So you want to measure adherence… Subjective Measures: provider or patient’s evaluation of medication-taking behavior General advantages: inexpensive, low burden, non- invasive, simple General disadvantages: tendency to underestimate nonadherence to avoid disapproval

Questionnaires and Scales validated scales that ask patients about adherence in a time frame Advantages: standardized, validated measurement specific to disease or medication types, can assess beliefs or attitudes about medication adherence Disadvantages: impacted by patient’s psychological state, negativity in questions may lead to blaming patients, influenced by literacy

8-item Morisky Medication Adherence Scale (MMAS-8)

4-item Morisky Medication Adherence Scale (MMAS-4)

Patient Interviews patients are asked to estimate medication taking behavior- percentage of doses missed Advantages: can inquire about patient’s knowledge of prescribed regimen Disadvantages: subject to self-report bias and avoidance of clinician disapproval

Patient Diaries patient records medication taking behavior with calendar or other form Advantages: only self-report tool that consistently documents how they follow regimen. Disadvantages: may overestimate adherence, patient may fail to return diary

Objective Measures Objective Measures: directly track or monitor medication-taking behavior General advantages: removes patient manipulation of self-report, increases accuracy General disadvantages: costly, time-consuming, moderately burdensome and invasive

Electronic Measures Monitors adherence by incorporating tracking device into packaging of prescription medication. An embedded microprocessor records the date and time that medication is removed from the container. Advantages: Records and stores dose events, real-time monitoring, feedback on adherence performance; may have improved accuracy Disadvantages: Costly, assumes that the dose is taken at the time it is removed from the container. Requires patient to place medication into the MEMS, Glowcap, or Wisepill bottle after pick-up from pharmacy, is difficult for use with medications that are not to be taken every day, in which the patient may be told to hold medication for a period of time due to side effects (e.g., oral chemotherapies);

Electronic Measurement Wisepill GlowCaps MEMSCap

Pill counts counts number of doses taken between two scheduled appointments to calculate an adherence ratio. Advantages: low cost, simple Disadvantages: not effective for PRN dosing, underestimates adherence if amount dispensed is in surplus of the amount that is supposed to be taken. Subject to patient manipulation

Secondary database analyses Evaluation of sequences and patterns of prescription refills from data in electronic prescription services or pharmacy insurance claims. See attached Table for adherence equations from secondary database analysis and pill counts. Perhaps most commonly used is the Medication Possession Ratio (MPR) that computes the days the medication was supplied out of the refill interval. Advantages: Can assess multidrug adherence; identify patients at risk for treatment failure Disadvantages: Assumes that refill adherence corresponds to actual medication taking behavior. Assumes that medication is taken exactly as prescribed so cannot account for partial adherence. Does not give information about barriers to adherence for individual patients.

Biochemical measures Measurement of the drug or metabolite concentration in body fluids (e.g., blood or urine), or measurement of the presence of a biomarker given with the drug Advantages: most accurate; provides physical evidence of medication taking Disadvantages: generate a yes/no without details of patterns or causes of nonadherence, not all drugs have measurable biomarkers, drug metabolism must be accounted for, expensive, may lead to increased adherence around the time of the visit

Adherence Ratios/Equations

An additional note: Depending on your study, you may want to consider objective or subjective measures. Multi-subjective measure approaches may have high sensitivity, but not accuracy over a single objective measure. Subjective and objective measures should be used in conjunction; however, controversy exists around how well these rates map onto one another.

References Svarstad, B. L., Chewning, B. A., Sleath, B. L., & Claesson, C. (1999). The Brief Medication Questionnaire: a tool for screening patient adherence and barriers to adherence. Patient education and counseling, 37(2), 113-124. Tan, X. I., Patel, I., & Chang, J. (2014). Review of the four item Morisky medication Adherence Scale (MMAS-4) and eight item Morisky medication Adherence Scale (MMAS-8). Innov Pharm, 5(3), 5. Culig, J., & Leppée, M. (2014). From Morisky to Hill-bone; self-reports scales for measuring adherence to medication. Collegium antropologicum, 38(1), 55-62. Lam, W. Y., & Fresco, P. (2015). Medication adherence measures: an overview. BioMed research international, 2015.