compliance with antihypertensive drug therapy

COMPLIANCE WITH ANTIHYPERTENSIVE DRUG THERAPY *

D. W. Taylor, D. L. Sackett, R. B. Haynes, A. L. Johnson, E. S. Gibson t and R. S. Roberts

McMaster University, Health Sciences Centre Hamilton, Ontario, Canada

and t Dominion Foundries and Steel Company of Canada, Ltd.

Hamilton, Ontario, Canada

The treatment of hypertension shares with other long-term preventive regimens, a reliance on the patient for the day-to-day management of therapy. Unfortunately, poor patient compliance with drug regimens is well-documented by recent research. Also, clinicians who previously viewed patient compliance as beyond their area of responsibility and expertise are devoting more attention to compliance problems. With the current awakening of interest in this area has come the demand to provide clinicians and other health care professionals with methods of detecting the existence of compliance problems and with effective strategies for improving patient compliance. Before forging ahead with such efforts however, we must be assured that they are both medically and ethically justified. Four general criteria must be met before attempts are made to alter compliance with any treatment program. These are of immediate importance in the consideration of drug therapy for mild hypertension. First, the disease must represent an important source of morbidity and mortality; second, the prescribed therapy when fully complied with must have proven efficacy in reducing this toll of morbidity and mortality; third, the negative consequences in terms of adverse drug reactions, reduced quality of psychosocial functioning and cost must not outweigh the benefits of treatment; and fourth, poor compliance must be documented at levels that are insufficient for therapeutic benefit. In the case of drug treatment for mild hypertension only the last of these criteria is well-established. Thus, the widespread implementation of compliance detection and intervention programs must await more definitive data on the three remaining criteria. With this provision in mind, this paper will discuss the measurement of patient compliance, document the magnitude of the compliance problem in hypertension, discuss its clinical significance, identify risk factors for noncompliance and describe compliance improving strategies that have been experimentally tested. Because of the scarcity of papers on compliance with antihypertensive drug regimens we will frequently refer to other compliance studies in order to illustrate important points. As well as reviewing what we know this paper will point out what we need to know and suggest research priorities for the study of compliance.

*Supported in part by the Medical Research Council of Canada, the Ontario Council of Health, the Ontario Heart Foundation and the National Health Grant of Health and Welfare Canada.

390 0077-8923/78/0304-0390 $01.75/0 @ 1978 New York Academy of Sciences

Taylor et al.: Compliance With Drug Therapy 391

MEASUREMENT

Since our knowledge of any phenomenon is in large part determined by the reliability and validity of our methods of observation, all results reported in this paper must be considered in light of current compliance measurement tech- nology. Compliance with drug regimens consists not of a single event that can be easily observed but rather of a cumulation of many events of pill-taking occurring over time. Thus measurement techniques must be capable of sum- marizing pill-taking behavior over periods of time and must not be unduly influenced by single acts of taking or missing an individual dose. Also, if the measurement of compliance is to be clinically useful we should strive toward quick and easy methods that will allow clinicians to identify those patients in need of compliance intervention.

Blood Pressure Reduction

Although it seems reasonable that blood pressure reduction should itself be indicative of compliance this clinical outcome is inadequate as a compliance measure for several reasons. First, the extent to which compliance correlates with blood pressure fall will depend upon the dose of the drugs prescribed. It the dose is too low, even total compliance may not substantially reduce blood pressure and if too high therapeutic effect might be achieved with considerably less than total compliance. Second, if multiple medications are prescribed that vary in their hypotensive effect and if compliance differs across these medications then compliance measured on only one of these drugs or average compliance computed across drugs may not coincide with the actual hypotensive effect achieved. And third, compliance with the prescribed regimen is only one factor among many that can influence a change in blood pressure. Changes in body weight and recent ingestion of alcohol or nicotine may also alter blood pressure.

Clinical Judgment and Patient Interviews

Although willing to hold reservations about clinical outcome as a measure of compliance, physicians may feel that they can accurately gauge a patient's compliance through their personal clinical skills. The research evidence does not support this belief.' Caron and Roth2 found that 27 ward residents could not judge patient compliance with antacid regimens at better than a chance level. Furthermore, 22 of these residents overestimated patient compliance. Evidence indicates that patients also tend to overestimate their compliance.' A useful observation in this area however, is that patients who admit to noncompliance are almost always telling the truth.3 Furthermore, these self- confessed noncompliers are more likely to benefit from compliance intervention strategies than are patients who deny their nonc~mpl iance .~~

Urinalysis

While patient interviews are useful for identifying some noncompliers in the clinical setting more objective techniques are required both for research

392 Annals New York Academy of Sciences

studies and for clinical practice. Urinalysis techniques for drug and drug metabolites have recently been reported for hydrochlorothiazide,O, 7 alpha- methyldopa and propranolol.* The development of simple urinary or salivary dipstick techniques would be highly useful to clinicians. The development and use of such techniques will depend on the excretion patterns of the substances being tested and on variation among patients in excretion patterns. If excretion occurs too rapidly, the test will be highly influenced by it’s time relationship to ingestion of the drug and if excretion occurs very slowly, with accumulation of the substance over time, then even low compliance may result in a positive test.

