C H APTE R 98

Patient Compliance
Daniel A Hussar, PhD

The important advances that have been made in the under- Although some patients make a conscious decision to deviate
standing ortbe etiology of many disease states, and the devel- from the prescribed regimen (ie, intentional noncompliance),
opment of many new therapeutic agents, have made it possible many intend to take their medication according to instructions
to cure or provide symptomatic control of many clinical disor- and, in some cases, even may be unaware that their use ofmed-
ders. However, accompanying the increasing sophistication rel- ication differs from what the prescriber intended.
ative to diagnostic and therapeutic knowledge and skills has The termpatienl noncompliance suggests that the patient is
been the recognition that in many circumstances, drugs are not at fault for the inappropriate use of medication. Although this is
being used in a manner conducive to optimal benefit and safety. often the case, in a number of situations, the physician and
In many situations, efforts to maintain or improve health fall pharmacist have not provided the patient with adequate in-
short of the goals that are considered attainable, and fre- structionsorhave not presented the instructions in such a man-
quently, the failure to achieve the desired outcomes has been ner that the patient understands them. The most basic ques-
attributable to patient noncompliance or partial compliance. tions regarding drug usage mustbe addressed-Has the patient
With regard to the provision of health care, the concept of been provided with adequate instructions? Does the patient un-
compliance can be viewed broadly, as it relates to instructions derstand how the medication is to be taken? Nothing should be
concerning diet, exercise, rest, return appointments, etc, in ad- taken for granted regarding the patient's understandingofhow
dition to the use of drugs. However, it is in discussions con- to use medication, and appropriate steps must be taken to pro-
cerningdrug therapy that the designation patient compliance is vide patients with the information and counseling necessary to
employed most frequently. It is in this context that it will be use their medications as effectively and as safely as possible.
used in this discussion, and compliance can be defined as the
extent to which an individual's behavior coincides with medical
or health instructions/advice. NONCOMPLIANCE
Compliance with therapy implies an understanding of how
the medication is to be used, as well as a positive behavior in Types
which the patient is motivated sufficiently to use the prescribed
treatment in the manner intended, because ofa perceived self- The situations most commonly associated with noncompliance
benefit and a positive outcome (eg, enhanced daily functioning with drug therapy include failure to have the prescription dis-
and well-being). Some have recommended the use of the terms pensed or renewed, omission of doses, errors of dosage, incor-
cu1herence or concordance rather than the designation compli- rect administration, errors in the time of administration, and
ance; however, the latter term continues to be the most widely premature discontinuation.
accepted and used. Some patients for whom medication has been prescribed do
The term persistence is also used to identifY the duration not even take their prescriptions to a pharmacy, and some oth-
of time over which a patient continues to take prescribed ers who do take their prescriptions to a pharmacy fail to pick
medication. them up when they are completed. In a survey! ofconsumers, 2%
Problems concerning patient compliance with instructions responded that they had brought prescriptions to the pharmacy
have been recognized for years and, indeed, Hippocrates once but failed to pick them up. The most common explanations for
cautioned, "Keep watch also on the fault of patients which often not taking the prescriptions to a pharmacy or not picking them
makes them lie about the taking ofthings prescribed. n Twenty- up are that patients feel that they have reoovered from the con-
three centuries later, attaining patient compliance in the use of dition or othelWise don't need the medication, they think they
their medications continues to represent a formidable chal- have a similar medicine at home, they don't like to take medicine,
lenge for health care providers. the cost is too high, or they forget to pick up the prescription from
When the complexity of the patient's illnesses and the ac- the pharmacy. In the many situations in which infection is asso-
tions of potent therapeutic agents are taken into account, the ciated with fever and local discomfort, patients already may be
physician, pharmacist, and other health professionals easily taking nonprescription medications, such as acetaminophen.
can become preoccupied with the diagnosis of the disease state The ability ofthese agents to provide some, ifnot complete, relief
as well as the selection and implications of drug therapy and ofthe symptoms ofearly infection may lead some patients to con-
asswne that the patient will follow the instructions provided. clude that the condition is improving, or better, and that itis not
After all, since the medication is being provided to improve necessary to have a prescription dispensed.
and/or maintain the patient's health, why would the patient not The omission of doses is one of the most common types of
follow instructions? Yet, studies continue to show that a large noncompliance and is more likely to occur when a medication is
percentage of patients, for a varietyof reasons, do not take their to be administered at frequent intervals and/or for an extended
medication in the manner intended. period oftime. Errors ofdosage include situations in which the

