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Access to Opioid Medication in Europe

Final Report Summary - ATOME (Access to Opioid Medication in Europe)

Executive Summary:
1. Executive Summary

The Access To Opioid Medication in Europe (ATOME) project was initiated by the Access to Controlled Medications Programme of WHO. It was a five-year project funded under the 7th Framework Programme of the European Community [FP7/2007-2013] under grant agreement n° 222994. The project consortium consisted of partners from the field of law, governance and public health, palliative care, and harm reduction. The project investigated why opioid medicines for moderate to severe pain and for the treatment of opioid dependence are not used adequately in twelve European countries, and developed tailor-made solutions for improved access to opioid medicines in these countries.

1.1 ATOME goals and activities

A central feature of the ATOME work plan was close collaboration with national counterparts. Key stakeholders were invited to become a member of the national country teams which then comprised government officers, legal experts, palliative care and harm reduction specialists, and patient representatives. Collaboration with the national counterparts cumulated in a series of ATOME conferences in the 12 target countries. The basic foundation of the project activities was the production of the revised WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances, Guidance for Availability and Accessibility for Controlled Medicines using an expert consensus process. Building on this milestone, the ATOME project followed two types of activities in parallel: one activity type focused on legal analysis, the other on the analysis of national policies. Both the legal and policy analysis were guided by the recommendations made in the guidelines document. The self-assessment checklist was an important tool for the national problem analysis and development of strategic action plans towards improving access to opioid medication; and the barriers addressed in the guidelines built an important framework for the lectures and working groups during national conferences.

1.2 ATOME key findings

Scientific research undertaken within the ATOME project provided information on four areas relevant for access to opioid medicines: challenges concerning policy and guidance on access to opioids, legal and regulatory barriers, policy barriers, and the perception of barriers in different stakeholder groups. Analysis from these fields resulted in individual reports: legislation review reports (also in national language), country reports and reports on the perception of barriers which were distributed to the country teams. Next to the findings of the scientific research activities, achievements of the project are publication and dissemination activities that were targeted at providing guidance and having a societal impact.

1.3 Conclusion

The ATOME project contributed to building a critical mass of interested parties, bringing together people from different fields such as pain therapy, palliative care, harm reduction, and from national governments. It is hoped that the activities initiated in ATOME will be sustained after the end of the project, improving accessibility, availability and affordability of essential medicines, including opioid analgesics and long-acting opioids used for the treatment of opioid dependence in the twelve participating European countries targeted in this project.
Project Context and Objectives:
2. Summary description of project context and objectives

2.1 Background and problem statement

The WHO European region has a population of 881 million. Each year, 1.3 million people in the European Union die from cancer and approximately 5.7 million from non-cancer chronic diseases. In the 12 ATOME countries each year 300,000 people die from cancer (1). With the aging population, the pattern of mortality also changes (2). As more people live to older ages, and as chronic diseases become more common with older age, the numbers of people living with and suffering from these diseases will increase as well. With ongoing medical progress, patients will survive longer with chronic disabling disease, and in consequence suffer from pain or breathlessness over a longer period of time. A considerable percentage of these patients will require treatment with morphine or other opioids to achieve symptom control. However, many of them will not receive adequate treatment of their pain.

Opium has been used as an analgesic as long as 4000 years ago. Today, medicines derived from opium such as morphine are still the mainstay of analgesic therapies and most people will require their use at least once throughout their lifetime for acute or chronic pain. The World Health Organization has acknowledged the importance of opioid medicines in its Model List of Essential Medicines (3) and its Model List of Essential Medicines for Children (4). WHO considers fentanyl, hydromorphone, methadone, morphine and oxycodone essential medicines both for adults and children. The WHO Guidelines for the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses and the WHO guidelines on cancer pain management (5,6) list a number of essential opioid analgesics equally.

The International Association for Hospice and Palliative Care lists not only codeine and morphine, but also tramadol, fentanyl, methadone and oxycodone as essential medicines for palliative care (7); and more recently the European Association for Palliative Care published new guidelines on the use of opioid medicines (8), reinforcing the value of these medicines as the mainstay of cancer pain management.

Opioids are also considered to be effective for the treatment of opioid dependence. Opioid maintenance treatment can interrupt the cycle of intoxication and withdrawal and reduces illicit opioid use and the risk of death through overdose and infection with hepatitis and HIV. In addition, it also reduces public nuisance and petty crime. The WHO Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence recommend opioid agonist maintenance treatment, combined with psychosocial assistance, as the most effective of all treatment options examined (9).

The United Nations Office on Drugs and Crime (UNODC) estimated that there are 15-39 million problem drug users in world, and 12 to 14 million heroin users (10). In Europe, it is estimated that between 3.1 and 3.5 million people use opioids illicitly.

In spite of the beneficial effects of opioid medicines, the fear of misuse has resulted in drug control regulations that have proven to be a major barrier against state-of-the-art medical use of opioids and other controlled medicines. In 1961, a number of treaties and protocols were merged into the Single Convention on Narcotic Drugs (11). Codeine, morphine and most other opioids are scheduled in the Single Convention and are subject to the measures of control detailed in this convention. This includes the estimation of medical needs for opioids, as well as rules concerning production, manufacture and distribution, and statistical reports. The broad purpose of the treaty is to prevent the misuse of ‘narcotics’ (a legal term referring to all substances regulated by this convention on ‘narcotic drugs’, but not a class of medicines) including opioids, while guaranteeing their availability for scientific and medical use. However, the implementation of the treaty rules in national legislation and national policies are often much stricter than the treaties require. For this reason the availability of opioids for medical purposes is low, if non-existent, in many countries.

A survey on availability and accessibility of opioids for the management of cancer pain in 41 countries in Europe found substantial limitations of the opioid formularies in many of the 21 Eastern-European countries included in the survey (12). Regulatory restrictions such as requirements for patients for registration or physicians to hold a special licence for the prescription of opioids were much more common in Eastern-European countries than in the West.

