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

Final Report Summary - ABC (Ascertaining barriers for compliance: policies for safe, effective and cost-effective use of medicines in Europe)

Executive summary:

Patient non-adherence to prescribed medication is common: on average, 30-50 % of prescribed medicines are not taken as prescribed. Non-adherence can have a negative impact on patient wellbeing and represents a major barrier for realising the benefits of evidence-based therapies. The economic impact of non-adherence on scarce health care resources is also significant. Despite much research to understand the causes, consequences and solutions or policy responses to medication non-adherence, numerous gaps in knowledge remained and clear research-based evidence of how to reduce non-adherence on a large scale remained elusive.

The ABC project was designed to produce evidence-based guidance for improving patient adherence and subsequent better use of medicines by Europeans in different clinical sectors, health care settings, and population segments.

Research under ABC project was conducted in several domains in order to:

-obtain European consensus on terminology used in the field of non-adherence (extensive literature review, and expert meeting);
-identify the determinants of non-adherence to short-term and long-term treatment (patient surveys, and literature review);
-obtain insight into current practices of adherence management (healthcare practitioners survey, pharmaceutical industry survey, review of clinical guidelines, review of medical schools curricula);
-assess the effectiveness and cost-effectiveness of adherence-enhancing interventions (literature reviews);
-develop policy recommendations for promoting patient adherence in European healthcare and help their implementation (Delphi study on experts, survey of national policymakers).

Results of the above-mentioned research were integrated into one cohesive set of evidence-based policy recommendations, and have been made available to the public. These recommendations are helping turning the vision of adherence-supporting environment into reality by providing all relevant European stakeholders with tailored solutions:

- Patients by assessing their perspective of problems arising along drug-taking, better understanding of perceived and objective barriers toward adherence was achieved. Thus, more effective adherence-enhancing interventions might be designed on that basis.
- Healthcare professionals by assessing their current skills, better tailored educational programs for healthcare professionals could be designed, in order to help them effectively manage this problem in their patients.
- Governments and policymakers are now equipped with evidence-based guidance on solutions able to improve patient adherence to medication as well as secure better, more effective and cost-effective healthcare across Europe.
- Payers have clear view on effectiveness and cost-effectiveness of different interventions targeting non-adherence, which would help them taking right decisions.
- Industry is provided with the cohesive set of data helping it to focus their activities in the field of non-adherence on the most promising directions.
- Researchers are provided with effective tools for further research in the field of non-adherence to medication, as well as with the guidance on which fields needs this research most.

Now, all stakeholders are encouraged to take the benefit of these recommendations, and implement them in their field of activity. With their widespread implementation, better, safer, more effective and cost-effective use of medicines in Europe may be obtained, with obvious gain in health, social, and economic domains.

ABC project consensus-based policy solutions for medication adherence for Europe

Patients benefit:

- When provided with support, education, and information about the benefits of adherence to their particular medication(s) and about potential side effects or adverse effects and how to manage them to assist the patient to weight up the benefit and harm of medication.
- When a medication is newly prescribed, focused on the patients treatment, tailored to the individual preferences or needs of the patient.

Healthcare professionals should receive education and training about:

- patient-centred care;
- identifying and assessing medication non-adherence;
- ways of addressing medication non-adherence when it is identified;

so that they can:

- adopt a non-judgmental approach;
- identify medication non-adherence;
- provide patients with ongoing feedback and support with medication-taking;
- support patients with concerns about, or experience of, side effects of medication;
- make sufficient time for the patient, for instance through more frequent, timely contact.

Together, healthcare professionals and patients should:

- discuss the patients' preferences for treatment;
- ensure a partnership approach in decision making and treatment;
- discuss the patients' health- and medication-related beliefs;
- build the patients trust in the healthcare professional.

Regarding medicines:

- simplify the patients medication regimen as appropriate (e.g. less frequent, modified formulation and/or dosage, tailored to individual need);
- stop medication(s) that the patient no longer needs or wants.

Healthcare providers should:

- promote a team approach, sharing information to deliver consistent adherence support;
- prioritise medication adherence support in service, organisation, and systems design.

Governments / healthcare payers should:

- increase public awareness of medication adherence for all citizens;
- develop and implement evidence-based interventions for medication adherence;
- provide training and guidance for all healthcare providers so they can deliver effective adherence interventions;
- invest in research to identify effective interventions demonstrating value for money.

Project context and objectives:

Non-adherence to medication is highly prevalent across all medical conditions, being present in approximately 50 % of patients. Thus, it represents a major barrier for realising the benefits of evidence-based therapies. This problem is especially relevant to European Union (EU) countries, where access to healthcare services is good and their utilisation is high. In such circumstances, no further improvement in the effectiveness of therapeutic and prophylactic medication can be realised without addressing patient non-compliance. Several factors make the problem of non-compliance of highest importance in Europe: ageing of the European societies, imbalance between financial resources and the medical services costs, rapid growth of medication costs, serious consequences of non-compliance, etc. All these negative consequences make the reduction of non-compliance a major societal need.

