Strategies for achieving global collective action on antimicrobial resistance

Stratégies visant l'accomplissement d'une action collective mondiale sur la résistance aux antimicrobiens

Estrategias para lograr una acción colectiva global frente a la resistencia a los antimicrobianos

الإستراتيجيات الهادفة لدفع التحرك الجماعي على مستوى عالمي بشأن المقاومة للميكروبات

在全球范围内实现有关抗菌剂耐药性集体行动的策略

Стратегии по стимулированию глобальных коллективных действий для сдерживания резистентности к противомикробным препаратам

Steven J Hoffman Grazia M Caleo Nils Daulaire Stefan Elbe Precious Matsoso Elias Mossialos Zain Rizvi John-Arne Røttingen About the authors

Abstracts

Global governance and market failures mean that it is not possible to ensure access to antimicrobial medicines of sustainable effectiveness. Many people work to overcome these failures, but their institutions and initiatives are insufficiently coordinated, led and financed. Options for promoting global collective action on antimicrobial access and effectiveness include building institutions, crafting incentives and mobilizing interests. No single option is sufficient to tackle all the challenges associated with antimicrobial resistance. Promising institutional options include monitored milestones and an inter-agency task force. A global pooled fund could be used to craft incentives and a special representative nominated as an interest mobilizer. There are three policy components to the problem of antimicrobials - ensuring access, conservation and innovation. To address all three components, the right mix of options needs to be matched with an effective forum and may need to be supported by an international legal framework.


Les dysfonctionnements de la gouvernance et du marché à l'échelle mondiale se traduisent par une impossibilité de garantir l'accès à des médicaments antimicrobiens durablement efficaces. De nombreuses personnes s'emploient à pallier ces dysfonctionnements, mais leurs institutions et leurs initiatives manquent de coordination, de direction et de moyens financiers. La création d'institutions, l'élaboration de mesures d'incitation et la mobilisation des parties intéressées font partie des options possibles pour promouvoir une action collective mondiale sur l'accès aux antimicrobiens et sur leur efficacité. Aucune option isolée ne suffira à venir à bout de tous les problèmes associés à la résistance aux antimicrobiens. Parmi les options institutionnelles prometteuses, il convient de mentionner le suivi des étapes importantes et une équipe spéciale interorganisations. Des fonds mis en commun à l'échelle mondiale pourraient être utilisés pour élaborer des mesures d'incitation et un représentant spécial pourrait être chargé de mobiliser les parties intéressées. Le problème des antimicrobiens comporte trois aspects stratégiques: garantir l'accès, la conservation et l'innovation. Pour agir à l'égard de ces trois aspects, il est nécessaire d'associer les options, harmonieusement combinées, à une structure efficace et, peut-être, de les inscrire dans un cadre juridique international.


Los fracasos de gobernanza mundial y de los mercados significan que no es posible garantizar el acceso a medicamentos antimicrobianos de efectividad sostenible. Muchas personas trabajan para solucionar estos problemas, pero sus instituciones e iniciativas no están lo suficientemente coordinadas, guiadas y financiadas. Las opciones para promocionar una acción colectiva global en cuanto al acceso a los antimicrobianos y la efectividad incluyen la creación de instituciones, la elaboración de incentivos y la movilización de intereses. Ninguna opción por sí sola es suficiente para afrontar todos los desafíos asociados con la resistencia a los antimicrobianos. Las opciones institucionales prometedoras incluyen hitos supervisados y un grupo de acción interinstitucional. Se podría utilizar un fondo combinado global para elaborar incentivos y nominar un representante especial como un movilizador de intereses. El problema de los antimicrobianos tiene tres componentes de las políticas: asegurar el acceso, la conservación y la innovación. Para abordar los tres componentes se necesita que la mezcla correcta de opciones se una a un foro efectivo, y podría necesitar el apoyo de un marco legal internacional.


يؤدي فرض الرقابة العالمية ووقوع أوجه قصور في الأسواق إلى عدم إمكانية ضمان تيسير سبل الحصول على الأدوية المضادة للميكروبات ذات الفعالية المستدامة. وهناك جهود تبذلها جهات عدّة للتغلب على هذه الأوجه من القصور، إلا أن المؤسسات والمبادرات التي تمثلها تلك الجهات تعاني من عدم كفاية التنسيق وقصور القيادة ونقص التمويل. ومن بين الخيارات المتوفرة لتشجيع التحرك الجماعي على المستوى الدولي لتوفير سبل الحصول على الأدوية المضادة للميكروبات وضمان فعاليتها يأتي بناء المؤسسات، وتقديم الحوافز، وغرس الاهتمام. ليس ثمة خيار أوحد يكفي بمفرده لمواجهة جميع التحديات المرتبطة بمقاومة الميكروبات. أما الخيارات المشجعة على مستوى تحرك المؤسسات، فتشمل تخطيط مراحل تخضع للمتابعة وتشكيل قوة عمل تجمع بين الجهات المختلفة. كما أنه من الممكن الاستعانة بصندوق يستمد مصادره من جهات عالمية لتقديم الحوافز، ويمكن أيضًا ترشيح ممثل خاص ليتولى حشد الاهتمام. هناك ثلاثة عناصر تتعلق بمشكلة الأدوية المضادة للميكروبات يمكن علاجها من خلال فرض السياسات؛ ألا وهي ضمان تيسير سبل الحصول على الدواء، والحفاظ على النتائج، والتفكير الخلاق. ومن أجل التعامل مع كل هذه العناصر الثلاثة، فإنه يلزم التوصل إلى التوليفة السليمة من الخيارات وربطها بمحفل قادر على تفعيل النتائج، كما يلزم دعمها من خلال إطار قانوني عالمي.


全球政府监管和市场调节不力,意味着无法保证持续有效抗菌剂药物的获取。许多人在努力克服这些不利因素,但是他们的机构未充分协调、积极性无法充分调动、没有正确的领导,同时缺乏经费支持。想要促进在全球范围内针对抗菌剂的可获得性和效果采取集体行动,可选方案包括:构建体系机构、建立激励机制和调动行动意愿。单独一项方案不足以应对与抗菌剂耐药性相关的挑战。可行的机构方案包括:对里程碑式的重要成果进行监控和在代理商间成立特别任务小组。全球范围内筹集到的资金,可用于建立激励机制和任命主管行动意愿调动相关事项的特别代表。抗菌剂问题由三个政策要素构成--确保可获得性、保存和创新。为了解决这三个构成要素,不同方案的正确组合需要符合相关管辖地法院要求,而且可能需要国际法律体系的支持。


Глобальное управление и неэффективность рыночного механизма обуславливают невозможность обеспечения доступа к противомикробным препаратам с постоянной эффективностью. Многие люди занимаются решением этих проблем, однако они сталкиваются с недостаточным координированием, руководством и финансированием их учреждений и инициатив. Добиться глобальных коллективных действий по обеспечению доступа к противомикробным препаратам и их эффективности можно в том числе путем организации учреждений, создания стимулов и привлечения заинтересованных лиц. Реализации какого-либо одного из предложенных вариантов недостаточно, чтобы решить все задачи, связанные с резистентностью к противомикробным препаратам. Перспективные варианты организационного действия включают в себя отслеживание основных этапов развития и создание межучрежденческой целевой группы. Для создания стимулов может быть задействован мировой объединенный фонд, а ответственным за привлечение заинтересованных сторон может быть назначен специальный представитель. Стратегия по преодолению проблемы противомикробных препаратов включает три составляющие: обеспечение доступа, рациональное использование и инновации. Чтобы направить силы на все эти три составляющие, необходим правильный набор вариантов в сочетании с площадкой для эффективного обсуждения и, возможно, подкрепление в виде международной правовой основы.