There is currently a strong momentum worldwide to improve access to opioid medication with strong international initiatives advocating policy reform activities and supporting change towards more appropriate controlled substances policies and better public health outcomes. Recognizing the requirement to balance the need to protect the population from harmful effects with the need to access controlled medicines for medical use, the World Health Organization (WHO) in 2007 established the Access to Controlled Medications Programme (ACMP) (13) in consultation with the International Narcotics Control Board (INCB) in response to resolutions of the World Health Assembly (WHA) and the Economic and Social Council of the United Nations (ECOSOC) (WHA58.22 and ECOSOC 2005/25) (14). The programme aims at promoting the availability, affordability, accessibility and rational use of controlled medicines.

The ACMP initiated the project Access to Opioid Medication in Europe (ATOME) with the aim to undertake applied research into the reasons why the consumption of opioid medicines for moderate to severe pain and for the treatment of opioid dependence in 12 Eastern European countries is ´low to very low´ (15). Developed in 2006-2007 by WHO, it started in 2009 as a five-year project. It has been funded by the European Community’s Seventh Framework Programme [FP7/2007-2013] under grant agreement n° 222994, which has a section on cancer research. The project aimed to deliver a clear set of recommendations to governments on making controlled medicines accessible for the treatment of patients in need of them for medical reasons such as pain, including from cancer and opioid dependence, based on the principle of balance as enshrined in the preambles of the drug control conventions and promoted by the World Health Organization (WHO) (16) – ensuring that in parallel to a system of control in order to prevent misuse, controlled medicines will be sufficiently available for patient care.

The ATOME Consortium aimed at helping to build a critical mass of interested parties, bringing people together from different fields such as pain therapy and palliative care, and from national governments. The work includes comprehensive legislative and policy reviews, in close cooperation with government officials and public health and medical experts in various countries.

2.2 ATOME concept to address the problem

The ATOME project aimed to investigate why opioid medicines for moderate to severe pain and for the treatment of opioid dependence are often not available where needed and not used adequately in twelve European countries (Estonia, Latvia, Lithuania, Poland, Slovakia, Hungary, Slovenia, Serbia, Bulgaria, Greece, Turkey, and Cyprus), and to elaborate and present tailor-made recommendations to each country for improving the accessibility, availability and affordability of controlled medicines.

To address this complex request, the ATOME consortium was composed out of 10 partners from various fields of expertise like universities, organisations from the field of harm reduction, international organisations from palliative care and the World Health Organisation: the Clinic for Palliative Care at University Hospital Bonn (UKB), the Department of Medicines Policy and Standards, World Health Organization (WHO), the Eurasian Harm Reduction Network (EHRN), Hospice Casa Sperantei (HCS), the National Anti-drug Agency, Romanian Ministry of Interior and Administrative Reform (NAA), Help the Hospices (HtH), Harm Reduction International (HRI; previously “International Harm Reduction Association”), Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University (UU), the International Observatory for End of Life Care at Lancaster University (ULANC) and the European Association for Palliative Care (EAPC). The partners of the ATOME project worked in close collaboration with the country teams, including government officials and public health and medicine experts, to carry out legislative and policy reviews. The integration of palliative care and harm reduction was a key aim of the project.

2.3 Objectives

The aim of the ATOME project was to undertake applied research into the reasons why opioid medicines for moderate to severe pain and for the treatment of opioid dependence are not used adequately in twelve European countries. Specific objectives were:
- To undertake a national situation analysis in twelve European countries with regard to access to controlled medicines, including their availability, rational use, and causes for underuse, and to make recommendations to their national governments; to prepare and realize twelve national follow-up conferences in each of the ATOME target countries.
- To undertake a review of the relevant legislation in twelve European countries and recommend, in compliance with the international drug conventions, appropriate amendments to governments in order to improve access for legitimate and rational use of opioid medicines.
- To increase awareness regarding the importance of appropriate access to opioid medicines for a country’s public health, and present the Country Reports including legislative recommendations to the Ministers of Health in the 12 targeted European countries, if not personally, to their representatives; to disseminate the findings of the national situation analysis and the legislation analysis among government officers and other decision makers, healthcare professionals, as well as opinion leaders.
- To coordinate the project in order to promote communication and collaboration and to coordinate the activities within the ATOME consortium.
- To maintain the ATOME website with regular updates.

To accomplish its objectives, the ATOME project followed two tracks of activities in parallel. One track was related to the analysis of national policies and national circumstances that affect the accessibility and availability of the medicines involved. The other track looked at optimising the relevant legislation in order to acknowledge both the prevention of abuse and dependence and the medical need for these medicines. Parallel to these two tracks, research and monitoring activities have been undertaken in order to illuminate the background situation and the socio-cultural context in each country, and to evaluate the impact of the ATOME project.

