Oncology Nursing Society
Putting Evidence into Practice (PEP)
Assessment and Measurement of Medication Adherence:
Oral Anti-Cancer Agents
Sandra L. Spoelstra, PhD, RN
Oncology Nursing Society Congress
April 20, 2015
Orlando, FL
Objectives
I. To define medication adherence.

In relation to oral anti-cancer agents (OAC).
II. To describe the methods
available to assess and measure
medication adherence.
The Problem
• Despite efforts to encourage adherence to
oral agents for cancer (OAC), rates are
sub-optimal. (Bassan, 2014)
• OAC adherence is a problem which may
impact treatment success. (Puts, 2013)
• There is need to assess and measure
OAC adherence.
Definition
Adherence: “The degree or extent of conformity to the
recommendations about day-to-day treatment by the
provider with respect to the timing, dosage, and
frequency for the duration of time from initiation to
discontinuation of therapy.”
(Cramer, 2007)
– Timing (e.g. time of day – 9:00 AM)
– Dosage (e.g. 200 mg)
– Frequency (e.g. daily, BID, TID)
• Examines:
– Taking < than prescribed
– Taking > than prescribed
– Doses taken too close together
Therapeutic Dosing
• FDA Guidelines OACs (U.S. Food & Drug Administration, 2014)
• Inadequate dosing can occur:
– Due to toxicities from side effects of treatment
– Dose reductions or stoppages
– Problems with obtaining the medication
(Bozic, 2013; Gebbia, 2012; Puts, 2013).
• Tumor response or survival dosing is not known:
– Whether 80% of the dosage is adequate
– Or if 90% may be effective (Alberto, 1994)
Relative Dose Intensity (RDI)
• Ratio of dose taken over time compared to the
ordered dose. (Amgen, 2008)
• Maintaining RDI reduces survival of resistant
clones, increases percent of cells killed per
dose, and decreases intervals between
treatment cycles.
• Results in greater treatment efficacy.
• Most oncologists prefer 100% OAC adherence
to assure RDI.
Complexities of OACs
• Simple:
– Once daily dosing
• Complex:
– More than daily dosing
– On-and-off cycling
– Two or more drugs
(Spoelstra et al., 2013)
The Process
• PEP Team Project: Literature search
to identify ways to assess and
measure medication adherence
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Oncology Nursing Society: Margaret Irwin PhD, RN, MN
Cynthia Rittenberg, MN RN FAAN, AOCN
Lee Ann Johnson, RN, PHDc
Carol Blecher, MS, APNC, OACN, CBPN-C, CBCN
Peggy Burhenn, MS, CNS, AOCNS
Larissa Day, MSN, RN, CONC
Diana McMahon, MSN, RN, OCN; AOCN
Theresa Rudnitzki, MS, RN, ACNS-BC, AOCNS
Josephine Smudde, MS, RN, BC, OCN
Holly Sansoucie, RN,MSN, DNP, AOCN, CBCN
Sandra Spoelstra, PhD, RN
Janelle Tipton, MSN, RN, AOCN
Results
• Measures:
– 3-Direct measures were identified
– 4-Indirect measures were identified
• 7-Tools were identified in the literature
– Tools were divided into two categories:
1. Ability to assess risk of non-adherence
2. Ability to measure adherence rates
Direct & Indirect
MEASURES
Direct Measures
• Drug assays of serum or urine – not
available for OACs
• Drug markers – do not exist for OACs
• Direct observation of medication ingestion6
• COSTLY AND
IMPRACTICAL
Indirect Measures
• Self-report
– Overestimates adherence due to questions not being specific,
desire to please providers, and decreased cognitive ability to
recall. Unreliable
• Pill counts
– Overestimate. Time consuming
• Electronic monitoring systems
– No way to know if ingested. Expensive and unrealistic for clinical
setting
• Pharmacy records and claims
– Proportion of days covered (PDC): summing # days in a time
period “covered” by the medication divided by # days in the
period. Unrealistic for clinical setting as doctors do not have this
access
To Assess
TOOLS
Morisky Medication
Adherence Scale (MMAS)
• Evaluates past medication use patterns
• Four “yes” or “no” questions (Moriskey, 1986)
– Scored with a 1 for “yes” and a 0 for “no”; summed
– Score of 0 is high adherence, 1-2 is medium, and 3-4 is low
• Psychometrics:
– Predictive validity 0.75 adherence; 0.47 nonadherence
– Sensitivity 0.81; Specificity 0.44
• Floor/ceiling effects likely, due to the nature of questions
– Makes tool unreliable to measure adherence
• May be effective at predicting risk of nonadherence
Adherence Estimator
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Three-item tool (McHorney, 2009)
Screens likelihood of nonadherence
Placed in categories: low, medium, high scores
Psychometrics:
– Sensitivity high: Cronbachs alpha at 0.88
– Specificity acceptable at 59%
• Does not assess adherence rate
• May accurately predict risk of nonadherence.
