9 Patient Compliance Lisa Dolovich John W. Sellors R.

Brian Haynes KEY POINTS Fifty percent is a representative compliance figure for many long-term therapies. Differentiating whether compliance is intentional (e.g., testing out lower doses or discontinuation) or unintentional (e.g., mental deterioration, change in work schedule) can be helpful when developing strategies to improve compliance. 3. Communication with a patient before prescription to discuss the benefits, adverse effects, and use of a medication as well as communication after prescription to verify a patient's medication-taking behavior are important steps to improve medication compliance. 4. Family physicians are unable to detect poor compliers among their patients, because no stereotypic poor complier exists. 5. Dropping out of care is one of the most frequent and most severe forms of noncompliance, and so watching the appointment book and using practice aids such as a manual or computerized ticker system can help identify noncompliance. 6. Provided that the treatment prescribed is known to be efficacious, failure of a patient to respond to treatment can be used as a readily available indicator of noncompliance. 7. Asking the patient directly about compliance can be a very valuable and practical way of determining the pattern of medication consumption. 8. Simple clear instructions are sufficient to improve compliance for short-term treatments. 9. Follow-up of nonattenders by telephone or mailed reminders and multifaceted strategies are needed to improve compliance for longer-term treatments. 1. 2. 10. The physician should be aware that patients often lie when they state that they have taken certain medicines. [The physician] should keep aware of the fact that patients often lie when they state that they have taken certain medicines. Hippocrates Although physicians have dispensed medicines and potions through the centuries in vast quantities, it is only in recent years that there has been systematic examination occurred of whether patients actually take the treatment. It was perhaps to the patient's benefit in the past that little attention was paid to compliance, as poor compliance probably saved the patient's life on many occasions. Some treatments, especially the massive purges and bleeding of the eighteenth century and arsenic and hydrochloric acid of the twentieth century, certainly had lethal rather than therapeutic potential. Recent incidents of concern with rofecoxib, hormone replacement therapy, nefazodone, and others demonstrate the complexities of balancing benefits and risks of drug interventions to ensure that, on balance, therapies will improve health when they are taken according to the intended management plan. On the whole, our armamentarium of useful treatments is sizable and expanding rapidly; low patient compliance stands squarely in the way of achieving the full benefit of modern therapy. Evidence levels Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs. Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, crosssectional studies, retrospective studies, certain uncontrolled studies. Consensus statements, expert guidelines, usual practice, opinion. The extent of poor compliance is distressing. Fifty percent is a representative compliance figure for many long-term therapies. Only 51% to 78% of patients with newly diagnosed hypertension persisted with antihypertensive therapy 1 year after receiving a new prescription (Caro et al., 1999 Morgan and Yan, 2004 Wogen et al., 2003 ). Fewer than 40% of patients continued to receive prescriptions for (S)-3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors 2 years after their first prescription (Jackevicius et al., 2002 ). Only about two thirds of those who continue under care take enough of their prescribed medication to achieve adequate blood pressure control (Haynes et al., 1978). If we look at compliance with lifestyle changes, such as diets and smoking cessation, the figures are considerably more dismal (Best and Block, 1979). Added to this, physicians-even family physicians-are not good at estimating compliance levels in patients (Gilbert et al., 1980). Physicians have a strong tendency to overestimate the compliance of their own patients and are usually unable to predict which patients will comply with treatment. This chapter reviews the practical methods of detecting poor compliance and strategies for improving it. DEFINITIONS The trend in medicine, and particularly in family medicine, is toward consumerism and a more democratic approach that involves the patient in medical decisions. The use of the word "compliance" has raised objections because it implies authoritarianism and anything but an equal relationship between physician and patient. Alternative terms such as adherence and concordance have been proposed to recognize that patients have primary control over the decision to take medications once prescribed and that the use of medications will be improved if patients are seen as partners in the development of treatment plans with their physicians (and other health care providers) (Marinker and Shaw, 2003; World Health Organization, 2003). Although we agree that the debate over terminology is helpful to gain better insight into how to improve the complex task of taking medications, and we sympathize with the views of those who oppose the term, we use compliance throughout this chapter because it is still the most widely used and recognized rubric. Compliance has been defined as the extent to which a person's behavior (in terms of keeping appointments, taking medications, and executing lifestyle changes) coincides with medical advice (Sackett, 1976). Poor compliance is more difficult to define. What percentage of prescribed medication can a patient forget or omit before being classed as a poor complier? How are patients who take

