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Adherence measures and their utility
Adherence Measures and Their Utility Jacqueline Dunbar Department of Psychiatry, Stanford University School of Medicine
ABSTRACT: This article addresses the variety of adherence measures available to the researcher, with particular reference to the utility of markers. It is proposed that the generic nature of the research question will suggest both the adherence definition and the appropriate assessment methodology. Each measurement procedure offers somewhat different information and has unique advantages and disadvantages. It is suggested that markers are limited by the relatively short duration of the measurement period, the lack of quantitative data on adherence, and, with some, the potential for confounding influences on their specificity. The probable value of markers lies in validating the subject's recent self-report, determining recent medication ingestion, and estimating the probability of adherence over time.
This article considers the advantages and disadvantages of various adherence measurement procedures available to the individual investigator. The question that a researcher addresses will suggest a definition for adherence, since there is no consistent definition in this field. That definition will further suggest some specific measurement techniques. Each adherence definition will have three components. First is the behavior of interest. In most of these cases, this is medication consumption. Second is how the researcher wants to describe that consumption. The third component is the time frame of interest. Given these components, there are three general categories of definitions [1]. The first category, and the one offering the most information, is a quantitative definition, which assumes that medication consumption is a continuous variable. Data are collected on the quantity of medication taken, contrasted with the quantity prescribed over a specific time period. This definition examines the patterns of adherence within subjects or groups and the distribution of adherence levels within a group of subjects and establishes criteria for various categories of adherence. This quantitative definition also provides specific adherence information that allows comparisons between studies. The second type of definition is qualitative and places subjects into categories of adherence, for example good, poor. In most studies, these categories have been arbitrarily defined and not reported by the individual investigator.
Address reprint requests to: Jacqueline Dunbar, Ph.D., R.N., Department of Psychiatry, Laboratory of the Study of Behavioral Medicine, Stanford University School of Medicine, TD-205, Stanford, California 94305. Controlled Clinical Trials 5:515-521 (1984) © Elsevier Science Publishing Co., Inc. 1984 52 Vanderbilt Ave., New York, New York 10017
515 0197-2456/84/$03.00
516
Jacqueline Dunbar Thus, the reader does not know the definition for any given category. This definition is most satisfactory for an examination of the proportion of persons who fall into various categories. It is not suitable for an examination of patterns of adherence. If a clear criterion has been established for each of the categories, a qualitative definition may describe the distribution of adherence levels by category within a group of subjects. A qualitative definition may also determine whether a therapeutic dose of medication has been ingested (in this case there are two categories: yes and no) and whether the ingested dose has been effective. The use of categories will be more satisfactory if some specific and reported quantitative definitions have been established. The third type of definition provides an index of adherence behaviors. In this case, adherence to a variety of health-care regimens or a variety of medications is summed. The summed score is reported as the ii~dex of adherence. The most familiar index is that used by Becker et al. [2]. These researchers combine knowledge of the regimen, appointment date, medication consumption, and appointment keeping. A composite score is estimated and serves as the compliance score. The utility of these definitions will vary depending on the period of time of interest to the researcher. The quantitative definition will be the most useful when adherence is described over time. The categorical definition will be useful over time if it is backed up by a quantitative definition. To determine whether a therapeutic dose has been ingested or whether an ingested dose has been effective, the category definition is going to be useful over a short time period. It is unlikely that the index definition will have great utility unless, as with the category type of definition, it is backed up by a quantitative definition and scores for each behavior are presented. The following generic questions will call upon one or some combination of these definitions of adherence and will indicate ~i variety of measurement methods, including the use of markers: 1. Has a therapeutic dose been ingested within some specific time period? 2. What proportion of people in some treatment program have been good or poor adherers within some specific time period? 3. What are the patterns of adherence within a subject or group of subjects over some time period? 4. What are the distributions of adherence levels within a group of subjects over some time period? 5. What is the adherence rate (index) for a total treatment program? 6. Has the dose that was ingested been effective and obtained a satisfactory biological outcome? In summary, the nature of the research question will suggest the most appropriate adherence definition. The question and the definition will suggest the type of data and, hence, assessment methodology that will be most useful. All of this must be examined within the context of the time period of interest to the researcher.