Introduction

Antimicrobial medicines now save millions of lives each year and many infectious diseases are far less deadly because of them.11. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)...
However, bacteria, viruses, parasites and fungi develop resistance to existing medicines and few novel antimicrobial products are being produced. Antimicrobial resistance - i.e. resistance of microorganisms to an antimicrobial drug that was originally effective for treating the infection it causes - is both natural and inevitable. However, inappropriate antimicrobial use, falsified or substandard drugs and poor infection control accelerate the pace of evolutionary processes.11. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)...

Today, diminishing antimicrobial effectiveness represents one of the greatest threats to human health.22. Global risks 2013 report. 8th ed. Geneva: World Economic Forum; 2013. Available from: http://www3.weforum.org/docs/WEF_GlobalRisks_Report_2013.pdf
http://www3.weforum.org/docs/WEF_GlobalR...

3. Jonathan HGE, Stoltenberg RHJ. UN commission on life-saving commodities for women and children. New York: United Nations; 2012. Available from: Available from: http://unfpa.org/webdav/site/global/shared/images/publications/2012/Final%20UN%20Commission%20Report_14sept2012.doc [cited 2014 Jul 17].
http://unfpa.org/webdav/site/global/shar...
-44. Davies SC, Fowler T, Watson J, Livermore DM, Walker D. Annual report of the Chief Medical Officer: infection and the rise of antimicrobial resistance. Lancet. 2013 May 11;381(9878):1606-9. http://dx.doi.org/10.1016/S0140-6736(13)60604-2PMID:23489756
http://dx.doi.org/10.1016/S0140-6736(13)...
Annual deaths from drug-resistant infection are projected to increase from 700 000 to 10 million by 2050, at a cumulative cost of 100 trillion United States dollars (US$).44. Davies SC, Fowler T, Watson J, Livermore DM, Walker D. Annual report of the Chief Medical Officer: infection and the rise of antimicrobial resistance. Lancet. 2013 May 11;381(9878):1606-9. http://dx.doi.org/10.1016/S0140-6736(13)60604-2PMID:23489756
http://dx.doi.org/10.1016/S0140-6736(13)...
,55. Review on Antimicrobial Resistance. Tackling drug-resistant infections globally [Internet]. London: Wellcome Trust; 2014. Available from:http://amr-review.org
http://amr-review.org...
The world might face a scenario where infection once again takes a heavy toll on a scale and severity not seen in over 80 years. Universal access to antimicrobials, on the other hand, represents one of the greatest opportunities to save millions of lives each year and improve the lives of millions more. For example, 244 000 deaths in neonates could be averted annually with basic injectable antibiotics.33. Jonathan HGE, Stoltenberg RHJ. UN commission on life-saving commodities for women and children. New York: United Nations; 2012. Available from: Available from: http://unfpa.org/webdav/site/global/shared/images/publications/2012/Final%20UN%20Commission%20Report_14sept2012.doc [cited 2014 Jul 17].
http://unfpa.org/webdav/site/global/shar...

Global action is needed to mitigate the threat of increased antimicrobial resistance. However, policies designed to improve access to antimicrobial medicines, to maintain their effectiveness and to increase the supply of new products have not been implemented.11. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)...
We argue that this lack of action is due to failures in global governance and global markets, rather than insufficient awareness or political priority. National governments would all benefit from cooperation and coordination on antimicrobial access, conservation and innovation, but none want to incur their part of the associated costs.66. Fidler DP. Legal issues associated with antimicrobial drug resistance. Emerg Infect Dis. 1998 Apr-Jun;4(2):169-77. http://dx.doi.org/10.3201/eid0402.980204PMID:9621187
http://dx.doi.org/10.3201/eid0402.980204...
,77. Smith RD, Coast J. Antimicrobial resistance: a global response. Bull World Health Organ. 2002;80(2):126-33. PMID:11953791 Global markets, meanwhile, undersupply antimicrobials for those who cannot afford them, oversupply them in wealthier contexts where individual benefits are not weighed against total costs and underinvest in research and development for new antimicrobials.88. Outterson K. New business models for sustainable antibiotics. London: Chatham House; 2014. p. 31. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/public/Research/Global%20Health/0214SustainableAntibiotics.pdf [cited 2014 Apr 22].
http://www.chathamhouse.org/sites/files/...

We examine ways of achieving global collective action to correct these governance and market failures. Overcoming these failures should make it possible to implement policies designed to improve access to antimicrobials, conserve those that are still effective and drive innovation in preventing and treating infections. We map the existing actors in this policy area, identify guiding institutional design principles and evaluate 10 options for achieving progress. Our goal is to bring the science of global strategy99. Hoffman SJ. A Science of Global Strategy. In: Frenk J, Hoffman SJ, editors. "To save humanity": what matters most for a healthy future. Oxford: Oxford University Press; 2015. to bear on the challenge of antimicrobial resistance.

Governance of antimicrobial use

Many institutions address the threat posed by antimicrobial resistance (Box 1), with numerous global strategies, political resolutions and regulatory standards generated from multilateral activities, industry initiatives and public-private partnerships. However, the mandates and objectives of these institutions are not all aligned. For example, antimicrobial growth-promoters can advance Food and Agriculture Organization (FAO) objectives by improving weight gain in farm animals, but can adversely affect human health, of concern for the World Health Organization (WHO). These institutions work through different policy fora which have different powers to influence state behaviour and are attended by different delegations with different priorities. Ministers of agriculture attend FAO meetings, while ministers of health are at WHO. There is no forum in which they meet to resolve issues of common concern - such as antimicrobial resistance - on the international level. Commitments made by ministers of health to address the issue have resulted in several World Health Assembly resolutions (e.g. WHA51.17, WHA54.11, WHA54.14 and WHA58.27) that have not been implemented. In 2007, WHO reported that:

Box 1Examples of key institutions in the global antimicrobial regime

United Nations entities

  • World Health Organization (WHO)

  • Roll Back Malaria Partnership

  • STOP TB Partnership

  • Joint United Nations Programme on HIV/AIDS (UNAIDS)