Pill Counts

In settings where the investigator has control over the dispensing of drugs, home visits to count remaining pills can be used to compute the percentage of prescribed pills which was consumed. The only assumption which must be made is that pills removed from pill bottles were in fact ingested by the patient and not taken by some other family member or simply discarded. Pill counts are more difficult when the investigator does not control dispensing of the drugs. In this situation he must either perform repeat visits to assess pill counts for at least two points in time or attempt to use pharmacy records of date and number of pills dispensed. Although some investigators have asked patients to bring their pills to clinic visits this request is not always complied with and also runs the risk that patients may empty their bottles beforehand in order to avoid being confronted with their lack of compliance. A simple pill-count procedure recommended by Mayer 9 for clinical practice is to prescribe pills per day in multiples of 7 to correspond to the number of weeks between clinic visits. Enquiry during clinic visits into whether the patient needs a new prescription or whether he still has pills left from the old one will help the physician identify noncompliers.

In addition to the problems noted with our current methods of measuring compliance, additional problems exist in the varying definitions and reporting practices of different investigators. The definition of what level of compliance should be used to separate patients with adequate from those with inadequate compliance has varied across studies. For clinical practice this level should be selected on the basis of the degree of compliance required to produce a therapeutic effect. This will of course differ among drug regimens. Gordis lo reports that 33% compliance is adequate for the treatment of streptococcal infection, while Sackett l1 has identified 80% as the degree of compliance necessary with current antihypertensive regimens to produce consistent progress toward blood pressure control. While such dichotomous measures are desirable for clinical decision-making, the study of compliance behavior should employ continuous measures such as the percentage of pills consumed over a given period, and reporting should include whole compliance distributions. The development of reliable, valid, and simple methods of measuring compliance and identifying patients with inadequate levels, is an imperative for both clinical practice and the conduct of research into the natural history, determinants, and modification of patient compliance.

MAGNITUDE

A true picture of the magnitude of noncompliance with antihypertensive drugs would require a longitudinal study of an inception cohort with multiple

Taylor et af.: Compliance With Drug Therapy 393

determinations of compliance at various points after the initiation of drug therapy. In the absence of such data we will review a number of studies of compliance with long-term regimens for asymptomatic illness with the following two reservations. First, studies that do not report on an inception cohort, or a group of subjects identified when just beginning a drug regimen but rather report compliance rates for a group of subjects currently on therapy, will under- estimate the magnitude of noncompliance because they will not include patients who refuse to continue therapy and leave the treatment setting. And second, studies which, although beginning with an inception cohort, are of short duration, cannot provide data on the extent to which people are likely to adhere to a life-long preventive drug regimen.

In the Australian blood pressure program, which is examining the treatment of mild asymptomatic hypertension, Abernathy13 has reported that 19% of patients have refused to continue with treatment within the first 2 years, most of whom withdrew in the first few months. Other studies of long-term regimens for prevention report average rates from 19% to 42% with penicillin prophylaxis for rheumatic fever l4 and with eyedrops for glaucoma.15 Among ambula- tory chronic asthmatic children receiving oral administration of theophylline, Eney l6 found that only 11 % complied enough to show therapeutic levels using a salivary test. Even with increased patient supervision only 42% achieved therapeutic levels. Using a medication dispenser containing radioactive material and a photographic film to determine the regularity with which medication packets were removed, Moulding l7 found that 31 % of 122 supposedly reliable tuberculosis outpatients took less than 70% of their medication.

Our own investigation4 of compliance among an inception cohort of 144 hypertensive steelworkers revealed a U-shaped distribution with only 53 % of patients complying with at least 80% of the prescribed drug regimen. The shape of this distribution is similar to that reported by Gordis lo for long-term penicillin prophylaxis for rheumatic fever and may thus represent an observation common to long-term preventive regimens.