Adherence Measures and Their Utility
517
MARKERS
Substances utilized for markers ought to be inert and noncumulative. Specific and sensible detection methods must be available, and the markers must be unaffected by the Chemical characteristics of the subject's biological fluid or tissue [3]. These requirements limit the utility of markers as measures of patient adherence. In general, markers do not assess the actual quantity of drug that has been ingested. They report whether the subject has ingested medication containing the marker. Furthermore, markers will not report adherence over time. Their usefulness is limited to specific and brief time periods. For example, riboflavin, a commonly used marker, is very rapidly excreted, limiting the measurement period to approximately 6-12 hours following medication ingestion. Riboflavin would not be a good marker for subjects being evaluated after a 6-12hour fast. Furthermore, the consumption of vitamin B tablets, multiple vitamin tablets, or vitamin B-enriched foods could produce a positive test, even though medication has not been ingested. Markers cannot determine whether medication has been ingested within a very specific and time-limited period, the proportion of subjects that are good or poor adherers, or the patterns of adherence within a subject or group of subjects over time. A marker will determine the proportion of subjects that have consumed medication within the past certain number of hours. Epstein and Masek developed a model technique using a marker to examine compliance over time [4]. In this procedure, subjects were placed on a fourtimes-daily vitamin C regimen. Three tablets each week contained phenazopyridine, a drug producing a bright, red-orange urine discoloration. Using a self-monitoring procedure, the subjects were asked to note when the urine discolorations occurred. Compliance was assessed by comparing the time of the report to the time when the urine discoloration was predicted, on the basis of the scheduled sequence of vitamin C alone and phenazopyridinecontaining tablets. Thus, an estimation of adherence over time could be determined. This provides a rough estimate, since the actual quantity of medication ingested on a daily basis cannot be evaluated. A slightly more refined and specific procedure was developed by Marshall, Johnson, and Taylor [5]. In this case, lactose capsules were flavored with four different flavorings. The capsules were prepared and numbered in a unit dose pack. Four subjects were asked to take these capsules for a week. The subjects were asked to self-record the unit dose number and taste of each capsule that was ingested. A comparison was made between the flavorings the subject identified and the order in which they were packaged by the researchers. Varying taste sensitivity among participants was a problem, with at least one subject consistently confusing the tastes of certain flavorings. Developing markers that the patient can monitor over time and that provide longer-term data is certainly a novel and exciting approach. This should not be confused with the provision of very specific information on the levels of adherence obtained by individual subjects. Markers do not provide data on the distributions of levels of adherence within a group of subjects. Presently, markers are limited to determining whether patients have taken
518
Jacqtieline Dunbar medication on or about the day in which such ingestion is being evaluated. They may be most useful with the interview or self-report measure to determine the validity of that report for the current or preceding day. The usefulness of markers would be greatly enhanced were they able to provide information over time, information on levels of adherence, and information on individual patterns of adherence over time. Like all measures of adherence, the usefulness is enhanced by the addition of other measures.
