Final Report of the ABC Project

542 Pages·2012·6.65 MB·English

Ascertaining Barriers for Compliance:
policies for safe, effective and cost-effective
use of medicines in Europe

Final Report of the ABC Project
(Deliverable 7.1)

June, 2012

http://www.ABCproject.eu
The ABC Project team
Aneta Andrzejczyk, Medical University of Lodz, Lodz, Poland
Wendy Clyne, Keele University, Keele, UK
Sabina De Geest, Katholieke Universiteit Leuven, Leuven, Belgium & University of Basel, Basel,
Switzerland
Jenny Demonceau, AARDEX Group Ltd, Sion, Switzerland
Fabienne Dobbels, Katholieke Universiteit Leuven, Leuven, Belgium
Emily Fargher, Bangor University, Bangor, Wales, UK
Dyfrig Hughes, Bangor University, Bangor, Wales, UK
Przemyslaw Kardas, Medical University of Lodz, Lodz, Poland
Pawel Lewek, Medical University of Lodz, Lodz, Poland
Michal Matyjaszczyk, Medical University of Lodz, Lodz, Poland
Sarah McLachlan, Keele University, Keele, UK
Val Morrison, Bangor University, Bangor, Wales, UK
Comfort Mshelia, Leeds University, Leeds, UK
Sadhia Parveen, Bangor University, Bangor, Wales, UK
Anna Piaszczynska, Medical University of Lodz, Lodz, Poland
Catrin Plumpton, Bangor University, Bangor, Wales, UK
Todd Ruppar, Katholieke Universiteit Leuven, Leuven, Belgium & University of Missouri, Columbia,
USA
Kaat Siebens, Katholieke Universiteit Leuven, Leuven, Belgium
John Urquhart, AARDEX Group Ltd, Sion, Switzerland & UCSF, San Francisco, USA
Bernard Vrijens, AARDEX Group Ltd, Sion, Switzerland
Simon White, Keele University, Keele, UK

Disclaimer
The research leading to these results has received funding from the European Community Seventh
Framework Programme (FP7 Theme Health, 2007-3.1-5, grant agreement n°223477). Sole
responsibility lies with the authors and the European Commission is not responsible for any use that
may be made of the information contained therein.

No part of this report may be reproduced, stored in a retrieval system, or transmitted in any form or by
any means without the written consent of the Medical University of Lodz, Lodz, Poland. The use of
figures, and/or text as clarification or support in articles is permitted, provided the source is clearly
mentioned.

Project details
Grant Agreement number: 223477, Funding Scheme: Collaborative Project
Name, title and organisation of the scientific representative of the project's coordinator: Przemyslaw
Kardas, PhD, Associate Professor, Medical University of Lodz
Tel: [phone], Fax: [phone], E-mail: [email protected]
| ABC Project – Final Report 2
Contents

1 Introduction to the ABC Project: introduction, overview and objectives 4
The ABC Project team
2 Consensus on European Taxonomy and Terminology of Patient Compliance 12
Bernard Vrijens, Sabina De Geest, Dyfrig Hughes, Przemyslaw Kardas, Jenny
Demonceau, Todd Ruppar, Fabienne Dobbels, Emily Fargher, Val Morrison, Pawel
Lewek, Michael Matyjaszczyk, Comfort Mshelia, Wendy Clyne, Jeffrey Aronson, John
Urquhart
3 Report on the determinants of patient non-adherence with short-term and long- 40
term treatment
Przemyslaw Kardas, Valerie Morrison, Emily Fargher, Sahdia Parveen, Catrin Plumpton,
Wendy Clyne, Sabina De Geest, Fabienne Dobbels, Bernard Vrijens, John Urquhart,
Pawel Lewek, Michal Matyjaszczyk, Dyfrig Hughes
4 Application of health psychology and economic behavioural models to explain 146
medication adherence in adult patients: a systematic review of empirical studies
Emily Fargher, Val Morrison, Dyfrig Hughes
5 Exploring the current practices of adherence management by healthcare 179
professionals and the pharmaceutical industry
Wendy Clyne, Comfort Mshelia, Sarah McLachlan, Sabina De Geest, Todd Ruppar, Kaat
Siebens, Fabienne Dobbels, Peter Jones, Pawel Lewek, Michal Matyjaszczyk,
Przemyslaw Kardas
6 Identification and assessment of adherence-enhancing interventions 263
Jenny Demonceau, Todd Ruppar, Paulus Kristanto, Dyfrig Hughes, Emily Fargher,
Przemyslaw Kardas, Sabina De Geest, Fabienne Dobbels, Pawel Lewek, John Urquhart,
Bernard Vrijens
7 Report on the cost effectiveness of interventions that promote adherence: a 294
systematic review of the literature and economic evaluation
Emily Fargher, Dyfrig Hughes
8 Preparation of policy recommendations for supporting medication adherence in 339
European healthcare
Wendy Clyne, Simon White, Sarah McLachlan, Comfort Mshelia, Przemyslaw Kardas
Appendices 402

| ABC Project – Final Report 3
1 Introduction to the ABC Project: introduction, overview and objectives

