lists the identified studies, the number of subjects, the methods of assessing adherence, and the criteria used to define adherence. Of 161 studies that were identified, 93 were classified as specifically adherence studies, and 68 were classified as general studies that included a measure of adherence to oral antipsychotic medication. The most common method used to assess adherence in both general and adherence studies was the report of the patient. Self-report was utilized alone or in combination with other methods a total of 107 times in 161 studies. Moreover, 25% (17/68) of general studies and over 36% (34/93) of all studies that specifically examined adherence to medication used self-report as the sole assessment of medication adherence. Self-report methodologies themselves differed greatly among studies and included ad hoc measures, interview (unspecified), semistructured interviews (unspecified), and semistructured interviews using the Rating of Medication Influences (ROMI),9
Treatment Compliance Interview (TCI),9
Drug Attitude Inventory (DAI),10
the medication compliance item from the Multnomah Community Ability Scale (MCAS),11
Medication Adherence Rating Scale (MARS),12
knowledge level, medication checklist, attitudes and insight, which asked subjects if there was a week or 2 weeks in the past variable period of time during which they stopped medication, and medication refusal.
Adherence Definitions and Methodology
Other methods were used less frequently. In order of frequency, methods were treatment provider report, family or significant other report, chart review, pill count, electronic refill information, electronic monitoring, blood level, urine analysis of medication, and urine analysis of a tracer substance. illustrates the specific frequencies of use of each method in the 161 studies. The subjective/indirect measures of assessing adherence were used 218 times (some studies used more than 1 of these methodologies) and were the only measures used in 124 of the 161 studies. Out of 161 studies, pill counts, blood levels, urine analysis, electronic monitoring, electronic refill records, or tracers that could provide objective or direct data regarding medication adherence were used only 43 times, representing a total of 37 of 161 studies. Of these 37 studies, 27 were specifically adherence studies and 10 were general studies. In one-fourth of these studies, the objective methodology was used only in part of the sample, only when reports by the patient were questioned (no criteria provided), only when the patient brought the urine or pills in to be examined, or only when available (usually with no information on how many subjects had such data available). One study used ability to take medication in a performance-based assessment.
Number of Times Specific Adherence Methodologies Have Been Utilized.
Even in cases where studies used the same methodology to assess adherence, the definition of adherence varied greatly. describes the various levels of discrimination between adherence and nonadherence and the numerous ways to define nonadherence to oral medication. Any inception cohort of individuals for whom it is recommended that medication be taken continuously can be divided into those who refuse and those who accept medication. In a study using this first level of discrimination depicted in , those who agree to take medication (accept) would be adherent, and all others would be considered nonadherent. For those who accept the medication, the next level divides subjects into those who continue to use it for a period of time and those who discontinue use for some time period, which varies across studies. At this level, those who discontinue use are nonadherent, all those who continue using the medication, even if dosages vary considerably from what is prescribed, are considered adherent. The next level of inquiry examines only those who continue to take medication. These individuals may take medication as prescribed or not. How much an individual can vary from the prescribed dosage and still be considered compliant differs by study. Dosage deviations can be due to a decision that less medication is better, due to unintentional factors such as forgetting, or due to environmental barriers such as poverty and lack of transportation.
Defining Subjects in Adherence Studies.
With respect to dosage deviation, in the 161 articles we found dosage cutoffs that ranged from 50% to 90% and categorical classifications ranging from taking any of the prescribed medication to taking nearly every dose. Likert-type scales that were not divided into percentage of medication taken varied from 3 points to 7 points, with a variety of different terms for each point, including “overreliance on medication” at the high end of 1 scale.
For electronic refill data, a common adherence measure was the mean gap or the length of time for which no medication was available to the patient. An alternative measure examined patients who had gone a quarter without a claim for medication.
Several studies reported using Medication Event Monitoring System, or MEMS—pill bottle caps capable of recording the time and date each time the bottle is opened. Openings for other reasons (eg, filling), if known to the researchers, must be deleted to provide an accurate estimate of the number of doses taken. While MEMS is sometimes described as a “gold standard” of adherence assessment, in the studies using MEMS for schizophrenia patients, the fact of missing data was identified as a problem. One study reported close to 45% of data missing due to failures on the part of the patient to bring in the MEMS caps in order to download the information.13