In a followup of a community population of individuals who had volunteered for a shopping-center screening program we found that of those who were started on treatment by their physician, 21 % had stopped treatment a year later and that of those individuals who remained in treatment, only 60% claimed to be fully compliant with the drug regimeas Since patients are known to overestimate their own compliance, the actual extent of full compliance is undoubt- edly even less. This brief summary of current evidence indicates that noncompliance is both common and substantial among patients on long-term regimens for prevention of disease.

CLINICAL SIGNIFICANCE

The above-documented magnitude of the compliance problem does not in itself indicate the clinical significance of noncompliance. Therapeutic benefit may be achieved with less than perfect compliance, thus clinical significance must be determined by comparing patient compliance with achievement of the treatment goal.

A simple conceptual model l8 of this relationship is presented in FIGURE 1. We would expect that patients should fall into either the lower right-hand cell where compliance is poor and the treatment goal is not achieved or preferably, into the upper left-hand cell where high compliance occurs together with


HIGH

achievement of the treatment goal. However, some patients do fall into the other two cells of this table and the possible reasons for this must be considered in clinical practice. Patients may not achieve the treatment goal despite high compliance because either the prescribed therapy is inadequate or the definition of high compliance is too lenient. Similarly patients who achieve the treatment goal despite low compliance may have been misdiagnosed as in need of treatment, may have received a regimen that was more potent than necessary so that partial compliance was sufficient for therapeutic effect or the definition of what constitutes adequate compliance may in fact be too stringent. Thus the course of action required of a physician is not automatically determined by compliance and treatment success or failure. The diagnosis, the treatment, and the patient’s level of compliance are all possible targets for change.

After the first 6 months of therapy among 134 steelworkers we observed that patients had to consume at least 80% of their prescribed medication before consistent progress was made toward control of blood pressure.I1 Defining high

IDEAL

I GOAL BLOOD PRESSURE 1

LOW

I ACHIEVED

MISDIAGNOSIS OVERADEQUATE THERAPY DEFINITION OF LOW COMPLIANCE TOO STRINGENT

1 NOT ACHIEVED

C 0 M P L I A N C E

INADEQUATE THERAPY DEFINITION OF HIGH COMPLIANCE TOO LENIENT

INTERVENTION NEEDED

FIGURE 1. Factors affecting the relationship between compliance and achievement of goal blood pressure.

compliance as consumption of at least 80% of prescribed medication and goal blood pressure as less than 90 mm Hg diastolic we found that only 23% of subjects achieved goal blood pressure together with high compliance, and another 12% achieved goal blood pressure despite inadequate compliance. Although a total of 65% of subjects failed to achieve goal blood pressure, this group was composed of 31% with low compliance and 34% with high compliance. Thus, after 6 months of therapy, the issues of diagnostic accuracy, adequacy of the prescribed drug regimen, and the appropriate definition of adequate compliance were of clinical importance for the subsequent management of these patients.

RISK FACTORS FOR NONCOMPLIANCE

The search for the determinants of noncompliance has been motivated by the hope that understanding might lead to the development of strategies for prevention and intervention, and by the belief that awareness of these risk


factors might help physicians identify noncompliant patients. Studies have examined the relationship between compliance and a multitude of factors asso- ciated with the patient, the illness, the treatment and the delivery of health care, but factors have usually been considered one at a time and few conceptual models have been proposed for considering combinations of factors. Although the determination of compliance behavior is potentially idiosyncratic and complex, a number of relationships have occurred consistently in reported studies. Most researchers have spoken of these factors as determinants of compliance behavior despite their basis in correlational analyses. Although these “determinants” may not be directly causitive, we may consider them as risk factors for noncompliant beha~ i0 r . l~ These factors cannot however, be considered as either sufficient or necessary to produce compliance or noncompliance and thus while they may serve as useful cues in clinical practice, they are not sufficiently reliable to replace objective measurements of compliance.

Duration of Therapy

The treatment of mild asymptomatic hypertension, like other preventive regimens, requires that the patient maintain good compliance with long-term therapy to achieve health benefits that lie far in the future. Studies of inception cohorts have consistently revealed compliance decay over time.20 Luntz,21 found that tuberculosis patients on long-term chemotherapy display progressive de- terioration in compliance over time with negative urine tests for all patients after 5 years of treatment. Abernathyl:’ has reported that 19% of patients treated for mild hypertension discontinue therapy in the first 2 years. In a recent followup of an inception cohort of 144 hypertensive steelworkers we successfully contacted 130 (90%) 2 to 3 years after the initiation of drug therapy. Only 63% of these men reported that they were still on treatment.