1782
 CHAPTER 98: PATIENT COMPLIANCE 1783

amount of an individual dose or frequency of administration is that most of the more than 50 million Americans with high
incorrect. blood pressure do not have their condition under good control.
Examples of the incorrect administration of medication in- For those hypertensive patients for whom treatment has been
clude not using the proper technique in using metered-dose in- prescribed, many do not have their blood pressure under effec-
halers and, in some cases, giving medication by the wrong route tive control, and a major reason for the failure to control hyper-
of administration. Errors in the time of administration of the tension is noncompliance with regimens that would work if
drug may include situations in which medication is adminis- administered as intended. Noncompliance is one of the most
tered in an inappropriate relationship to meals. Certain commonly missed diagnoses, and the manner in which patients
drugs---eg, tetracycline, alendronate (Fosamax}----should be ad- use their medication should be evaluated before the therapeu-
ministered apart from meals to achieve optimal absorption. The tic regimen is changed. In one study it is reported that the un-
time ofday at which a drug is administered also may be impor- deruse of antihypertensive medications may be associated with
tant in the use of some medications; eg, diuretics are best hospitalization that could have been prevented if patients had
administered in the morning. complied with their treatment regimens. 9
The premature discontinuation of treatment occurs com- The statins (eg, atorvastatin [Lipitor], simvastatin [ZocorJ)
monlywith the use of antibiotics as well as medications used in have been shown to significantly reduce morbidity and mortal-
the treatment of chronic disorders such as hypertension. ity in patients with coronary heart disease and in patients with
Patients must be apprised of the importance oftaking the med- hyperlipidemia, when they are used on a continuing basis.
ication in the manner instructed, even though their condition However, in two recent studies, compliance with statin therapy
may be asymptomatic or, as in the case of infections, the symp- declined more than 25% in the first 6 months after the original
toms may have subsided soon after the initiation of therapy. prescription, with further declines in compliance occurring the
Studies reflect a wide variation in the degree of noncompli- longer the patients were followed.IO,11
ance. Many reports indicate that at least one-third of patients Noncompliance has major implications for those with HIV
failed to comply with instructions, and for patients with chronic infection/AIDS. The complexity of the treatment regimens used
illnesses on long-term treatment regimens the results suggest in the treatment of HIV infection/AIDS and its complications
a rate of noncompliance of approximately 50%. results in a ~pill burden~ that is often associated with noncom-
pliance. Surveys have demonstrated that approximately one-
third of the patien is missed doses during the 3-day period prior
to the surveys. The Guidelines for the Use of Antiretroviral
Consequences Agents in HIV-l-lnfected Adults and Adolescents include the
The importance and scope ofthe difficulties that result from the following observations:
failure to use medications in the manner intended have re-
KAdherenw is a key deu.rminllnt in the degroo and dUJ"ution ofviro-
sulted in the National Council on Patient Information and Ed- logic 8uppre8sion. Among 8tudie8 reporting on the l~~socintion between
ucation designating noncompliance as America's other drug suboptimlll adherence and virologic nLilure, nonlldhercflOO IImong Im-
problem, and others have described it as an ~invisible epi- tienls on HAART (highly IIctive IIntiretrovirlll therllPY) WIIS the
demic.~2 Others have noted that noncompliance may be the stronge8t predictor for the failure to IIchievevirlllsuppression below the
most significant problem that faces medicine today.1 and that level of det.ection,"12
~knowledge of patient compliance is of critical importance in
interpreting drug response, whether it be in the individual An additional concern is that the irregular treatment that re-
patient or in a clinical trial. M In response to concerns regarding sults from noncompliance appears to accelerate the emergence
mismedica tion among elderly patients, including observations of resistant strains of HIV.
that 55% of this patient population is noncompliant, the Office It has been observed that aoout one-half of patients with
of the Inspector G€neral conducted a study to determine whr, schizophrenia are noncompliant in using their medications and
elderly people fail to follow prescription medication regimens.' experience a relapse of symptoms within a year of initiation of
''Drugs don't work ifpeople don't take them. ~This observation antipsychotic treatment. The inadequate control of schizophre-
made by former Surgeon G€neral C Everett Koop in his keynote nia has, in some situations, been associated with violent actions.
address at a symposium on Improving Medication Compliance,6 One report l .1 has called attention to the hazards of noncom-
provides a clear statement of one of the consequenoos of noncom- pliancewith antiepileptic drug regimens. In examining autopsy
pliance. In many cases nonoompliance results in underuse of a records pertaining to 11 cases of unattended, unexpected
drug, thereby depriving the patient of the anticipated therapeu- deaths of epileptic patients, no antiepileptic drugs were found
tic benefits and possibly resulting in a progressive worsening or in 4 patients and subtherapeutic concentrations were noted in
other complications of the condition being treated. 6 others. It is suggested that a nUIllber of these deaths may
Noncompliance also may result in the overuse of a drug. have been preventable had there been better compliance with
When excessive doses are employed or when the medication is the instructions for using the medication(s).
given more frequently than intended, there is an increased risk Similarly, a leading cause of death in transplant patien ts,
of adverse reactions. These problems may develop rather inno- some ofwhom had waited for years for a donor organ, is the re-
cently, as when a patient recognizes that he has forgotten a jection that results from noncompliance in using immunosup-
dose of medication and doubles the next dose to make up for it. pressant medication. 14
Some other patients appear to believe that if the one-tablet dose The economic consequences of noncompliance also are
that has been prescribed provides some relief of symptoms, two alarming, and some have estimated that the costs associated
or three tablets will be even more effective. with noncompliance in the US exceed $100 billion a year. The
Numerous hospital admissions and nursing-home admis- cost of noncompliance and the capacity of improved compli-
sions are related to noncompliance. In a study of 315 consecu- ance to reduce health-care expenditures are the subject of a
tive medical admissions of elderly patients to a community review of a nUIllber of studies in which it is observed that the
hospital, 28% were medication-related~17%because of ad- benefits realized from improved compliance outweigh, in some
verse reactions and 11% because of noncompliance. 7 A review of cases far outweigh, the costs of programs designed to improve
published studies of drug-related hospital admissions noted compliance.~16
that 11 reports indicated that 22.7% of adverse drug reaction Noncompliance also may take other forms. The problems as-
hospitalizations were induced by noncompliance. 8 sociated with drug misuse and abuse, whether unintentional or
Hypertension is the most frequently studied disease with re- deliberate, are well recognized. Although usually not thought of
gard to compliance. Although educational and screening pro- in terms of noncompliance, drug-abuse problems sometimes re-
grams have significantly reduced the number of individuals sult from excessive use of medications that have been pre-
who are unaware that they have hypertension, it is thought scribed for existing clinical disorders.
1784 PART SA: FUNDAMENTALS OF PHARMACY PRACTICE

Another implication relates to the storage of drugs that are ever, pill dumping (ie, attempts by patients to misrepresent
not used completely during the intended period of treatment. their compliance by discarding medication) is common, and sev-
Keeping these drugs may result in their inappropriate use at eral studies have shown that return counts grossly overesti-
some later time. Accidental poisonings have resulted, and mate actual compliance rates. 19,20
stockpiled medications have been used to commit suicide. The achievement of treatment goals sometimes has been
The recognition that noncompliance is so prevalent has used as a measure ofa patient's compliance. When a particular
raised questions regarding the attention this variable has treatment is associated with a successful outcome (eg, normal
received in clinical studies of therapeutic agents. For example, blood pressure, glucose concentration, or intraocular pressure),
an analysis of the sources and the amount of overt and hidden satisfactory compliance with the regimen may be inferred. How-
bias in reports of double-blind studies of nonsteroidal anti- ever, patients may lood-up on medication or comply with other
inflammatory drugs published between 1966 and 1985 revealed treatmen t regimens (eg, diet)just before their return visit. Such
that only 13% of the studies measured compliance. IS The po- behavior has been called the toothbrush effect, after the way peo-
tential changes in therapeutic response resulting from non- ple brush their teeth just before seeing a dentist. The toothbrush
compliance dictate that close attention be given to this aspect of effect can invalidate almost completely the health-outcome
the study of the action of therapeutic agents. strategy, as well as certain other detection methods (eg, deter-
Although the consideration of the consequences of noncom- mination of drug concentrations in a body fluid).
pliance should focus primarily on the problems that may de- Computerized compliance monitors are the most recent and
velop, there also should be an awareness of situations in which reliable of the indirect-detection methods, but their cost may
some patients may benefit from being noncompliant. Desig- preclude their use in most practice settings. The Medication
nated by one investigator '1 as intelligent noncompliance, it is Event Monitoring System (MEMS) is a microprocessor housed
noted that certain individuals have a rational basis (eg, avoid- in the cap ofthe medication container. Each time the patient re-
ing adverse effects) for altering the dosage of their medication, moves the cap, the time and date are recorded. Data are re-
and that good treatment outcomes are still attained. However, trieved by connecting the microprocessor unit to a computer.
the fact that certain patients may benefit from not complying The data not only provide an indication of individual dosing
with a treatment regimen must not be considered a reason patterns, but also allow correlations with clinical events. Such
for health professionals to be less diligent in detecting noncom- data might be useful to the clinician in understanding why
pliance and initiating the appropriate corrective measures, as treatment has not been fully successful. Although the comput-
any situation in which noncompliance occurs requires careful erized monitors provide no direct information on whether or
evaluation. how much medication was actually taken, their use helps to
supplement other methods. For example, in one study21 in
which pill counts indicated near-perfect compliance, the moni-
tor in the cap showed that fewer than half of all cap openings
Detection occurred at the prescribed interval of 12 ± 2 hr.
Like the diagnosis of medical disorders, detection ofnoncompli- In a study designed to compare multiple measures of com-
ance is a necessary prerequisite for adequate treatment. In ad- pliance with the use of HIV protease inhibitors, it is noted that
dition, like many diseases, complian t or noncompliant behavior compliance may be underestimated by MEMS and overesti-
mated by pill count and interview. Z.1 These investigators also
is not stable and may change over time, necessitating the regu-
lar use ofdetection methods to measure this behavior as part of combined these three measures to determine a composite ad-
the assessment of treatment efficacy. herence score (CAS) that was more clearly related to clinical
The ideal detection method would measure compliance at outcome than any of the three measures used individually.
the time and place of the medication-taking (or other treat- DmECT METHODS-Biological markers and tracer com-
ment) event. Direct observation of the patient would come clos- pounds indicate patient compliance over an extended period.
est to providing this ideal measure ofcompliance. However, this For example, measurement of glycosylated hemoglobin in pa-
method usually is not practical. tients with diabetes mellitus gives an objective assessment of
Current detection methods include indirect measures, such metabolic control during the preceding 3-month period. Tracer
compounds-small anlOunts of agents with long half-lives such
as self-report, interview, therapeutic outcome, pill count,
change in the weight of metered-dose inhaler canisters, medi- as phenobarbital-have been added to drugs in some studies
cation-refill rate, insurance prescription claims databases, and and measured in biological fluids as pharmacological indicators
computerized compliance monitors, and direct measures, such of compliance.
as biological markers, tracer compounds, and assay of body flu- Finally, compliance also has been measured through deter-
mination of drug concentrations in patients' biological fluids.
ids. In general, the direct methods of detection have a higher
sensitivity and specificity than the indirect methods. However, However, the usefulness of data on drug concentrations in bio-
all of these methods have their limitations. To help overcome logical fluids is limited because (1) concentrations of drugs are
limitations of the assessment methods and to provide corrobo- affected by individual differences in absorption, distribution,
rative information, it is recommended that at least two differ- metabolism, and excretion, and low or erratic drug concentra-
ent detection methods be used to measure compliance. tions are not necessarily an indication of noncompliance zz; (2)
INDIRECT METHOD~Self-reportsand interviews with drug concentrations do not provide data regarding the timing of
doses consumed; and (3) brief intake of rapidly cleared drugs
patients are the most common and simplest methods of at-
tempting to determine compliance with therapy. However, before testing can produce results that show adequate drug
many studies have demonstrated thateven the most skilled and concentrations, erroneously suggesting regular medication use.
highly refined interviewing techniques substantially overesti-
mate medication compliance. In spite of the limitations of inter-
views, asking carefully constructed questions {eg, "Most people The Noncompliant Patient
have trouble remembering to take their medicine. Do you have
trouble remembering to take yours?~)18 in a nonthreatening Efforts have been made to demonstrate the relationshipofnon-
manner will help to identifY some noncompliant patients. compliance to a nunlber of variables such as age, education,
Pill counts are another detection method used to measure occupation, socioeconomic status, personality factors, physio-
compliance and frequently are used in clinical drug studies. A logical variables, and the number, types, and severity of ill-
patient's compliance with a medication regimen can be as- nesses. Although certain patterns have been noted in some
sessed by the difference between the number of dosage units studies, the results, in general, have been inconsistent, and it
initially dispensed and the number remaining in the container continues to be difficult to identifY which patients are most
on a return visit or during an unscheduled home visit. How- likely to be noncompliant.
 CHAPTER 98: PATIENT COMPLIANCE 1785