Recent advances in medicine, which have led to the introduction of more powerful oral medications (e.g. for HIV, oncology, organ transplantation), increasingly require patients to self-administer complex and burdensome regimens in their home conditions.

For all these reasons, the European Commission (EC) has called for proposals focusing on the causes of poor compliance and development of policy recommendations for enhancing patient compliance and thus assuring safe, effective and cost-effective use of medicines in Europe. In response to this call, the ABC project was designed, with primary objective of producing evidence-based policy recommendations for European policymakers to improve patient adherence and the use of medication in Europe.

The six specific objectives of the ABC project were:

1. to obtain European consensus on terminology used in the field of non-adherence;
2. to identify the determinants of non-adherence with short-term and long-term treatment for different clinical sectors, health care settings and population segments in Europe;
3. to obtain insight in current practices of adherence management by healthcare professionals and the pharmaceutical industry;
4. to assess the effectiveness of adherence-enhancing interventions;
5. to estimate the cost-effectiveness of adherence-enhancing interventions;
6. to develop policy recommendation for promoting patient adherence in European healthcare.

Project results:

1. The main S&T results of work package (WP) 1: The new taxonomy and terminology in the field of deviations from assigned treatment

The objective of WP 1 was to identify the terminology that has been used in the literature to describe deviations from assigned treatment. A systematic literature review was performed using 5 electronic databases from database inception to 1 April 2009 in order to identify the different conceptual approaches to adherence research. 142 papers have been included in the review for their direct relevance to taxonomy. Definitions were analysed according to time and methodological perspectives.

More than ten different terms describing medication-taking behaviour were identified through the literature review, often with differing conceptual meanings. A taxonomic approach was subsequently derived, evaluated, and discussed with international experts. The major strength of this research is a sound taxonomy which has integrated findings from different initiatives while remaining independent of any measurement method.

The conceptual foundation for a new, transparent taxonomy relies on three elements, which make a clear distinction between processes that describe actions through established routines (adherence to medications, management of adherence) and the discipline that studies those processes (adherence-related sciences). Adherence to medications is the process by which patients take their medication as prescribed, further divided into three quantifiable phases: initiation, implementation, and discontinuation.

The new taxonomy should provide researchers and clinicians with a common language for describing different experimental investigations. We hope that the proffered taxonomy will stimulate discussion, informed by shared concepts, methods, and research findings. The terms and definitions are focused on promoting consistency in taxonomy and methods, to aid in the conduct, analysis, and interpretation of scientific studies of adherence to medications. The adoption of these terms and definitions will also help to standardise the medical literature and therefore facilitate health policy decisions based on consistent evidence.

The main limitation of this work is associated with the development of the taxonomy based on English-language literature only. This problem has been identified very early on in the process towards a unified taxonomy. During the European consensus meetings, issues regarding translation into German, French, Polish, and Dutch have been discussed. Translation remains however an important step for medical practice and teaching in the different countries. It is however important to have set-up a sound taxonomy in the English language and translation will be the topic of further work in this field.

The main S&T results of WP 2: Identifying the determinants of patient adherence to short-term treatment and treatment for chronic diseases in Europe

The main S&T results of a systematic literature review on determinants of patient adherence

The systematic review of recent literature identified 51 reviews, covering 19 different disease categories. Identified studies exclusively assessed non-adherence to chronic therapies. In these studies, 771 individual factor items were identified, out of which most were determinants of implementation, and only 47 were found to be determinants of persistence with medication. The lack of standardised definitions and poor measurement methods resulted in many inconsistencies, which make it difficult to draw firm conclusions. Factors with unambiguous effect on adherence were further grouped in 8 clusters of socio-economic-related factors, 6 clusters of healthcare team- and system-related factors, 6 clusters of condition-related factors, 7 clusters of therapy-related factors, and 14 clusters of patient-related factors. These factors can, however, change with time and can appear at times either to be a cause, or a consequence, of patient non-adherence. Therefore, the prediction of non-adherence of individual patients is difficult if not impossible. With suitable measurement, however, non-adherent dosing patterns can come promptly into view, thus bypassing the problem of non-predictability.