References:
(1) World Health Organization, Mortality Indicator Database, online version [cited 2014 11.11]. Available from: http://data.euro.who.int/hfamdb
(2) Davies E, Higginson IJ, editors. Better Palliative Care for Older People. Copenhagen: World Health Organisation Regional Office or Europe; 2004.
(3) World Health Organisation. WHO Model list of Essential Medicines. 2013 [updated April 2013; rev. Oct. 2013]; 18th Edition. Available from: http://www.who.int/medicines/publications/essentialmedicines/en/index.html.
(4) World Health Organization, Mortality Indicator Database, online version [cited 2014 11.11]. Available from: http://data.euro.who.int/hfamdb
(5) World Health Organization. Cancer pain relief with a Guide to Opioid Availability. Geneva: Word Health Organization; 1996 [October 2010]; 2nd Edition; Available at: http://whqlibdoc.who.int/publications/9241544821.pdf.
(6) World Health Organization. WHO Guidelines for the Pharmacological Treatment of Persisting Pain in Children with Medical Illness. Geneva: World Health Organization; 2012; Available at: http://whqlibdoc.who.int/publications/2012/9789241548120_Guidelines.pdf.
(7) De Lima L. International Association for Hospice and Palliative Care list of essential medicines for palliative care. Ann Oncol. 2007;18(2):395-9.
(8) Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012;13(2):e58-e68. Epub 2012/02/04.
(9) World Health Organisation. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence 2009 6.2.2012. Available at: http://www.who.int/substance_abuse/activities/treatment_opioid_dependence/en/index.html.
(10) United Nations Office on Drugs and Crime. World Drug Report 2011. 2012; 6.2.2012. Available at: http://www.unodc.org/unodc/en/data-and-analysis/WDR-2011.html.
(11) United Nations. Single convention on narcotic drugs, 1961 - as amended by the 1972 protocol1977 6.2.2012. Available at: http://www.incb.org/incb/convention_1961.html.
(12) Cherny NI, Baselga J, de Conno F, Radbruch L. Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Europe: a report from the ESMO/EAPC Opioid Policy Initiative. Ann Oncol. 2010;21(3):615-26.
(13) Word Health Organization. Access to Controlled Medications Programme - Framework. Geneva: Word Health Organization; 2007 [cited 2014 06.11.]; Available at: http://www.who.int/entity/medicines/areas/quality_safety/Framework_ACMP_withcover.pdf.
(14) World Health Organization. Access to Controlled Medications Programme. World Health Organization Briefing Note - April 2012. Geneve: World Health Organization; 2012; Available at: http://www.who.int/entity/medicines/areas/quality_safety/ACMP_BrNote_Genrl_EN_Apr2012.pdf
(15) B. Duthey and W. Scholten. Adequacy of opioid analgesic consumption at country, global and regional level in 2010, its relation to development level and changes compared to 2006. Journal of Pain and Symptom Management. 47(2); 2014: 283-97 doi:10.1016/j.jpainsymman.2013.03.015
(16) World Health Organization. WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances, Guidance for Availability and Accessibility for Controlled Medicines. Geneva, 2011. Available at: http://www.who.int/medicines/areas/quality_safety/guide_nocp_sanend/en/.
Project Results:
3. Description of the main S&T results/foregrounds

The specific objectives of the ATOME project (as described in the previous chapter) were implemented through 11 work packages (WP; see Table 1). The realisation of these work packages produced relevant scientific results as reported in this chapter. The contents refer to scientific deliverables and dissemination activities as well as to the ATOME Final report and recommendations to the Ministers of Health for more information on the research activities and the description of detailed research results.

3.1 WP1: Revision of WHO policy guidelines Guidelines Achieving Balance in National Opioids Control Policy: Guidelines for Assessment

As the basic foundation for all following work packages, the first project activity was the revision of the WHO guidelines on Achieving Balance in National Opioids Control Policies. A panel of 30 renowned experts from law and governance, public health, human rights, palliative care and pain treatment, and harm reduction was invited to a four stage revision process. As the first step, a qualitative inventory of required changes was made by means of a structured checklist. Based on the experts’ feedback, a draft revision of the guidelines was prepared and submitted to a two-round online consensus Delphi process. The results of this procedure were discussed in a WHO advisory meeting designed to be the final step in the consensus process for the document. During the advisory meeting persisting controversies were systematically discussed for agreement on the final wording of the updated guidelines. The text of the final version was edited and translated into various languages. The Ministries of Health and several health related agencies of all WHO Members States received a copy.

The four-stage multimethod revision process with a multiprofessional expert panel resulted in a substantiated revision of the WHO guidelines. Hereby the increasing knowledge on opioid medication since the first edition of the guidelines was taken into account. The consensus process with experts revealed the difficulty of defining concepts such as ‘rational (medical) use’ versus. ‘misuse’ of controlled substances, and reflected the challenge of outweighing the risks and benefits of certain substances. The consensus process underlined the complexity of political guidance in balancing between control and availability, between protection and harm. The revised version represents a highly relevant instrument for policy makers to identify barriers – and eventually for the improvement – of the availability, access and affordability of opioids for medical use.

The production and publication of the World Health Organization (WHO) policy guidelines Ensuring Balance in National Policies on Controlled Substances, Guidance for Availability and Accessibility for Controlled Medicines provides an up-to-date and internationally agreed standard for decision makers in Europe and other countries on how to ensure balanced drug control policies. The scientific output of WP1, i.e. the revised WHO policy guidelines are available in 15 languages (see Figure 1) and the PDF documents are freely accessible from the homepage of WHO:
http://www.who.int/medicines/areas/quality_safety/guide_nocp_sanend/en/. The 21 recommendations and the country self-assessment checklist as part of the revised WHO policy guidelines provide important tools to survey legal and regulatory settings in each country and to develop strategic action plans towards improving access to opioid medication.

3.2 WP7 & WP8: Analysis of national legislations in 12 Eastern European countries

The legal analysis looked at optimising the relevant legislation by identifying provisions that may impede access to controlled medicines in the 12 Eastern European countries and by making recommendations for improvement in consultation with the national counterparts. For this specific objective a two-step method was developed to undertake an external review of national legislation: A 'quick scan' of national legislation (WP7) followed by a deeper review (WP8). The revised WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances provided the basis for the identification of potential barriers to access to opioids. The legislation review focused on nine different categories of potential legal and regulatory barriers, i.e. barriers related to prescribing; dispensing; usage; trade and distribution; manufacturing; affordability; penalties; language; and other.

3.3 ‘Quick scan’ of national legislation (WP7)
Legislation intended or used in regulating opioid substances and opioid medicines (case law excluded) was obtained from key experts in each country. Key experts were selected based on their expertise in the field of pharmaceutical law and health policy in the twelve target‐countries (WP2). All key experts were trained in identifying and selecting relevant information during a two‐day workshop (WP6). In addition, two documents where provided to all national counterparts:
1. A guidance document created to help the national counterparts identifying the most important laws, decrees, regulations, etc.
2. An example of a list of legislation according to the situation in the Netherlands.
Based on this input lists of relevant legislations was provided by the national counterparts and translated, if necessary, into the English language.