A distinction has been made between attitudinal and focuses more specifically on health decisions. This health·
behavioral compliance, since often the attitude and behavior of decision model combines decision analysis, behavioral decision
a patient may be incongruent. For example, patients fully may theory, and health beliefs to yield a model of health decisions
intend to take the medication according to instructions but and resultant behavior. The components of this model and
actually not do so because they are forgetful or really do not the manner in which they are interrelated are outlined in
understand the instructions. On the other hand, some patients Figure 98-1.
may have no intention of complying but nevertheless do so. With respect to the relationship between health beliefs and
Some individuals are intentionally noncompliant, and this compliance, if compliance is to be achieved, patients must
further underscores the complexity of the challenge to develop believe that
strategies to improve compliance. Although considerable
progress has been made in recognizing and addressing the They llctually Imve the illnes8that hns been diagn08oo.
problems associated with noncompliance, an observation made The illnes.s could ClIUse severe consequences with regard to their health
in an early discussion of this subject contin ues to be valid to- and daily functioning.
day-"It has not proved possible to identifY an uncooperative The treatment pre8criOOd will reduce the present or future severity of
the condibon.
type. Every patient is a potential defaulter; compliance can The benefits of the regimen prescribed outweigh the perreivoo dis.nd-
never be assumed."Z4 In a recent commentary on the challenge nmlage8 IUld co>;(.s of following the recommended llction.
of attaining compliance, the authors observe: "BlWltly, we are
very human physicians in corruptible institutions treating fal- In addition, there must be a stimulus to trigger the advocated
lible patients. Everyone takes shortcuts. This is the ragged health behavior, which can be either internal (eg, concern about
edge of medicine in the 21st century.n2l; the disease) or external (eg, interaction with the physician or
Considerable attention has been directed toward the so- phannacist).
ciobehavioral determinants of compliance, and a number of Patient education and cOWlseling initiatives should be de-
models based on behavioral principles have been described. 26 signed to encourage the beliefs noted above, particularly since
A health-belief model, which initially was developed 27 to many patients believe that "you only need to take medication
explain preventive health behaviors such as obtaining immu- when you are ill and experience symptoms" and/or "you need
nizations and prophylactic dental care, was revised subse- to stop taking medication once in awhile or else your body
quently28 to apply to compliance with prescribed medical reg- becomes dependent on it or the medication will become less
imens. A third-generation model was then proposed·3 that effective."

I HEALll1 DECISIONS t-- HEALll1 BEHAVIOR

1= tEAlll1 QUTeot.£S
-
COMPLIANCE Short ~~
Shor\ term Long tem'l
Long term

fI
A. GENERAL HEALTH BELIEFS B. PATIENT PREFERENCES

concern about health matters Health provider recommel'ldatioos

in general Decision analysis. Iracle-i:llfs between
Willingness to seek and to accept _Bet1efit and risk
medical directioo _Quality and quantlty of lile
Satisfacllon with pa!ient.physician Behavlorlal declsioll theory
relallonshlp and other medical heuristics and biases
~t~

SPECIFIC HEALTH BELIEFS

Perceived susceptibility to disease

(loch..des belief In dlagooslsj
P6rceived severity 01 condition
(physical and social dirnellSlons)

1I
C. EXPERIENCE D. KNOWLEDGE

Disease, diagnostic and Disease. d1agllOStic and

therapeutic irrterventiOfls therapeutic inlervanlions
health care providers

E. SOCIAL iNTERACTION SOCIOOEMOGfIAPHIC

Social networks Age, sex, Income,

Social support education.
Patient St4*'Visloo health insUfimce

Figure 98-1. The health-decision model, combining the health-belief model and patient preferences, including decision analysis and behavioral deci-
sion theory. (From Eraker SA, et al. Ann Intern Moo 1984; 100:258.)
1786 PART SA: FUNDAMENTALS OF PHARMACY PRACTICE

