Measuring adherence – an “Achilles heel” in medication adherence

  • Adherence measurement is a complex task, which can be performed through various direct and indirect methods
  • Each method has its advantages and limitations with no universal consensus on a gold standard technique
  • The use of combinatorial methods might offer the best solution. Further, there is a need to optimize techniques for different populations as well as for complex medication regimens1-3

Medication adherence is of great significance for the effective pharmacological treatment of any disease. A low rate of adherence is associated with poor outcomes and decreased quality of life, which results in an additional burden for the healthcare systems4. Therefore, accurately quantifying the medication adherence rate, is a crucial step in estimating the effectiveness of various interventions as well as formulating recommendations for patients regarding their medication-taking behavior5.

Adherence measurement – Direct & Indirect methods

Adherence measurement techniques can be broadly classified into two types: direct and indirect methods. Direct methods include firsthand monitoring of the patient taking the medication (through direct observation or smart adherence products) or the detection of the drug or its metabolite in the patient’s biological fluid. Indirect methods refer to self-reporting, electronic adherence monitoring tools (e.g. MEMS – medication event monitoring system), pharmacy refill rates, and pill counts. The choice of using direct or indirect methods depends on the intended use of adherence measurement information, the available resources, patient acceptance, and the convenience of the method5. Some commonly used adherence measurement techniques are listed below:

Direct method:

  1. Smart adherence products: These products (such as, ingestible biosensors, smart pill containers, wearable sensors and others) capture and transmit real-time medication intake by using various means of connectivity, thus allowing for instantaneous remote monitoring.Adherence feedback is a major component of these type of products. For instance, digital pills contain ingestible electronic sensors capable of measuring medication adherence instantaneously and also providing adherence supports accordingly6,7.
  1. Biologic fluid drug levels/biomarkers: Biologic detection of drug or other biomarker levels in a patient’s bodily fluids can be used for obtaining proof that a patient has recently taken a dose of medication; however in case of a short half-life of a drug, this method has limited usefulness5,8.
  1. Direct observation: The direct observation of a patient’s medication-taking behavior by healthcare providers can be used as proof of the intake of the medicine. While, this method is simple and easy to implement for hospitalized or institutionalized patients, but can be impractical to use in large population settings4.

Indirect methods:

  1. Self-reporting: Self-reporting methods include patient-kept medication records/diaries, interviews, and responses to adherence-specific questionnaires. Several multi-item questionnaires, such as the Morisky scale, Hill-Bone scale, and others are developed intending to find out reliable estimates of adherence. While this is the most common method for assessing adherence behavior in research and clinical care5,9, there exists non-uniformity across various interviews and questionnaires due to differences in their methodology as well as the nature and format of questions.
  1. Electronic-adherence monitoring devices: Electronic devices such as MEMS consist of a computer chip in the bottle cap, which records the date and time each time the pill bottle is opened. These devices can be used to reliably report the adherence rate, however, researchers have argued on the scope of reactivity bias, that is, change in adherence behavior of patients if they have prior knowledge of his or her behavior being monitored, also known as the Hawthorne effect4,5,10.
  1. Pharmacy Refill Rates: Pharmacy data may serve as a source for the calculation of refill rates which describe the number of picked-up prescriptions as a percent of the total prescribed doses. This provides an objective measurement of medication adherence and highly correlates with dose-count adherence assessed by electronic monitoring systems at the patient end. However, refill rates do not measure the actual administration of the medication, and only provide an estimation of the acquisition and possession of medication3,5.
  1. Pill Counts: This is a simple method to count the dosage units (tablets, capsules, or vials) that the patient has not taken between two scheduled clinic visits. It requires patients to bring the entire medication supply to every visit with the healthcare provider for record keeping. Moreover, this method is subjective as patients might remove the drugs from the container before their next clinic visits in order to register a good adherence rate5,11.

Current scenario: Advantages & Limitations

Every adherence measurement method has its advantages and limitations that should be considered before employing a given method and subsequently while interpreting results (Table 1). Direct methods are considered to be more accurate than indirect methods; however, the complicated logistics of performing these measurements are its limitations. Also, direct measurements are relatively costly and are more labor-intensive for the healthcare provider. On the other hand, indirect methods are more commonly employed, due to their overall ease of use and less costly implementation2.