The main S&T results of a multi-national cross-sectional survey on the determinants of patient adherence to antihypertensive medication

A total of 2630 adult patients with hypertension in ambulatory care settings from 12 countries completed an online questionnaire. Adherence to medication was assessed using the Morisky (primary outcome) and MARS (secondary) scales. Patients in the Netherlands sample were most adherent, with 24.0 % classed as non-adherent according to the Morisky score. This was followed by patients from Germany (33.2 %), Austria (33.7 %), Wales (38.1 %), Belgium (38.9 %), England (41.5 %), Greece (50.2 %) and Poland (57.6 %). Low self efficacy (OR 0.73 95 % CI 0.68 to 0.77) and a high number of perceived barriers to taking medication (OR 2.18 95 % CI 1.64 to 2.89) were significant determinants of non-adherence across countries. 11 % of the variance in non-adherence was due to country differences. This suggests patient self efficacy and perceived barriers should be key targets in the development of interventions aimed at improving adherence to antihypertensive medications. In addition interventions should be sensitive to culture and tailored to individuals needs.

The main S&T results from a multi-national discrete choice experiment on preferences for persistence with medications

2856 patients recruited in ambulatory care settings across Austria, Belgium, England, Germany, Greece, Hungary, the Netherlands, Poland and Wales completed the online questionnaire. In eight out of the nine countries, all four attributes were statistically significant in influencing patients choice to persist with treatment (p less than 0.01). The probability of treatment benefit was not significant in Greece (p = 0.57). Patients were most likely to persist with medications with higher treatment benefit, lower levels of dose frequency, lower risk of ADR, and lower probabilities of severe ADR. The study demonstrated that patients were willing to forego improvements in treatment benefits in order to: reduce the risk of ADR, reduce the frequency of dose, and reduce the risk of mild ADRs. They were also willing to forego reduction in risk of common, mild ADR to avoid severe (but rare) ADR and to move to a less frequent dosing schedule. With the exception of Austria (p less than 0.05) there was no evidence from other counties that self-reported adherence to antihypertensive medications influences stated preferences to persist. The results of the study suggest that in addition to treatment benefits, patients place a high value on reducing the risk of severe (but rare) ADR and frequency of dose when choosing to continue taking a medicine. Persistence is therefore associated with willingness to trade potential benefits, harms, and convenience. The total utility produced by different combinations of these attributes may have value in assessing patients likelihood of persisting with medicines, and in the personalisation of medicines, or formulations thereof, to maximise persistence.

The main S&T results of a multi-national cross-sectional survey on the determinants of patient adherence to shorter antibiotic treatment

An online survey conducted in 12 European countries aimed at the assessment of determinants of patient adherence to antibiotics, assumed to be an exemplar of short-term treatment. Self-reported non-adherence was about half that to chronic-use, anti-hypertensive medications. Reasons for not initiating or not completing antibiotic treatment were closely associated with clinical effects (adverse effects or/and perceived efficacy). Acknowledged reasons for poor implementation of the dosing regimen appeared mainly to arise from forgetfulness. Adherence to long-term treatment of chronic diseases and to short term treatment of acutely symptomatic conditions was very different. Here again, reliable and detailed measurement of patients dosing histories remains the cornerstone of realistic, practical approaches to identify and characterize patient non-adherence.

The main S&T results of WP 3: Review of behavioural models of non-adherence

Eighty-nine papers (67 health psychology, 22 economic) were identified for inclusion in the review. Self-report was the most common measure of adherence (n = 50 studies). The extent to which individual components of the relevant model were tested varied. Health psychology models derived from social cognitive theory, self-regulation theory or social support; and, economic theories of consumer demand and time preference have been used to explain medication adherence. The most commonly tested determinants were cost (n = 21) and self-efficacy (n = 19). The majority of studies included in the review were disadvantaged by being reliant on self-reported adherence, which has been shown to deviate from objective measures of adherence; and from use of inadequate definitions. The review was restricted by date, and to adults, and did not consider behavioural models outside of the health psychology or health economic literature.

The main S&T results of WP4: Exploring the current practices of adherence management by healthcare professionals and the pharmaceutical industry

The main S&T results of the European healthcare professionals survey

Healthcare professionals have an important role to play in providing support to patients in order to ensure that if patients agree to take medicines, they are used in a safe, effective, and cost-effective way. However, evidence suggests that healthcare professionals may not be fulfilling this role, as they tend to underestimate the incidence of non-adherence in their patients.

In order to gain a more complete understanding of non-adherence and address the gap in current knowledge, this cross-sectional study assessed the perceptions, beliefs and behaviours of healthcare professionals - doctors, nurses and pharmacists in 10 European countries with regard to patients adherence to prescribed medication. Online surveys were used to gather data on healthcare professionals perceptions of the extent of non-adherence to medication, beliefs about adherence to medicines, use and perceived effectiveness of interventions to manage non-adherence in their patients, perceived barriers to the use of adherence management interventions, and training in medication adherence.