too much medication classified? One way of looking at the problem is to use patient outcomes as a guide. For instance, in hypertension studies, patients taking 80% or more of prescribed medication were considered compliant because this amount of medication was found to produce systematic blood pressure reduction (Sackett et al., 1975 ). Patients taking less than 75% of -blockers prescribed after an acute myocardial infarction were more than 2.5 to 3 times more likely to die within 1 year (for men) or approximately 2 years (for women) (Gallagher et al., 1993 Horwitz et al., 1990 ). Compliance also can be thought of in terms of intentionality. The deliberate not starting, stopping, or altering of a drug regimen by the patient has been called intentional noncompliance. Unintentional noncompliance may be due to forgetfulness or may be due to other patient characteristics such as changes in work shifts, mental deterioration, or inability to pay for medications (Royal Pharmaceutical Society of Great Britain, 1997). The differentiation of compliance behavior by intention can be helpful when trying to identify noncompliance or to develop strategies to improve compliance. It makes sense that efforts directed at poor compliers should be concentrated on those not achieving therapeutic goals. This obviously leads to more efficient use of resources. However, some patients who respond to treatment may be doing so because of overprescribing rather than because of compliance. Should these patients be hospitalized or placed in some other situation in which compliance may be close to 100%, they may well run into serious effects of overdose. FACTORS INFLUENCING COMPLIANCE Many approaches, ranging from complex psychological theories to simplistic or intuitive ideas, have been taken to explain compliance behavior. None is entirely satisfactory, and many address only components of the complex undertaking of compliance; many are lamentably wrong (Leventhal and Cameron, 1987). In looking at the many factors involved, a natural tendency exists for the physician to feel that poor compliance is the patient's fault; after all, it is the patient who must swallow the pill or keep the appointment. But many other factors leading up to the act of pill taking or returning for an appointment must be considered. For instance, what about the disease or condition being treated: Is it symptomatic or asymptomatic, life threatening or purely a nuisance? Is it an acute or chronic condition? What about the treatment itself: Is it efficacious? Does it have bothersome adverse effects? Is it unpleasant, inconvenient, or expensive? Is the medical environment conducive to regular follow-up? Does the physician inspire confidence in the treatment, or do certain attitudes interfere with compliance? Only some of these factors have an important effect on compliance behavior. The Patient General attributes such as age, gender, marital status, education, occupation, intelligence, race, religion, urban versus rural living, and economic status bear no consistent relation to compliance. Two exceptions are the very young and the very old, whose compliance characteristics tend to conform to those of their caregivers. Another exception is the presence of extreme disturbances in functioning and motivation in patients such as those with mental health disorders (DiMatteo et al., 2000 World Health Organization, 2003). Patients will regularly modify their medication regimens or dosing in an attempt to assert control over their health. As Conrad states, "People will change their medication practice, including stopping medication altogether, in order to test for the existence or 'progress' of the disorder" (Conrad, 1985). Patients will not usually share the intentional changes they make to their medications unless they are asked about whether they have carried out any medication-taking "tests" within the context of a trusting physician-patient relationship. Numerous theories and models of behavior change have been generated or adapted to explain or better understand compliance. Perhaps the most widely held theory of compliance behavior, probably because of its intuitive appeal, is the communications approach (Leventhal and Zimmersman, 1984). In this model, it is proposed that patients generally do not know enough about their illness or treatment and that this ignorance leads to poor compliance. It follows that adequate instruction or message generation and reception, comprehension, and retention of the message should result in improved compliance. Although it appears that this is true for short-term treatments (<2 weeks in duration), knowledge on its own bears little relation to compliance with chronic disease regimens (Haynes, 1979). Another popular theory looks at patient motivation and beliefs. By using the health-belief model, Becker (1976) argues that the likelihood of "all individuals undertaking a recommended health action depends on the perception of the level of personal susceptibility to the particular