Regimen Complexity

Studies have consistently shown a negative correlation between the complexity of the drug regimen and patient compliance. In a review of 15 articles dealing with regimen complexity, Haynes ’’” identified only four that disagreed with this conclusion. Porter :‘‘ has shown poorer compliance for a thrice daily regimen of ferrous sulphate compared to a once daily regimen, and Weintraub 2s

found that adding potassium and a diuretic to a digoxin regimen led to decreased compliance. Thus both frequency of dosings per day and number of drugs prescribed may influence compliance.

Patient Factors

The most sophisticated and promising attempt to identify risk factors for noncompliance is the health belief model. Originally formulated by Rosen- stock 24 to explain participation in immunization and screening programs, this model has recently been extended to compliance behavior.25 The model identi- fies a number of patient perceptions and beliefs which are thought to influence compliance. These include the general valuing of personal health, which must


be sufficiently strong to make health-related behavior competitive with other life goals and attractions, perceived susceptibility to the negative consequences of the disease, and the belief that these consequences are of sufficient severity to cause disruption of one’s life if they occur. These three factors having established motivation to comply, the initiation of specific health action depends on the patient’s perception of the efficacy of various treatment possibilities and on treatment barriers, including cost, convenience and psychosocial pressures, which may hinder action.

We have tested this model among hypertensive patients in two settings. First, health beliefs were assessed among steelworkers during blood pressure screening before the diagnosis of hypertension had occurred and again after 6 months of therapy. Health beliefs measured during screening were generally unrelated to compliance following 6 and 12 months of drug therapy. The one exception was expression of the concern that illness led to undesirable dependency on others, which predicted subsequent noncompliance ( r = -.22, p < .01). When beliefs expressed after 6 months of therapy were correlated with compliance over the next 6 months, significant correlations were observed for perceptions of the seriousness of hypertension, ( r = .27, p < .01) negative attitudes toward drug taking (r=-.32, p < .01) and the belief that illness led to dependency (r = -.23, p < .01). This suggests that inquiring into health beliefs concerning the treatment of hypertension is most likely to predict compliance when assessed after the diagnosis has been made and probably after the patient has had some experience with the treatment regimen.

In a community setting we measured health beliefs, compliance and blood pressure in the patient’s home following a minimum of one year of therapy.5 For 136 patients whose diastolic blood pressure remained at or above 95 mm Hg on two consecutive home visits, these variables were again assessed at a return home visit 6 months later. A composite scale was constructed, which included beliefs in the seriousness of hypertension, the health benefits of therapy and the usefulness of drugs in controlling blood pressure. Changes in this scale over the 6-month period correlated (partial correlation controlling for entry health beliefs) with changes in compliance, measured both by pill counts ( r = .21, p < .05) and by the patient’s verbal report ( r = .23, p < .01). It thus appears that changes in health beliefs are indicative of changes in patient compliance.

Podell 26 reporting on hypertensive patients in a single practice, found that patient denial and rationalization of the need for treatment was a major factor among 9 of 19 patients who either dropped out of therapy or remained in poor blood pressure control while this factor was present in only one of 22 patients who were in fair or good control.

Another important patient factor is the extent to which the patient obtains support from family members. In a review of six studies, five showed higher compliance among patients with supportive intact families, while one showed no association.2o

Patient-Therapist Interaction

The study of patient-therapist interactions has been difficult and frequently of uncertain validity. However, two consistent findings exist in this area. First a positive correlation has been found between the degree of patient supervision


and compliance, with increased compliance resulting from increased frequency of out-patient visits, home visits by public health nurses, hospitalization and engaging the patient’s family to assist with supervision.20 The second consistent finding is a positive correlation between compliance and patient satisfaction with the therapist and clinic and with the filling of patient’s expectations. The attitude expressed by the physician toward the treatment may also influence compliance. Abernathy partly attributes the drop-out rate in the Australian blood pressure study to the ambivalence expressed to patients by physicians concerning the efficacy of treating mild hypertension.

Side Effects

Although drug side effects are frequently reported among hypertensive patients they rarely constitute a major reason for noncompliance. Podell 28

reported that side effects were important contributors to poor blood pressure control in only 2 of 53 patients. During home visits on 416 community patients who had all been on treatment for at least one year we found that 63 (1 5% ) claimed to be currently experiencing side effects from hypotensive medications. However, self-reported compliance was not related to self reports of side effects; 29% of patients experiencing side effects reported less than perfect compliance, compared to 34% for patients who reported that they were not experiencing side effects.