BIOLOGICAL ASSAYS A measurement procedure related to the use of markers is the detection of a drug or its metabolites in the serum or urine of the patient. This procedure can offer information on whether a drug has been ingested. Moreover, it can offer information on whether a therapeutic dose has been ingested, although the time period is fairly restricted. Furthermore, biological assays do not provide information on the proportion of subjects w h o are good or poor adherers. They do not provide information on patterns of adherence within subjects or groups of subjects or on the distribution of levels of adherence within a group. The problems unique to the biological assays involve individual variations in the absorption, metabolism, and excretion of drugs. All of these factors influence serum and urine levels. For example, in a study by Weintraub, utilizing patients with low serum digoxin levels and self-reported high compliance, abnormal patterns were detected in half of the patients [6]. The problems included an unusually rapid fall in serum concentration and decreased or less-than-normal absorption of the medication. Classification of patients into adherers and nonadherers would be misleading on the basis of the biological evaluation alone. Furthermore, the drug-taking habits of patients may alter the ability to classify them on adherence dimensions using these biological assays. A patient could take medication for some time period prior to the assessment, but not for the duration of time between assessments, and still show positive, that is, compliant, evaluations. The patient might take a less than full prescribed dose and still show evidence of medication ingestion, possibly even at a therapeutic level. If the biological assay is positive, one can assume that the subject has ingested medication within some fairly specific time period before the assessment procedure was carried out. If the results of the evaluation are negative, one needs to determine whether the patient is noncompliant or has an abnormal or unusual metabolism of the medication. Thus, the biological assays provide a screening device regarding recent adherence.
PILL COUNT The pill count can determine whether a therapeutic dose has been ingested, the proportion of subjects that have been good or poor adherers, the patterns of adherence within a subject or group of subjects over time, and the distributions of levels of adherence within a group of subjects. It does provide a quantitative determination of the degree of compliance or level of compliance
Adherence Measures and Their Utility
519
over an extended period of time. The pill count is probably the most useful in the research setting, where the dispensing of medication can be controlled. In the clinical setting, the pill count is much more problematic since patients may elect to use a variety of pharmacies or may have a favored pill bottle in which all medication goes. Problems may occur with the labeling of the bottle itself; for example, the number of pills dispensed and/or date may be missing from the label. The return of unused medication is a problem in both the research and clinical setting. The patient needs to be reminded to bring back unused medication, particularly until they form the habit of doing so. This was a problem, for example, in the study by Fletcher, Pappius, and Harper in which serum digoxin levels and pill count methods of assessing compliance were compared [7]. After contacting the patients by telephone and asking them to return medication at their next appointment, the researchers found that 20 percent still left medications at home. Furthermore, medication might be consumed by family members or friends. Patients may share medication with a spouse or a friend. We have all heard reports from patients or friends who have shared their water pills, sleeping pills or tranquilizers, and antibiotics with friends and relatives. The pill count tends to report somewhat higher compliance than the biological assays and has a reasonable correlation with self-monitoring [7]-[9]. In a small investigation conducted in the Lipid Research Clinics program, we compared adherence reports based on self-monitoring with the compliance reports based on a standard packet count. In this case, the correlations were about 0.9. MONITORS Mechanical monitors offer another method of assessing compliance [10,11]. In this case, medication adherence is evaluated by examining the mechanical recording of medication being withdrawn or dispensed from the monitor. As with the pill count, actual consumption cannot be evaluated. If one makes the assumption that medication taken from the dispenser is likely to be ingested, this method of adherence assessment can determine whether the medication was consumed. Over time, one can evaluate patterns and levels of adherence within subjects and within groups by an examination of the day-to-day and, indeed, within each day consumption of medication. A disadvantage of these procedures is that they tend to be relatively expensive. Most such monitors are in the process of development and are not readily accessible to the general public or the general researcher. It is likely that a major utility for the monitors, given their cost, is as a validation for the pill count or self-monitoring strategies in patients for w h o m such data appear unreliable. SELF-MONITORING
As with the pill count and medication monitor, self-monitoring can determine medication consumption and whether subjects are good or poor adherers, identify patterns of adherence within subjects and within groups of
520
Jacqueline Dunbar subjects, and identify distribution levels of adherence over time. More discrete information is offered than can be obtained through the pill count, since theoretically each adherent or nonadherent episode is recorded. This procedure is particularly useful for determining specific patterns of non-compliance in an effort to offer remedial intervention and for collecting information on natural compliance patterns over time. One of the difficulties of the selfmonitoring process is that it may be reactive. In a clinical setting, the selfmonitoring program may be useful in terms of both intervention and assessment. However, in the research setting, if one is primarily interested in a description of adherence without intervention, accurate information may not be obtained. Furthermore, it may be difficult to get subjects to self-monitor over a long time period. Self-monitoring may be particularly useful in conjunction with other assessment procedures such as markers. These require markers that subjects can self-observe be developed and utilized with medications. Patients could do periodic self-monitoring, reporting on the detection or nondetection of the marker. The researcher could then do an assessment based on the self-reported daily adherence pattern as well as obtain a validity check through use of self-reported detection of the marker.