illness or condition; the degree of severity of the consequences of contracting the condition; the potential benefits or efficacy of the treatment in preventing or reducing susceptibility and/or severity; and the physical, psychological, financial, and other barriers or costs involved in initiating or continuing the treatment." The model also requires a stimulus or cue to action to trigger the appropriate behavior (compliance); this cue can be either internal (e.g., a symptom) or external (e.g., screening campaign or physician's advice). This model has been shown to have predictive value for some preventive and short-term therapeutic health actions, such as immunizations and medical regimens for acute disease, but the extent of its predictive value is modest at best (Janz and Becker, 1984). The information-motivation-behavior skills model (IBM) is a more recently developed model that combines elements from previous literature and models to describe the influences on behavior change (Fisher and Fisher, 1992; Fisher et al., 1996 ). This model proposes that information and motivation influence behavioral skills (tools and strategies to perform compliance behavior) and that all three of these elements directly influence behavior change. Initial reports evaluating interventions constructed by using this model have shown some promise in influencing behavior change. The model has high face validity; however, more studies are needed to better understand how well the model explains the full extent of behavior change across a variety of conditions. The transtheoretical stages-of-change model maintains that behavior progresses through five stages-precontemplation, contemplation, preparation, action, and maintenance-and that a decisional balance exists between the pros and cons of the behavior (Prochaska and DiClemente, 1992). It follows that all patients may not be at the same stage of readiness for change in compliance (Keefe et al., 2000 Prochaska et al., 1998), so it is more helpful to identify their highest priority and work on this one behavior. Controlled trials have demonstrated that interventions based on the stages-of-change model can improve health behaviors such as increased exercise in older women (Conn et al., 2003) and smoking cessation (Velicer et al., 1999). Assessment of the stage of change of a noncompliant patient should facilitate counseling that is appropriately tailored to move him or her toward action (Table 9-1) (Willey 1998; Willey et al., 1999).

Other models have been studied, including the behavioral-learning model, which is based on cognitive and social learning theory, and the self-regulating model. As yet, no model adequately explains a person's compliance behavior or gives a clear rationale for modifying it (Haynes et al., 1982). The behavior models help clinicians understand compliance behavior a bit better, but for helping patients to follow prescribed treatments better the strategies from studies showing successful interventions in the section on prevention and treatment of poor compliance may be of more practical use for helping patients follow prescribed treatment. The Disease Table 9-1. Behavior-change Strategies for Improving Compliance Stage Characteristics Precontemplation Resistant to taking medication, fearful, in denial, defensive, misinformed, or demoralized Contemplation Ambivalent about taking the medication, concerned about the cons of medication use, lacking commitment to the regimen Preparation Understands the pros of taking the medication as directed; planning toimprove adherence soon Action Recently began taking medication as directed, but this new behavior may still be an effort Maintenance Taking medication as directed for 6 months, "Now it's easy for me" Relapse risk Has been taking the medication as directed for 6 months, but "tests" the degree to which adherence is necessary by taking "drug holidays" With few exceptions, disease factors are relatively unimportant as determinants of compliance. Psychiatric patients with schizophrenia, paranoid features, and personality disorders are less compliant than are other psychiatric patients-a fact that probably reduces the compliance of psychiatric patients as a whole below that of patients with nonpsychiatric disorders. No relation has been demonstrated between the severity of symptoms and compliance. Surprisingly, the more symptoms a patient reports, the lower his or her compliance is likely to be. Conversely, increasing disability produced by a disease appears to be associated with better compliance. Whether this is a result of increased severity of disease or specifically the result of the increased supervision that often accompanies increased disability has not been sorted out. Chronic diseases requiring long-term treatment have been clearly shown to result in increasingly poor compliance. This fact is of great clinical importance in such potentially serious diseases as tuberculosis and hypertension and is more likely to be a function of the duration of the treatment regimen than the duration of the disease itself. The Regimen Generally speaking, the greater the behavioral demands of a treatment, the poorer the compliance. Regimens requiring changes in lifestyle, such as dieting, exercising, and stopping harmful habits, result in much poorer compliance than does simply taking pills, because of the substantially greater behavioral changes needed. Conventional wisdom and