Beliefs about Medication
Questionnaire (BMQ)
• 17-item two-section, self-report tool (Horne, 1999)
1. BMQ-Specific assesses medications prescribed for personal use
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Two 5-item factors assess beliefs about necessity of medication and concerns
based on beliefs about the danger of dependence and long-term toxicity and the
disruptive effects
2. BMQ-General assesses beliefs about medicines in general.
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Two 4-item factors assessing beliefs about medicine overuse and safety
• Score:
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1-point strongly disagree; 2-disagree, 3-uncertain, 4-agree, 5-strongly agree
Higher scores (range 10—50) indicate better adherence
Cronbachs Alpha each sub-scales >0.80
Sensitivity and specificity lacking to measure adherence
• Can possibly predict nonadherence
• Tedious process for clinical setting.
Adherence Starts with
®
Knowledge (ASK-20 )
• ASK-20® (Hahn et al., 2008)
– 20 clinically actionable items
• Whether medication was taken >, < than prescribed,
skipped, or stopped.
• During past week, month, 3-months, >3-months, never
– Cronbachs alpha 0.85
– Convergent reliability with self-reported
adherence is good
– Tool is not scored
– Cannot assess adherence rates.
• May be useful to assess risk of nonadherence
Adherence Starts with
®
Knowledge (ASK-12 )
• Shorter version of ASK-20 (Matza et al., 2009)
• Three subscales that are scored:
– Adherence behavior
– Health beliefs
– Inconvenience or forgetfulness
• Psychometrics:
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Internal consistency reliability (α=0.75)
Test-retest reliability (Intraclass Correlation 0.79)
Convergent validity correlations with MMAS p<0.001\
Proportion days covered pharmacy claims data p=0.06.
• Can possibly be adequate in predicting risk of
nonadherence and measuring adherence rates
Medication Adherence Report
Scale (MARS)
• Ten “yes” or “no” questions
– Scores 0-10; 10 represents high likelihood of adherence
• Developed from 30-item Drug Attitudes Inventory (DAI) and
4-item Medication Adherence Questionnaire (MAQ)
• Create more reliable and valid tool (Fialko, 2008)
• Good internal consistency (α=0.75)
• Insufficient sensitivity (53%), specificity (57%), positive
predictive value (42% to 57%) to detect nonadherence
• Receiver operating curve 0.56 (95% CI 0.521 to 0.616;
p=0.01), does not accurately predict risk of nonadherence
• Does not accurately predict risk of non-adherence or rates
of adherence
Brief Adherence Rating Scale
(BARS)
• 4-items: 3-questions plus visual analog scale to assess
the proportion of doses taken in past month (Byerly, 2008)
– # prescribed doses taken per day
– # days, over the past month, the patient did not take the prescribed doses
– # of days over the past month, the patient took less than the prescribed doses
• Psychometrics:
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BARS and MEMS® medication adherence significant p<0.0001
Cronbachs very high internal reliability (α=0.92)
A moderate/strong test–retest reliability 0.53 to 0.92
Concurrent validity significant to PANSS p=0.002
Good sensitivity (73%) and specificity (74%)
• Sufficient validity, reliability, sensitive and specific to
estimate risk of nonadherence and adherence rates
Assessing and Measuring Medication Adherence
STATE OF THE SCIENCE
• Ability to assess and/or measure OAC
medication adherence is poor.
– Most measures are indirect, and include a
form of self-report that cannot truly capture if
the medication was taken.
– A few tools are able to assess risk of
nonadherence
– Lack specificity to determine adherence
– Nor can both OAC underadherence and
overadherence can be examined.
Tools that may be useful for
measuring adherence rates:
• ASK-12®
• BARS
Tools that may assess risk of
non-adherence:
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Adherence Estimator
Morisky
ASK-12®
BARS
Implications for Research
• Need for practice-based tools
• Technology
– Including timing, dose, frequency, & duration
Implications for Nursing Practice
• Adherence needs
to be defined,
assessed, and
documented.
References
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Cancer, 82(Suppl.1), 3s–8s. Retrieved from http://www.jle.com/en/revues/bdc/revue.phtml
Amgen. (2008). Increasing awareness of relative dose intensity in an evidence-based practice. Retrieved from
http://www.onsedge.com/pdf/amgenEBP.pdf
Bassan, F., Peter, F., Houbre, B., Brennstuhl, M. J., Costantini, M., Speyer, E., & Tarquinio, C. (2014). Adherence to oral antineoplastic agents
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