ABC project team

Contents Page number

1.1 Introduction 5
1.2 Overview of the ABC Project 6
1.3 Summary of objectives 8

References 10

|Chapter 1– Introduction 4
1.1 Introduction

This final report, part of the FP-7 funded ABC project ‘Ascertaining Barriers to Compliance: policies
for safe, effective and cost-effective use of medicines in Europe’ (HEALTH-2007-3.1-5: Better use of
medicines), aims to present research evidence to contribute to our knowledge about the nature,
causes, consequences and policy responses to medication non-adherence. In so doing we hope to
achieve our overarching aim of supporting policies for safe and cost-effective use of medicines in
Europe.

Non-adherence to medicines is a global issue of major public health concern. Non-adherence to
medication is a frequent and widespread phenomenon, can be a major barrier for realising the benefits
of medicines presents and is a significant barrier to the safe, effective and cost-effective use of
medicines. Many patients do not adhere to effective treatments for the preservation of life1,2, quality of
life3-5, organs6, or sight7,8, with direct clinical9,10 and economic consequences11,12.

Non-adherence is recognised as one of the major factors contributing to therapeutic partial or non-
response13,14. It is highly prevalent, associated with increased morbidity and mortality, costly to
manage, and until recently a very much neglected aspect of prevention and treatment of illness13,14,15.
A report by the World Health Organisation13 has called non-adherence “a worldwide problem of
striking magnitude”. Indeed, R. Haynes goes further and states, ‘increasing the effectiveness of
adherence interventions may have a far greater impact on the health of the population than any
improvement in specific medical treatments’17. This problem is especially relevant to European Union
countries, where access to healthcare services is good and their utilisation is high. In such
circumstances, further improvement in the effectiveness of medication cannot be realised without
addressing patient non-adherence.

In 2007 when the ABC Project was conceived, world pharmaceutical market growth was estimated to
be 5-6%, and global pharmaceutical sales were estimated to reach $665-685 billion
(www.imshealth.com). In 2007, each European citizen spent on average approximately € 430 on
medicines. In total, the market for medicines was worth over € 138 billion at ex factory prices and
approximately € 214 billion at retail prices, corresponding to 2% of the GDP18. Pharmaceutical
expenditure is the third largest component of health expenditure, following hospital and ambulatory
care spending, among EU member states19.

In the past decade there has been substantial growth in adherence research – partly owing to
increasing awareness of the size and scope of the problem, partly because of the pervasiveness of
non-adherence across all therapeutic fields, and partly because of its potentially large contribution to
the overall variance in drug responses. The medication adherence field is characterised by the lack of
effective policies toward the problem of non-adherence at both national and European levels.
Therefore, there is a need to produce evidence-based policy recommendations for European
|Chapter 1– Introduction 5
policymakers in order to help both Europeans and European healthcare services improve patient
adherence and make the most of available resources.

1.2 Overview of the ABC project

This final report of the ABC Project describes our work to investigate the following aims:

1. To obtain European consensus on terminology used in the field of non-adherence
Nowadays, a number of common terms – ‘compliance’, ‘adherence’, ‘persistence’, and ‘concordance’ -
are used to define the act of seeking medical attention, filling prescriptions and taking medicines
appropriately. These terms are sometimes used interchangeably, though they impose different views
about the relationship between the patient and the health care professional. For example, the term
‘compliance’ has been criticised for its built-in paternalistic approach. Moreover, there is no consensus
on a common definition on methods to measure ambulatory patients’ exposure to prescribed drugs.
The definitions that are currently used in the literature do not support quantitative assessment, thus
compromising any sound analysis aimed at describing or comparing patients’ adherence to prescribed
drug dosing regimens. Those limitations preclude the finding of useful methods to enhance patient
adherence with prescribed therapies in daily practice. Therefore, to allow for the benchmarking of
existing adherence enhancing strategies at the European level, and support the preparation of policy
recommendations, the starting point of the project was the clarification of existing terminology used in
this field. Chapter 2 describes this part of the ABC Project.