common sense suggest that the greater the number of drugs or treatments prescribed for a patient, the greater the probability of poor compliance. However, recent studies have found that patients prescribed (and dispensed) more cardiovascular medications had better medication compliance (based on an examination of their pharmacy records) (Shalansky and Levy, 2002 Grant et al., 2004 ). Likely a set of circumstances exists under which compliance does improve with more medications, and more research is needed to clarify this issue. Despite these recent reports, simplifying the treatment regimen to reduce the number of medications a patient is taking is one of the most important strategies to improve compliance. Compliance decreases when the frequency of dosing increases. Although no differences in compliance have been identified between once- and twice-daily dosing, compliance decreases with 3- or 4-times daily dosing (Claxton et al., 2001 Eisen et al., 1990 Pullar et al., 1988 ). Alternative oral medications for the same condition do not appear to result in substantial differences in compliance, but a difference may be found for different problems. For example, Closson and Kikugawa (1975) found a range from 17% compliance with antacids to 89% with cardiac drugs. The injection of long-acting preparations, such as benzathine penicillin for acute streptococcal pharyngitis and rheumatic fever prophylaxis, long-acting phenothiazines for schizophrenia, and streptomycin for tuberculosis, has been shown to be acceptable to patients and more effective than oral preparations. The cost of treatment is an important barrier to compliance for many people (Gregoire et al., 2002 Tamblyn et al., 2001 Tseng et al., 2004 ). However, a complete understanding of the effect of cost is not as obvious as it might first appear. For instance, one study showed that hospital admissions increased among psychiatric outpatients given drugs at nominal cost compared with admissions for a group paying regular prices (Cody and Robinson, 1977 ). Patients without full drug coverage are more likely to use less medication, switch medications, use samples, and report difficulty paying for medications (Tamblyn et al., 2001 Tseng et al., 2004 ). The Physician The physician is obviously in a key position to influence compliance. For example, if the frequency of dose affects compliance, then by the very act of prescribing a medication to be taken 4 times a day, the physician is potentially reducing compliance below the level achievable with a single daily dose.

More complex than the mechanics of prescribing, however, is the interaction between physician and patient. Patients are more likely to comply with treatment if their expectations are met by the visit and if they are well satisfied with their care (Francis et al., 1969; Kincey et al., 1975). The concept of a personal physician or the feeling of knowing a physician well also has been associated with increased compliance (Ettlinger and Freeman, 1981 ). Dissecting the physician-patient relationship and measuring the factors that result in increased satisfaction are not easy. This is demonstrated in one study in which some patients felt that they knew their physician well after only one visit, whereas others felt that they still did not know their physicians after as many as 14 visits (Ettlinger and Freeman, 1981). Communication with a patient before prescription to discuss the benefits, adverse effects, and use of a medication as well as after prescription to verify a patient's medication-taking behavior are important steps to improve medication compliance (Roberts and Volberding, 1999 ). DETECTION OF POOR COMPLIANCE Clinical Judgment Most of us would like to believe that a good physician can detect poor compliance in patients; surely, this goes along with clinical judgment. Unfortunately, studies have shown that this is not the case: Using clinical judgment has been shown to be no better than flipping a coin as a detection method. The first studies demonstrating this were carried out in specialty settings and with physicians who did not have an ongoing relationship with patients. Unfortunately, the hope that family physicians with their ongoing relationships with their patients might be in a better position to make predictions also has been dispelled. Not only were family physicians unable to detect poor compliers among their patients, but also the length of time that they had known their patients had no effect on their ability to predict (Gilbert et al., 1980 ). The emphasis on the inaccuracy of clinical judgment is important in that it serves to direct us to alternative approaches to detect poor compliance. Monitoring Attendance As mentioned previously, more than 50% of hypertensive patients stop visiting their physicians within a year of starting treatment, and those who do not appear for follow-up appointments are unlikely to be compliers with treatment. Many physicians are unable to detect this type of noncompliance because their appointment systems are inadequate or because the patients do not make follow-up appointments. It follows, then, that an important method of detecting poor compliance is to watch the appointment book and to use practice aids such as a manual or computerized tickler system. Although no guarantee exists that patients who keep appointments will comply with treatment, no doubt those who do not appear for follow-up will not be