The legislation was analysed (‘quick scanned’) and overly restrictive provisions were identified. Provisions that contained stigmatizing language and incorrect use of terminology and definitions were also identified. Selected provisions were independently scored by two reviewers into two categories: 1) probable barriers and 2) potential barriers. A barrier was recorded if both reviewers concurred with each other. The results were disseminated to the ATOME country teams and posted on the ATOME website (17).

The significant scientific result of WP7 is the provision of a tool which enables to identify potential legal and regulatory barriers specific to the legal situation of any country: “The ATOME Quick Scan of legislation can be used as a relatively simple method by any person with basic knowledge of the system in place to control ‘narcotic drugs’ to identify potential hurdles to accessing opioid medicines, using eight of the 21 WHO guidelines as a tool to locate unbalanced legislation. The practical approach of scoring provisions into two categories to identify obvious impediments, not only gives insight in ‘quick wins’ in terms of improvement (category 1 provisions), but also provides a good basis for a more detailed review of legislation (category 2 provisions).”(18)

3.4 ‘Deep scan’ of national legislation (WP8) (19)

A method was developed for a more thorough evaluation of national legislation with the aim to identify legal and regulatory barriers to opioid medication and to draft recommendations for improvement. For the ‘deep scan method’ a template was developed based on the WHO policy guidelines (see above) and additional literature regarding barriers to access (20) in consultation with two experts in the field of pharmacy and law. Relevant national legislation (compiled during the activities of WP7 and updated if necessary) was reviewed by one expert and provisions were selected for further review.

The reliability of the selection by one reviewer was validated by assessing the inter-rater reliability between two reviewers (including the reviewer responsible for the selection) ofthe main controlled substances law of three randomly selected countries. The agreement between the two reviewers was measured using Cohen’s kappa statistics (21) and was rated to be very good (kappa= 0,87). Following validation of the selection of provisions, the template was piloted by all three reviewers: selected provisions of one country (Greece) were analysed based on the template and the three reviewers met to discuss disagreements which concerned general interpretation of the template. Figure 2 illustrates the methods of the ‘deep scan’ of legislation.

The selected provisions of national legislation were subsequently reviewed - using the template - by all three reviewers independently. Disagreements between the reviewers regarding the identification of potential barriers were discussed until consensus was reached. Newly identified barriers were added to the template and the reviewed legislation was checked retrospectively to complete the process. The draft reports containing the provisional results were disseminated to the ATOME country teams. In order to assure the quality of the recommendations, a two-day workshop was held in Utrecht, the Netherlands (January 31st –February 1st 2013) where the results of the legislation analysis were discussed and validated in consultation with the national counterparts (22).

The country specific reports were translated into the national language of the respective country in order to make the reports accessible for policy makers and to make the recommendations simple to implement. The final legislation review reports were disseminated to the responsible Ministers of Health and to the ATOME country teams. The research results are available on the ATOME website (23), they are part of the ATOME final report and recommendations to the Ministers of Health (24) as well as of the ATOME annex (25).

The in-depth evaluation of the legislative and regulatory barriers in the participating countries showed a wide range of potential barriers in the national legislation. The review identified potential legal and regulatory barriers in the following areas: prescribing, dispensing, and usage of opioid medicines; trade and distribution; manufacturing; affordability; penalties; and language. The outcomes of the legislation review resulted in detailed reports for each of the countries, describing the potential barriers, explaining the potential negative impact of the respective provisions on access to opioid medicines, and making a set of recommendations on how to lift these barriers and thereby improving the availability of opioids for those in need of them. Information on the methodology can be found in the legislation review country reports. A manuscript with the preliminary title Over-regulation of opioid medicines: results of the ATOME review of national legislation of 11 Eastern European countries has been drafted by Utrecht University and will be submitted for a scientific publication in due course.

3.5 WP3; WP4; WP5: Analysis of national policies in 12 Eastern European countries

The policy analysis was related to an examination of national policies and circumstances affecting the accessibility and availability of opioid medicines. The goals were both to make recommendations to the government and to make professionals aware of problems arising from their professional practice, by undertaking a national situational analysis with regard to controlled medicines, including their availability, rational use and reasons for underuse. Activities in this track were two six-country-workshops (WP3; WP4) where the national delegations developed a national action plan for the improvement of the access to and availability of opioids in their country. The situation analysis, the identification of relevant challenges and appropriate proposals for solutions were elaborated by the national representatives themselves by using the value of an international exchange framework and by learning from models in other countries with similar problems. The national strategic action plans developed during these workshops were an important foundation for the subsequent activities of the country teams.

As a follow-up to the six-country workshops, national conferences were held in the respective countries (WP5). The aim of these one-day events was the sensitisation of key stakeholders towards opioid availability in their country, and dissemination of the results of the legislation analysis and the strategic action plan for improving access to opioids on a national level. The conferences also provided an opportunity for national experts to present their analysis and views and for national and international professionals from the fields of palliative care and harm reduction to network and engage in discussion about issues relating to opioid access. Building on the previously developed national strategic action plans, the conferences resulted in specific recommendations being developed in relation to improving opioid availability and accessibility at national level.

Documents developed and collected during the project (protocols of national problem analyses, strategic action planning worksheets, and minutes of national ATOME conferences) were systematically analysed. The findings of the review of national policies illustrate that beside barriers in the national legislation there are also several challenges concerning national policy strategies with regard to improved access to opioids and the use of these medicines for medical treatment. For the twelve Eastern European countries participating in this project the major challenges to opioid access were identified in four main categories: financial/ economic aspects and governmental support, formularies, education and training and societal attitudes. The identified policy barriers and the resulting recommendations were sent to the respective national country teams for review and verification. The analysis resulted in individual reports for each country, including recommendations on how to address the identified barriers and improve access to opioid medicines in relation to country specific backgrounds.

3.6 Perception of barriers

Discussions with different stakeholders throughout the ATOME project revealed that perceptions may differ considerably with regard to what is seen as a ‘barrier’. A questionnaire survey among different stakeholder groups provided insights into the different perceptions in a range of relevant stakeholder groups such as government officers, legal experts, healthcare professionals or advocacy workers. Government representatives often saw the impact of certain provisions on access to opioids less problematic than, for example, healthcare professionals. The outcomes of this survey underlined the importance of intensified dialogue between different stakeholder groups to facilitate a mutual understanding and establish a common ground for discussion on access to opioid medicines, and to develop effective solutions for improvement.