Symptom

The absence of physical complaints among patients with hypertension means that the immediate cues and motivation for taking medication common to acute, symptomatic illnesses are not operative. While the literature does not clearly relate lack of symptoms to noncompliance, studies of self-reported reasons for noncompliance reveal that “feeling that drugs weren’t needed” is the most common reason given for noncompliance by patients on antihypertensive drug regimens. Among our 416 community patients5 15% reported that they had stopped taking medication at some point during treatment because they felt they didn’t need it. In addition, 11 % reported stopping on their doctor’s advice, 3% because of drug side effects, 2% through forgetfulness and 2% for other reasons.

METHODS OF IMPROVING COMPLIANCE

For the physician who has identified a compliance problem the need to prescribe or perform an effective compliance improving maneuver is just as important as was the original need to prescribe efficacious therapy for the disease or illness. Although few randomized trials of compliance-improving strategies exist, and very few within the treatment of hypertension, research in this area is beginning to gain momentum. After considering those compliance-improving strategies that have been studied with hypertensive patients and attempting to identify the active ingredients of these strategies we will consider the limitations of past research and consider possible directions for future research.


Increased Patient Supervision

Three studies have shown substantial improvement in compliance and blood pressure when supervision of hypertensive patients was increased with specific attention to compliance problems. After conducting a door-to-door blood pressure screen on a random sample from a middle Georgia community, Wilbur and Barrow 27 selected 220 hypertensive individuals whom they thought might benefit from regular home visits by a public health nurse. Only 88 of these individuals accepted the maneuver, which involved regular home visits to check on blood pressure and to instruct patients on the nature and treatment of high blood pressure with emphasis on the importance of taking pills. Over a 2-year period this strategy raised the percentage of subjects on treatment from 25% to 86% and the percentage with blood pressure control from 15% to 80%. However, after terminating the home visits and leaving patients on their own for another two years, the percentage on treatment dropped to 5 5 % , and only 29% had good blood pressure control. The lack of permanence in the substantial benefits achieved by a 2-year home visiting program is particularly dis- couraging in light of the fact that the group studied was composed of volunteers who would presumably have been far more motivated than the majority of subjects who did not volunteer.

In a recent controlled trial, 50 hypertensive patients were randomly assigned to receive or not receive increased supervision from their pharmacist.2R This involved monthly visits for 5 months during which the pharmacist identified and managed complaints, adverse drug reactions and problems related to compliance. Compliance was measured by pill counts and defined as taking plus or minus 10% of the doses prescribed. During the study period the percentage of subjects meeting this definition of compliance rose from 25% to 79% in the experimental group while control patients changed from 16% to 17%. Similar results were obtained for blood pressure control. During a 6-month followup however, after the service was withdrawn, the percentage of patients defined as compliant had returned to 25% for experimental patients and 16% for control patients. Thus all of the benefit achieved by the pharmacist-supervision program disappeared upon termination of the intervention.

We observed similar results in a study among hypertensive steelworker^.^ After their first 6 months of therapy 38 subjects who remained hypertensive (diastolic 2 9 0 mm Hg) and exhibited less than 80% compliance by pill count were randomly assigned to receive or not receive an intensive set of intervention maneuvers directed toward improving compliance. These included regular visits to the company medical clinic where patients were taught to measure their own blood pressure, given home blood pressure kits and asked to keep daily charts of blood pressure and pill taking. Also, attempts were made to solve compliance problems and patients were asked to try linking pill taking to other well-established daily rituals, like shaving in the morning. At the end of a 6-month period, average compliance had risen from 44% to 66% in the intervention group and fallen from 45% to 43% in the control group. Diastolic blood pressure had fallen by 5.4 mm Hg in the intervention group and by 1.9 mm Hg in the control group. However, upon reexamining these patients one year after termination of the study, average compliance had dropped to 39% in the experimental group and to 23% in the control group.

Because all three of these intervention programs employed a combination of tactics, it is not possible to determine which of the tactics account for the


short term benefits observed. We have recently completed a randomized trial in a community population which sheds some light on this issue.5 A group of 136 hypertensive patients with diastolic blood pressure consistently at or above 95 mm Hg on two separate home visits were randomly assigned to receive or not receive monthly home visits for a six month study period. Within each of these groups, patients were also randomly assigned to receive or not receive self-monitoring of blood pressure. Monthly home visits were conducted by survey interviewers who had been trained to measure blood pressure and to report readings to both the patient and his physician. Compliance was measured by pill counts at the beginning and end of the trial and blood pressure was assessed at the end of the trial by an independent observer who was unaware of the group to which patients had been randomized. This monthly home visit maneuver did not produce benefits in terms of compliance or blood pressure. A key difference between this and the three previous trials is the lack of any attempt to confront the patient directly with his compliance problems or to stress the need to comply. It thus appears that increased supervision of patients may need to include this tactic to have an impact upon compliance behavior. Whether compliance problem solving or mere social pressure or support is the active ingredient remains unknown, however. Studies have not displayed results of compliance and blood pressure change by degree of success at problem resolution. Such a breakdown should reveal a gradient of effect if problem solving per se is responsible for the benefits observed. The possibility that problem solving is not responsible is suggested by the return of compliance and blood pressure to pre-study levels once the supervision is terminated when problem solutions have presumably already been achieved.