INTERVIEW
The interview is particularly useful in evaluating problems the patient may have and the factors that enhance adherence. Highly reliable data should not be expected, however, particularly if adherence is being assessed over a fairly long time period. Without specific attention focused on medication consumption, as it is in self-monitoring, it is easy for patients to inaccurately observe their own behavior. The patient may develop a habit of medication taking such that he may not be aware if medication has been taken, even in time periods quite adjacent to the usual medication-taking period. Further problems occur with memory over a long period. The patient may not remember his compliance rates. When compared with other measures, the interview tends to overestimate adherence. It is likely that the subject remembers when medication was taken but perhaps forgets when it was not taken and thus overestimates adherence. In a small study we did with a selected group of poor adherers, subjects overestimated their own adherence on interview by as much as one third when compared with a pill count assessment. The interview may provide information on whether the patient perceives himself to be a good or poor adherer. The interview may also provide information on the types of problems that contribute to an individual adherence pattern over time. However, it is unlikely to provide reliable information on these patterns due to the memory problems just noted. The interview is also unlikely to provide reliable information on the distribution of levels of adherence within a group. This assessment procedure is probably best utilized as an adjunct to more quantitative measures of adherence, specifically to provide in-depth information on the routine the patient follows and on the problems the patient has following the regimen.
Adherence Measures and Their Utility
521
SUMMARY
The selection of an adherence measurement procedure will follow from the question that is addressed. Each of the measurement procedures offers somewhat different information. None of the procedures by themselves are perfect, and they may be most useful when offered in combination. Markers may be best utilized in combination with pill counts or self-monitoring procedures. It is unlikely, given their current problems, that markers could be utilized as a solitary index of patient adherence.
REFERENCES
1. Dunbar JH: Assessment of medication adherence: A review. In: Patient Compliance to Prescribed Antihypertensive Medication Regimens: A Report to the NHLBI 1980, Haynes RB, Mattson ME, Engebretson TO, Jr., Eds. NIH Publication No 81-2102 2. Becker MH, Drachman RH, Kirscht JP: Predicting mothers' compliance with pediatric regimens. J Pediatr 81:843--845, 1972 3. Gordis L: Conceptual and methodologic problems in measuring patient compliance. In: Compliance in Health Care, Haynes RB, Taylor DW, Sackett DL, Eds. Baltimore: The Johns Hopkins University Press, 1979 4. Epstein JH, Masek BJ: Behavioral control of medicine compliance. J Appl Behav Anal 11:1-9, 1978 5. Marshall G, Johnson L, Taylor CB: Personal communication 6. Weintraub M, Au WYW, Lasagna L: Compliance as a determinant of serum digitoxin concentration. J Am Med Assoc 224:481--485, 1973 7. Fletcher SW, Pappius EM, Harper SJ: Measurement of medication compliance in a clinical setting: comparison of three methods in patients prescribed digoxin. Arch Intern Med 139:635-638, 1979 8. Roth HP, Caron HS, Hse BP: Estimating a patient's cooperation with his regimen. Am J Med Sci 262:269-273, 1971 9. Soutter BR, Kennedy HB: Patient compliance assessment in drug trials: usage and methods. Aust NZ J Med 4:360-364, 1974 10. Moulding T, Onstad GD, Sbarbaro JA: Supervision of outpatient drug therapy with the medication monitor. Ann Intern Med 73:559-564, 1970 11. NoreU SE, Granstr6m PA, Wassin R: A medication monitor and fluorescein technique designed to study medication behavior. Acta Ophthalmol (Copenh) (in press)
ABSTRACT: This article addresses the variety of adherence measures available to the researcher, with particular reference to the utility of markers. It is proposed that the generic nature of the research question will suggest both the adherence definition and the appropriate assessment methodology. Each measurement procedure offers somewhat different information and has unique advantages and disadvantages. It is suggested that markers are limited by the relatively short duration of the measurement period, the lack of quantitative data on adherence, and, with some, the potential for confounding influences on their specificity. The probable value of markers lies in validating the subject's recent self-report, determining recent medication ingestion, and estimating the probability of adherence over time.