3.7 Key recommendations from the ATOME project

Several of the countries participating in the ATOME project are already in the process of revising legislation and policies, and implementing recommendations for improvement. As a result, several changes in legislation and policy have already come into force, lifting potential barriers to access to opioids.

Based on the analyses and the outcomes of the ATOME project general recommendations can be derived for all countries aiming to achieve and to ensure a balanced approach in national policies on controlled substances. A selection of them is presented in Textbox 1.

References:
(17) Vranken MJM, Mantel-Teeuwisse AK, Schutjens M-H. ATOME Results of the ‘quick’ scan of national legislation of twelve European countries (Work Package 7). 2011; Available from: http://www.atome-project.eu/documents/ATOME_Report_QuickScan_Legislation.pdf accessed January 16 2015.
(18) Vranken MJ, Mantel-Teeuwisse AK, Junger S, Radbruch L, Lisman J, Scholten W, et al. Legal Barriers in Accessing Opioid Medicines: Results of the ATOME Quick Scan of National Legislation of Eastern European Countries. J Pain Symptom Manage. 2014;48(6):1135-44.
(19) Parts of the text of this paragraph as well as Figure 2 were taken from the original legislation review country reports with permission of the authors Vranken MJM, Mantel-Teeuwisse AK, Schutjens MDB.
(20) Cherny N.I. Baselga J., de Conno F., Radbruch L., Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Europe: a report from the ESMO/EAPC Opioid Policy Initiativ’, Ann Oncol. 2010, 21(3), p. 615-626; Human Rights Watch: ‘‘Please, do not make us suffer any more...’’: Access to Pain Treatment as a Human Right. New York: Human Rights Watch, 2009; Joranson DE, Ryan KM. Ensuring opioid availability: methods and resources. J Pain Symptom Manage 2007;33(5):527-532; De Lima L et al. Legislation analysis according to WHO and INCB criteria on opioid availability: a comparative study of 5 countries and the state of Texas. Health Policy, 2001, 56: 99‐110.
(21) Armitage P, Berry G, Matthews J.N.S. (2002), Statistical Methods in Medical Research, Blackwell, ISBN 0-632-05257-0, p. 698-701.
(22) Report of the ATOME legislation review workshop, available from: http://www.atome-project.eu/documents/atome_legislation_review_workshop.pdf accessed January 16 2015.
(23) http://www.atome-project.eu/ accessed January 16 2015.
(24) Radbruch L., Jünger S., Payne S., Scholten W. (eds.) (2014). Access to Opioid Medication in Europe. Final report and recommendations to the Ministries of Health. Pallia Med Verlag. ISBN 987-3-933154-60-6; Available from: http://www.atome-project.eu/documents/final-reports/ATOME-Final-Report.pdf accessed January 16 2015.
(25) Radbruch L., Jünger S., Payne S., Scholten W. (eds.) (2014). Access to Opioid Medication in Europe. Final report and recommendations to the Ministries of Health - Annex. Pallia Med Verlag. ISBN 987-3-933154-61-3, Available from: http://www.atome-project.eu/documents/final-reports/ATOME-Final-Report-ANNEX.pdf accessed January 16 2015.
Potential Impact:
4. The potential Impact

The ATOME project was designed to have strategic impact on six levels: 1. developments of tools and standards; 2. national policy making processes and access to pain medication and substitution treatment; 3. national capacity building; 4. research collaboration and sharing of experiences in Europe; 5. contribution towards the implementation of European policies; and 6. impact on the patients and populations themselves – those in need of pain medication, people with opioid dependence, and related to the latter, populations at risk for HIV and HCV infections.

ATOME has produced some remarkable changes in the participating countries throughout the lifetime of the project. There are examples of the changes that may be directly attributable to the ATOME project. Here are some examples from 10 participating countries that have been reported from members of the country teams: (for respective textboxes including the examples see attached PDF version of this report).

Some of these changes might have been triggered not only by ATOME activities, but also by other recent initiatives focusing on access to opioids. The target countries of the ATOME project had been selected to include only countries where no major palliative care and harm reduction initiative had been reported, but parallel activities from other projects were evident in some countries. In Serbia, the project on ‘Development of Palliative Care Services in Serbia’ also looked at the legislation on controlled medicines and contributed to a change in legislation in December 2013 allowing non-governmental organizations to provide palliative care and prescribe medicines in the same way as public health institutions. However, feedback from the country teams (see Textbox above this paragraph) suggested that ATOME activities had contributed significantly to these developments.

ATOME results also have to be discussed in the context of recent advances in the global development of palliative care. Palliative Care has received considerable support from several international activities during the project time of ATOME. Foremost, a resolution on strengthening of palliative care at the World Health Assembly in May 2014 (26) has raised much attention on a global level. This was the first time that the highest global health authority published a statement on palliative care. The resolution urged member states to support access to essential medicines, and strengthen palliative care as a component of integrated treatment throughout the life course, and stated that palliative care is an ethical responsibility of health systems.

Similarly, the inclusion of a palliative care indicator in the Action Plan for the Global Strategy for the Prevention and Control of Non-communicable Diseases (27) (NCD) of the World Health Organization (WHO) has acknowledged pain relief and palliative care as among the top 12 issues on the global health agenda. The proposed indicator is: access to palliative care assessed by morphine-equivalent consumption of strong opioid analgesics (excluding methadone) per death from cancer. This indicator has some limitations and weaknesses, and morphine-equivalent consumption of strong opioid analgesics (excluding methadone) per capita has been suggested as an alternative (28).