Educational Strategies

Increasing patient knowledge about hypertension and its treatment has usually been tried as only one component of a much larger package of intervention maneuvers. This makes an evaluation of the acquisition of information per se impossible. In order to separately evaluate the information component of educational programs, we developed a slide-tape show and accompanying booklet that explained hypertension, the benefits of treatment and the need to take medication. For the first 6 months of therapy, 144 hypertensive steelworkers were randomly assigned to receive or not receive this education program." By the end of the 6-month education program, 85% of the subjects assigned to receive education had mastered the information. This was defined as achieving a knowledge test score of at least 80% correct. Testing of non- educated patients revealed that only 18% scored at this level. Despite this difference in knowledge about hypertension and it's management, educated patients did not achieve better compliance or blood pressure control. Further- more, compliance rates after 6 months of therapy bore no relation to knowledge about hypertension, when measured either at entry to the study ( r = -.03) or at six months (r = .08).

In McKenny's ** study of pharmacist supervision, education tests at the end of the study revealed that subjects who had received the experimental program knew more about hypertension than did controls ( p < .001). This improvement in knowledge did not have a long term beneficial effect, however. As already noted, compliance rates returned to pre-study levels within 6 months after termination of the study.


Joubert and Lasagna 2o have recommended the use of patient-oriented package inserts which would accompany dispensed drugs and inform the patient concerning their use. Despite the demonstrated ineffectiveness of most informa- tional efforts this strategy should be experimentally evaluated for its possible effect on patient compliance.

Although there are reasons for informing patients about their illness and its treatment and although it is obvious that patients need to know the require- ments of a regimen before they can comply with it, present evidence indicates that increasing patients’ knowledge about hypertension will not have a significant impact on compliance.

Self-Monitoring of Blood Pressure

The vast majority of hypertensive patients are without symptoms, and lack of health complaints is the most frequently expressed reason for noncompliance. Thus, home blood pressure machines, which permit frequent, convenient, self- monitoring of blood pressure might improve compliance by providing patients with a visible sign of their illness. This strategy has been evaluated in three randomized controlled trials. The 6-month trial among hypertensive, noncompliant steelworker^,^ previously described, found an intervention package containing self-monitoring of blood pressure effective in raising compliance from a mean of 44% to a mean of 66%. However, during the following year when subjects were left on their own with their blood pressure machines, mean compliance dropped to 39%. This fall in compliance occurred despite the fact that most of the experimental patients continued to self-monitor blood pressure.

Our second trial among 136 hypertensive community patients employed a 2 X 2 factorial design in which subjects were randomly assigned to receive or not receive monthly home visits, blood pressure kits, both of these or neither of these.G We have already noted that home visits did not improve compliance or blood pressure control; in addition, blood pressure kits also proved ineffective in this group of patients.

In order to examine the potential of self-monitoring among patients just starting an antihypertensive regimen, Carnahan and Nugent 30 randomly assigned 100 new patients to receive or not receive a sphygmomanometer with a built in stethoscope. Although compliance was not measured, changes in blood pressure after 6 months of drug therapy revealed an identical drop of 10.4 mm Hg diastolic for both groups. Systolic blood pressure, however, showed a significant ( p < .05) difference dropping 10.5 mm Hg among controls and 18 mm Hg among experimental patients.

It thus appears that self-monitoring of blood pressure is not likely to improve compliance when applied either to all patients who remain refractory to treatment or to all new patients just starting drug therapy. Although self-monitoring cannot be established as a panacea for all compliance problems, the possibility remains that it may be effective in certain cases. It may prove productive for example, to experimentally test the value of self-monitoring among patients who report that they fail to comply because they feel well.

Modifying Drug Regimen Complexity

Although descriptive studies have found a negative correlation between the complexity of the drug regimen and patient compliance, no controlled trials

Taylor et al.: Compliance With Drug Therapy 40 1

have been conducted to determine the effect of varying regimen complexity on compliance. A randomized controlled trial varying dosings per day and also comparing combination versus separate-tablet regimens would provide valuable new information. Although there may be good pharmacologic reasons for administering divided doses spaced over time, the therapeutic effect achieved may in fact be greater with a simpler regimen if it results in greater patient compliance.

