Defining Adherence and Persistence
Sapna N. PatelUCSF Pharm. D. Candidate 2008Preceptor Dr. Craig S. SternMarch 21, 2008
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Relevance Evaluating adherence & persistence is necessary for
accurate assessment of:Cost-effectiveness of therapyQuantifying drug exposure in a population
over timeDrug Utilization Patterns for Formulary
DevelopmentIdentifying appropriate therapy for patientsAssessing clinical outcomes of treatmentPrior Authorization Criteria
Impact of A&P
Low adherence & persistenceIncreased morbidity & mortalityIncreased health-care costs“Forgiveness”: therapeutic effects
of drug therapy despite noncompliance
Proposed Definitions International Society for Pharmacoeconomics and
Outcomes Research (ISPOR)
Adherence (compliance): the extent to which a patient acts in accordance with the prescribed interval & dose of a dosing regimen
Persistence refers to the act of continuing treatment for the prescribed duration
Treatment adherence & persistence together contributes to overall drug effectiveness
CMS Definitions
Current Issues
Multiple definitions and measurement models Hinder health outcomes & cost-effectiveness
analysis Prevent comparisons of different studies
Standardized definition would:Help develop more effective strategies to
enhance medication related A&P and decrease health-care costs
Measures of Adherence
Direct Indirect Desired observation or study
evaluation period “Between fills” periods Treatment Gaps
Direct MethodsMethod Pros Cons
Directly Observed Therapy
Most accurate Time consumingImpracticalHiding pills
Medicine or Metabolite Blood Levels
Objective ExpensiveMetabolism variationWhite coat
adherence
Biologic Markers in blood
Objective Time consumingExpensive
Indirect MethodsMethod Pros Cons
Questionnaires, self-reporting
Cost-effectiveTime consumingUseful in clinical setting
SubjectiveInfrequent visits =
increased error
Prescription rate refills Objective ExpensiveMetabolism variationWhite coat Adherence
Pill Counts ObjectiveEasy-to-doQuantitative results
SubjectiveEasily altered by
patient
Measuring Adherence: Medication Possession Ratio (MPR)
MPR = total days’ supply
total # days evaluated
X 100
Equals overall percent adherence value (medication availability)
353/365 X 100 = fill in%
MPR (cont) Pros:
Easy to calculateWidely used adherence measure
Cons:Participants get >1 fill in one day (ex: vacation supply)Change in prescribing directionsRefills occur close to study termination
“Between Fills” Measures Days Between Fills Adherence Rate
(DBR) DBR =
(last claim date – 1st claim date) – total days’ supply
last claim date – 1st claim dateX 1001 -
Compliance Rate (CR) CR =
total days’ supply – last days’ supply
last claim date – 1st claim dateX 100
Refill Compliance Rate (RCR) RCR =
total days’ supply
last claim date – 1st claim dateX 100
Medication Possession Ratio, Modified (MPRm)
MPRm = total days’ supply
(last claim date – 1st claim date) + last days’ supplyX 100
“Between Fills” Measures Pros:
Helps accounts for cutoff examination date period Consistent results seen with denominator of total
study evaluation period Cons:
In cases of single refills Smaller denominator
Cannot assess/overestimation of adherence
Treatment Gaps
total days’ study participation – total days’ supply
total days’ study participation
CMG =
Ex: (362-365)/362 = 0.00 or -0.01
total gap days
Range: 0.0 = complete adherence 1.0 = complete non-adherence (-) values = surplus days (due to early refill or
overfill)
Continuous Measure of Medication Gaps (CMG) :Provides time patient does not have medication available (%)
Measuring Persistence
Minimum-Refills Model Proportion of Days Covered Model Refill Sequence Model Anniversary Model
Minimum-Refills Model
Persistence: Pt being dispensed a minimum # of Rx’s per year
Minimum-Refills Model
Pros:Might be useful for describing “as
needed” medication use Cons:
Does not account for length of time between refills
Does not account for amount of time each refill should last
Proportion-of-Days-Covered Model
Persistence: Enough medication dispensed to cover a specified proportion of days within a fixed interval (ex: 1 year)
Example: 210 days’ supply/365 day interval = 58% PDC during the 1st year
Pros: Relies on uniform evaluation period for all patients Shorter follow-up times create bias in PDC (higher
numbers) Fewer opportunities for
noncompliance/nonpersistence Cons:
Cut-off arbitrary No info about timeliness of refilling or persistence
Proportion-of-Days-Covered Model
Refill-Sequence Model
Persistence: total duration of a continuous sequence of refillsUnacceptable gap: Interval between the
date of the 1st Rx and refill considered to be nonpersistence
PG: Permissible gap
Refill-Sequence Model
Pros: Permit switches between Rxs with same indication Increased accuracy of measuring persistence when Information can be used to assess effect of an intervention
aimed at improving persistency Cons:
May not consider all refilling behavior across the observation period.
Once an individual is classified as nonpersistent, future refilling behavior is no longer considered
Patient could have discontinued or switched medications
PG not well defined
Anniversary Model
Persistence: Rx refilled within a specified interval (e.g., +/- 30 days) surrounding the anniversary of 1st Rx
Both patients are persistent at 1 yearPatient 1: more consistent
Monthly Fill
4 Fills
Anniversary Model
Pros: Simple to useAccurate method for timeliness of medication
refilling IF small refill gaps are small
Cons: No consideration given to refills
within the 1-year interval Patient is persistent, but not
necessarily adherent
Summary
References Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med
2005;353;5:487-497. Caetano PA, Lam JMC, Morgan SG. Toward a standard definition and
measurement of persistence with drug therapy: Examples from research on statin and antihypertensive utilization. Clin Therapeutics 2006;28:1411-1424.
Cramer JA, Roy A, Burrell A, et al. Medication compliance and persistence: Terminology and definitions. Value Health 2008;11. [Epub June 25, 2007]
Sikka R, Xia F, Aubert RE. Estimating medication persistency using administrative claims data. Am J Managed Care 2005;11:449-457.
Hess LM, Raebel MA, Conner DA, Malone DC. Measurement of adherence in pharmacy administrative databases: A proposal for standard definitions and preferred measures. Ann Pharmacother 2006;40:1280-1288.
Hughes D, Cowell W, Koncz T, Cramer JA. Methods for integrating medication compliance and persistence in pharmacoeconomic evaluations. Value Health 2007;10(6):498-509.
www.cms.org assessed March 20, 2008.