There are also other patient factors that may contribute to The similarity ofappearance(eg, size, color, or shape) ofcer-
noncompliance. Patients who live alone are less likely to com- tain drugs may contribute to the confusion that can exist in the
ply than those who live with another family member who can use ofmultiple drugs. It is desirable that there be an awareness
take an interest in and/or supervise their therapy. The increas- ofthe physical characteristics of the drugs used, so that the pa-
ing problems of drug abuse and addiction have increased the tient will not be taking, for example, only small white tablets.
awareness and concern about becoming dependent on agents The observations in an editorial~ provide a perspective that
that are prescribed for legitimate medical reasons. Although is helpful in understanding the challenge for the patient who is
drugs that carry a potential for abuse and development of de- to take a number of medications.
pendence often are prescribed and used too casually, some pa-
tients develop a fear of dependence regarding use of any drug ~A common consequence of too many pills is organizational
that is to be employed for a prolonged period. To avoid such a breakdown. Given a regimen of four pills once a day, one pill
possibility or to prove to themselves that they are not depen- twice a day, three pills three times daily, and two pills four
dent, they may interrupt or stop therapy or use the medication times daily, compliance suffers. Even the best intentions strug·
in smaller amounts. gle under such complexity. Day·to'<iay pill-taking becomes a lit·
Numerous other factors have been suggested to contribute tIe like a chun:h dinner, at which no one takes exactly the same
to patient noncompliance, and the most important of these are foods or the same portions. An assortment of dishes bewilders
considered in the following discussion. the senses. Except for the most compulsive patient, a regimen of
many pills many times a day breeds more variety than regular-
ity. Reducing pills and reducing intervals hel~ minimiw the
randomness oftaking drugs. Potluck becomes a balanced diet."
FACTORS ASSOCIATED WITH Although combination drug products have certain disadvan-
NONCOMPLIANCE tages, their use may help improve compliance with therapy,
in addition to the patient factors previously considered, a num- since only one product need be administered rather than
ber of other determinants of patient compliance have been several. Therapy usually should not be initiated with a combi-
cited. Some ofthe more important and/or commonly considered nation product but rather with the individual agents. Once the
factors are discussed below. Although the relationship of some optimal dosages of the individual drugs have been determined,
of these factors to the occurrence of noncompliance has not been if they correspond to the amounts included in the combination,
proven, there should be an awareness of the potential implica- these products can be used to advantage.
tions in selected patients. FREQUENCY OF ADMINISTRATION-The adminis-
tration of medication at frequent intervals makes it more likely
that the patient's normal routine or work schedule will have to
be interrupted to take a dose of medication, and in many cases
Disease the patient will forget, not want to be inconvenienced, or be em-
barrassed to do so.
The nature ofthe patient's illness may, in some circwnstances, In a study in which compliance was observed to improve
contribute to noncompliance. In patients with psychiatric dis- from 59% on a three-times-a-day regimen to 75% on a twice-a-
orders, the ability to cooperate as well as the attitude toward day regimen to 84% on a once-a-day regimen, the investigators
treatment may be compromised by the illness, and these indi- noted that ~probably the single most important action that
viduals may be more likely than other patients to be noncom- health-care providers can take to improve compliance is to se-
pliant. Several studies of patients with conditions such as lect medications that permit the lowest daily prescribed dose
schizophrenia have shown a high incidence of noncompliance, frequency. "aQ
and this is thought to be due, in part, to a distorted view of re- The attitudes of patients toward their illnesses and treat-
ality that does not allow these patients to recognize their illness ment regimens also should be anticipated and addressed. In
as well as the need for treatment. most situations, it is reasonable to expect that patients will fa-
P;,lients with t;hronie disorders, partit;ullirly oondition5 5Ut;h as hyper-
~nsion lind hypereholes~rolemill, which often lire not IIsoocinted
vor, and be more inclined to comply with, a dosage regimen that
with sympUlms are 11160 more likely t.o be noncomphers. Patients un- is simple and convenient.
derst.nndllbly tend to beoome disoourng..od with extended thernpeutit; DURATION OF TIlERAPY-The potential for noncompli-
progrllms that do not produoo t;ure$ of the oondilion5. Even when ance is greater when the treatment period is long. Ai; noted ear-
t;ures (:I\n be IInticipnted 1t5 II result of long-teon therapy, problems lier, a greater risk of noncompliance should be anticipated in
still wn ocrur, 115 exemplified by plltients with tuoort;ulo>is who fre- pa tients with chronic disorders, especially if discontinuation of
fluently oc'OOme nonoomplillnt as the treatment period continues. therapy is not likely to be associated with prompt recurrence of
It might be anticipated that patients who experience signif- symptoms or worsening ofthe illness. Noncompliance with reg-
icant symptoms if the therapy is discontinued prematurely will imens for the treatment oftuberculosis is a major reason for the
be more attentive to taking medication correctly. However, few development of resistance to multiple antitubercular agents
studies have demonstrated a correlation between disease sever- and is a very important problem for many patients with this in-
ity and compliance, and it cannot be assumed that these fectious disease.
patients will comply with their therapeutic regimens. The rela- ADVERSE EVENT~The development of unpleasant ef-
tionship between the degree of disability caused by a disease fects of a drug is a likely deterrent to compliance. In an AARP
and compliance is defined better, and it can be expected that survey of people 45 years of age and older, 40% of the respon-
increased disability will motivate compliance in most patients. dents stated they had experienced some form ofside effect dur-
ing medication use. 3l Of this 40%, 50% responded that they
stopped taking the medication as a result of the side effect. Of
Therapeutic Regimen the respondents who were 65 years of age and older, only 47%
informed their physicians of the discontinuation.
MULTIPLE DRUG THERAPY-It generally is agreed In some situations it may be possible to change the dosage or
that the greater the number of drugs a patient is taking, the use alternative drugs to minimize adverse events. However, in
higher is the risk of noncompliance. For example, many elderly other cases such alternatives may not exist, and the benefits ex-
patients are taking five or six or more medications several pected from therapy must be weighed against the risks. Particu-
times a day at different times. In addition, some elderly pa- larly disconcerting are those situations in which the develop-
tients may experience lapses of memory that make noncompli- ment of adverse events makes patients feel worse than they did
ance even more likely. Even when specific dosage instructions before therapy was initiated, as often occurs in hypertensive
for the medications are provided, problems still can occur. patients.
 CHAPTER 98: PATIENT COMPLIANCE 1787