Medication Packaging

Specially designed pill containers and calendar dispensers have been shown to improve compliance with a l0-day regimen of oral penicillin31 and in a 3-month study of compliance with antituberculosis medi~ation.~* In a randomized controlled trial, Eshelman found that a medication dispenser improved compliance, as measured by urine assay, with a once-daily regimen of chlorthalidone. Unfortunately, neither pill counts nor subjects’ self reports of compliance confirmed this result. Also, follow-up was completed on only 67 of the initial 100 subjects making interpretation of these results difficult. While specially designed pill dispensers have shown some promising results in short- term studies with once-daily regimens, they require further experimental study over longer periods and with more complex regimens.

CONCLUSIONS AND DIRECTIONS FOR COMPLIANCE IMPROVING STRATEGIES

Supervision versus Self-Management

Increasing patient supervision with direct attention to patient compliance is the only intervention strategy that has consistently improved compliance. The benefits achieved, however, have always undergone substantial or total decay upon termination of the supervision program. We therefore require studies to determine whether long-term supervision would maintain improved compliance, to identify the active ingredients responsible, to consider possible negative consequences including the development of over dependence on health care professionals and to evaluate the cost-effectiveness of various supervision maneuvers.

Further, a proper balance must be found between the provision of effective medical supervision and the development of personal responsibility and self- management techniques for hypertensive patients.

Panacea versus Problem-Specific Interventions

The search for methods of improving patient compliance has been domi- nated by a research strategy that applies a single method to all patients without attention to the specific determinants of noncompliance or to the patient’s par- ticular resources for solving compliance problems. These studies represent the search for a compliance panacea. While a single effective means of dealing with all compliance problems would be highly desirable, the complexity of compliance behavior may mean that problem-specific interventions will have to be found, and that current research strategy should be replaced by experimental testing of different intervention techniques among patients with different problems and resources.


Prevention versus Intervention

As well as considering methods of intervening among noncompliant patients, we should also consider strategies for establishing good compliance at the beginning of therapy and for preventing the development of noncompliant behavior patterns. While experimental studies have investigated the preventive power of patient education," a work-site clinic,11 and self-monitoring of blood pressure,J0 none of these strategies has proven effective in establishing and maintaining good compliance.

Circumvention of the Compliance Issue

In view of the enormous difficulties encountered in establishing or changing human behaviors, methods of treatment that do not depend on long-term patient compliance would be highly desirable. Although the possibilities of a cure or long acting drug for hypertension appear remote, we should not dismiss the search for simple solutions. The possibility of maintaining adequate compliance with a life-long preventive drug regimen among most hypertensive patients, may prove equally remote.

REFERENCES

1. GORDIS, L. 1976. Methodological issues in the measurement of patient compliance. I n Compliance With Therapeutic Regimens. D. L. Sackett and R. B. Haynes, Eds. : 51-66. Johns Hopkins University Press. Baltimore, Md.

2. CARON, H. S. & H. P. ROTH. 1971. Objective assessment of cooperation with an ulcer diet. Am. J. Med Sciences. 261: 61-66.

3. FEINSTEIN, A. R. & H. F. WOOD, J. A. EPSTEIN, A. TARANTA, R. SIMPSON, & E. TURSKY. 1959. A controlled study of three methods of prophylaxis against streptococcal infection in a population of rheumatic children. New Engl. J. Med. 260 697-702.

4. HAYNES, R. B., D. L. SACKEIT, E. S. GIBSON. D. W. TAYLOR, B. C. HACKEIT, R. S. ROBERTS & A. L. Johnson. 1976. Improvement of medication compliance in uncontrolled hypertension. Lancet i: 1265-1268.

5. JOHNSON, A. L., D. W. TAYLOR, D. L. SACKEIT, C. W. DUNNEW & A. G. SHIMIZU. 1977. Self blood pressure recording-an aid to blood pressure control? Ann. Royal College of Physicians and Surgeons of Canada 10( 1): 32.

6. ESHELMAN, F. N. & J. FITZLOFF. 1976. Effect of packaging on patient compliance with an antihypertensive medication. Curr. Ther. Res. 20: 215-219.

7. LOWENTHAL, D. T., W. A. BRICCS, R. M. MUTTERPERL, B. ALDERMAN & M. A. CREDITOR. 1976. Patient compliance for antihypertensive medication: the usefulness of urine assays. Cum. Ther. Res. 19: 405-409.

8. BRIGOS, W. A., D. T. LOWENTHAL, W. J. CIRKSENA, W. E. PRICE, T. P. GIBSON, & W. FLAMENBAUM. 1975. Propranolol in hypertensive dialysis patients: efficacy and compliance. Clin. Pharmacol. Ther. 18: 606-612.