in a position to comply with treatment. The importance of monitoring attendance cannot be overstressed: Dropping out of care is one of the most frequent and most severe forms of noncompliance (Stephenson et al., 1993). Response to Treatment Provided that the treatment prescribed is known to be efficacious, failure of a patient to respond to treatment can be used as a readily available indicator of compliance levels. For example, high compliance was associated with a 10% lower total A1c in patients on a stable medication regimen for type 2 diabetes relative to patients with low compliance (Krapek et al., 2004 ). However, this method of assessing compliance is not infallible. For example, patients who appear to respond to treatment may do so because they were misdiagnosed and do not have the condition of interest or because their physicians' overprescribing is compensating for their poor compliance. Nevertheless, from the compliance perspective at least, concern is less necessary for patients who have reached the therapeutic goal. Conversely, patients not showing a response to treatment will include those who genuinely do not respond to therapy or who have been prescribed inadequate amounts and will also include a high proportion of poor compliers or noncompliers. If therapeutic response is suboptimal, then noncompliance should be considered and explored as a possible reason for lack of response to treatment before changing management strategies. Asking the Patient Although it is not always reliable, asking the patient directly about compliance can be a very valuable and practical way of determining the pattern of medication consumption (see Table 9-2). When asked directly, about half of noncompliant patients will admit to missing at least some medication (Haynes et al., 1980 Stephenson et al., 1993). One can be assured that it is highly improbable that a compliant patient will admit to poor compliance, so patients admitting to missing medication have a very high likelihood of being poor compliers. The converse is not true, however, as even under optimal interview conditions about half of noncompliant patients will deny the fact. Patients who admit to missing medication generally overestimate the amount of medication they do take. In one study, the average overestimate was in the region of 20% (Haynes et al., 1980 ). It must be emphasized that the method of questioning is of paramount importance. Asking in a threatening or belligerent manner will result in reflex denial. Approaching the patient with a face-saving, nonthreatening, nonjudgmental question will yield a higher proportion of accurate responses. One way of doing this is to use an approach such as the following: "Many people find it difficult to remember to take medicines: During the past week, have you missed any of your pills?" Taking into account the tendency to overestimate compliance, admission of any noncompliance is associated with an average compliance rate of less than 80% (Haynes et al., 1980 . A similar approach is to ask the four questions based on the simplified Morisky measure of medication adherence (Morisky et al., 1986) (see Table 9-2). If the use of either method of questioning results in the patient answering "yes" to any of the questions asked, then the clinician has the opportunity to engage in further dialogue with the patient to better understand factors associated with noncompliance. The methods of detecting low compliance described so far can be easily applied in any treatment setting and, if applied with care, will detect the majority of poor compliers. The methods outlined in Table 9-2 may be of help in detecting some of the remainder. Counting Pills Table 9-2. A Simple Method to Detect Noncompliance

Asking the Patient The easiest way to detect medication noncompliance is to ask the patient About 40% of noncompliant patients will admit to missing at least some medications If patients admit to noncompliance, you can believe them Patients admitting to poor compliance are most responsive to attempts to improve compliance How to Ask: One Question Use a matter-of-fact, nonjudgmental, nonthreatening manner Use an introduction that allows a patient to save face: "Many people find it difficult to remember to take medicines. During the past week, have you missed any of your pills?" How to Ask: Four Questions (Risk Increases with Number of Positive Responses) (Morisky, 1986) Do you ever forget to take your medicine? Are you careless at times about taking your medicine? When you feel better, do you sometimes stop taking your medicine? Sometimes if you feel worse when you take the medicine, do you stop taking it? Yes No Yes No Yes Yes No No Yes No