  • United Nations Children's Fund (UNICEF)

  • United Nations Office on Drugs and Crime

  • United Nations Development Programme (UNDP)

  • Food and Agriculture Organization of the United Nations (FAO)

  • Joint FAO/WHO Codex Alimentarius Commission

  • United Nations General Assembly

  • United Nations Security Council

Other multilateral organizations

  • Global Fund to Fight AIDS, Tuberculosis and Malaria

  • International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

  • World Bank group

  • World Organisation for Animal Health (OIE)

  • International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products

  • Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S)

  • World Trade Organization (WTO)

  • Consultative Group on International Agricultural Research (CGIAR)

  • G7 and G20

  • Global Health Security Initiative

Civil society

  • Alliance for the Prudent Use of Antibiotics

  • Action on Antibiotic Resistance (ReAct)

  • Antibiotic Action Team

  • Health Action International (HAI)

  • Médecins Sans Frontières (MSF)

Public-private partnerships

  • Innovative Medicines Initiative

  • European Platform for the Responsible Use of Medicines in Animals

Industry groups and professional associations

  • European Federation of Pharmaceutical Industries and Associations

  • International Dairy Federation

  • International Federation for Animal Health

  • International Federation of Pharmaceutical Manufacturers & Associations

  • International Hospital Federation

  • International Meat Secretariat

  • International Poultry Council

  • World Farmers' Organisation

  • World Medical Association

  • International Pharmaceutical Federation

  • World Health Professions Alliance

"...few countries have a national task force or strategy for containment of resistance, a reference laboratory for surveillance, or enforcement of policies such as limiting the availability of antibiotics to prescription only."1010. Progress reports on technical and health matters. Report No. A60/28. Geneva: World Health Organization; 2007. Available from: http://apps.who.int/gb/ebwha/pdf_files/WHA60/A60_28-en.pdf
http://apps.who.int/gb/ebwha/pdf_files/W...

Nonetheless, some progress towards global collective action on antimicrobials has been made in recent years, in areas such as disease surveillance and food safety. Numerous pathogen- and region-specific surveillance networks are supported by WHO. The International Health Regulations require that all WHO Member States monitor and report disease outbreaks. The World Organization for Animal Health (OIE) sets global standards for antimicrobial surveillance programmes.1111. Terrestrial animal health code [Internet]. Paris: World Organisation for Animal Health; 2013. Available from: Available from: http://www.oie.int/international-standard-setting/terrestrial-code/ [cited 2014 Jul 16].
http://www.oie.int/international-standar...
FAO, WHO and OIE are currently developing an agreed strategy on antimicrobial resistance.1212. The FAO-OIE-WHO Collaboration: Sharing responsibilities and coordinating global activities to address health risks at the animal-human-ecosystems interface. Paris: World Organisation for Animal Health ; 2010. Available from: Available from: http://www.oie.int/fileadmin/home/eng/current_scientific_issues/docs/pdf/final_concept_note_hanoi.pdf [cited 2015 Sep 25].
http://www.oie.int/fileadmin/home/eng/cu...
,1313. Otto P. FAO-OIE-WHO tripartite positions and actions on antimicrobial resistance. Rome: Food and Agriculture Organization; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/12.OTTO.pdf [cited 2015 Sep 25].
http://www.rr-africa.oie.int/docspdf/en/...
FAO and WHO already cooperate in the Codex Alimentarius Commission, which develops harmonized international food standards that protect consumer health.1414. Codex Alimentarius Commission. Guidelines for risk analysis of foodborne antimicrobial resistance. Geneva: Food and Agriculture Organization; 2011. Available from: Available from: http://www.codexalimentarius.net/input/download/standards/11776/CXG_077e.pdf [cited 2015 Sep 25].
http://www.codexalimentarius.net/input/d...

However, it is not clear that the promise of these collaborative efforts will be realized. Debates between human and animal health researchers over drivers of antimicrobial resistance have hindered joint efforts;1515. Strategic and Technical Advisory Group on Antimicrobial Resistance: report of the first meeting. Geneva: World Health Organization ; 2013. Available from: Available from: http://www.who.int/drugresistance/stag/amr_stag_meetingreport0913.pdf [cited 2015 Sep 25].
http://www.who.int/drugresistance/stag/a...
the global antimicrobial regime lacks clear leadership and remains fragmented.1616. Transatlantic Taskforce on Antimicrobial Resistance. Recommendations for future collaboration between the US and EU. Stockholm: European Centre for Disease Prevention and Control; 2011. p. 44. Real-world achievements have been elusive. Of the 152 OIE Member States that responded to a 2012 survey, only 27% had systems for monitoring antimicrobial usage in animals, as prescribed by theTerrestrial Animal Health Code , with implementation lowest in Africa (5%) and the Americas (4%).1717. Diaz F. Collection of quantitative data on the use of antimicrobial agents. Paris: World Organisation for Animal Health ; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/13.DIAZ.pdf [cited 2015 Sep 25].
http://www.rr-africa.oie.int/docspdf/en/...
A recent systematic review found that use of human antimicrobial medicines without prescription in countries outside northern Europe and North America ranged from 19% to 100%.1818. Morgan DJ, Okeke IN, Laxminarayan R, Perencevich EN, Weisenberg S. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis . 2011 Sep;11(9):692-701. http://dx.doi.org/10.1016/S1473-3099(11)70054-8PMID:21659004
http://dx.doi.org/10.1016/S1473-3099(11)...
The International Health Regulations have potential to improve this situation, but in 2014, 81 Member States requested a second two-year extension to their original June 2012 deadline for attaining minimal core public health capacities. An additional 48 Member States did not communicate their implementation status or intentions.1919. Ijaz K, Kasowski E, Arthur RR, Angulo FJ, Dowell SF. International Health Regulations - what gets measured gets done. Emerg Infect Dis . 2012 Jul;18(7):1054-7. http://dx.doi.org/10.3201/eid1807.120487PMID:22709593
http://dx.doi.org/10.3201/eid1807.120487...

20. Edge JS, Hoffman SJ. Strengthening national health systems' capacity to respond to future global pandemics. In: Davies S, Youde JR, editors. The politics of surveillance and responses to disease outbreaks. Surrey: Ashgate Publishing; 2015. pp. 157-79.
-2121. Implementation of the International Health Regulations (2005): report by the Director-General. Geneva: World Health Organization ; 2015. Available from: http://apps.who.int/gb/ebwha/pdf_files/WHA66/A66_16-en.pdf
http://apps.who.int/gb/ebwha/pdf_files/W...
The World Health Assembly approved aGlobal Action Plan on Antimicrobial Resistance in May 2015, but its full implementation has yet to be funded and is far from guaranteed.2222. Draft global action plan on antimicrobial resistance. Geneva: World Health Organization ; 2014. Available from: Available from: http://apps.who.int/gb/ebwha/pdf_files/EB136/B136_20-en.pdf [cited 2015 Oct 9].
http://apps.who.int/gb/ebwha/pdf_files/E...