The main objectives of the study were:

(1) to determine the perceptions of doctors, nurses and pharmacists of the extent of non-adherence in their nations and, in particular, their own patients;
(2) to identify methods used by doctors, nurses and pharmacists in assessing patients non-adherence to medication;
(3) to determine the methods used by healthcare professionals to enhance patients adherence, and the perceived effectiveness of these methods;
(4) to ascertain the barriers faced by healthcare professionals in the use of adherence-management interventions, and
(5) to explore differences between nations and professional groups in each of the aforementioned areas.

Between July 2011 and April 2012, cross-sectional data was collected in an online anonymous questionnaire survey of doctors, pharmacists and nurses working in primary care and community settings in ten European countries - Austria, Belgium, England, France, Germany, Hungary, the Netherlands, Poland, Portugal, and Switzerland.

A mixed-method approach was used to recruit participants in each country, adapted as necessary in each country dependent upon the availability and accessibility of, for example, national registers of healthcare professionals.

About half of the healthcare professionals in the survey ask patients with long term conditions whether they have missed any doses of their medication on a regular basis, a question identified as a key method for healthcare professionals to assess adherence and so support patients with medicines. However, the finding that healthcare professionals who report that they have had some element of training in medication adherence are more likely to ask this key question, indicates that healthcare professional behaviour may perhaps be amenable to change in this regard.

Robust differences are found in the extent to which doctors, pharmacists and nurses report that they manage and support patients with medication adherence. For the primary outcome, and all five categories of adherence intervention, pharmacists persistently report that they intervene less than the other two professions to support patients with medicines. In three instances of five, nurses reported more intervention than doctors to assist patients with prescribed medicines.

Healthcare professionals in the study report that, of the interventions they use, provision of information to patients and talking with patients about their medicines use, are more effective than other ways of intervening, in their view. However, the sample does not strongly endorse the effectiveness of many of the interventions they use; just 10 of the 50 interventions have a modal response of extremely effective. It is possible then that healthcare professionals struggle to get feedback.

We recommend that a quality standard for medication adherence support for people with long term conditions should be introduced for primary care settings in Europe with the following quality statement: people prescribed medication(s) for long term conditions receive an assessment that identifies the extent of non-adherence to medication. This survey serves as one source of evidence against which performance for this quality standard can be benchmarked. The aim of this quality standard is to make medication adherence assessment a regular and routine part of primary health care, and so provide a basis for healthcare professionals to support patients reporting non-adherence with medicines use when necessary.

Further study is needed to investigate ways in which healthcare professionals can receive feedback about the impact and effectiveness of specific adherence-enhancing interventions used in routine clinical practice, to support healthcare professionals in reflecting upon and improving their practice. Options include patient satisfaction reporting, peer and self-assessment methods and more standardised outcome measurement.

The main S&T results of the systematic review of clinical practice guidelines for the improvement of medication adherence

While numerous interventions have been tested to address the problem of medication non-adherence, very few comprehensive practice guidelines have been developed for clinicians to use when addressing medication non-adherence with patients. We therefore conducted a systematic review of national and international guidelines on the management of patients adherence to medications, using four sources, i.e.:

1) guidelines known to the ABC project partners;
2) guidelines known to members of the European Society for Persistence, Adherence, and Compliance (ESPACOMP);
3) a structured database search, using MEDLINE (PubMed), CINAHL, EMBASE, and the Cochrane Library; and
4) internet searches using applicable search engines (e.g. Google, Google Scholar, Yahoo, Bing).

Seventeen guidelines were found, of which the majority originated in the United States (n = 8). Regarding the intended scope of the guidelines, nine focused were intended for their country of origin, three were intended for an international audience, and five guidelines did not include specific information about the guideline's intended scope. The guidelines treatment foci included HIV/AIDS, cardiovascular disease, contraception, menopause, mental health or depression, and asthma. Two guidelines were general guidelines, and did not specify a health condition focus.

These 17 guidelines generated 41 recommendations on adherence management, including educational (N = 14), motivational (N = 4), and behavioural strategies (N = 14), as well as regular assessment of medication adherence (N = 14) and improving the patient-provider relationship (N = 13).

However, the identified practice guidelines for improving adherence to medications demonstrated considerable variation in the recommendations provided. The quality of evidence in the guidelines varied considerably, with limited details about the methodologies used to determine the recommendations. The guidelines often provided vague strategies, with few specifics, and often lacked an evidence base.

The results of the survey on European healthcare professional educational programs content on managing medication adherence

The objective of management of adherence is to achieve the best use by patients of appropriately prescribed medicines in order to maximise the potential for benefit and minimise the risk of harm. This objective necessitates professionals who are prepared to support patients in this medication taking process. Ideally education and skills training on assessing the extent of non-adherence, its risk factors and evidence-based interventions is embedded already in the curricula of medical, pharmacy and nursing schools as these are the disciplines most closely involved in medication management. It was however unknown to what extent these curricula contain training on these topics.