The adverse events (eg, nausea, vomiting, hair loss) associ- in better patient understanding and performance of the correct
ated with the use of many antineoplastic drugs are sufficiently steps for inhaler use.
distressing to a nwnberofpatients with cancer that they do not TASTE OF MEDICATION-Medication taste problems
take their medication in the manner intended. The reduction in are encountered most commonly with the use of oral liquids by
the quality of life resulting from effects such as severe na usea children. Getting a child to take a dose of medication may be
and vomiting may be of such importance to some individuals such a difficult task for a parent that doses may be missed
that they do not comply with a regimen that in some cases may or administration of the drug discontinued as soon as the par-
even offer the hope of being curative. ent sees any sign of improvement. Experiences such as these
The ability of certain drugs to cause sexual dysfunction is a have resulted in initiatives to flavor liquid medications so that
reason for noncompliance by some patients, with the antipsy- they are acceptable to children. FLAVO l~ has used more
chotic agents, antidepressants, and antihypertensive agents than three dozen flavors in the development of a medication-
being implicated most frequently. flavoring formulary system that has been used successfully in
Even a warning about possible adverse events may result in pharmacies around the country. This system also has been ex-
some individuals not complying with instructions. It is inadvis- tended for use in medications prescribed for pets.
able for patients being treated with sedatives or other agents Compliance problems relating to the taste of medication are
with a central nervous system depressant effect to conswne not limited to children. Objections to the taste of liquid potas-
alcoholic beverages, because of the possibility of an excessive sium chloride preparations often are raised; a number of pa-
depressant response. However, there should be a realistic tients discontinue taking the medication for this reason.
recognition that some patients, if faced with a mandate not to
drink while on drug therapy, will choose not to take their pre-
scribed medication. Although problems of combined alcohol- PatientlHealth Professional Interaction
drug usage are well known, this situation continues to present The circumstances surroWlding the visit of a patient with a
a challenge of effectively communicating with the patient so physician and pharmacist and the quality and effectiveness of
that optimal benefit can be achieved at minimal risk. the interaction ofthese health professionals with the patient are
PATIENTS MAY BE ASYM:PTOMATIC OR SYMP- major determinants of the patient's understanding of, and atti-
TOMS SUBSIDE-It is understandably difficult to convince a tude toward, the illness and therapeutic regimen. One ofthe pa-
patient of the value of drug therapy when the patient has not tient's greatest needs is psychological support provided in a com-
experienced symptoms prior to initiation of therapy. Such is of- passionate manner, and it has been observed that patients are
ten the case in the treatment of hypertension, and the lack of more inclined to comply with the instructions ofa physician they
previous symptoms coupled with the probable lack of appear- know well and respect and from whom they receive information
ance of symptoms iftherapy is discontinued contributes to the and assurance about their illnesses and medications.
high rate of noncompliance in these patients. The patient-physician interaction has been described as a
in other circumstances patients may feel better after taking negotiation between two active and equal participants with a
the drug and feel that they no longer need to take it once the strategy that includes the elements of "putting the ill at ease,"
symptoms subside. Situations frequently occur in which pa- respect, positive attitude, information, translation, feedback,
tients do not complete a full course of antibiotic therapy once patient response, and negotiation. Respect for the patient and
they feel that the infection has been controlled. This practice a realistic appraisal of the circumstances of the individual pa-
increases the likelihood of a recurrence of the infection and tient are essential if therapeutic goals are to be achieved.
increased resistance of the microorganisms causing the in- In a discussion of the influence of the patient-physician re-
fection, and patients must be advised to take the full course of lationship on compliance, the following observation was made:
antibiotic therapy.
COST OF MEDICATION-Noncompliance may occur "Our only true inlluence on the patient is balSCd on the strength of
with the use of drugs that have a relatively low cost; however, our professional rellltionship with that patient. And it is this relation-
it might be anticipated that patients may be even more reluc- ship that is central to improving plltient complillnce with both mediCll-
tant to use the entire prescribed quantity of more-expensive tiOfl and treatment regimenS. B32
agents. The expense involved has been cited by some patients
as the reason for not having prescriptions dispensed at all, These observations are equally important with respect to the
whereas in other cases the medication is taken less frequently interaction between the pharmacist and the patient. The fol-
than intended or prematurely discontinued because ofthe cost. lowing factors are among those that could influence compliance
Concerns regarding the consequences of noncompliance or adversely ifinadequate attention is given to the scope and qual-
partial compliance that result because patients are not able to ity of the interaction with the patient.
afford their prescribed medications are an important reason for FMLURETO COMPREHEND THE IMPORTANCE OF
the high level of attention that has been devoted to the devel- THERAPY-A major reason for noncompliance is that the im-
opment of Medicare coverage of prescription drugs for outpa- portance of the drug therapy and the potential consequences if
tients, as well as initiatives to import medications from Canada the medication is not used according to instructions have not
and other countries in which they are available at lower costs. been impressed upon the patient. Patients usually know rela-
ADMINISTRATION OF MEDICATION-Although pa- tively little about their illnesses, let alone the therapeutic
tients may fully intend to comply with instructions, they may benefits and problems that could result from drug therapy.
inadvertently receive the wrong quantity of medication because Therefore, they establish their own beliefs and expectations
of incorrect measurement of medication, use of inappropriate with respect to their drug therapy.lfthe therapy does not meet
measuring devices, or incorrect use of medication-administra- these expectations they are more likely to become noncompli-
tion devices. The inaccuracy of using teaspoons to administer ant. Greater attention to educating patients about their condi-
liquid medications is well known and iscompoWlded by the pos- tions as well as the benefits and limitations ofdrug therapy will
sibility of spillage and asking the patient to measure a fraction contribute to better compliance with therapeutic regimens.
of a teaspoonful. This problem has been long recognized, but POOR UNDERSTANDING OF THE INSTRUCTIONS-
problems still occur. The importance of providing the patient Prescriptions that state that medication should be taken as di-
with measuring cups, or calibrated droppers for the use of oral rected can be the source of misunderstanding as well as serious
liquids is evident. consequences. Even when instructions are more specific, confu-
Some patients do not use metered-dose aerosol inhalation sion still may occur, and there have been many errors of inter-
devices correctly, and this could result in inadequate control of pretation of instructions that the prescriber considered to be
the conditions (eg, asthma) for which their use are intended. clear. For example, many prescriptions are written and labeled
The provision oforal instruction by the pharmacist has resulted to indicate how many doses are to be taken each day with no
1788 PART SA: FUNDAMENTALS OF PHARMACY PRACTICE