Four institutional weaknesses contribute to the global lack of action on antimicrobial resistance. The first is a governance problem - an absence of effective coordination across the actors working in different sectors to address this challenge. The second is a compliance problem - a gap between the many actions that have been promised by states and the few that have been delivered. The third is a leadership problem - insufficient political will to stop the inappropriate use of antimicrobials in humans and animals. The fourth is a financing problem - insufficient resources to implement antimicrobial policies.

In the absence of consent-based global action, governments may resort to unilateral measures to coerce collective action, such as direct financing, conditionality, import and export bans or sanctions. These approaches may work but they have several disadvantages (Table 1).

Table 1
Unilateral options for promoting state action

Strengthening institutions

To correct governance gaps and market failures, the global antimicrobial regime can be changed by adding to or reforming three sets of institutional mechanisms: (i) decision-making mechanisms for setting norms, soliciting advice, making decisions, appealing decisions and resolving disputes; (ii) operational mechanisms for administering activities, for raising, managing and spending funds and for financial auditing; and (iii) accountability mechanisms for making commitments, encouraging compliance, promoting transparency, ensuring oversight and learning from experience.2323. Hoffman SJ, Røttingen J-A. Assessing implementation mechanisms for an international agreement on research and development for health products. Bull World Health Organ . 2012 Nov 1;90(11):854-63. http://dx.doi.org/10.2471/BLT.12.109827PMID:23226898
http://dx.doi.org/10.2471/BLT.12.109827...

The optimal package of institutional mechanisms would address current weaknesses by offering effective governance, universal compliance, competent leadership and sufficient financing. Past experience and knowledge of international relations, law and political science offer at least six institutional design principles that can guide us.

First, global institutions are well positioned to serve some functions and not others because governments commit to and comply with international rules for particular reasons. For example, realist scholars argue international relations primarily reflect states' own rational self-interests and pursuit of wealth, power and status.2424. Baldwin DA, editor. Neorealism and neoliberalism: the contemporary debate. New York: Columbia University Press; 1993.Institutionalists believe states cooperate and coordinate to maximize utility under conditions of interdependence.2525. Keohane RO. Institutionalist theory and the realist challenge after the cold war. Boston: Center for International Affairs, Harvard University; 1993. pp 54. Liberal theorists suggest that domestic ideas, interests and institutions affect states' international relations by shaping state preferences.2626. Simmons BA. Mobilizing for human rights: international law in domestic politics. Cambridge: Cambridge University Press; 2009. pp. 451.http://dx.doi.org/10.1017/CBO9780511811340
http://dx.doi.org/10.1017/CBO97805118113...
Constructivists argue that state behaviour is shaped by ideas, including those derived from international engagement.2727. Finnemore M. National interests in international society. Ithaca, NY: Cornell University Press; 1996. pp. 180. While these theories sometimes conflict, together they suggest global institutions should advance states' rational self-interests, address cooperation and coordination problems, empower domestic actors or change ideas about the world. The impact of any function that global institutions serve also depends critically on states perceiving the function to be a legitimate exercise of delegated authority,2828. Franck TM. The power of legitimacy among nations. Oxford: Oxford University Press ; 1990. pp. 318. having sufficient capacity to change2929. Chayes A, Chayes AH. The new sovereignty: compliance with international regulatory agreements. Cambridge, MA: Harvard University Press; 1996. pp. 432. and being able to internalize international norms into domestic processes.3030. Koh HH. Why do nations obey international law? Yale Law Journal. 1997;106:2599-659. http://dx.doi.org/10.2307/797228
http://dx.doi.org/10.2307/797228...

Second, global institutions addressing antimicrobial access, conservation and innovation should have clear mandates to ensure they maximize benefits, minimize costs, manage risks and balance trade-offs. International activities are not without costs or risks of harm. There are direct costs like staff salaries, meetings, travel, communications, governance structures and management, and indirect opportunity costs and potential risks of paternalism in placing international norms above local priorities.3131. Hoffman SJ, Røttingen J-A. A framework convention on obesity control? Lancet. 2011 Dec 17;378(9809):2068. http://dx.doi.org/10.1016/S0140-6736(11)61894-1PMID:22177507
http://dx.doi.org/10.1016/S0140-6736(11)...
Global institutions thus need to be cognizant of these costs and risks, maximize existing institutional architecture and work with others to minimize destructive competition and inefficient duplication.

Third, the forum through which global institutions are created or reformed is important. Different fora have different members, mandates and powers that place structural limits on their activities and competence. The choice of forum for international action also matters because different communities and groups work through different international fora.3232. Slaughter A-M. A new world order. Princeton: Princeton University Press; 2005. Available from: Available from: http://site.ebrary.com/id/10312479 [cited 2014 Jul 16].
http://site.ebrary.com/id/10312479...
For example, since the Framework Convention on Tobacco Control was negotiated through WHO, the influence of health authorities was amplified and the tobacco industry was marginalized. The United Nations (UN) General Assembly, alternatively, has facilitated higher-level whole-of-government engagement with the issues raised by human immunodeficiency virus (HIV), noncommunicable diseases (NCDs) and universal health coverage in a way that seems particularly useful for intersectoral challenges.3333. Declaration of commitment on HIV/AIDS: United Nations General Assembly special session on HIV/AIDS. New York: United Nations ; 2001. p. 47. Available from: Available from: http://data.unaids.org/publications/irc-pub03/aidsdeclaration_en.pdf [cited 2014 Jul 10]
http://data.unaids.org/publications/irc-...
,3434. Global health and foreign policy A/67/L.36. In: Sixty-seveth session United Nations General Assembly, Agenda item 123 [Internet] . New York: United Nations ; 6 December 2012. p. 6. Available from: Available from: http://www.un.org/ga/search/view_doc.asp?symbol=A/67/L.36 [cited 2015 Sep 25].
http://www.un.org/ga/search/view_doc.asp...
However, even the most theoretically well-suited fora may sometimes need to be bypassed if they are too slow, inefficient or otherwise ineffective.3535. Prado MM. Institutional bypass: an alternative for development reform [Internet]. Rochester: Social Science Research Network; 2011. Available from: Available from: http://papers.ssrn.com/abstract=1815442 [cited 2014 Jul 22].
http://papers.ssrn.com/abstract=1815442...
,3636. Hoffman SJ, Røttingen J-A. Split WHO in two: strengthening political decision-making and securing independent scientific advice. Public Health. 2014 Feb;128(2):188-94. http://dx.doi.org/10.1016/j.puhe.2013.08.021PMID:24434035
http://dx.doi.org/10.1016/j.puhe.2013.08...