We conducted a survey on the methods currently used by educational programs in medicine, pharmacy and nursing (bachelor and master level) in 16 European countries covered by the ABC project (Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Poland, Portugal, Spain, Switzerland, and the United Kingdom). A list of schools was composed via internet searches and personal contacts of the ABC partners in the respective countries. Up to five schools per discipline were randomly selected for the survey (i.e. five nursing schools, five medical schools and five pharmacy schools). Invitations were sent to a total of 201 schools of which 75 schools of medicine, 61 schools of pharmacy and 65 schools of nursing in 16 countries. Of those, only 22 respondents provided data for 24 schools, resulting in a response rate of 12 %, 7 medicine, 9 pharmacy and 8 nursing training programs.

Twenty-one percent of the schools (n = 5) indicated that how to assess medication adherence was not addressed in their school's curriculum. Twenty-five percent of the respondents (n = 6) reported their school's curriculum did not address content on how to improve or promote medication adherence. Those who offered specific content did so via didactic / classroom / lecture training, 38 % (n = 9) via clinical / practicum / hands-on skills training and 25 % (n = 6) via case-studies. The median number of contact hours was 3, with nursing schools seeming to offer more hours, followed by schools of pharmacy compared to medical schools. Ten of the responding schools (42 %) indicated the adherence education is offered at Bachelor level and 11 respondents (46 %) at Master level. Two institutions indicated planning to start new medication adherence training initiatives over the next 12 months.

Although the response rate was low, our results clearly show a gap in the current curricula on adherence management, making it questionable if health professionals possess the necessary skills to adequately assess and manage adherence to medications.

The main S&T results of the survey of pharmaceutical company initiatives to improve medication adherence in Europe

Pharmaceutical industry seeks to maximize profit on the resources they invest in developing and marketing medications. Thus, the industry has a vested interest in identifying and promoting methods to enhance adherence to medications. The type and extent of industry programs and efforts to improve medication adherence remain unknown, however, by the research, clinical, and policymaking communities.

The 40 full-member companies and 31 national associations of the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the 27 member companies of the European Generic Medicines Association (EGA) were invited to participate in an online survey. Of the 40 companies and 31 national associations of EFPIA and the 27 companies of EGA, 9 companies completed the questionnaire.

Four (44 %) of the nine companies indicated that medication adherence interventions are currently addressed in the company's strategic plan. Four (44 %) companies reported to provide initiatives to enhance medication adherence at a global level, four (44 %) at a regional level (e.g. Europe, Asia-Pacific, etc.), seven (78 %) at a national / country level and one (11 %) company at a local (within country) level. Six companies (67 %) indicated not having a dedicated division or staff addressing medication adherence within their company and three (33 %) reported they had: one within the medical division, two within the marketing division and all three within research and development. Eight (89 %) companies reported to have programs for adults and two (22 %) for paediatric patients. Seven (78 %) of the responding companies reported developing or providing interventions to improve medication adherence for patients, seven (78 %) for healthcare professionals and one (11 %) company for community-based intervention strategies (e.g. public health, population-based initiatives).

Unfortunately, the response rate was too low to draw firm conclusions. Our results nevertheless show that less than half of the participating companies address medication adherence interventions in their strategic plan, and that only one out of three employ a staff member dedicated to therapy adherence.

The main S&T results of WP5: Identification and assessment of adherence-enhancing interventions

The objective of WP5 was to identify strategies for enhancing adherence, and components thereof which successfully improve implementation of the prescribed drug dosing regimen and maintain long-term persistence.

Medicine, Embase, Cinahl, the Cochrane Library, and PsycINFO were systematically searched for randomized controlled trials that tested the efficacy of adherence-enhancing strategies with self-administered medications. The searches were limited to papers in the English language and were included from database inception to 28 April 2010. Our review included studies in which adherence were reliably assessed by electronically compiled drug dosing histories.

Sixty-five controlled clinical trials published between 1979 and April 2010 were included in the review. The linear regression model showed that the effect of interventions on adherence decreases 1 % each month (p = 0.0022). Intervention strategies that included feedback to the patients of his/her recent dosing history data were 8 % more effective than intervention strategies that did not include such feedback (p = 0.0142). The meta-analysis, conducted over 40 studies, showed that patients randomized to an intervention group had, on average, a combined adherence outcome which was 12 % higher than in patients randomised to standard care. The average combined adherence outcome among patients receiving adherence-feedback was 21 % (95 % CI: 10 % - 32 %) higher than among patients randomised to standard care. However, a large heterogeneity between studies, despite a common measurement, was evident across the studies. Only four studies reported a significant improvement in clinical outcome.