This article considers the advantages and disadvantages of various adherence measurement procedures available to the individual investigator. The question that a researcher addresses will suggest a definition for adherence, since there is no consistent definition in this field. That definition will further suggest some specific measurement techniques. Each adherence definition will have three components. First is the behavior of interest. In most of these cases, this is medication consumption. Second is how the researcher wants to describe that consumption. The third component is the time frame of interest. Given these components, there are three general categories of definitions [1]. The first category, and the one offering the most information, is a quantitative definition, which assumes that medication consumption is a continuous variable. Data are collected on the quantity of medication taken, contrasted with the quantity prescribed over a specific time period. This definition examines the patterns of adherence within subjects or groups and the distribution of adherence levels within a group of subjects and establishes criteria for various categories of adherence. This quantitative definition also provides specific adherence information that allows comparisons between studies. The second type of definition is qualitative and places subjects into categories of adherence, for example good, poor. In most studies, these categories have been arbitrarily defined and not reported by the individual investigator.
Address reprint requests to: Jacqueline Dunbar, Ph.D., R.N., Department of Psychiatry, Laboratory of the Study of Behavioral Medicine, Stanford University School of Medicine, TD-205, Stanford, California 94305. Controlled Clinical Trials 5:515-521 (1984) © Elsevier Science Publishing Co., Inc. 1984 52 Vanderbilt Ave., New York, New York 10017
515 0197-2456/84/$03.00
516
Jacqueline Dunbar Thus, the reader does not know the definition for any given category. This definition is most satisfactory for an examination of the proportion of persons who fall into various categories. It is not suitable for an examination of patterns of adherence. If a clear criterion has been established for each of the categories, a qualitative definition may describe the distribution of adherence levels by category within a group of subjects. A qualitative definition may also determine whether a therapeutic dose of medication has been ingested (in this case there are two categories: yes and no) and whether the ingested dose has been effective. The use of categories will be more satisfactory if some specific and reported quantitative definitions have been established. The third type of definition provides an index of adherence behaviors. In this case, adherence to a variety of health-care regimens or a variety of medications is summed. The summed score is reported as the ii~dex of adherence. The most familiar index is that used by Becker et al. [2]. These researchers combine knowledge of the regimen, appointment date, medication consumption, and appointment keeping. A composite score is estimated and serves as the compliance score. The utility of these definitions will vary depending on the period of time of interest to the researcher. The quantitative definition will be the most useful when adherence is described over time. The categorical definition will be useful over time if it is backed up by a quantitative definition. To determine whether a therapeutic dose has been ingested or whether an ingested dose has been effective, the category definition is going to be useful over a short time period. It is unlikely that the index definition will have great utility unless, as with the category type of definition, it is backed up by a quantitative definition and scores for each behavior are presented. The following generic questions will call upon one or some combination of these definitions of adherence and will indicate ~i variety of measurement methods, including the use of markers: 1. Has a therapeutic dose been ingested within some specific time period? 2. What proportion of people in some treatment program have been good or poor adherers within some specific time period? 3. What are the patterns of adherence within a subject or group of subjects over some time period? 4. What are the distributions of adherence levels within a group of subjects over some time period? 5. What is the adherence rate (index) for a total treatment program? 6. Has the dose that was ingested been effective and obtained a satisfactory biological outcome? In summary, the nature of the research question will suggest the most appropriate adherence definition. The question and the definition will suggest the type of data and, hence, assessment methodology that will be most useful. All of this must be examined within the context of the time period of interest to the researcher.
