Transcript Defining Adherence and Compliance

Defining Adherence
and Persistence
Sapna N. Patel
UCSF Pharm. D. Candidate 2008
Preceptor Dr. Craig S. Stern
March 21, 2008
Pictures
Relevance

Evaluating adherence & persistence is
necessary for accurate assessment of:
 Cost-effectiveness of therapy
 Quantifying drug exposure in a population over time
 Drug Utilization Patterns for Formulary
Development
 Identifying appropriate therapy for patients
 Assessing clinical outcomes of treatment
 Prior Authorization Criteria
Impact of A&P

Low adherence & persistence
Increased morbidity & mortality
Increased 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 Methods
Method
Directly Observed
Therapy
Medicine or Metabolite
Blood Levels
Pros

Most accurate
Objective
Cons
Time
consuming
Impractical
Hiding pills
Expensive
Metabolism
variation
White
coat
adherence
Biologic Markers in
blood
Objective
Time
consuming
Expensive
Indirect Methods
Method
Questionnaires, selfreporting
Prescription rate refills
Pros
Cons
Cost-effective
Subjective
Time
consuming
Useful in clinical setting
Infrequent
Objective
Expensive
visits =
increased error
Metabolism
variation
White coat Adherence
Pill Counts
Objective
Subjective
Easy-to-do
Easily
Quantitative
results
altered by
patient
Measuring Adherence: Medication
Possession Ratio (MPR)

MPR =
total days’ supply
X 100
total # days evaluated
353/365 X 100 = fill in%

Equals overall percent adherence value (medication
availability)
MPR (cont)
Pros:
Easy to calculate
Widely used adherence measure
 Cons:
Participants get >1 fill in one day (ex:
vacation supply)
Change in prescribing directions
Refills occur close to study termination

“Between Fills” Measures

Days Between Fills Adherence Rate (DBR)
DBR

=1-
total days’ supply – last days’ supply
last claim date – 1st claim date
X 100
Refill Compliance Rate (RCR)
RCR =

last claim date – 1st claim date
Compliance Rate (CR)
CR =

(last claim date – 1st claim date) – total days’ supply
total days’ supply
X 100
last claim date – 1st claim date
Medication Possession Ratio, Modified (MPRm)
MPRm =
total days’ supply
(last claim date – 1st
X 100
claim date) + last days’ supply
X 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 gap days

CMG =

total days’ study participation – total days’ supply
total days’ study participation
Continuous Measure of Medication Gaps (CMG)
:Provides time patient does not have medication
available (%)
Ex: (362-365)/362 = 0.00 or -0.01

Range:
 0.0 = complete adherence
 1.0 = complete non-adherence
 (-) values = surplus days (due to early refill or
overfill)
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
Proportion-of-Days-Covered Model

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
Refill-Sequence Model
PG: Permissible gap

Persistence: total duration of a continuous
sequence of refills
 Unacceptable
gap: Interval between the date of the
1st Rx and refill considered to be nonpersistence
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
 PG not well defined
switched medications
Anniversary Model
4 Fills
Monthly
Fill
Persistence: Rx refilled within a specified
interval (e.g., +/- 30 days) surrounding the
anniversary of 1st Rx
 Both patients are persistent at 1 year

Patient
1: more consistent
Anniversary Model

Pros:
 Simple
to use
 Accurate method for timeliness of medication
refilling IF small refill gaps are small

Cons:
No consideration given to refills within the 1year interval
Patient is persistent, but not necessarily
adherent
Summary
References

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



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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.