As a quantitative estimate of compliance over a certain period, pill counts can be relatively reliable so long as they are carried out in the patient's home with strict attention to bookkeeping (Haynes et al., 1980 ). Unless the count can be carried out in such a manner that the patient is unaware of what is going on, it becomes a one-time-only procedure. It follows that whereas pill counts are very important research tools, they are not very practical for most clinical situations. It can be reasoned that using pill counts in the office or clinic will result in a bias in the direction of overestimating compliance, in that patients will consciously or unconsciously bring only some of their unused pills with them, giving the appearance that they have taken more of the medication than is actually the case. It is virtually impossible for the bias to go in the opposite direction unless the patient is receiving the same prescriptions from two or more physicians at the same time. In general, pill counts give higher estimates of compliance than do quantitative drug assays and lower (but more accurate) estimates than do patient self-reports or administrative pharmacy claims data (Grymonpre et al., 1998 ). Pharmacy Refill Records Pharmacy refill records can be used to identify patterns of dispensed medications as a proxy for medication use. These records are especially helpful to detect whether a patient may have stopped taking a long-term medication (Jackevicius et al., 2002 Morgan and Yan, 2004 Pilon et al., 2001 Rijcken et al., 2004 ) or did not stop an old medication when a new one was prescribed, especially in cases in which patients cannot remember this information. Pharmacies cannot provide complete medication refill history profiles without the patient's permission; however, pharmacists often provide the date of the previous refill when requesting renewals from the physician's office, and this information can be useful in determining whether the patient appears to be taking his or her medication on schedule. This is an indirect measure, however, and cannot assure whether a patient is actually taking a medication. The patient could, for example, be sharing or hoarding the medications. Drug Levels A laboratory test to detect the presence or absence of good compliance is an unrealistic dream in the case of most drugs. For some drugs, however, especially those with long serum half-lives resulting in relatively steady serum levels, the measurement of serum levels can be an extremely useful indicator of compliance. The best examples of this are digoxin and phenytoin, for which plasma levels have been used successfully both to monitor compliance and to improve it through feedback to the patient. Other drugs commonly measured in this way are anticonvulsants, theophylline, tricyclic antidepressants, lithium, and a variety of cardiac drugs. The caution is, however, that a great deal of individual variation is found in drug absorption, metabolism, and excretion. In addition, serum levels of drugs with short half-lives indicate only how recently a dose was taken and give no information on long-term compliance. Drug levels in urine have also been used as compliance indicators. For instance, the presence or absence of penicillin can be easily detected by observing inhibition of growth of a microorganism, Sarcina lutea. Although these methods and others involving inactive markers such as riboflavin and carbon 14 have been used in research, they are not practical methods for the clinician. What is more, as a measure of compliance, single qualitative assessments of urine samples have been shown to be inferior to simply asking the patient (Haynes et al., 1980 ). PREVENTION AND TREATMENT OF POOR COMPLIANCE Misconceptions Before discussing prevention and treatment, it is worthwhile to reexamine some popular misconceptions about compliance. The first misconception is that a good clinician can identify poor compliers, as no stereotypic poor complier exists (Vik et al., 2004 ). This is very important, because restricting prevention and treatment strategies to patients thought to be potentially poor compliers must result in neglect of a large number of patients who need attention as well as unnecessary attention to some patients who do not. Another popular and important misconception is that all that stops patients from being near-perfect compliers is their ignorance of either the condition being treated or the treatment being used. Although some evidence indicates that written instructions help improve

compliance for short-term regimens, even mastery learning, in which patients were given detailed step-by-step instruction on hypertension, had no beneficial effect on long-term compliance (Sackett et al., 1975 . The belief that it is possible to scare a patient into complying with treatment also has been dispelled (Leventhal et al., 1967; Logan, 1978). A survey of primary care physicians showed that the methods they used to improve compliance were predominantly those that have been found lacking. Methods that have been shown to be effective were not generally applied. The transtheoretical stages-of-change model of readiness to change behavior also can be applied to a physician's own counseling behavior and predicts that unless realistic goals are set for improving monitoring and follow-up of compliance, the physician may become frustrated and slip into inaction (precontemplation) (Prochaska and DiClemente, 1992). Changing the long-term behavior of physicians to manage compliance successfully cannot be done by simply informing or instructing them about efficacious interventions (Evans et al., 1986 ; Haynes et al., 1984 ). Prevention The main thrust in the prevention of poor compliance is to remove barriers to compliance (see Table 9-3). Preventing patients from dropping out of care is of primary importance. Longer waiting times are associated with higher no-show rates (Rockart and Hoffman, 1969), so that one aim is to keep patient waiting time to a minimum. Individual appointments at mutually convenient times help achieve this goal. Ensuring that patients leave the office with a specific time for a future appointment rather