Another important window of opportunity to put palliative care on the global health agenda: opens with the Sustainable Development Goals (SDGs) of the United Nations that will define global health priorities from 2015 to 2030 29). The SDGs replace the eight millennium development goals (MDGs) that have been in place from 2000 until 2015. Palliative care is relevant to two of the targets related to the third goals in the SDGs. The target of achieving universal health coverage (UHC, target 3.8) includes access to essential health care services, and access to safe, effective, quality, and affordable essential medicines and vaccines for all. In addition target 3.9b aims to support research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries, and provide access to affordable essential medicines and vaccines.

The outcome of the policy barrier analysis led to recommendations for national action in the area of opioid agonist therapy. Better treatment of opioid dependence would contribute to decreased mortality rates, most importantly due to decreased HIV and hepatitis C infections, as well as addressing issues related to the prevention of opioid abuse.

Results from the ATOME project such as the guidelines on ensuring balance (16) will be useful in the implementation of these global activities. The ultimate goal is to ensure access to adequate pain management, palliative care and harm reduction for every patient who needs it, no matter where he or she lives. Access to controlled medicines is needed for this goal.

4.1 Main dissemination activities

4.1.1 Development of tools and standards

The revised WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances (16) available in 14 languages, provided an up-to-date and internationally agreed standard on policies concerning opioid medicines for policy and decision makers in Europe and other countries alike.

The development and introduction of the ATOME database (www.atome-project.eu) provides a platform for qualitative information on the legal, societal, and policy context regarding access to opioid medication. It hereby complements the statistical opioid consumption database provided by the Pain & Policy Studies Group (PPSG) providing quantitative data on opioid consumption (http://www.painpolicy.wisc.edu/opioid-consumption-data). The ATOME database has been updated with recent information, reports, videos and links throughout the project and will still be available after the project closes.

4.1.2 National policy-making processes and access to pain medication and opioid agonist treatment in European countries

One of the main results and dissemination activity is the final report (Access to Opioid Medication in Europe - Final report and recommendations to the Ministries of Health; ISBN 978-3-933154-60-6; www.atome-project.eu) reporting the outcomes of the research undertaken in 12 European countries including identified legal and policy barriers, providing concrete recommendations for legislative and policy changes, and including reports on the national conferences and legislation review reports. The report is available as a comprehensive book condensing all 12 countries plus an annex book; and additionally in a smaller version for each of the 12 countries. These are available as printed copies, as pdfs for download on the ATOME webpage, and as e-book via amazon (30).
The hard copy versions have been sent to the Ministers of Health of the 12 participating countries, the country teams, relevant national organizations and health-care professionals. This systematic dissemination to key stakeholders and decision makers is expected to promote the adoption of policies that will ultimately result in improved access to pain medication, including the treatment of cancer, and improved palliative care.

4.1.3 National capacity building

The six-country workshops, national follow-up conferences in 11 countries and review training for national and external lawyers built national capacities in a direct and indirect way among civil servants and national lawyers in the area of policies for pain management, palliative care and opioid dependence. More precisely, 12 civil servants and three attorneys or lawyers have been trained in recognizing barriers to opioid access and in analysing controlled substances legislations; the 713 people who attended the ATOME country conferences (between 47 and 115 people in 11 countries) were informed about the rational use of opioid analgesics and the rational use of opioid agonist treatment. The establishment and active operation of 11 country teams will ensure that the knowledge acquired in these training sessions will be shared among others in the country also beyond the duration of the project. The eleven country conferences and the legislation review workshop on 31st of January 2013 have vitally contributed to the dissemination and impact in each of the eleven countries that participated in these activities.
There have been blog posts on all 11 country conferences in the EAPC blog (https://eapcnet.wordpress.com/) and additional posts on the final results also in other blogs. Examples are: “Conversations in a ballroom – Hungary ATOME national conference on improving access to opioid medication” (May 2013); Hungary: Budapest“Harm reduction in focus: Final ATOME conference held in Poland” (July 2014); or “Strengthening our understanding of ‘Access to Opioid Medication in Europe’ (ATOME): Highlights of results and achievements” (January 2015). Members of the project management team also tweeted about the country conferences and other ATOME activities.

Even if not directly related to changes in legislation, ATOME activities resulted in more subtle changes, bringing together stakeholders from government, palliative care and pain management as well as harm reduction. This collaboration and networking has resulted in a change of atmosphere, and will hopefully produce more changes in legislation on the medium and long-term run with a potential to overcome regulatory and legislative barriers.

4.1.4. Research collaboration and sharing of experiences in Europe

The ATOME project stimulated close collaboration, both among a wide range of health-related professionals in the country teams, and among the representatives participating in each of the two six-country workshops. The multi-country workshops ensured that the applied research (situational analysis, policy and legislative reviews and recommendations) and country specific experiences were shared among participating countries. The project represents a first initiative to undertake research into opioid availability at European level and it did surely stimulate the creation of a network that will last beyond the duration of the project. Access to opioid medication varies greatly between countries in Europe. European level collaboration is especially a key for countries with lower availability of opioid medication, as the capacity-building activities and the support by colleagues in countries with better availability has been important in pushing forward an agenda for change. Another added value of a European approach is the scale of the achieved outcomes in terms of efficiency and cost effectiveness.

The results of the research undertaken in this project were presented to relevant Ministries and Health professionals in all the participating countries and other relevant organizations at European and national level. Furthermore, the activities of the ATOME project were in line with related ongoing activities by a number of consortium members. For instance, the EAPC developed the Budapest Commitments together with national palliative care associations, aiming at activities for improved palliative care in almost every European country. WHO has developed activities under the Access to Controlled Medicines Programme, a programme with the objective to make controlled medicines available for appropriate medical purposes worldwide, and hence also in Europe. Most other participants also had objectives that include improved access to opioid medicines in Europe for pain management and treatment of dependence and these activities will not stop after the ATOME project.

In May 2014 WHO organized in collaboration with the ATOME consortium a side event to the 67th World Health Assembly in order to present preliminary results of the project on 19th May 2014 in Geneva, Switzerland. The meeting was entitled “Access to Opioid Medicines in Europe and the World: Findings of the ATOME project for Eastern Europe and consequences for other countries and for palliative care”. It was hosted by the International Association for Hospice and Palliative Care, an NGO in official relations with WHO. The meeting was co-sponsored by Latvia, Hungary, Panama, Romania, the World Health Organization, the European Association for Palliative Care, Harm Reduction International, Help the Hospices, Human Rights Watch and the World Palliative Care Alliance.