Fourth, global institutions must be specifically tailored for the nature of the problems they are created or reformed to solve. Many global institutions are state-centric which means that they primarily involve national governments and depend on them to regulate nongovernmental actors within their territories. More meaningful involvement of civil society, industry and health-care organizations may strengthen functions that depend on them. Although in this case, reliance on coercive regulation - such as restricting access to antimicrobials - means that states must take centre stage.3737. Hoffman SJ. The evolution, etiology and eventualities of the global health security regime. Health Policy Plan. 2010 Nov;25(6):510-22.http://dx.doi.org/10.1093/heapol/czq037 PMID:20732860
http://dx.doi.org/10.1093/heapol/czq037...

Fifth, there seems to be an inverse relationship between the strength of international commitment mechanisms and the activities, norms or standards they involve.3838. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027...
This is because agreements are negotiated as a whole, explaining why states regularly adopt treaties - the strongest international commitment mechanism available - then empty them of ambitious content, which they instead reserve for non-binding commitment mechanisms like political declarations and unilateral statements.3838. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027...
For example, regimes governing trade, human rights, disarmament, prisoners of war and money laundering generally rely on different enforcement mechanisms based on the type of problems addressed and the commitments states are willing to undertake (Box 2).3939. Hoffman SJ, Ottersen T. Addressing antibiotic resistance requires robust international accountability mechanisms. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:53-64. PMID:26243244 There is no general hierarchy of impact or influence among global institutions. To strengthen global collective action on antimicrobials, the functions sought, the form that follows and the forum of implementation need to be carefully matched.4040. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247

Box 2   Examples of accountability mechanisms in existing international regimes

International trade provides an example of a problem addressed through a reciprocal exchange of benefits among the World Trade Organization's (WTO's) Member States. The political economy of trade policy creates incentives for states to protect domestic firms by erecting barriers to trade. This problem is addressed through trade agreements under which parties have made commitments not to impose particular barriers to trade. In the WTO context, these commitments are enforced through a system of dispute settlement that permits one member to bring a claim against another. This system of enforcement relies on reciprocity in the sense that there is a mutual exchange of concessions between members on a reciprocal basis.

Human rights, in contrast, do not create comparable reciprocal interests between state parties in the observance of treaty commitments. There is no mutual exchange of benefits on a reciprocal basis between parties and no comparable interest in an other's compliance. As such, accountability mechanisms include reporting, monitoring and individual complaint processes.

Disarmament and fair treatment of prisoners-of-war are both goals in which all states have an interest in ensuring adherence to commitments by a single state acting alone. This collective interest explains the importance of independent inspection and verification in disarmament and humanitarian treaties.

Anti-money laundering efforts by the Financial Action Task Force exemplify a problem addressed through non-binding international recommendations that have considerable coercive power shown by the blacklisting of financial institutions in certain countries. This exclusion has incentivized countries to raise standards to continue transacting with financial institutions abroad.

Sixth, global institutions should be designed for political robustness to withstand inequalities in decision-making and diplomacy.4141. Hoffman SJ. Mitigating inequalities of influence among states in global decision making. Glob Policy. 2012 Nov;3(4):421-32. http://dx.doi.org/10.1111/j.1758-5899.2011.00153.x
http://dx.doi.org/10.1111/j.1758-5899.20...
A realistic view is needed on what different actors can and will do both domestically and internationally, whether by choice or limited by domestic regulations, resources and political constraints. This also means supporting institutions that help enact policy, incentives for those with power to act upon them and interest mobilizers to make the case for their implementation.4242. Hoffman SJ, Røttingen J-A. Assessing the expected impact of global health treaties: evidence from 90 quantitative evaluations. Am J Public Health. 2015 Jan;105(1):26-40. http://dx.doi.org/10.2105/AJPH.2014.302085PMID:25393196
http://dx.doi.org/10.2105/AJPH.2014.3020...

Ten policy options

There are many options for global collective action on antimicrobial medicines, ranging from setting implementation milestones,11. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)...
to providing new financial models,4343. Brogan DM, Mossialos E. Incentives for new antibiotics: the options market for antibiotics (OMA) model. Global Health. 2013;9(1):58.http://dx.doi.org/10.1186/1744-8603-9-58PMID:24199835
http://dx.doi.org/10.1186/1744-8603-9-58...
,4444. Hollis A, Ahmed Z. Preserving antibiotics, rationally. N Engl J Med. 2013 Dec 26;369(26):2474-6. http://dx.doi.org/10.1056/NEJMp1311479PMID:24369073
http://dx.doi.org/10.1056/NEJMp1311479...
to creating new structures,4545. Woolhouse M, Farrar J. Policy: an intergovernmental panel on antimicrobial resistance. Nature. 2014 May 29;509(7502):555-7. http://dx.doi.org/10.1038/509555a PMID:24877180
http://dx.doi.org/10.1038/509555a...
to adopting legally-binding treaties.77. Smith RD, Coast J. Antimicrobial resistance: a global response. Bull World Health Organ. 2002;80(2):126-33. PMID:11953791,4646. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
http://dx.doi.org/10.2471/BLT.15.152710...
,4747. Behdinan A, Hoffman SJ, Pearcey M. Some global policies for antibiotic resistance depend on legally binding and enforceable commitments. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:68-73. PMID:26243246We present 10 options for achieving global collective action that illustrate the range of what is possible. Each is assessed according to the global institutional weaknesses addressed and the antimicrobial policy imperatives served (Table 2).

Table 2
Ten options for achieving global collective action on antimicrobials

Options one to four primarily involve building institutions, ranging in formality. The first is for a global governing body to create milestones and indicators that would then be annually monitored.11. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
http://dx.doi.org/10.1016/S1473-3099(13)...
Like the Millennium Development Goals, milestones can serve as a commitment device and help promote action if actors know they will be regularly assessed, praised for progress and shamed for any lapses. The second option is a code of practice that outlines minimum expectations for willing signatories. Like the Monterrey Consensus on development assistance targets and the WHO Code of Practice on the International Recruitment of Health Personnel, norms can promote compliance through informal governmental networks and the desire to avoid being seen as "bad". The third option is a UN inter-agency task force that coordinates the activities of the many UN entities working in this policy area and provides clear direction and leadership for stakeholders. Such task forces exist for NCDs, disaster reduction and violence against women. The fourth option is an intergovernmental panel - like the UN Intergovernmental Panel on Climate Change - that marshals available evidence to inform policies on global antimicrobial resistance.4545. Woolhouse M, Farrar J. Policy: an intergovernmental panel on antimicrobial resistance. Nature. 2014 May 29;509(7502):555-7. http://dx.doi.org/10.1038/509555a PMID:24877180
http://dx.doi.org/10.1038/509555a...
,4848. Sandberg K, Hoffman SJ, Pearcey M. Lessons for global health from global environmental governance. London: Chatham House ; 2015. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/field/field_document/20150119GlobalHealthEnvironmentSandbergHoffmanPearcey.pdf [cited 2014 Jul 16].
http://www.chathamhouse.org/sites/files/...