Adherence Measures and Their Utility
517
MARKERS
Substances utilized for markers ought to be inert and noncumulative. Specific and sensible detection methods must be available, and the markers must be unaffected by the Chemical characteristics of the subject's biological fluid or tissue [3]. These requirements limit the utility of markers as measures of patient adherence. In general, markers do not assess the actual quantity of drug that has been ingested. They report whether the subject has ingested medication containing the marker. Furthermore, markers will not report adherence over time. Their usefulness is limited to specific and brief time periods. For example, riboflavin, a commonly used marker, is very rapidly excreted, limiting the measurement period to approximately 6-12 hours following medication ingestion. Riboflavin would not be a good marker for subjects being evaluated after a 6-12hour fast. Furthermore, the consumption of vitamin B tablets, multiple vitamin tablets, or vitamin B-enriched foods could produce a positive test, even though medication has not been ingested. Markers cannot determine whether medication has been ingested within a very specific and time-limited period, the proportion of subjects that are good or poor adherers, or the patterns of adherence within a subject or group of subjects over time. A marker will determine the proportion of subjects that have consumed medication within the past certain number of hours. Epstein and Masek developed a model technique using a marker to examine compliance over time [4]. In this procedure, subjects were placed on a fourtimes-daily vitamin C regimen. Three tablets each week contained phenazopyridine, a drug producing a bright, red-orange urine discoloration. Using a self-monitoring procedure, the subjects were asked to note when the urine discolorations occurred. Compliance was assessed by comparing the time of the report to the time when the urine discoloration was predicted, on the basis of the scheduled sequence of vitamin C alone and phenazopyridinecontaining tablets. Thus, an estimation of adherence over time could be determined. This provides a rough estimate, since the actual quantity of medication ingested on a daily basis cannot be evaluated. A slightly more refined and specific procedure was developed by Marshall, Johnson, and Taylor [5]. In this case, lactose capsules were flavored with four different flavorings. The capsules were prepared and numbered in a unit dose pack. Four subjects were asked to take these capsules for a week. The subjects were asked to self-record the unit dose number and taste of each capsule that was ingested. A comparison was made between the flavorings the subject identified and the order in which they were packaged by the researchers. Varying taste sensitivity among participants was a problem, with at least one subject consistently confusing the tastes of certain flavorings. Developing markers that the patient can monitor over time and that provide longer-term data is certainly a novel and exciting approach. This should not be confused with the provision of very specific information on the levels of adherence obtained by individual subjects. Markers do not provide data on the distributions of levels of adherence within a group of subjects. Presently, markers are limited to determining whether patients have taken
518
Jacqtieline Dunbar medication on or about the day in which such ingestion is being evaluated. They may be most useful with the interview or self-report measure to determine the validity of that report for the current or preceding day. The usefulness of markers would be greatly enhanced were they able to provide information over time, information on levels of adherence, and information on individual patterns of adherence over time. Like all measures of adherence, the usefulness is enhanced by the addition of other measures.
BIOLOGICAL ASSAYS A measurement procedure related to the use of markers is the detection of a drug or its metabolites in the serum or urine of the patient. This procedure can offer information on whether a drug has been ingested. Moreover, it can offer information on whether a therapeutic dose has been ingested, although the time period is fairly restricted. Furthermore, biological assays do not provide information on the proportion of subjects w h o are good or poor adherers. They do not provide information on patterns of adherence within subjects or groups of subjects or on the distribution of levels of adherence within a group. The problems unique to the biological assays involve individual variations in the absorption, metabolism, and excretion of drugs. All of these factors influence serum and urine levels. For example, in a study by Weintraub, utilizing patients with low serum digoxin levels and self-reported high compliance, abnormal patterns were detected in half of the patients [6]. The problems included an unusually rapid fall in serum concentration and decreased or less-than-normal absorption of the medication. Classification of patients into adherers and nonadherers would be misleading on the basis of the biological evaluation alone. Furthermore, the drug-taking habits of patients may alter the ability to classify them on adherence dimensions using these biological assays. A patient could take medication for some time period prior to the assessment, but not for the duration of time between assessments, and still show positive, that is, compliant, evaluations. The patient might take a less than full prescribed dose and still show evidence of medication ingestion, possibly even at a therapeutic level. If the biological assay is positive, one can assume that the subject has ingested medication within some fairly specific time period before the assessment procedure was carried out. If the results of the evaluation are negative, one needs to determine whether the patient is noncompliant or has an abnormal or unusual metabolism of the medication. Thus, the biological assays provide a screening device regarding recent adherence.