Despite a common measurement, the meta-analysis was limited by the heterogeneity of the pooled data and the different measures of medication adherence. The funnel plot showed a possible publication bias in studies with high variability of the intervention effect.

Notwithstanding the statistical heterogeneity among the studies identified, and potential publication bias, the evidence from our meta-analysis of RCTs employing unbiased methods of medication adherence measurements suggests that electronically-monitored adherence feedback is a potentially effective approach to enhance medication adherence. The limitations of this research highlight the urgent need to define guidelines and study characteristics for research protocols that can guide researchers in studies designed to assess the effects of adherence-enhancing interventions.

The main S&T results of WP6: Assessment of the cost-effectiveness of interventions that promote adherence

The main S&T results of the systematic review of the literature and economic evaluation of the cost effectiveness of interventions that promote adherence:

The review of the cost-effectiveness literature over the past 30 years shows a distinct lack of evidence on the cost-effectiveness of adherence-enhancing interventions. Very few studies were identified that were full economic evaluations, when compared to the influx of medication adherence literature this is most disappointing and highlights the need for further research. The review concluded that evidence on the cost-effectiveness of adherence-enhancing interventions is of insufficient quality and quantity to inform healthcare decision makers. In response to this, we developed a decision analytic model populated by data from the literature and other secondary sources to assess the cost-effectiveness of two adherence-enhancing interventions: education (verbal and written information) and a combination of education and behavioural counselling (verbal and telephone back-up). In application to antibiotic prescribing for upper respiratory tract infection in the United Kingdom (as per NICE guidelines), the addition of verbal and written information regarding adherence during the GP consultation was cost-effective for both immediate and delayed prescribing strategies. These results, however, should be interpreted with caution, as they are highly sensitive to small changes in parameter estimates. Further, more robust, evidence on the costs and effectiveness of these interventions is necessary to validate the finding within this WP; however, the analysis illustrated the application of decision analytical modelling to gain economic evidence of the cost-effectiveness of interventions that could be adopted alongside prescribing strategies that have been previously recommended for use in routine clinical practice.

The main S&T results of WP7: Preparation of policy recommendation for promoting patient adherence in European healthcare

There were a number of objectives for WP7 which mainly focused around the need to develop policy recommendations for improving adherence to medication and to investigate the reasons for non-adherence. Research suggests that despite much research on the causes, consequences and solutions or policy responses to medicines non-adherence, numerous gaps in knowledge remain and clear evidence of how to reduce non-adherence on a large scale remains elusive.

In order to attempt to ascertain the reasons for non-adherence and to develop recommendations to improve the behaviour of medical professionals and patients we conducted two related studies within WP7, which aimed to develop medicines adherence policy for Europe.

The first study employed Delphi methodology and a consensus conference to seek consensus on solutions to medicines non-adherence and the operational and political feasibility of these solutions.

A key objective of the study was to seek consensus on solutions to medicines non-adherence. The studies also aimed to obtain consensus on the operational and political feasibility of the solutions, and to assess the extent to which these activities have been implemented across Europe.

The Delphi expert panel comprised participants from across Europe and elsewhere who were representatives of patient / carers organisations, healthcare providers and professionals, commissioners and policy makers, academics, and industry representatives. They all participated in the study remotely, anonymously and electronically throughout a series of rounds, summarised as follows:

Round 1: Panelists responded to open-ended questions on causes and consequences of and solutions to non-adherence. Responses were categorised into emergent themes, which were fed back to the panel.
Round 2: Panelists accepted, rejected or amended the solutions generated from round 1. Amendments were made to solutions on the basis of panelists feedback.
Round 3: Participants rated the solutions for importance, and operational and political feasibility. Solutions that achieved consensus regarding importance and feasibility were not included in round 4.
Round 4: Panelists were reminded of their own ratings for each remaining solution, were fed back the group's mean ratings for each item, and asked to rate each item again in light of this information.

Solutions that achieved a mean importance score of 4.0 or more (score range: 1; not at all important' to 5 'extremely important') were further discussed and refined at a consensus conference.

The study resulted in 355 statements being generated by expert panelists about the solutions to medication non-adherence.

From these statements, further analysis of the statements was then conducted along with feedback and amendments by the expert panel, which resulted in 43 policy solutions to medication non-adherence being agreed by the panel. Of these, 25 policy solutions were then discussed at a consensus conference held in London. As a result of this meeting a further policy solution was added. Overall consensus was achieved about the importance and feasibility of each potential solution to medication non-adherence for the majority of solutions.