Options five to seven primarily involve crafting incentives. Option five is a funding agreement between development agencies and institutions that can promote antimicrobial access, conservation and/or innovation. Option six is a global pooled fund that allocates contributions from various donors to finance policies, reward milestones achieved or provide incentives for research and development. Option seven is for multilateral organizations to impose conditions on any support that they provide, such as requiring governments to share surveillance data or ensure that their citizens have access to antimicrobial medicines before receiving additional aid, gaining trade advantages or participating in international initiatives.

Options eight to 10 primarily involve mobilizing interests at a range of scales. Option eight is to appoint a special representative, like the UN Human Rights Council's special rapporteurs or the UN Secretary-General's envoys, who would use the prestige of their office to rally interest groups, coordinate advocacy, attract attention and encourage action. Option nine is to appoint a high-level panel of eminent persons that would use their access to people in power to apply political pressure. Option 10 is a multi-stakeholder partnership, like the UN Secretary-General's Every Woman Every Child movement, which involves an alliance of many actors, working groups and advocacy across fora.

While each option has its merits, none is individually sufficient. Instead, multiple options will need to be adopted - with global decision-makers able to mix-and-match, hopefully in a way that builds on comparative advantages. As a starting point, the optimal package of options probably includes at least one from each of the three categories: institutions, incentives and interest mobilizers.4242. Hoffman SJ, Røttingen J-A. Assessing the expected impact of global health treaties: evidence from 90 quantitative evaluations. Am J Public Health. 2015 Jan;105(1):26-40. http://dx.doi.org/10.2105/AJPH.2014.302085PMID:25393196
http://dx.doi.org/10.2105/AJPH.2014.3020...
Within the institutional options, monitored milestones and an inter-agency task force seem most promising, especially given the failure of previous codes of practice,4949. Edge JS, Hoffman SJ. Empirical impact evaluation of the WHO global code of practice on the international recruitment of health personnel in Australia, Canada, UK and USA. Global Health. 2013;9(1):60. http://dx.doi.org/10.1186/1744-8603-9-60PMID:24228827
http://dx.doi.org/10.1186/1744-8603-9-60...
including those involving antimicrobial medicines.1717. Diaz F. Collection of quantitative data on the use of antimicrobial agents. Paris: World Organisation for Animal Health ; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/13.DIAZ.pdf [cited 2015 Sep 25].
http://www.rr-africa.oie.int/docspdf/en/...
,5050. Bruno AV, Mackay C. Antimicrobial resistance and the activities of the Codex Alimentarius Commission. Rev Sci Tech. 2012 Apr;31(1):317-23. PMID:22849286 Existing mechanisms to achieve scientific consensus in medicine and public health probably make a big intergovernmental panel unnecessary.4848. Sandberg K, Hoffman SJ, Pearcey M. Lessons for global health from global environmental governance. London: Chatham House ; 2015. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/field/field_document/20150119GlobalHealthEnvironmentSandbergHoffmanPearcey.pdf [cited 2014 Jul 16].
http://www.chathamhouse.org/sites/files/...
For incentives, a global pooled fund seems to dominate the other options. Funding agreements address few of the political economy challenges faced and it could be unethical to put conditions on support given to states. Appointing a special representative seems the most practical option for mobilizing interests. A special representative could achieve similar outcomes to a far costlier high-level panel and is more feasible than a multi-stakeholder partnership.

An international legal framework

In addition to options for building institutions, crafting incentives and mobilizing interests, an international legal framework for antimicrobial resistance could be used to combine different options.4646. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
http://dx.doi.org/10.2471/BLT.15.152710...
Of the many global health challenges for which treaties have been proposed, the problem of antimicrobial resistance is a strong candidate for an international treaty.3838. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027...
,5151. Hoffman SJ, Røttingen JA, Frenk J. International law has a role to play in addressing antibiotic resistance. J Law Med Ethics . 2015 Jun;43(2) Suppl 3:65-7. PMID:26243245

Support for an international legal framework is justified given that antimicrobial resistance is a major transnational risk involving the global exploitation of an essential common resource for which legal instruments have a reasonable chance of achieving benefits and alternative commitment mechanisms have thus far proven ineffective.3838. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
http://dx.doi.org/10.2105/AJPH.2015.3027...
,5151. Hoffman SJ, Røttingen JA, Frenk J. International law has a role to play in addressing antibiotic resistance. J Law Med Ethics . 2015 Jun;43(2) Suppl 3:65-7. PMID:26243245 Like the legs of a tripod, each antimicrobial policy imperative - access, conservation and innovation - requires a strong, simultaneous level of support from the other two. This is because the policy imperatives are mutually reinforcing: untreated infections spread resistance and the size of market is smaller when many people have no access to antimicrobials; resistance diminishes the value of access to existing antimicrobials and puts a time-limit on their sale; and innovation needs both appropriate access and conservation policies to ensure there can be a return on investment.4646. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
http://dx.doi.org/10.2471/BLT.15.152710...
An international legal framework may be the best way to achieve progress on all three components at once.4747. Behdinan A, Hoffman SJ, Pearcey M. Some global policies for antibiotic resistance depend on legally binding and enforceable commitments. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:68-73. PMID:26243246

Fora for implementation

If decision-makers take action, they must decide whether to reform existing global institutions or to create something new. From a policy perspective, it is appealing to create stand-alone initiatives either under sponsorship of an existing organization or through a new forum. WHO is the most obvious existing organization, especially given its unusually expansive powers for making new international treaties under Articles 19 and 21 of its Constitution. Yet WHO's current financing and governance challenges indicate that an alternative forum may be needed.3636. Hoffman SJ, Røttingen J-A. Split WHO in two: strengthening political decision-making and securing independent scientific advice. Public Health. 2014 Feb;128(2):188-94. http://dx.doi.org/10.1016/j.puhe.2013.08.021PMID:24434035
http://dx.doi.org/10.1016/j.puhe.2013.08...
,5252. Clift C. What's the World Health Organization for? London: Chatham House ; 2014. Available from: Available from: http://observgo.uquebec.ca/observgo/fichiers/88303_20140521WHOHealthGovernanceClift.pdf [cited 2014 Jul 9].
http://observgo.uquebec.ca/observgo/fich...
Alternatives include bodies like FAO, OIE, the UN General Assembly and UN Security Council, or smaller groupings like the G7/G8, G20, G77, or the Oslo-7 Foreign Policy and Global Health countries.4040. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247 Other platforms, like the UN Office for Disarmament Affairs and the Biological Weapons Convention, could also be relevant for specific functions such as antimicrobial surveillance as they have become increasingly important fora for addressing infectious disease threats.