than with instructions to call for an appointment in, for example, 3 months, makes detection of those who do drop out much easier. Simplifying the treatment regimen will remove another barrier to compliance. An essential element of this approach is to eliminate unnecessary medications. In addition, medications should be prescribed that should to be taken as few times daily as possible. The frequency of dosing with many drugs can be reduced below usually prescribed levels with no reduction in efficacy. For example, tricyclic antidepressants can be given as a single bedtime dose, thus reducing dosing frequency and timing side effects so that they occur mainly during sleep. A final strategy is titration to the least amount of medication necessary to achieve the therapeutic goal. Arranging for a comprehensive medication review carried out by a clinical pharmacist or clinical pharmacologist may generate recommendations on how to simplify a patient's medication regimen (Dolovich and Levine, 1997 ; Hanlon et al., 1996 ; Sellors et al., 2003 ). It has been shown that patients who believe that they are actively involved in their own care are better compliers than are those who do not (Schulman, 1979 Studies also have shown that negotiating care with the patient rather than simply dictating or prescribing it results in better compliance (Eisenthal et al., 1979 Tracy, 1977). Encouraging patients to take greater responsibility for their care by asking more questions of their physicians results in improved attendance (Roter, 1977 ). It follows that encouraging patients to participate in and take more responsibility for their own care is another strategy for preventing poor compliance, and it not only makes scientific sense but also is consistent with trends in physician-patient relationships. Treatment Detection

Monitor attendance and achievement of the therapeutic goal Ask the patient Ask the pharmacist Prevention

Make appointments convenient Simplify the regimen Give clear instructions, preferably written Engage the patient as an active participant Use telephone or mail reminders Treatment

Follow up nonattenders Increase attention and supervision Use cuing, feedback, and positive reinforcement Collaborate with pharmacist on strategies and patient follow-up Schedule frequency of visits to compliance need Involve spouse or other partner Maintain compliance interventions as long as compliance is desirable

Dropping out of care constitutes a compliance crisis (Table 9-3). Mail and telephone reminders to increase attendance, at least in the short term, can help prevent dropout (Macharia et al., 1992). If the patient does fail to attend, it calls for prompt action by the receptionist or office nurse to reschedule (Takala et al., 1979 ). A simple method of identifying those patients for whom compliance is important (e.g., the use of chart stickers or special symbols on the written or computerized day sheet) may make the receptionist's task simpler. Personal contact by the physician and the use of outreach services such as public health nurses are other ways of "treating" persistent nonattendance. Most successful compliance interventions have two features in common: increased supervision of, or attention to, the patient; and intentional reinforcement of, reward for, or encouragement of compliance (Haynes et al., 1987).

Low compliance is a chronic condition without a "one-shot" cure, so treatment of poor compliance must continue as long as the regimen of prescribed treatment. To make matters worse, none of the following has improved compliance when tested alone: special learning packages (Rawlings et al., 2003 ; Sackett et al., 1975 ) and pamphlets (Swain and Steckel, 1981); special unit-dose reminder pill packaging (Becker et al., 1986 ); counseling about medication and compliance by a health educator (Levine et al., 1979 ) or by nurses (Morice and Wrench, 2001 ; Shepard et al., 1979 ); visits to patients' homes (Johnson et al., 1978 ) or pharmacists (Nazareth et al., 2001 ; Stevens et al., 2002 ); provision of care at the worksite (Sackett et al., 1975 ); self-monitoring of blood pressure (Johnson et al., 1978 ); tangible rewards (Shepard et al., 1979 ); or group discussions (Shepard et al., 1979 ). Although these tactics have not worked alone, many have been part of more complex interventions that have been successful; whether they are essential parts of these complex interventions or just along for the ride is difficult to say (McDonald et al., 2002 ; Von Korff et al., 2003 ). A variety of inducements to comply have been used, including feedback of blood-pressure response to hypertensive patients either by the provider (McKenney et al., 1973; Takala et al., 1979 ) or by patients' taking their own blood pressure (Haynes et al., 1976 ; Nessman et al., 1980 ); small tangible rewards for improved compliance or therapeutic response or both (Haynes et al., 1976 ; Shepard et al., 1979 ; Swain and Steckel, 1981); medication tailored to daily schedules to decrease forgetting and inconvenience (Haynes et al., 1976 ; Logan et al., 1979 ); encouragement of family support (Levine et al., 1979 ); stimulation of self-help through group support and discussion (Levine et al., 1979 ; Nessman et al., 1980 ); negotiation of a brief written contract with the patient to improve health behavior (Swain and Steckel, 1981); and calling back patients who miss appointments (Bass et al., 1986 ) It is