2. To explore patient beliefs and behaviour regarding medication adherence.
This project takes an inventory of determinants of patient adherence described in the research
literature, taking into account variation across different clinical sectors, health care settings and
population segments. In addition, European surveys have been conducted to explore patients’ beliefs
and behaviour about their medicines and medicines taking behaviour. Further a discrete choice
experiment is reported which investigates how participants weigh up the different attributes and
outcomes of medicine taking which influence their potential treatment choices. Chapter 3 describes
components of the ABC Project which explore patient beliefs and behaviour. Chapter 4 describes the
integration of health psychology and economic models of patient behaviour that may be used to
explain medication adherence. Systematic reviews were conducted to consolidate evidence into a
new conceptual framework of determinants of medication adherence.

3. To obtain insight in current practices of adherence management by healthcare professionals, health
educators and the pharmaceutical industry
Patient non-adherence is a frequent phenomenon in everyday clinical practice. Little is known about
how healthcare professionals approach patient adherence and their reasons for choosing to intervene
to support patients with medication adherence or not20. Equally, little is known about the ways in which
educators prepare and provide continuing support to healthcare professionals to manage medication
education. We are unaware of any European level data about healthcare professional education.
|Chapter 1– Introduction 6
Chapter 5 describes a number of studies to investigate the education that healthcare professionals
receive about medication adherence, the interventions that healthcare professional report that they
use to support patients with medicine taking, and the guidelines that exist to support clinical practice.
The pharmaceutical industry is becoming an increasingly influential stakeholder in the provision of
adherence support for patients. Chapter 5 also includes a survey of pharmaceutical industry
perceptions about their role in supporting patients with adherence to medication.

4. To assess the effectiveness of adherence-enhancing interventions
Although a number of adherence-enhancing interventions have been tested in clinical settings,
evidence suggests that no single intervention strategy is satisfactorily effective across all patients,
conditions and settings. Even the most effective interventions did not lead to large improvements in
adherence and health outcomes21,22. Several reviews22-24 of interventions for enhancing adherence to
medications have consistently highlighted methodological weaknesses in the study designs and
methods used, often precluding quantification and permitting only qualitative assessments. In
particular, there are major between-study differences in methods used to assess adherence, differing
not only in reliability but also in the degree of temporal resolution of their measurements. These
methodological differences have thus hampered the identification of interventions that can effectively
enhance adherence to medications. Chapter 6 presents a meta-analysis of intervention studies,
focused only on those studies using electronic measurement of medicine-taking, to address this
problem in the research evidence.

5. To estimate the cost-effectiveness of compliance-enhancing interventions
In order to develop strategies for successful policy recommendations that represent good value for
money, and allow for effective benchmarking of existing European strategies, information about the
cost-effectiveness of interventions aimed at enhancing patient adherence with both short-term and
long-term treatments is key. A systematic review conducted by Elliott et al.25 did not identify any robust
economic evaluations, and the results of those that were included, were largely inconclusive. Chapter
7 presents an update of this review and an economic model, based on evidence from a systematic
review of the literature, designed to estimate the cost-effectiveness of adherence-enhancing
interventions in relation to antibiotics for adults with upper respiratory tract.

6. To develop policy recommendation for promoting patient adherence in European healthcare
Based on the activities listed above, the ABC Project developed policy recommendations for
supporting patient adherence in order to assure safe, effective and cost-effective use of medicines in
Europe. These are described in Chapter 8, alongside studies to develop consensus about policy
solutions for medication adherence across Europe, and a key informant study of European
policymakers’ perceptions of the extent and adequacy of medication adherence policy implementation.
Finally, a number of key multi-stakeholder dissemination events to share the learnings of the ABC
Project are described.

|Chapter 1– Introduction 7
1.3 Summary of objectives

Chapter 2
to search the literature systematically, in order to identify the terms that have been used to describe
medication-taking behavior, and to propose a new taxonomy, in which adherence to medications is
conceptualized, based on behavioural and pharmacological science, and which will support
quantifiable parameters.