PILL COUNT The pill count can determine whether a therapeutic dose has been ingested, the proportion of subjects that have been good or poor adherers, the patterns of adherence within a subject or group of subjects over time, and the distributions of levels of adherence within a group of subjects. It does provide a quantitative determination of the degree of compliance or level of compliance
Adherence Measures and Their Utility
519
over an extended period of time. The pill count is probably the most useful in the research setting, where the dispensing of medication can be controlled. In the clinical setting, the pill count is much more problematic since patients may elect to use a variety of pharmacies or may have a favored pill bottle in which all medication goes. Problems may occur with the labeling of the bottle itself; for example, the number of pills dispensed and/or date may be missing from the label. The return of unused medication is a problem in both the research and clinical setting. The patient needs to be reminded to bring back unused medication, particularly until they form the habit of doing so. This was a problem, for example, in the study by Fletcher, Pappius, and Harper in which serum digoxin levels and pill count methods of assessing compliance were compared [7]. After contacting the patients by telephone and asking them to return medication at their next appointment, the researchers found that 20 percent still left medications at home. Furthermore, medication might be consumed by family members or friends. Patients may share medication with a spouse or a friend. We have all heard reports from patients or friends who have shared their water pills, sleeping pills or tranquilizers, and antibiotics with friends and relatives. The pill count tends to report somewhat higher compliance than the biological assays and has a reasonable correlation with self-monitoring [7]-[9]. In a small investigation conducted in the Lipid Research Clinics program, we compared adherence reports based on self-monitoring with the compliance reports based on a standard packet count. In this case, the correlations were about 0.9. MONITORS Mechanical monitors offer another method of assessing compliance [10,11]. In this case, medication adherence is evaluated by examining the mechanical recording of medication being withdrawn or dispensed from the monitor. As with the pill count, actual consumption cannot be evaluated. If one makes the assumption that medication taken from the dispenser is likely to be ingested, this method of adherence assessment can determine whether the medication was consumed. Over time, one can evaluate patterns and levels of adherence within subjects and within groups by an examination of the day-to-day and, indeed, within each day consumption of medication. A disadvantage of these procedures is that they tend to be relatively expensive. Most such monitors are in the process of development and are not readily accessible to the general public or the general researcher. It is likely that a major utility for the monitors, given their cost, is as a validation for the pill count or self-monitoring strategies in patients for w h o m such data appear unreliable. SELF-MONITORING
As with the pill count and medication monitor, self-monitoring can determine medication consumption and whether subjects are good or poor adherers, identify patterns of adherence within subjects and within groups of
520
Jacqueline Dunbar subjects, and identify distribution levels of adherence over time. More discrete information is offered than can be obtained through the pill count, since theoretically each adherent or nonadherent episode is recorded. This procedure is particularly useful for determining specific patterns of non-compliance in an effort to offer remedial intervention and for collecting information on natural compliance patterns over time. One of the difficulties of the selfmonitoring process is that it may be reactive. In a clinical setting, the selfmonitoring program may be useful in terms of both intervention and assessment. However, in the research setting, if one is primarily interested in a description of adherence without intervention, accurate information may not be obtained. Furthermore, it may be difficult to get subjects to self-monitor over a long time period. Self-monitoring may be particularly useful in conjunction with other assessment procedures such as markers. These require markers that subjects can self-observe be developed and utilized with medications. Patients could do periodic self-monitoring, reporting on the detection or nondetection of the marker. The researcher could then do an assessment based on the self-reported daily adherence pattern as well as obtain a validity check through use of self-reported detection of the marker.