Invitation letters were sent to the Ministers of Health and the Genevan Ambassadors of the 12 ATOME target countries, Romania (being an ATOME partner through its National Anti-drug Agency; P5), the European Union, the Netherlands and Panama. Furthermore, over 230 invitations were sent by email and 400 announcement flyers were distributed at the World Health Assembly.

In addition to the 12 speakers, 50 people attended the meeting, including representatives of the Ministries of Health of Greece, Hungary, Latvia, Kyrgyzstan, Romania, Slovenia, Spain and the Ukraine. Permanent Missions to the UN in Geneva attending the meeting were Australia, Hungary and Slovenia. During this side event, a representative from Utrecht University disseminated the results of the review of legislation and highlighted recommendations to overcome legal barriers to accessing opioids.

The side event laid an important foundation for the dissemination of ATOME results through the final country reports at the end of the project, by raising awareness for the relevance of adequate access to opioid medicines, as well as by drawing attention to the publication of the final ATOME report amongst the Ministers of Health of the 12 target countries, as well as key stakeholders and policy makers.

A short post in the blog of the European Association for Palliative Care (EAPC) provides an impression of the event including links to the speakers’ presentations (31).

4.1.5 Contribution towards the implementation of European policies

The ATOME project has contributed towards the implementation of European policies in various ways. It helped to provide a networking platform and also practical resources for enhancing awareness, facilitating activities, and promoting implementation in a political and societal context characterised by an international momentum towards improved access to opioid medicines.

The Slovenian Minister of Health had committed to making cancer treatment a spearhead during Slovenia’s EU Presidency (January to June 2008), and one of Slovenia's aims had been to reduce the inequalities between the members of the European region. Access to opioid medication is integral to improved cancer treatment. Slovenia’s commitment was also intended to contribute towards the realization of the European Neighbourhood Policy for Turkey, as it "fosters closer cooperation both across the EU's external borders and among the EU's neighbours themselves - especially among those that are geographically close to each other" (32).

During the Lithuanian EU Presidency (June to December 2013), one of Lithuania’s priorities had been the accessibility of opioid medicines. At the official opening of the ATOME national conference in Lithuania, a representative of the Ministry of Health, who was a member of the Lithuanian ATOME country team, highlighted the symbolic and practical relevance of the conference (held in February 2014) as a continuation of their goals during the EU presidency (33).

The Council of Europe also established that palliative care is an inalienable element of a citizen’s right to health care and that it is therefore a responsibility of the governments to guarantee that palliative care is available to all who need it. The fact that pain treatment is an integral part of palliative care, and palliative care cannot be provided if adequate analgesia is not available, implicates a recommendation to address the issue of access to analgesia. The Council of Europe also states that the differences in the availability and quality of palliative care throughout Europe need to be addressed through increased co-operation between countries and recommended in 2004 that "the governments of member states (should) adopt policies, legislative and other measures necessary for a coherent and comprehensive national policy framework for palliative care" (34).

Furthermore, the project contributed towards the implementation of a number of priorities in the 2007 work plan for the implementation of the EC Programme of Community Action in the field of Public Health (2003-2008), particularly for priority 2.1.1 "improving the system for the transfer and sharing of information and health data including public access"; priority 2.1.1.7 "promoting patient safety and quality of health services by helping to develop European cooperation and collaboration between competent authorities and relevant stakeholders"; and priority 2.1.1.9 "creation of a network of lawyers working on legislation pertinent to health in EU Member State provide information on how law can be used to promote health and give input for policy development and impact assessments". It did likewise fit into the implementation of the proposed new Programme of Community Action in the field of Health (2007-2013) for example in the area of patient safety, helping to bridge inequalities, with a particular emphasis on the newer Member States and action to expand EU health monitoring and develop indicators and tools (35)." The WHO Office at the European Union has regular contact with EC focal points in the various Directorate-Generals and did therefore enable project outcomes to be channelled to the relevant bodies in the European Commission.

4.1.6 Impact on the patients and populations themselves

Patients and populations means those in need of pain medication and people with opioid dependence and, related to the latter, populations at risk for attracting HIV and HCV infections. For a wide variety of conditions, patients do not achieve pain relief (analgesia in medical terms) without the use of controlled medicines: for example in cancer pain, HIV neuropathy, diabetic neuropathy, chronic pain, surgery pain (both around and after surgery), traumatic pain and sickle-cell disease. About 80% of terminal cancer patients suffer moderate to severe pain, and every year, globally, 4.8 million people of them do not receive adequate pain management. Furthermore, an estimated 1.4 million people with moderate to severe pain during end-stage AIDS do not receive treatment. Opioid dependence increases mortality rates due to the poor quality and uncertain strength of heroin on the illicit markets and countries with a high prevalence of untreated illicit opioid use relate to high transmission rates of blood-borne diseases like HIV and HCV, even for the non-opioid dependent part of the population. In 15 out of the 25 European Union Member States, medical consumption of opioids was close to nonexistent, including in the newest 10 member states. Through its activities the ATOME project promoted equal access to opioid medication to millions of patients affected by the medical conditions above, in 12 European countries.

An article in the International Herald Tribune, 9 September 2007, "Fear of morphine dooms third world poor to die in fear", speaks about the poor masses that routinely are denied access to pain medicines. Quoting figures from the International Narcotics Control Board, the article states that 6 developed countries consume 79% of the world's morphine and 80% of the world's people living in poor and middle-income countries consume only 6%. Stating that third world doctors often have beliefs about narcotics that prevailed in Western medical schools decades ago (such as fear of dependence and risks of death), the article argues that the the benefits outweigh the efforts for the millions of poor fated to die in pain. In the future, the outcome of the ATOME project may help to inform EC development cooperation policy in health.