Chapter 3
To perform a systematic review to identify the determinants of patient compliance with short-term
and long-term therapies in Europe
To analyse the factors responsible for non-compliance with treatments for acute diseases, and
chronic conditions for different clinical sectors, health care settings and population segments
To identify the factors which influence patients’ decisions in relation to the process of execution of
short-term treatment and continuation with long-term treatments
To quantify patients’ preferences for a range of attributes relating to the decision-making process of
being compliant or non-compliant

Chapter 4
To draw from the health psychology, economics and clinical therapeutics literature, models of
mediation adherence.
To consolidate the evidence on the determinants of non-adherence in a conceptual framework of
patient behaviour.
To provide a theoretical basis for the development and assessment of adherence-enhancing
interventions.
To establish a basis for long-term behaviour modification for adherence with long-term therapies.
To establish a basis for short-term behaviour modifications for adherence with treatments of acute
diseases.

Chapter 5
To evaluate whether pharmaceutical companies in Europe include medication adherence in their
strategic plans.
To evaluate what general methods pharmaceutical companies identify as ways in which they
support medication adherence-enhancing interventions.
To evaluate what specific interventions pharmaceutical companies report to be taking to improve
patient adherence to prescribed medicines.
To evaluate whether European high schools or universities of medicine, pharmacy, and nursing
include medication adherence as a defined topic in their curricula.
To evaluate what content is provided about medication adherence in health care professional
training programs.
|Chapter 1– Introduction 8
To evaluate what specific methods European schools of medicine, pharmacy, and nursing use to
educate future health care providers to address and improve patient adherence to prescribed
medicines.
To determine the methods that European healthcare professionals (medical doctors, nurses,
pharmacists, etc.) currently use to support medication adherence.
To determine what national and international medication adherence guidelines exist.
To determine the characteristics of existing national- and international-level medication adherence
guidelines.
To determine what processes have been used to develop medication adherence guidelines.
To determine how medication adherence guidelines have been distributed and where they have
been published.

Chapter 6
To systematically search the literature to identify randomized controlled trials containing empirical
data on the efficacy of interventions to enhance adherence to prescribed medications, as assessed
by electronic medication-event monitoring methods.

Chapter 7
To update reviews of the literature associated with the cost-effectiveness of adherence-enhancing
interventions.
To estimate the economic impact of adherence-enhancing interventions using a decision analytic
model populated by data from the literature review and other secondary sources.

Chapter 8
To develop a common European educational framework specifying curriculum for schools of
medicine, pharmacy and nursing for managing and supporting patients with medication adherence
To reach consensus among medication adherence stakeholders on strategies to address patient
adherence
To develop policy recommendations for enhancing medication adherence in Europe
To tailor medication adherence policy recommendations toward the needs of different healthcare
settings and population segments, taking into account cultural differences between European
regions.

|Chapter 1– Introduction 9
References

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treatment. CA Cancer J Clin. 2009;59:56-66.
2. Wu JR, Moser DK, Lennie TA, Burkhart PV. Medication adherence in patients who have heart
failure: a review of the literature. Nurs Clin North Am. 2008;43:133-53.
3. Horne R. Compliance, adherence, and concordance: implications for asthma treatment. Chest.
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4. Rapoff MA. Management of adherence and chronic rheumatic disease in children and
adolescents. Best Pract Res Clin Rheumatol. 2006;20:301-14.
5. van der Wal MH, Jaarsma T. Adherence in heart failure in the elderly: problem and possible
solutions. Int J Cardiol. 2008;125:203-8.
6. Loghman-Adham M. Medication noncompliance in patients with chronic disease: issues in
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Ophthalmol. 2008;53 Suppl 1:S57-68.
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Ophthalmol. 2005;16:114-21.
9. Cramer JA, Benedict A, Muszbek N, Keskinaslan A, Khan ZM. The significance of compliance
and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review. Int J
Clin Pract. 2008;62:76-87.
10. Vrijens B, Urquhart J. Patient adherence to prescribed antimicrobial drug dosing regimens. J
Antimicrob Chemother. 2005;55:616-27.
11. McLean W. Medication adherence initiatives - Part I. Canadian Pharmacists Journal
2007;140:254-61.
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adherence. Am J Health Syst Pharm. 2003;60:657-65.
13. World Health Organisation. Adherence to long-term therapies: evidence for action. Geneva:
WHO; 2003.
14. Osterberg L, Blaschke T. Adherence to medication. N Eng J Med. 2005;353:487-97.
15. Hughes DA. When drugs don't work: Economic assessment of enhancing compliance with
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16. Rand CS. Measuring adherence with therapy for chronic diseases: implications for the
treatment of heterozygous familial hypercholesterolemia. Am J Cardiol. 1993;72:68D-74D.
17. Haynes RB. Interventions for helping patients to follow prescriptions for medications.
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18. European Commission. Pharmaceutical sector inquiry report [Internet]. European
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|Chapter 1– Introduction 10