Table 1: Advantages and limitations of commonly used adherence measurement techniques2,4-6,12

Measurement methodsAdvantagesLimitations
Smart adherence productsReal-time data sharing; Multiple functionalities like adherence support, alarms, and notificationsExpensive; technology-intensive
Biologic fluid drug levels/biomarkersObjective measurement, reliableInvasive, unsuitable for multidrug regimen/ short half life drugs
Direct observationSimple, physical evidenceunsuitable for wider implementation, human resource intensive
Self-reportingConvenient, low costRecall and response bias, low accuracy, overestimation
Electronic-adherence monitoring devicesReal-time data sharing, synchronization with reminder systems, complex dosing regimenExpensive, incompatibile  with conventional packaging, technical and mechanical failures
Pharmacy Refill RatesUnobtrusive, simple, low costOverestimation, non-standardized database, delay in data availability
Pill CountsSimple, easy to implement, mostly used in clinical trialsScope of undermining the result as no evidence of ingested medicine

Electronic monitoring systems: Preferred solution

While there is no consensus on a universal gold standard technique, MEMS has emerged as the practical and the best-suited choice. Research shows a close correlation between medication adherence based on MEMS and the clinical efficacy of different treatments in various therapeutic areas. It has also been used to validate other adherence measurement methods2. However, its high costs and lack of information regarding the types of nonadherence (intentional or unintentional) means that there is still a need for better electronic monitoring systems10.

New developments in this area include the Real Time Medication Monitoring (RTMM) system, and the real-time wireless Electronic Adherence Monitor (EAM), which can also potentially intervene with the underlying adherence challenges3.

Multidirectional approach: Present need for adherence monitoring

Different estimation methods for measuring adherence often produce varying results. A meta-analysis comparing different estimation methods for medication adherence found that only about half of these self-reported methods and non-self-reported methods were consistent2. Therefore, it has been suggested that utilizing more than one method of measuring adherence simultaneously can increase overall accuracy. The weaknesses of one method can be overcome by using the strengths of a complementary method. For instance, combining direct methods like biological testing intermittently with indirect methods like counting pharmacy refill rates, might strengthen the overall evaluation. The combination strategy is based on the concept called the composite reference standard (CRS), where the results of several imperfect tests are used to define a single reference standard. The premise relies on the assumption that the combination is more accurate than each of the methods making up CRS independently2.

Additionally, there is limited evidence for a standardized method to measure adherence to multiple medications. With the increasing prevalence of polypharmacy, more efforts should be directed toward combining various methods that can be used to evaluate adherence to complex regimens13.


Measuring medication adherence is a first and crucial step towards a better understanding of non-adherence, which has profound consequences on both, an individual health outcome as well as on the whole healthcare system. Although several methods for measuring medication adherence are available, it is generally acknowledged that a gold standard method has not been yet identified through the consensus from the scientific community. Hence, the perfect method to measure medication adherence does not exist. The future research scope includes investigating combinations of methods to provide an accurate assessment of adherence and optimizing the best-suited measurement technique for different populations such as pediatrics and the elderly.

“Alone we can do so little. Together we can do so much.” – Helen Keller


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10.  Chan AHY, Horne R, Hankins M, Chisari C. The Medication Adherence Report Scale: A measurement tool for eliciting patients’ reports of nonadherence. Br J Clin Pharmacol. Jul 2020;86(7):1281-1288. doi:10.1111/bcp.14193

11.  Ernawati I, Lubada EI, Lusiyani R, Prasetya RA. Association of adherence measured by self-reported pill count with achieved blood pressure level in hypertension patients: a cross-sectional study. Clin Hypertens. Apr 15 2022;28(1):12. doi:10.1186/s40885-022-00195-5

12.  Lam WY, Fresco P. Medication Adherence Measures: An Overview. Biomed Res Int. 2015;2015:217047. doi:10.1155/2015/217047

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