The second study involved inviting national leads for medicines policy in the 27 Member States of the EU to participate in either a self assessment survey or a telephone interview in order to benchmark current implementation activity across Europe for the policy solutions, as reported by National Leads for medicines policy. Of these 27 Member States, 10 completed the survey and seven were interviewed.

The survey was structured around the policy solutions developed through the Delphi study and consensus meeting and meant that we were able to then tailor the needs of different healthcare settings and population segments and take into account the cultural differences between European regions.

The survey concluded that implementation of policy for adherence varied across nations. Some nations reported good provision for medication adherence, while others reported little activity to support adherence.

Across the nations, the greatest amount of activity was reported for patient-focused policy solutions, while the least activity was reported for solutions at the government/healthcare payer level.

In conclusion, consensus about the actions necessary to address non-adherence to medication have now been developed for Europe. The study also informed us about the operational and political feasibility of these actions, and the extent to which the policy solutions have been implemented in 10 European nations. These findings offer a valuable framework for policymakers and healthcare providers seeking to address medicines non-adherence.

As a result of the findings of both Delphi and the self-assessment study of the national leads, the final objective of WP7 was met; whereby it was agreed that an educational framework should be produced in order to develop a common European policy which would specify curriculum for schools of medicines and pharmacy in Europe on the prevention and management of patient non-adherence.

The framework comprised of four parts: a competency framework describing the skills, knowledge, attributes and behaviours of healthcare professionals that can support patients with medicines; a curriculum for educational organisations to guide education and training for healthcare professionals in their work with patients and their medicines; and a diagnostic tool that can be used both by healthcare professionals to reflect on their practice against specific criteria and by educational organisations to assess their curricula against the competencies that healthcare professionals need to support patients with medicines and medicines taking. The educational framework ends with a brief reading list for managing and supporting medication adherence.

This educational framework for managing and supporting medication adherence was principally developed for the professions of medicine, pharmacy and nursing, although it will also be of relevance to other health professions that are involved in medicines adherence. The framework of competencies and the diagnostic tool for assessing competence included in the educational framework should help individuals and teams to effectively manage and support medication adherence with patients. They are best used as a starting point for discussion of competencies required by individuals or teams. Specifically, they can be used by education and training providers in the initial education of health professionals and in competency-led postgraduate training.

The educational framework was distributed to all university schools of pharmacy, medicine and nursing in 16 European countries and a further 70 health profession organisations and federations.

Potential impact:

The following ABC final results potentially have powerful socio-economic impact:

A new consensus on terminology and taxonomy in the field of patient adherence. This new taxonomy sets the stage for ongoing research on patient adherence and for the development of evidence-based, commercial solutions for achieving and maintaining therapeutically effective levels of patient adherence to prescribed medications (WP1).

2. The complete inventory of determinants of patient adherence throughout the EU is an essential tool for designing adherence enhancing interventions, or any intervention for adherence management. The determinants were identified for short-term and long-term treatment, different clinical sectors, health care settings and population segments in Europe, thus allowing development of strategies tailored to the specific needs of target groups (WP2).

3.Theoretical basis of adherence behaviour to inform further research as well as the development of adherence enhancing interventions (WP3)

4. Detailed description of the current practices of adherence management by healthcare professionals in various European countries provide a necessary basis to design educational programs and develop any effective strategy for adherence management (WP4)

5. Scientific framework for evaluating interventions aimed at achieving and maintaining therapeutically effective levels of patient adherence to prescribed medications (WP5). The resulting findings support regulatory approval for marketing and label claims for efficacy and safety. Premarket clinical research studies on the clinical and economic impact of various levels of patient adherence, and on methods for managing patient adherence, define the impact of variable adherence on the efficacy and safety of each pharmaceutical so studied. The prevalence of non-adherence and its clinical and economic impact is known a wide-enough range of different drugs to support estimates of the costs of non-adherence. Each drug, however, has its own story, which varies widely from drug to drug because of wide differences in the ability of given drugs to continue to act in the face of intermittent delays or interruptions in dosing. Defining these is a task for future clinical research, which should be prioritized according to the therapeutic roles of the drugs in question.

6. A comprehensive review of cost-effectiveness of available interventions has identified a field for further research. With a paucity of well-designed studies, there is an urgent need for more quality evidence to accumulate on the cost-effectiveness of adherence-enhancing interventions (WP6).

7. The evidence-based policy recommendations for promoting patient adherence in European healthcare, based on the results of the ABC project, address the needs of different clinical sectors, health care settings, and population segments, and take into account cultural differences between European regions (WP7). With these recommendations, European policymakers may improve the design of both local and national healthcare systems. The effect of these activities will directly help improvement of patient adherence to medication. Indirectly, this will increase effectives and cost-effectiveness of European healthcare systems.