From a political economy perspective, stand-alone initiatives may not be possible. Institutions, incentives and interests may not coalesce into a workable package of policy prescriptions and implementation mechanisms. The momentum generated by existing institutions, incentives in other policy areas and interest mobilizers may need to be harnessed. Incorporating policies and mechanisms into existing platforms may help overcome the high threshold for starting something new while simultaneously facilitating cross-forum bargaining. Such incorporation will influence the final policies adopted, depending on how decisions are made, who is involved, which actors dominate, where priorities lie, and pre-existing informal bargains. Rules made through sector-based fora will naturally favour the relevant sector.4040. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247

Conclusion

Despite considerable challenges and a history of inaction on antimicrobial resistance, progress should be possible if policy options are matched with the right forum that aligns institutions, incentives and interests towards global collective action. What is needed is a commitment to action and implementation of the many recommendations that have already been made, especially WHO's Global Action Plan on Antimicrobial Resistance .2222. Draft global action plan on antimicrobial resistance. Geneva: World Health Organization ; 2014. Available from: Available from: http://apps.who.int/gb/ebwha/pdf_files/EB136/B136_20-en.pdf [cited 2015 Oct 9].
http://apps.who.int/gb/ebwha/pdf_files/E...
Global decision-makers must now combine the science of strategy with the art of the possible. Preserving and continuing advances in global health depend on doing so.

Acknowledgements

We thank participants of seminars at Chatham House in London, England, the Dag Hammarskjöld Foundation in Uppsala, Sweden, and the International Studies Association Conference 2014 in Toronto, Canada.