4.1.7 Other dissemination activities and scientific publications

Dissemination aiming at the scientific community has been achieved at several conferences during the last five years (e.g. the EAPC congress 2011 in Lisbon, Portugal, 2012 in Trondheim, Norway, 2013 in Prague, Czech Republic and 2014 in Lleida, Spain,) by poster and oral presentations. At the EAPC congress 2013 in Prague a dedicated ATOME session has been held.

The results of the ATOME project were also disseminated at a meeting on the Societal Impact of Pain 2014 in Brussels, Belgium on 18th November 2014 and a meeting with the Permanent Missions to the United Nations in Geneva at 5th December 2014. During the five year period of the project there have also been several publications of articles in the popular press about ATOME.

In spring 2013, the International Harm Reduction conference had been held in Vilnius, co-organised by two ATOME consortium partners – the Eurasian Harm Reduction Network (EHRN, based in Vilnius) and Harm Reduction International (HRI). During this conference, access to opioid medication had been highlighted as an important issue for healthcare during a presentation held by the ATOME representative of EHRN.

So far there have been nine publications in scientific journals about the ATOME project. Starting in 2011 with ATOME training of lawyers and national counterparts workshop: a report in the European Journal of Palliative Care (EJPC), followed by publication of five scientific abstracts in Palliative Medicine. In 2013, an article on “Consensus Building on Access to Controlled Medicines: A Four-Stage Delphi Consensus Procedure” was published in the Journal of Pain and Symptom Management. A report on “Legal Barriers in Accessing Opioid Medicines: Results of the ATOME Quick Scan of National Legislation of Eastern European Countries” was published in 2014 in the same journal.

Together with the above mentioned contributions at scientific congresses it can be said that these dissemination activities have created a high visibility of the ATOME project and its results in the scientific community – both in the area of palliative care and harm reduction - in Europe and other regions of the world.

4.2 Exploitation of results

ATOME has demonstrated the effectiveness of the methodology, using a combination of guidelines, legislation review, country teams and national workshops. This has raised interest from other organizations, who want to apply the methodology in other countries or regions. The final report and the annex to this report can be used as a blueprint for such activities.

ATOME has made an impact not only in the 12 participating countries, but also in other countries in Europe as well as in other regions of the world. The guidelines on ensuring balance in access to opioid medications of the World Health Organization have been used by government and non-government stakeholders, and the methodology with country teams and country workshops has also been used in other regions. National conferences with government representatives and palliative care experts from non-governmental organizations for example have been organized in Central and South American countries by the International Association for Hospice and Palliative Care.

Within the scope of the mailing of the final report the documents have also been sent to a list of about 200 potentially interested persons, some of which have been responding in a very thankful and interested way. As a concrete example, leading scientists from palliative care in Uganda are currently preparing an adaption of the ATOME methodology for several countries in Africa. Support and participation by ATOME leaders are currently being discussed. Interest has already been voiced by non-governmental organizations such as Hospice Africa Uganda to use the ATOME methodology in other parts of the world.

Additional dissemination activities are planned for 2015, including for example a side event on the ATOME methodology and results as an example for other regions at the 58th Session of the Commission of Narcotic Drugs (CND) on 10th March 2015 in Vienna, Austria, sponsored by the governments of Germany and Lithuania and cosponsored by the International Association for Hospice and Palliative Care (IAHPC) and the Union for International Cancer Control (UICC).

After the mailing of the final report and further results to the country teams several emails have reached the coordinator reporting on the benefit from these results for presentations and meetings in the respective countries. The results have been disseminated among experts from harm reduction and palliative care, as well as policy decision makers; and further development towards a better availability of opioids is intended.

These long-term developments can be exptected to create tremendous improvements for patients suffering from pain as well as their relatives, and for people suffering from illicit drug use.

References:
(26) World Health Assembly. Strengthening of palliative care as a component of comprehensive care within the continuum of care2014: Available at: http://apps.who.int/gb/ebwha/pdf_files/WHA67/A67_R19-en.pdf.
(27) World Health Organization. A comprehenive global monitoring framework, including indicators, and a set of voluntary global targets for the prevention and control of noncommunicable diseases.; 2012. Available at: access date: 13.11.2014.
(28) De Lima L, Wenk R, Krakauer E, Ferris F, Bennett M, Murray S, Bruera E, Radbruch L. Global framework for noncommunicable diseases: how can we monitor palliative care? J Palliat Med 2013; 16: 226-9.
(29) Sustainable Development Knowledge Platform. Outcome Document - Open Working Group on Sustainable Development Goals. 2014. Available from: access date: 13.11.2014.
(30) http://www.amazon.de/s/ref=nb_sb_noss?__mk_de_DE=%C3%85M%C3%85%C5%BD%C3%95%C3%91&url=search-alias%3Daps&field-keywords=Access+to+Opioid+Medication+in+Europe&rh=i%3Aaps%2Ck%3AAccess+to+Opioid+Medication+in+Europe
(31) https://eapcnet.wordpress.com/2014/06/01/a-deeply-respectful-programme-presentation-of-atome-outcomes-side-event-67th-world-health-assembly-in-geneva/
(32) European Neighbourhood Policy: Strategy Paper. COM(2004) 373 final.
(33) https://eapcnet.wordpress.com/2014/03/26/pride-and-prejudice-access-to-opioid-medicines-in-lithuania/
(34) Report from the 54th Meeting of the European Health Committee, Strasbourg, November 2004, Dissemination of the Council of Europe Recommendation on the organization of palliative care.
(35) EUROPA website: Public Health, Overview of health policy, Programme for CommunityAction in the field of Heath 2007-2013.

List of Websites:
5. Further Details of the project

5.1 The address of the project public Website

http://www.atome-project.eu/

Contact after the end of the project:
Prof. Lukas Radbruch: Lukas.Radbruch@ukb.uni-bonn.de

The attached PDF version of this report provides tables and figures as referred to in the chapters above as well as the following additional information:
5.2 The Project logo
5.3 List of all beneficiaries
5.4 Impressions from ATOME