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.