INTERVIEW
The interview is particularly useful in evaluating problems the patient may have and the factors that enhance adherence. Highly reliable data should not be expected, however, particularly if adherence is being assessed over a fairly long time period. Without specific attention focused on medication consumption, as it is in self-monitoring, it is easy for patients to inaccurately observe their own behavior. The patient may develop a habit of medication taking such that he may not be aware if medication has been taken, even in time periods quite adjacent to the usual medication-taking period. Further problems occur with memory over a long period. The patient may not remember his compliance rates. When compared with other measures, the interview tends to overestimate adherence. It is likely that the subject remembers when medication was taken but perhaps forgets when it was not taken and thus overestimates adherence. In a small study we did with a selected group of poor adherers, subjects overestimated their own adherence on interview by as much as one third when compared with a pill count assessment. The interview may provide information on whether the patient perceives himself to be a good or poor adherer. The interview may also provide information on the types of problems that contribute to an individual adherence pattern over time. However, it is unlikely to provide reliable information on these patterns due to the memory problems just noted. The interview is also unlikely to provide reliable information on the distribution of levels of adherence within a group. This assessment procedure is probably best utilized as an adjunct to more quantitative measures of adherence, specifically to provide in-depth information on the routine the patient follows and on the problems the patient has following the regimen.
Adherence Measures and Their Utility
521
SUMMARY
The selection of an adherence measurement procedure will follow from the question that is addressed. Each of the measurement procedures offers somewhat different information. None of the procedures by themselves are perfect, and they may be most useful when offered in combination. Markers may be best utilized in combination with pill counts or self-monitoring procedures. It is unlikely, given their current problems, that markers could be utilized as a solitary index of patient adherence.
REFERENCES
1. Dunbar JH: Assessment of medication adherence: A review. In: Patient Compliance to Prescribed Antihypertensive Medication Regimens: A Report to the NHLBI 1980, Haynes RB, Mattson ME, Engebretson TO, Jr., Eds. NIH Publication No 81-2102 2. Becker MH, Drachman RH, Kirscht JP: Predicting mothers' compliance with pediatric regimens. J Pediatr 81:843--845, 1972 3. Gordis L: Conceptual and methodologic problems in measuring patient compliance. In: Compliance in Health Care, Haynes RB, Taylor DW, Sackett DL, Eds. Baltimore: The Johns Hopkins University Press, 1979 4. Epstein JH, Masek BJ: Behavioral control of medicine compliance. J Appl Behav Anal 11:1-9, 1978 5. Marshall G, Johnson L, Taylor CB: Personal communication 6. Weintraub M, Au WYW, Lasagna L: Compliance as a determinant of serum digitoxin concentration. J Am Med Assoc 224:481--485, 1973 7. Fletcher SW, Pappius EM, Harper SJ: Measurement of medication compliance in a clinical setting: comparison of three methods in patients prescribed digoxin. Arch Intern Med 139:635-638, 1979 8. Roth HP, Caron HS, Hse BP: Estimating a patient's cooperation with his regimen. Am J Med Sci 262:269-273, 1971 9. Soutter BR, Kennedy HB: Patient compliance assessment in drug trials: usage and methods. Aust NZ J Med 4:360-364, 1974 10. Moulding T, Onstad GD, Sbarbaro JA: Supervision of outpatient drug therapy with the medication monitor. Ann Intern Med 73:559-564, 1970 11. NoreU SE, Granstr6m PA, Wassin R: A medication monitor and fluorescein technique designed to study medication behavior. Acta Ophthalmol (Copenh) (in press)