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A FRAMEWORK FOR CONDUCTING INITIAL MEDICATION ADHERENCE

RESEARCH

An ISPOR Workshop by the Medication

Adherence Good Research Practices Working

Group of the Medication Adherence and

Persistence Special Interest Group

Medication Adherence Good Research Practices Working Group

Co-Chairs: David Hutchins, MHSA, MBA Executive Advisor, Pharmacy Networks, CVS Caremark (Scottsdale, AZ, USA)

Andrew M. Peterson, PharmD, PhD Dean, Mayes College of Healthcare Business and Policy, University of the Sciences (Philadelphia, PA, USA)

Leadership Group:

Maria Malmenäs, MSc - Director, Health Economic Modeling Unit, HERON (Stockholm, Sweden)

Elizabeth Manias, RN, BPharm, MPharm, PhD - Deakin University, School of Nursing and Midwifery, Victoria; Adjunct Professorial Fellow, Department of Medicine, Royal Melbourne Hospital, the University of Melbourne (Melbourne, Australia)

Craig S. Roberts, PharmD, MBA Senior Director, Global Health & Value, Pfizer Inc (Collegeville, PA, USA)

Allison F. Williams, RN, PhD - School of Nursing and Midwifery, Monash University (Victoria, Australia)

John E Zeber, MHA, PhD - Co-director, Health Outcomes at Scott & White Healthcare, Center for Applied Health Research; Investigator, Central Texas Veterans Health Care System; Associate Professor, Texas A&M College of Medicine (Temple TX, USA)

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WORKSHOP Presenters

Andrew M. Peterson David Hutchins – Discussion Leader

Craig S. Roberts John E. Zeber

PURPOSE of WORKSHOP:

To provide guidance on measuring initial

medication adherence (IMA), including

developing standard nomenclature and key

components of quality IMA research

Encourage discussion among a diverse

audience of investigators, health system

practitioners, patients and policy makers

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John E. Zeber Central Texas VA; Scott & White Healthcare;

Texas A&M Health Science Center

Initial Medication Adherence – Study Background

Our first project* delved into complex IMA arena

Observed complexity of topic, definitions

overlap, problematic study design issues

Recognized need to summarize current IMA

research, benefits and limitations

Focused on factors associated with poor IMA

* Zeber JE, Manias EF, Williams AF, Hutchins D, Udezi WA, Roberts CS, Peterson AM. (2013). A systematic literature review of psychosocial and behavioral factors associated with initial medication adherence: a report of the ISPOR medication adherence & persistence special interest group. Value in Health, 16(5):891-900.

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Background (continued)

Systematic literature review through 2012:

Medline, PsychInfo, CINAHL, others

Started with 865 articles … 63 read in full; 24

were eligible (moderate quality at best)

Variety of terms for very first Rx

Numerous study design approaches with

inconsistent abstract, key words, methods

Most examined patient factors; some covered

role of system and providers

Background (continued)

Key factors => medication class (16), patient

characteristics (14), physical comorbidities

(14), co-payments (11), health beliefs (6)

Strongest predictors = RX cost (ORs up to 7.3),

specific drug, illness severity, SES, lack of

discharge counseling

Similar factors influence IMA as for longer-term

adherence, but …

Discussion led into need for more standardized

Methodological approach, i.e., this study!

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David Hutchins CVS Caremark

Overview of Current Methodological Study

Background: Second Project Second working subgroup

Purpose: meta-analysis

Findings: similar to those in our first project

Current project Provide guidance to and encourage more studies

Summarize current body of research

different methods

Feedback’s unanticipated stumbling block taxonomy

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Cramer Taxonomy

Cramer JA, Roy A, Burrell A, et al. Medication compliance and persistence: terminology and definitions. Value in Health. Jan-Feb 2008;11(1):44-47

Vrijens Taxonomy

Vrijens B, De Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. May 2012;73(5):691-705

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Taxonomies

Initial Medication Adherence (IMA)

• Initial medication adherence is when a patient presents and receives a medication prescription for the treatment of a disease for the first time

• Nonadherence encompasses both unpresented and unclaimed prescriptions

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Taxonomy Challenge: AUDIENCE INTERACTION #1

Break into groups (~10”)

Discuss Pros and Cons of “Initial

Medication Adherence” (IMA)

Re-gather and report

Summarize ideas

Initial Medication Adherence (IMA)

• Initial medication adherence is when a patient presents and receives a medication prescription for the treatment of a disease for the first time