additional clarification as to how the doses are to be scheduled. physicians and pharmacists are too busy or not interested in
How should instructions to take one tablet three times a day be talking with the patient. Improving communications must be
interpreted? Does this mean every 8 hr, or with meals, or possi. considered the key to increasing compliance and some ofthe ap-
bly some other schedule? If the drug is to be given with meals or proaches and recommendations directed toward this goal are
at a specified time before or after meals, it usually is assumed reviewed in the following discussion. Pharmacists have a par-
that the patient eats three meals a day. Yet this is not always ticularly valuable opportunity to encourage compliance since
the case. In one study,3,3 patients being treated with medications their advice accompanies the actual dispensing of the medica-
with instructions to take them three times a day were inter- tion, and they usually are the last health professional to see the
viewed with respect tothe times at which they administered the patient prior to the time the medication is to be used.
individual doses of medication. Of 137 patients, only 1 was ad-
ministering the medication at regular 8-hr intervals between
doses, and 79% of the patients reported taking all three doses Identification of Risk Factors
within 12 hr, leaving a dosage interval of 12 hror more.
A patient may be knowledgeable about the dosage and the All patients should be viewed as potential noncom pliers. A first
specific times at which the medication is to be administered but step in efforts to improve compliance should be to recognize in-
not Wlderstand the meaning of auxiliary instructions. Some pa- dividuals who are most likely to be noncompliant, as judged by
tients have received prescriptions for a tetracycline derivative a consideration of the risk factors noted earlier. These factors
in a container to which is affixed an auxiliary label with a pre- should be taken into account in planning the patient's therapy
caution about exposure to sunlight. However, in the absence of so that the simplest regimen that is, to the extent possible, com-
additional explanation, some have concluded that it is the med- patible with the patient's normal activities can be developed.
ication that needs to be protected from sunlight (and have
placed the container in the refrigerator) and have not recog-
nized that the information applies to an adverse event for Development of Treatment Plan
which they are at risk. The more complex the treatment regimen, the greater is the
Pharmacists should be certain that patients are familiar risk of noncompliance, and this must be recognized in the de-
with special considerations pertaining to the particular dosage velopment of the treatment plan. The use oflonger-acting drugs
form dispensed, such as the importance of not chewing or in a therapeutic class, or dosage forms that are administered
crushing controlled-release capsules or tablets. In one report less frequently, also may simplifY the regimen.
the death of a patient is suspected to be due to chewing dilti- The treatment plan should be individualized on the basis of
azem extended-release capsules (Cardizem CD) because she the patient's needs, and when possible, the patient should be a
thought the capsules were too big to swallow whole. M participant in decisions regarding the therapeutic regimen.
In some cases the uncertainty or confusion on the part of the Compliant patients see themselves as active members of the
patient is such that medications are given by the wrong route team involved in their care, not as passive victims of a disease
of administration (eg, instilling oral pediatric antibiotic drops and the health-care system. Involving patients in the develop-
into the ear for an ear infection or administering suppositories ment of a treatment plan will help them view the regimen as
by the oral route). something that increases their control and options, rather than
A patient being prepared for an electrocardiogram was ob- something that is done to them.
served to have 20 transdernlal nitroglycerin patches at various To help reduce inconvenience and forgetfulness, the regimen
locations on his body. Although he had understood. the instruc- should be tailored so that the doses of medication are adminis-
tions to apply one patch a day, no instruction had been provided tered at times that correspond to regular activities in the pa-
regarding their removal. tient's daily schedule. When prescriptions are written, the
Although not a complete listing of all factors that result in instructions should be as specific as possible.
noncompliance, those discussed give an indication of the diffi- Instructions such as "as directed" or other directions that
cult challenge of assuring optimal drug therapy. are subject to misinterpretation should be avoided. Even such
seemingly specific instructions as olle tablet three times a day
often are misinterpreted, as discussed previously. Where possi-
IMPROVING COMPLIANCE ble and with a recognition of the patient's normal routine, the
specific times of day at which the patient is to take the medica-
It often is assumed that health professionals recognize the im- tion should be indicated.
portance of noncompliance and will take the steps necessary to The APhA and the American Society of Internal Medicine
achieve the compliance of their patients with the instructions have developed a statement on prescription writing and pre-
provided. However, this assumption may not always be valid. scription labeling (Appendix A). Not only do the guidelines pro-
In one study, physician compliance with public health recom- vide important information and suggestions, but the statement
mendations for tuberculosis control wasevaluated.:J.S The study reflects the type of interdisciplinary cooperation that also must
revealed poor compliance by physicians with recommended be achieved in practice if patient needs are to be served best.
policies for the prevention of tuberculosis in health-care work- The prescription can be used as the organizing instrument
ers, thereby raising concerns about the personal risk of tuber- of instruction. However, ~most often the prescription slip sim-
culosis for these physicians, as well as questions about how ply is handed over as the closing act of the encounter, while the
effectively such physicians will promote preventive actions patient or parent is outward bound."37 The prescription should
among their patients. An accompanying editorial''l6 noted that signal the start of an alliance, and it behooves the physician to
~onemightwonder how much patient noncompliance is fostered
emphasize its importance.
by a less than enthusiastic endorsement by the health-care Many prescriptions that patients receive from their physi-
provider." For strategies to improve compliance to be effective, cians are never dispensed. Little progress has been made in
health professionals must not only believe that noncompliance detecting and correcting these occurrences, further emphasiz-
is an important problem, but also be willing to make a greater ing the need for more-effective communication and a closer
commitment to the steps that will help their patients be com- working relationship between physicians and pharmacists.
pliant.
A number of strategies to enhance compliance have been
proposed. Inherent in many of the factors considered is the mat-
ter of commWlication of the physician and pharmacist with the
Patient Education
patient. This communication is, in many cases, not only incom- One of the findings of the report of the Office of the Inspector
plete and ineffective, but often there is also the impression that General is ~education is the best way to improve compliance."
 CHAPTER 98: PATIENT COMPLIANCE 1789

However, former FDA Commissioner David Kessler has ex- receive a telephoned prescription from a physician that is to be
pressed concern that "the nation also is facing a communica- delivered to the patient's home or picked up at the pharmacy by
tions gap that has serious implications for the public health_ a relative or friend. In these circumstances, when appropriate,
This gap extends from what patients want to know about their the pharmacist might call the patient to discuss the use ofthe
medicines to what they actually learn from their physicians medication.
and pharmacists."38 He further observes that "physicians ... The effect of pharmacist counseling on patient compliance
need to re-examine the amount of information they give their has been evaluated in a number of studies. Studies assessing
patients and the way they deliver it. In addition, they need to pharmacist counseling of patients with hypertension have
acknowledge that pharmacists should have a larger role in pa- demonstrated a significant increase in the patients' knowledge
tient education and advise their patients to expect counseling of hypertension and its treatment, their compliance with pre-
when they fill their prescriptions."38 scribed therapy, and the number of patients whose blood pres-
Many factors influence the effectiveness of educational ef- sures were maintained in the normal range.
forts and a patient's development of compliant behavior. Deci- A compliance clinic has been described J9 in which pharma-
sions must be made as to what information should be provided cistsendeavored to improve the compliance afpatients referred
to patients about their illnesses and drug therapy. It must be to the clinic by physicians. Six of the 14 patients seen on a reg-
recognized that when the information is too comprehensive or ular basis demonstrated a significant reduction in emergency
detailed or is presented inappropriately (eg, a discussion of ad- room visits, and 8 patients exhibited reduced hospitalizations,
verse events that alarms the patient), the patient actually may as determined by a comparison of pre- and postclinic records.
be discouraged from taking the medications. Thus, compliance In addition ta the therapeutic benefits most patients will expe-
may be compromised rather than enhanced. rience as a result of improved compliance, there is a consider-
In discussing an illness or drug therapy with a patient, a dis- able cost savings to be achieved as a result of the reduced
tinction should be made between information and education. hospitalization.
Patients may receive information but not understand it and use WRITTEN COMMUNICATION-The emphasis on oral
it correctly, whereas education implies understanding and be- communication should not be interpreted to indicate that writ-
havioral change. Patients should be encouraged to participate ten communication is not important. Although at the time of
in the discussion, and when possible, they should be brought in the visit to the physician or pharmacist patients may under-
on the decision-making process. stand how the medication is to be used, later they may not re-
The goal of patient education is to provide information that member the details relating to administration of the drug.
the patient is able to understand and use. The anticipated ben- Therefore, specific instructions for use should be placed on the
efits of the therapy should be explained, as should the impor- prescription labeL
tance of complying with the provided instructions. Complex It is also desirable and sometimes required to provide
terms and unnecessary jargon that can interfere with patient supplementary written instructions or other information per-
understanding should be avoided. Patients should be asked to taining to the patient's illness or drug therapy, and many phar-
repeat the instructions for administering their medications to macists provide patients with medication instruction cards or
show that they understand them, and they also should be en- inserts. Information that pertains to the specific medication/for-
couraged to ask questions. At the least, the questions noted in mulation being dispensed is preferred to information that ap-
Table 98-1 should be addressed. It is recommended by the Na- plies to a therapeutic class of agents or a general statemen tthat
tional Council on Patient Information and Education (NCPlE) applies to all dosage forms ofa particular medication. The pro-
that these questions be discussed each time a patient obtains vision of supplementary written information appears to be most
prescription medication. effective in improving compliance with short-term therapeutic
ORAL COMMUNICATION/COUNSELING-Communi- regimens (eg, antibiotic therapy). For drugs used on a long-term
cation between the pharmacist and patient regarding the use of basis, written information as a sole intervention has not been
medication can be both oral and written. Although it may be shown to be sufficient for improving patient compliance.
supplemented and reinforced by written instructions, oral Although the supplemental instructions and information
communication is the most important component of patient ed- may be thorough and well written, it must be recognized that
ucation because it directly involves both the patient and the many patients cannot read. Millions of adults in the US are
pharmacist in a two-way exchange and provides the opportu- functionally illiterate (ie, they cannot perform the basic reading
nity for the patient to raise questions. For such communication tasks required to function in societ;1) and millions more are only
to be most effective it should be conducted in a setting that pro- marginally literate. In one study4 of more than 2600 predomi-
vides privacy and is free of distractions. nantly indigent and minority patients, 42% were unable to com-
Although many pharmacies do not presently have a sepa- prehend directions for taking medication on an empty stomach.
rate patient consultation area, this is a desirable goal. Not only Written instructions and information also must be viewed as
will this emphasize to the patient the importance the pharma- one-way communication unless patients are permitted to dis-
cist attaches to the information being discussed, but it also will cuss and ask questions about their therapy. Therefore, oral and
strengthen further the recognition of the pharmacist as one written communication should be used to complement each
who is contributing to the patient's health care. other, and both should be viewed as important components of
Medication often is obtained in a manner that does not lend the effort to educate patients regarding their drug therapy.
itself to oral communication. For example, the pharmacist may AUDIOVISUAL MATERIALS-The use of audiovisual
aids may be particularly valuable in certain situations because
patients may be better able to visualize the nature ofthe illness
Table 98-1. Patient Questions Regarding Medication- or how their medication acts or is to be administered (eg, the ad-
ministration of insulin, the use of a metered-dose inhaler). An
1. What is the name of the medicine, and what is it supposed to increasing number of health-care professionals have used such
do? aids effectively by making them available for viewing in a pa-
2. How much of the medicine should I take, when should I take it tient waiting area or consultation room and then answering
and for how long? questions the patient may have.
3. What foods, beverages, and other medicines should I avoid CONTROLLED THERAPY-It has been proposed that
while taking it? hospitalized patients be given the responsibility for self- medi-
4. What are the possible side effects, and what should I do if they cation prior to discharge. Usually, patients go from a complete
occur? dependence on others for the administration of their medica-
S. What written material is available about the medicine?
tion while hospitalized to a situation in which they are given
• Que5tions that palient~ ~hould a<;k. a~ recommended by the NCPIE. the full responsibility when discharged, often with the assump-
1790 PART SA: FUNDAMENTALS OF PHARMACY PRACTICE

