods to improve compliance

Despite the limitations of published evidence for methods to improve adherence, several strategies have been suggested and can be employed.

Combining several methods is likely to be more effective. Verbal and written instructions and education are likely to improve adherence to some extent. Patients should prove understanding of the instructions and drug information given.

Perhaps clinicians should view themselves not only as clinicians, but also as teachers. Negative reinforcement, however, has not been shown to be effective, and generally is not recommended. It is important to consider that verbal instructions are easily forgotten (only 50% recall immediately after an office visit, by one study). Some evidence indicates that patients may be more adherent when the same physician is seen at office visits. Discussion with the patient and caregiver about the illness and their beliefs and concerns about the medication regimen may be a very effective means to affect and improve adherence.

Clinicians should negotiate with patients about the treatment strategy most adaptable to the patient’s lifestyle and environment. It is important to present a nonjudgmental manner, attempting not to imply that nonadherence is “bad.” Focusing on potential barriers to adherence and methods to improve adherence may be more effective. Adequate communication with the patient about the purpose and use of the medication regimen maybe one of the most important determinants of adherence. Medication reminders (eg, calendars) may be helpful. Simplifying medication regimens are likely to improve adherence. Once- or twice-daily dosing avoids the necessity of administering a dose during school. Shorter acute medication regimens are more likely to be followed as compared with longer regimens. When simplifying regimens, however, it is important to balance adherence with expected efficacy. This may apply to some antibiotics that may be easier to adhere to, but potentially less likely to provide efficacy toward the expected pathogens or infectious process. Follow-up (eg, telephone follow-up) can be employed to increase adherence. Frequent reminders on the benefits and importance of adherence should be provided, and adherence should be determined at each office visit.

Physicians can effectively employ other health care professionals (eg, pharmacists and nurses) to address adherence, as has been documented by published studies.

For more information:

• McDonald HP. Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA. 2002;288:2868-2879.
• Winnick S. How do you improve compliance? Pediatrics. 2005;115:e718-e724.
• Haynes RB. Helping patients follow prescribed treatment: clinical applications. JAMA. 2002;288:2880-2883.
• Elliot V. Parental health beliefs and compliance with prophylactic penicillin administration in children with sickle cell disease. J of Pediatr Hematology/Oncology. 2001;23:112-116.
• Matsui D. Drug compliance in pediatrics: clinical and research issues. Pediatric Clinics of North America. 1997;44:1-15
• Liptak GS. Enhancing patient compliance in pediatrics. Pediatrics in Review. 1996;17:128-134.

• Edward A. Bell, PharmD, BCPS, is an associate professor of pharmacy practice at Drake University College of Pharmacy and a clinical specialist at Blank Children’s Hospital, Des Moines, Iowa.