9. MAW, T. C. 1969. Drug defaulting in general practice. Br. Med. J. 1: 783. 10. GORDIS, L., M. MARKOWITZ & A. M. LILIENFELD. 1969. Studies in the epi-

demiology and preventability of rheumatic fever. Pediatrics 43: 173-182. 11. SACKEIT, D. L., R. B. HAYNES, E. S. GIBSON, B. HACKEIT, D. W. TAYLOR, R. S.

ROBERTS, A. L. JOHNSON. 1975. Randomized clinical trial of strategies for improving medication compliance in primary hypertension. Lancet i: 1205- 1207.


12. SACKETT, D. L. 1976. The magnitude of compliance and noncompliance. I n Compliance With Therapeutic Regimens. R. L. Sackett & R. B. Haynes, Eds. : 9-25. Johns Hopkins University Press. Baltimore, Md.

13. ABERNATHY, J. D. 1976. The problem of non-compliance in long-term antihypertensive therapy. Drug 11( 1 ) : 86-90.

14. HEINZELMANN, F. 1962. Factors in prophylaxis behavior in treating rheumatic fever: An exploratory study. J. Health Human Behav. 3: 73-81.

15. VINCENT P. 1971. Factors influencing patient noncompliance: A theoretical approach. Nurs. Res. 20: 509-516.

16. ENEY, R. D. & E. 0. GOLDSTEIN. 1976. Compliance of chronic asthmatics with oral administration of theophylline as measured by serum and salivary levels. Pediatrics 57(4): 513-517.

17. MOULDING, T., G. D. ONSTAD & J. A. SBARBARO. 1970. Supervision of outpatient drug therapy with the medication monitor. Ann. Intern. Med. 73:

18. SACKETT, D. L. 1976. I n Compliance With Therapeutic Regimens. D. L. Sackett & R. B. Haynes, Eds. : 1-6. Johns Hopkins University Press, Baltimore, Md.

19. BLACKWELL, B 1976. Treatment adherence. Br. J. Psychiatry 129: 513-531. 20. HAYNES, R. B. 1976. A critical review of the “determinants” of patient com-

pliance with therapeutic regimens. I n Compliance With Therapeutic Regimens. D. L. Sackett & R. B. Haynes, Eds. : 26-50. Johns Hopkins University Press. Baltimore, Md.

21. LUNTZ, G. R. & R. AUSTIN. 1960. New stick test for P.A.S. in urine; report on use of “Phenistix” and problems of long-term chemotherapy for tuberculosis. Br. Med. J. 1: 1679-1684.

22. PORTER, A. M. W. 1969. Drug defaulting in a general practice. Br. Med. J. 1:

23. WEINTRAUB, M., W. Y. W. AU & L. LASAGNA. 1973. Compliance as a deter- minant of serum digoxin concentration. JAMA 224: 481485.

24. ROSENSTOCK, I. M. 1966. Why people use health services. Milbank Mem. Fund Q. 44:94-124.

25. BECKER, M. H. & L. A. MAIMAN. 1975. Sociobehavioral determinants of corn- pliance with health and medical care recommendations. Medical Care 13: 10-24.

26. PODELL, R. N., D. K. KENT & K. K. KELLER. 1976. Patient psychological de- fenses and physician response in the long-term treatment of hypertension. J. Family Practice 3: 145-149.

27. WILBER, J. A. & J. G. BARROW. 1969. Reducing elevated blood pressure. Minn. Med. 52: 1303-1306.

28. MCKENNEY, J. M., J. M. SLINING, H. R. HENDERSON, D. D. DEVINS & M. BARR. 1973. The effect of clinical pharmacy services on patients with essential hypertension. Circulation 4 8 1104-1 I l l .

29. JOUBERT, P. & L. LASAGNA. 1975. Patient package inserts, nature, notions and needs. Clin. Pharmacol. Ther. 18: 507-513.

30. CARNAHAN, J. E & C. A. NUGENT. 1975. The effects of self-monitoring of patients on the control of hypertension. Am. J. Med. Sci. 269: 69-73.

31. LINKEWICH, J. A., R. B. CATALANO & H. L. FLACK. 1974. The effect of packaging and instruction on outpatient compliance with medication regimens. Drug Intell. Clin. Pharm. 8: 10-15.

32. MOULDING, T. 1961. Preliminary study of the pill calendar as a method of improving the self-administration of drugs. Am. Rev. Respir. Dis. 84: 284-287.

559-564.

218-222.

compliance with antihypertensive drug therapy

Documents