• Nonadherence encompasses both unpresented and unclaimed prescriptions

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State of Current IMA Research

Andrew M. Peterson University of the Sciences

Data Sources for IMA

Surveys of Patients

Prescribers

Pharmacists

Databases Pharmacy

Hospital/Clinic

Prescriber Office

Prescription Tracking Manual

Electronic

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Perspectives

• Provider Perspective

• 13 studies

• Patient Perspective

• 3 studies

• Pharmacist Perspective

• 6 studies

• System Perspective

• 17 studies

IMA Process

Provider Pharmacist Patient

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Framework for Analysis of IMA

Two key events required for an IMA Prescribing Event

Dispensing Event

Parameters involved in an IMA Core: must be provided to calculate a valid IMA

measurement

Supplemental: refine accuracy of IMA

measurement

Ancillary: influence IMA measurement

Craig S. Roberts Pfizer, Inc.

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Defining IMA Study Parameters

• Must be provided for valid IMA measurement

• Examples: clear prescribing and dispensing information, specified time window for adherence, etc.

Core

• Refine accuracy of IMA measurement

• Examples: Consideration of substitution at the pharmacy, addressing potential out-of-network fulfillment, etc.

Supplemental

• Influence IMA measurement

• Examples: consider influence of behavioral factors, pharmacy characteristics, prescriber characteristics on adherence outcome.

Ancillary

Core parameters Study parameters that must be defined and

described for IMA research

Parameters include:

Identification and scope of prescribing events

Identification and scope of dispensing events

Means by which prescription may be

transmitted from prescriber to dispensing

Defined time window after which qualifies as

non-adherent

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Supplemental parameters Parameters that may impact the validity of IMA measurement

Impact may depend on data source, characteristics of

medication

Considerations include:

Process to ensure initial prescription is a new prescription (e.g.

360 days history)

Address potential for substitution (Therapeutic substitution, OTC

self-care)

Address potential for out-of-network prescribing/dispensing

(outside network pharmacy, cash payment) Potential for

alternate instructions to patient (e.g., ‘fill if not feeling better in

3 days’)

Considerations regarding censoring (e.g. hospitalization or death

of patient)

Ancillary parameters

Study parameters that help understand

attributes that influence IMA

Parameters include:

Patient factors: age, sex, race, health beliefs,

income, comorbidities, support network,

stated reasons for adherence/non-adherence

Non-patient factors: health system

characteristics, covered benefits, provider and

pharmacy characteristics

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AUDIENCE INTERACTION #2: Study parameters

Consider the three classifications of parameters

(core, supplemental, ancillary)

What study parameters may go in each category?

What considerations should researchers have

when addressing these parameters?

Is there a fourth category of study parameters that

is relevant to initial medication adherence?

Recommendations for Conducting Solid IMA Research

Based upon our initial systematic review and the current deeper exploration into Methodological issues, we have developed the following set of recommendations for conducting solid IMA research:

Hutchins D, Zeber JE, Peterson AM, Roberts CS et al. Initial Medication Adherence: A Review and Analysis of Methodology: A report by the ISPOR Medication Adherence Good Research Practices Working Group [manuscript to be submitted soon to Value in Health]

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IMA Research Recommendations

I. Use the term “initial medication

adherence”

II. State and define the specific perspective

taken (e.g., patient vs. system)

III. Delineate the core, supplemental, and

ancillary parameters that will be covered

General:

Recommendations (continued)

IV. Provide sufficient details on the prescribing

event and the procedures for determining

a new therapeutic class/initial Rx

V. Specify the timeframe between the

prescribing and dispensing event and

justify selection

Core:

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Recommendations (continued)

Supplemental:

VI. Address perspective bias by ensuring the

comprehensiveness of information

sources

VII. Address substitution bias regardless of the

source

Recommendations (continued)

Ancillary:

VIII. Include patient characteristics information

IX. Include non-patient characteristics

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Wrap-up and Final Issues

Summary

Final Audience Input, Questions, or Concerns

Recommended next steps and future research directions

Contact Information

David Hutchins, MHSA, MBA Senior Advisor, Pharmacy Networks

CVS Caremark - Scottsdale, AZ david.hutchins@caremark.com

** The Working Group expresses our thanks and appreciation

to Theresa Tesoro (ttesoro@ispor.org) for coordinating all of

our activities, and to the two rounds of internal ISPOR

reviewers for their recent comments on the manuscript draft

summarizing this study.