8. A European curriculum for schools of medicine, nursing and pharmacy, on prevention and management of patient non-adherence has been developed and been made available to the stakeholders (WP7). This will help equipping the healthcare workers with relevant skills useful in both preventing, and managing non-adherence, and thus, obtain European patients the best available medical outcomes, with parallel positive effect on the healthcare costs.

The ABC team is in the process of assuring that the project's findings reach European policymakers and relevant stakeholders. A 542-page final scientific report, including the detailed description of the project results, was prepared by 30 June 2012. The executive summary of the report is to be mounted on the ABC website as well as circulated to all ABC project stakeholders identified throughout the project's lifetime.

The ABC project results are helping turning the vision of adherence-enhancing environment into reality by providing all relevant European stakeholders with tailored solutions:

-Patients by assessing their perspective of problems arising along drug-taking, better understanding of perceived and objective barriers toward adherence was achieved. Thus, more effective adherence-enhancing interventions might be designed on that basis.
-Healthcare professionals by assessing their current skills, better tailored educational programs for tailor their educational programs for healthcare professionals could be designed, in order to help them effectively manage this problem in their patients.
- Governments and policymakers are now equipped with evidence-based guidance on solutions able to improve patient adherence to medication as well as secure better, more effective and cost-effective healthcare across Europe.
- Payers have clear view on effectiveness and cost-effectiveness of different non-adherence-targeting interventions, which would help them taking right decisions.
- Industry is provided with the cohesive set of data helping it to focus their activities in the field of non-adherence on the most promising directions.
- Researchers are provided with effective tools for further research in the field of non-adherence to medication, as well as to the guidance on which fields needs this research most.

In addition to these general impact areas, several details are worth pointing out, inter allia:

The findings suggest a number of implications for the development of adherence-enhancing interventions. Most importantly, the common variables identified within the study as having strong association with non-adherence that is, self efficacy (odds ratios 0.73 95 % CI 0.68 to 0.77) and perceived barriers (OR 2.18 95 % CI 1.64 to 2.89) are amenable to change through improved communication with health care professionals or brief cognitive-behavioural intervention. Our analysis suggests that a theoretically informed, controlled trial of cognitive-behavioural interventions, focused at increasing self-efficacy and reducing perceived barriers to adherence behaviours is warranted. Given the broad spectrum of potential barriers and the observation of independent, country-level differences which may be related to cultural, health service or other factors interventions which are tailored specifically to the population in which they are being delivered are the most likely to be effective.

The results of the patient survey suggest that, in addition to treatment benefits, patients place a high value on reducing the risk of severe (but relatively rare) adverse drug reactions and frequency of dose when choosing to continue taking a medicine. Persistence is therefore associated with the willingness to trade potential benefits, harms, and convenience. The total utility produced by different combinations of these attributes may have value in assessing patients likelihood of persisting with medicines, and in the personalisation of medicines, or formulations thereof, to maximise persistence.

Behavioural models based on both health psychology and economics have been applied to empirical studies of determinants of adherence to medicine. Findings related to behavioural models drawn from the economic literature indicate that when access to medicines requires payments, patients adherence to therapy follows the consumer demand theory, as if medicines were a normal good. However, the theory fails to explain all the variation in adherence, as lack of adherence, and premature discontinuation is highly prevalent in countries where health systems enable free access to medicines. Findings related to models derived from social cognitive theory, self regulatory theory and social support also indicate that psychological factors can explain variance in medication adherence. Distal and proximal parameters derived from behavioural theories have been shown to be significant predictors of adherence. The potential for these factors to be consolidated in a conceptual framework of patient behaviour has been demonstrated. This will provide a theoretical basis for the development and assessment of adherence-enhancing interventions. The interpretations of these findings are limited by unreliable measures of adherence. The dynamic properties of intentional and unintentional adherence warrant further investigation. Future research is needed to test the effectiveness of adherence-enhancing interventions that are based on the theoretical models identified to have the greatest explanatory power of behaviour. To our knowledge this was the first study to review both health economic and health psychology behavioural models of adherence.

The addition of written information, during GP consultations, to:

(i) emphasise the importance of completing the antibiotic treatment,
(ii) respect intervals between doses and
(iii) detail the drawbacks of an early dropout, is a cost-effective approach to immediate or delayed antibiotic prescribing in URTI, as per the UK NICE (2008) clinical guidelines.

The economic evaluation suggests that interventions targeted at acute conditions with small health benefit will need to have a low per patient cost to be economically worthwhile. A degree of caution is required in interpreting the results, however, as they are sensitive to small changes in parameter estimates.

ABC project website URL: http://www.abcproject.eu

ABC project contact e-mail: info@abcproject.eu