important to note here that many individuals other than physicians have taken an effective part in this process. Nurses, pharmacists, health educators, a psychologist, and even an individual with no formal health training played a key role in successful interventions. In summary, the treatment of poor compliance involves many approaches. For short-term treatments, simple clear instructions are sufficient (Al Eidan et al., 2002 ; McDonald et al., 2002 ). For longer-term treatments, follow-up of nonattenders by telephone or mailed reminders must occur. In addition, the practitioner must increase the attention paid to poor compliers and provide rewards or positive reinforcement for good compliance that could include simple praise and extending the time between appointments for those responding to treatment. Inui and colleagues (Inui et al., 1976 ) showed that such maneuvers can be successfully incorporated into regular practice by simply focusing on compliance for a few moments during each encounter, not only to emphasize the importance of following the regimen but also to tailor medication to daily routines. This can be accomplished without necessarily prolonging the visit. It is most important that all compliance interventions applied to noncompliers be maintained for as long as treatment is prescribed. Ethical Issues Am I my brother's keeper? Genesis 4:9 This question highlights the dilemma in which physicians may find themselves when they are pressed to extend their complianceimproving strategies beyond a simple office visit. The decision to apply tactics deliberately designed to change the compliance of patients should meet several ethical standards that apply to all therapeutic interventions (Levine, 1980). First, the diagnosis must be correct. Second, the therapy to be complied with must be of established efficacy. Third, neither the illness nor the proposed treatment should be trivial. Fourth, the patient must be an informed and willing partner in any attempt to maximize his or her compliance. Finally, the method used to improve compliance must be of demonstrated effectiveness. After applying these standards and embarking on a course of treatment, it makes no sense, ethically or otherwise, for the physician to abandon a patient at the first sign of poor compliance. Most physicians consider it unethical to withhold efficacious treatment from a patient with a serious physical disease. Why then should it be ethical to consider withholding treatment when the condition is noncompliance? Future Trends The advent of the personal computer has resulted in increasing use of microcomputers in physicians' offices. Although initial applications have been for business purposes, the computerization of appointment systems and, increasingly, health records affords potential for monitoring patient compliance and assisting in the implementation of reminder systems that allow enhanced management of the poor complier (Hunt et al., 1998 ). Computerized appointment systems make it possible to provide patients with appointment times for long periods ahead and can easily be modified to flag nonattenders and produce automatic reminders. The ability to record age, gender, and diagnoses makes it possible to design a system that can improve provider compliance with screening and preventive maneuvers (Bypass et al., 1988 ). Medication databases that store prescribing information can form the basis of a system that monitors whether patients are at least requesting prescription refill on time (Steiner et al., 1988 ). Automated telephone messaging technology, Internet-based computer programs, and other new technologies are under development to help improve compliance. The potential is great, but it will require both effort and expenditure by physicians or patients to make it work. What of other advancements? The technology that brought us the efficacious treatments is also helping with compliance: drugs with long half-lives, long-acting parenteral preparations, conjunctival inserts, and continuous transcutaneous absorption systems. The burgeoning use of high technology could result in an artificial pancreas that will not only dispense insulin but also adjust the dose according to blood levels. What is to stop the development of implanted arterial pressure sensors with automatic dispensing of parenteral antihypertensives? These thoughts make concerns about telephoning nonattenders seem trifling. CONCLUSION In dealing with compliance, we have consciously concentrated on compliance with medication, emphasizing long-term medications. This is not because we think that compliance with short-term medications is inconsequential or that no problem of compliance exists

with lifestyle or other behavioral changes. On the contrary, both these areas are very important, and noncompliance with lifestyle changes is a monster not to be tamed. It is our hope that we have raised the level of compliance consciousness in the reader. Awareness of the problem and the difficulties in detecting it is essential before any of these practical treatments can be instituted. The past two decades have brought the therapist together with the patient, the family, and other members of the health care team in jointly working toward the full effectiveness of potent treatments. The rewards of this alliance are great: reduction of morbidity, disability, and preventable deaths. The family physician is in an ideal position to help