tion that they know about their drugs because they were taking leaflets has been demonstrated to have a positive effect in the
them in the hospital. Similarly, many ambulatory patients who acquisition and understanding of infomtation regarding medi-
are expected to be responsible for their own treatment have not cations prescribed for patients with limited literacy skills. 4.3
been provided with adequate information. MEDICATION CALENDARS AND DRUG REMINDER
The suggested arrangement would permit patients to start CHARTS-Various forms, such as medication calendars, have
using the medications on their own before discharge, so that been developed and are designed to assist patients in self-ad-
health-care professionals can more directly identify problems ministering drugs. In addition to their use in helping patients
or situations that might undennine compliance, and answer pa- understand which medication to take and when to take it, the
tient questions. forms on which patients are to check the appropriate area for
Special programs for providing information about medica- each dose of medication they take, can be evaluated by the
tion are needed for some individuals including sight-impaired pharmacist or physician when the patients return for more
and hearing-impaired patients. Some pharmacists prepare medication or have their next appointment.
prescription labels in Braille for the blind and use a telecom- SPECIAL MEDICATION CONTAINERS, CAPS, AND
munication device for the deaf (TDD) to communicate with SYSTEMS-Several types of medication containers have been
hearing-impaired patients over telephone lines. The Medifier is developed to help patients organize their medications and
a molded plastic device (in four sizes) into which a prescription to monitor self-administration of the drugs. An eX<'lmple is the
vial is placed. A clear lens magnifies the print on the label so 28-compartment MEDISET container that contains four com-
that patients with vision problems can read the instructions. partments for different time periods (ie, morning, midday,
evening, bedtime) for each day of the week. The Med Light
Tablet Organizer also has 28 compartments as well as an alarm
Patient Motivation and flashing light.
Specially designed caps for prescription containers also have
Many health care professionals assume that patients who are been developed to facilitate compliance, and include features
knowledgeable about their illness and therapeutic regimen are such as a digital timepiece that displays the time and day on
likely to be compliant. Although this premise is valid for many which the last dose of medication was taken, and an alann and
patients, increased patient knowledge does not necessarily al- flashing light when it is time to take the next dose. Contain-
ter patient behavior and compliance. Therefore, there must be ers/caps that contain all or some of these features include The
an awarenessofthe need to motivate patients to use the knowl- Prescript Time Cap, The Pill Timer, and Remind Cap Closures.
edge they have acquired to achieve optimum benefit from their The use of microelectronic medication monitors (Medication
therapy. Event Monitoring System) in the caps of prescription contain-
Infonnation must be provided to patients in a manner that ers has been described earlier.
is not coercive, threatening, or demeaning. The best inten- For patients with vision impainnent or who otherwise have
tioned, most comprehensive educational efforts will not be ef- difficulty reading information on prescription labels, products
fective if the patient cannot be motivated to comply with the in- such as Talking Rx, ScripTalk, and Aloud Talking Prescription
structions for taking the medication. In addition to counseling Labels have been developed to playa prerecorded message
the patient and providing specific written instructions, supply- when activated. Instructions for using the medication are
ing cues for appropriate behavior (prompting) may be of value recorded in a small electronic unit or microchip that is attached
in motivating the patient to be compliant. Cues may be verbal to the bottom of the container or embedded in a labeL
or nonverbal, with examples of the latter including the use of Although these special prescription containers, caps, and
special packaging or reminder systems. systems are not needed by most patients, they may be effective
The physician-patient interaction has been characterized as in achieving compliance by patients who forget doses or who are
a negotiation.. This concept may be extended further by the de- confused by the complexity of the regimen.
velopment of con.tracts between patients and health-care COMPLIANCE PACKAGING-The manner in which
providers in which the agreed-upon treatment goals and medication is packaged also has an influence on patient com-
responsibilities are outlined. As summarized in a review,a con- pliance. A compliance package has been dermed as a prepack-
tracts offer "a written outline ofexpected behavior, the involve- aged unit that provides one treatment cycle of the medication to
ment of the patient in the decision-making process concerning the patient in a ready-to-use package, and a comprehensive re-
the regimen and the opportunity to discuss potential problems view of the use of such packaging as a patient education tool
and solutions with the physician, a fonnal commitment to the has been published. 4.3 This type of packaging usually is based
program from the patient, and rewards ... which create incen- on blister packaging using unit-of-usedosing and is designed to
tives for achieving compliance goals." Although such a struc- serve as a patient-education tool for health professionals and to
tured approach will not be needed with most individuals, itmay make it easier for patients to understand and remember to take
be effective for patients who have not responded to other initia- their medications correctly at home. Specially designed pack-
tives to ensure compliance. aging for oral contraceptives was one ofthe first initiatives of
Noncompliance is the greatest challenge in the control oftu- this type and has been valuable in increasing patient under-
berculosis, and the difficulties currently encountered in the standing of how these agents are to be taken.
management of this infection have prompted one clinician to Special packages of certain corticosteroids (eg, Medrol
make the following observations: "Sometimes it takes a little Dosepak)also have been designed to facilitate the use of steroids
imagination. Give them a cup ofcoffee. Talk to them. Pay them in dosage regimens that may be difficult to understand or
an honorarium to come in and take the medicine. If the public remember.
doesn't want drug-resistant TB, and ifbribing people is the way The Medicine-On-Time system is an example ofa packaging
to get them to take their medicine, then I say bribe them.0>41 system that provides unit-of-use dosing with specific labeling in
a plastic card that is set up like a calendar. In addition to sim-
plifying the use of medications for patients who self-administer
Compliance Aids their medications, these systems also have been very useful in
the distribution and administra tion of medications in assisted-
LABELING-The importance of the accuracy and speci- living and other patient-care facilities.
ficity ofthe information on the label ofthe prescription container A possible negative effect of drug packaging on patient
has been noted. Auxiliary labels that provide additional infor- compliance is seen with the use of the child-resistant contain-
mation regarding the use, precautions, and/or storage of the ers. Some patients, particularly the elderly and those with
medication also will contribute to the attainmentofcompliance. conditions like arthritis and parkinsonism, have difficulty
The inclusion of pictograms in labeling and patient infonnation opening some of these containers and may not persist in their
 CHAPTER 98: PATIENT COMPLIANCE 1791

efforts to do so. There also may be difficulty opening some unless the patient understands and follows the instructions for
foil-packed drugs. Pharmacists should be alert to problems of use of the drugs prescribed. One also cannot help but wonder
this type and, when appropriate, suggest use of standard how often patients have been categorized as treatment failures
containers or caps. and have had their therapy changed, possibly to more potent
DOSAGE FORMS-New dosage forms of certain drugs and toxic agents, when the reason for the lack of response or an
also have been developed, in large part in recognition of prob- unanticipated altered response was noncompliance.
lems of noncompliance. For example, the development of Despite the increasing attention directed to the issue of
longer- acting, controlled-release dosage forms of numerous noncompliance, the problem continues to be prevalent. Al-
medications (eg, calcium channel blocking agents) has permit- though not uniformly successful, the approaches taken and
ted less frequent administration of these agents, which facili- suggestions advanced in an effort to improve compliance have
tates compliance. The use of transdermal delivery systems contributed substantially to recognition of the problem and
pennits less-frequent administration of the drugs (eg, nitro- provided a valuable base on which to develop modified or new
glycerin, fentanyl) given by this route. approaches to the problem. Certain approaches that involve a
significantly increased commitment of time on the part of
health-care professionals may be viewed by some as impracti-
Monitoring Therapy caL Yet can this increased commitment of time compare with
the time and money that are currently being wasted as a re-
SELF·MONlTORING-Patients should be apprised of the sult of noncompliance?
importance of monitoring their own treatment regimen and, in The improvement of compliance will result in a situation in
some situations, the response parameters. The attention to the which all parties benefit. Most importantly patients benefit
responsibility that patients must personally assume also has from the enhancement of the efficacy and safety of their drug
been considered in consumer publications, as illustrated by an therapy. Pharmacists benefit because there is an increased
article in Good Housekeeping titled "If your medicine isn't recognition and respect for the value of the advice and service
working.... Itmaynot be the medicine at alL ltcould beyoU!»44 that they provide. Phannaceutical manufacturers benefit from
PHARMACIST MONITORING-The phannacist's role in the favorable recognition that accompanies the effective and
minimizing noncompliance does not end when the prescription safe use of their drugs as well as from the increased sales re-
is dispensed. The phannacist is in an excellent position to de- sulting from the larger number of prescriptions being dis-
tect noncompliance pertaining to drugs used in the manage- pensed. Finally, society and the health care system benefit as a
ment of chronic conditions, such as hypertension and diabetes, result of fewer problems associated with noncompliance.
by being alert to situations in which the frequency of requested Although an increase in compliance will result in more pre-
refills is not consistent with the directions for use. Phannacist scriptions being dispensed and a higher level of expenditures
follow-up with telephoned or mailed refill reminders has been for prescription medications, this increase in costs will be more
found to increase compliance. than offset by a reduction in costs (eg, physician visits, hospi-
One approach in which both health professionals and pa- talizations) attributable to problems due to noncompliance.
tients have collaborated effectively in reviewing/monitoring the For too long patients have been deprived of close attention
use of medication has been the brown bag program. The to, and monitoring of, their drug therapy. An excuse that
Administration on Aging and National Council on Patient In- health-care professionals are too busy to advise patients
formation and Education (NCPIE) have encouraged older con- regarding their drug therapy cannot be accepted; the highest
sumers to put all their medicines in a bag and take them to priority must be assigned to taking the steps to ensure that pa-
their health professional for a personalized medicine review. tients will use their medications in the appropriate manner.
DIRECTLY OBSERVED TREATMENT (DOT)-Even
when many ofthe steps described earlier have been taken, non-
compliance may still result. For example, there is greatconcern REFERENCES
about the high rates of treatment failure in patients with tu- L &hering Report XVIll. 1996.
berculosis and the increasing prevalence of drug-resistant tu- 2. Smith Me. In Smith I\IC, Wertheimer AI, eds. Social find Behnviorfll
berculosis. In one study that used self-administered treatment, Aspe<;ts of Phllrmllooutical Cllre. New York: PhllrmllooutiCIII Pro-
39% of patients were lost from the study with a 6-month anti- duct>; PreS!>, 1996.
tubercular regimen and 49% with a 9-month regimen. 45 In con- 3. ErllkerSA, etllL Ann Intern Med 1984; 100:258.
trast, in a study that used a 6-month regimen of directly 4. l'el:k C. Medic El'f!llt Monil OlJ<!rview 1991; 3: 1.
observed treatment (ie, giving patients their medications and 5. Kusserow RP. Office of the InsptJl:lor Generlll, OEI-04-89-89121,
seeing that they are swallowed), fewer than 10% of the patients Mar 1990.
6. Koop CE. Proc Symp Natl Pharm Council 1984; L
were lost to further treatment. 46 A commentary advocating the 7. Col N,etld.Arch In/ern Med 1990; 150:841.
use of directly observed treatment regimens for patients with 8. Einal'l;on TR. Ann P}Ulrmacolher 1993; 27:832.
tuberculosis observed that "we can't afford not to try it.»47 9. Mllronde RF, et aL Med Cure 1989; 27:1159.
Many of the recommendations for improving patientcompli- 10. BennerJS. et aL JAMA 2002: 288:455.
ance are included in a comprehensive set, Recommendations for 11. JuckevidusCA,et Ill. JAMA 2002; 288:462.
Action to Advance Prescription Medicine Compliance that has 12. Guidelines for the Use of Antiretrovirfl1 Agents in HIV·I-Infected
been developed by NCPlE (Appendix B). A meta-analysis of153 Adults fino Adolescents. Oepllrtment of Helllth find Human Ser-
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1792 PART SA: FUNDAMENTALS OF PHARMACY PRACTICE

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