References

  • 1. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013 Dec;13(12):1057-98.http://dx.doi.org/10.1016/S1473-3099(13)70318-9PMID:24252483
    » http://dx.doi.org/10.1016/S1473-3099(13)70318-9
  • 2. Global risks 2013 report. 8th ed. Geneva: World Economic Forum; 2013. Available from: http://www3.weforum.org/docs/WEF_GlobalRisks_Report_2013.pdf
    » http://www3.weforum.org/docs/WEF_GlobalRisks_Report_2013.pdf
  • 3. Jonathan HGE, Stoltenberg RHJ. UN commission on life-saving commodities for women and children. New York: United Nations; 2012. Available from: Available from: http://unfpa.org/webdav/site/global/shared/images/publications/2012/Final%20UN%20Commission%20Report_14sept2012.doc [cited 2014 Jul 17].
    » http://unfpa.org/webdav/site/global/shared/images/publications/2012/Final%20UN%20Commission%20Report_14sept2012.doc
  • 4. Davies SC, Fowler T, Watson J, Livermore DM, Walker D. Annual report of the Chief Medical Officer: infection and the rise of antimicrobial resistance. Lancet. 2013 May 11;381(9878):1606-9. http://dx.doi.org/10.1016/S0140-6736(13)60604-2PMID:23489756
    » http://dx.doi.org/10.1016/S0140-6736(13)60604-2
  • 5. Review on Antimicrobial Resistance. Tackling drug-resistant infections globally [Internet]. London: Wellcome Trust; 2014. Available from:http://amr-review.org
    » http://amr-review.org
  • 6. Fidler DP. Legal issues associated with antimicrobial drug resistance. Emerg Infect Dis. 1998 Apr-Jun;4(2):169-77. http://dx.doi.org/10.3201/eid0402.980204PMID:9621187
    » http://dx.doi.org/10.3201/eid0402.980204
  • 7. Smith RD, Coast J. Antimicrobial resistance: a global response. Bull World Health Organ. 2002;80(2):126-33. PMID:11953791
  • 8. Outterson K. New business models for sustainable antibiotics. London: Chatham House; 2014. p. 31. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/public/Research/Global%20Health/0214SustainableAntibiotics.pdf [cited 2014 Apr 22].
    » http://www.chathamhouse.org/sites/files/chathamhouse/public/Research/Global%20Health/0214SustainableAntibiotics.pdf
  • 9. Hoffman SJ. A Science of Global Strategy. In: Frenk J, Hoffman SJ, editors. "To save humanity": what matters most for a healthy future. Oxford: Oxford University Press; 2015.
  • 10. Progress reports on technical and health matters. Report No. A60/28. Geneva: World Health Organization; 2007. Available from: http://apps.who.int/gb/ebwha/pdf_files/WHA60/A60_28-en.pdf
    » http://apps.who.int/gb/ebwha/pdf_files/WHA60/A60_28-en.pdf
  • 11. Terrestrial animal health code [Internet]. Paris: World Organisation for Animal Health; 2013. Available from: Available from: http://www.oie.int/international-standard-setting/terrestrial-code/ [cited 2014 Jul 16].
    » http://www.oie.int/international-standard-setting/terrestrial-code/
  • 12. The FAO-OIE-WHO Collaboration: Sharing responsibilities and coordinating global activities to address health risks at the animal-human-ecosystems interface. Paris: World Organisation for Animal Health ; 2010. Available from: Available from: http://www.oie.int/fileadmin/home/eng/current_scientific_issues/docs/pdf/final_concept_note_hanoi.pdf [cited 2015 Sep 25].
    » http://www.oie.int/fileadmin/home/eng/current_scientific_issues/docs/pdf/final_concept_note_hanoi.pdf
  • 13. Otto P. FAO-OIE-WHO tripartite positions and actions on antimicrobial resistance. Rome: Food and Agriculture Organization; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/12.OTTO.pdf [cited 2015 Sep 25].
    » http://www.rr-africa.oie.int/docspdf/en/2013/VP/12.OTTO.pdf
  • 14. Codex Alimentarius Commission. Guidelines for risk analysis of foodborne antimicrobial resistance. Geneva: Food and Agriculture Organization; 2011. Available from: Available from: http://www.codexalimentarius.net/input/download/standards/11776/CXG_077e.pdf [cited 2015 Sep 25].
    » http://www.codexalimentarius.net/input/download/standards/11776/CXG_077e.pdf
  • 15. Strategic and Technical Advisory Group on Antimicrobial Resistance: report of the first meeting. Geneva: World Health Organization ; 2013. Available from: Available from: http://www.who.int/drugresistance/stag/amr_stag_meetingreport0913.pdf [cited 2015 Sep 25].
    » http://www.who.int/drugresistance/stag/amr_stag_meetingreport0913.pdf
  • 16. Transatlantic Taskforce on Antimicrobial Resistance. Recommendations for future collaboration between the US and EU. Stockholm: European Centre for Disease Prevention and Control; 2011. p. 44.
  • 17. Diaz F. Collection of quantitative data on the use of antimicrobial agents. Paris: World Organisation for Animal Health ; 2013. Available from: Available from: http://www.rr-africa.oie.int/docspdf/en/2013/VP/13.DIAZ.pdf [cited 2015 Sep 25].
    » http://www.rr-africa.oie.int/docspdf/en/2013/VP/13.DIAZ.pdf
  • 18. Morgan DJ, Okeke IN, Laxminarayan R, Perencevich EN, Weisenberg S. Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis . 2011 Sep;11(9):692-701. http://dx.doi.org/10.1016/S1473-3099(11)70054-8PMID:21659004
    » http://dx.doi.org/10.1016/S1473-3099(11)70054-8
  • 19. Ijaz K, Kasowski E, Arthur RR, Angulo FJ, Dowell SF. International Health Regulations - what gets measured gets done. Emerg Infect Dis . 2012 Jul;18(7):1054-7. http://dx.doi.org/10.3201/eid1807.120487PMID:22709593
    » http://dx.doi.org/10.3201/eid1807.120487
  • 20. Edge JS, Hoffman SJ. Strengthening national health systems' capacity to respond to future global pandemics. In: Davies S, Youde JR, editors. The politics of surveillance and responses to disease outbreaks. Surrey: Ashgate Publishing; 2015. pp. 157-79.
  • 21. Implementation of the International Health Regulations (2005): report by the Director-General. Geneva: World Health Organization ; 2015. Available from: http://apps.who.int/gb/ebwha/pdf_files/WHA66/A66_16-en.pdf
    » http://apps.who.int/gb/ebwha/pdf_files/WHA66/A66_16-en.pdf
  • 22. Draft global action plan on antimicrobial resistance. Geneva: World Health Organization ; 2014. Available from: Available from: http://apps.who.int/gb/ebwha/pdf_files/EB136/B136_20-en.pdf [cited 2015 Oct 9].
    » http://apps.who.int/gb/ebwha/pdf_files/EB136/B136_20-en.pdf
  • 23. Hoffman SJ, Røttingen J-A. Assessing implementation mechanisms for an international agreement on research and development for health products. Bull World Health Organ . 2012 Nov 1;90(11):854-63. http://dx.doi.org/10.2471/BLT.12.109827PMID:23226898
    » http://dx.doi.org/10.2471/BLT.12.109827
  • 24. Baldwin DA, editor. Neorealism and neoliberalism: the contemporary debate. New York: Columbia University Press; 1993.
  • 25. Keohane RO. Institutionalist theory and the realist challenge after the cold war. Boston: Center for International Affairs, Harvard University; 1993. pp 54.
  • 26. Simmons BA. Mobilizing for human rights: international law in domestic politics. Cambridge: Cambridge University Press; 2009. pp. 451.http://dx.doi.org/10.1017/CBO9780511811340
    » http://dx.doi.org/10.1017/CBO9780511811340
  • 27. Finnemore M. National interests in international society. Ithaca, NY: Cornell University Press; 1996. pp. 180.
  • 28. Franck TM. The power of legitimacy among nations. Oxford: Oxford University Press ; 1990. pp. 318.
  • 29. Chayes A, Chayes AH. The new sovereignty: compliance with international regulatory agreements. Cambridge, MA: Harvard University Press; 1996. pp. 432.
  • 30. Koh HH. Why do nations obey international law? Yale Law Journal. 1997;106:2599-659. http://dx.doi.org/10.2307/797228
    » http://dx.doi.org/10.2307/797228
  • 31. Hoffman SJ, Røttingen J-A. A framework convention on obesity control? Lancet. 2011 Dec 17;378(9809):2068. http://dx.doi.org/10.1016/S0140-6736(11)61894-1PMID:22177507
    » http://dx.doi.org/10.1016/S0140-6736(11)61894-1
  • 32. Slaughter A-M. A new world order. Princeton: Princeton University Press; 2005. Available from: Available from: http://site.ebrary.com/id/10312479 [cited 2014 Jul 16].
    » http://site.ebrary.com/id/10312479
  • 33. Declaration of commitment on HIV/AIDS: United Nations General Assembly special session on HIV/AIDS. New York: United Nations ; 2001. p. 47. Available from: Available from: http://data.unaids.org/publications/irc-pub03/aidsdeclaration_en.pdf [cited 2014 Jul 10]
    » http://data.unaids.org/publications/irc-pub03/aidsdeclaration_en.pdf
  • 34. Global health and foreign policy A/67/L.36. In: Sixty-seveth session United Nations General Assembly, Agenda item 123 [Internet] . New York: United Nations ; 6 December 2012. p. 6. Available from: Available from: http://www.un.org/ga/search/view_doc.asp?symbol=A/67/L.36 [cited 2015 Sep 25].
    » http://www.un.org/ga/search/view_doc.asp?symbol=A/67/L.36
  • 35. Prado MM. Institutional bypass: an alternative for development reform [Internet]. Rochester: Social Science Research Network; 2011. Available from: Available from: http://papers.ssrn.com/abstract=1815442 [cited 2014 Jul 22].
    » http://papers.ssrn.com/abstract=1815442
  • 36. Hoffman SJ, Røttingen J-A. Split WHO in two: strengthening political decision-making and securing independent scientific advice. Public Health. 2014 Feb;128(2):188-94. http://dx.doi.org/10.1016/j.puhe.2013.08.021PMID:24434035
    » http://dx.doi.org/10.1016/j.puhe.2013.08.021
  • 37. Hoffman SJ. The evolution, etiology and eventualities of the global health security regime. Health Policy Plan. 2010 Nov;25(6):510-22.http://dx.doi.org/10.1093/heapol/czq037 PMID:20732860
    » http://dx.doi.org/10.1093/heapol/czq037
  • 38. Hoffman SJ, Røttingen J-A, Frenk J. Assessing proposals for new global health treaties: an analytic framework. Am J Public Health. 2015 Aug;105(8):1523-30. http://dx.doi.org/10.2105/AJPH.2015.302726PMID:26066926
    » http://dx.doi.org/10.2105/AJPH.2015.302726
  • 39. Hoffman SJ, Ottersen T. Addressing antibiotic resistance requires robust international accountability mechanisms. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:53-64. PMID:26243244
  • 40. Rizvi Z, Hoffman SJ. Effective global action on antibiotic resistance requires careful consideration of convening fora. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:74-8. PMID:26243247
  • 41. Hoffman SJ. Mitigating inequalities of influence among states in global decision making. Glob Policy. 2012 Nov;3(4):421-32. http://dx.doi.org/10.1111/j.1758-5899.2011.00153.x
    » http://dx.doi.org/10.1111/j.1758-5899.2011.00153.x
  • 42. Hoffman SJ, Røttingen J-A. Assessing the expected impact of global health treaties: evidence from 90 quantitative evaluations. Am J Public Health. 2015 Jan;105(1):26-40. http://dx.doi.org/10.2105/AJPH.2014.302085PMID:25393196
    » http://dx.doi.org/10.2105/AJPH.2014.302085
  • 43. Brogan DM, Mossialos E. Incentives for new antibiotics: the options market for antibiotics (OMA) model. Global Health. 2013;9(1):58.http://dx.doi.org/10.1186/1744-8603-9-58PMID:24199835
    » http://dx.doi.org/10.1186/1744-8603-9-58
  • 44. Hollis A, Ahmed Z. Preserving antibiotics, rationally. N Engl J Med. 2013 Dec 26;369(26):2474-6. http://dx.doi.org/10.1056/NEJMp1311479PMID:24369073
    » http://dx.doi.org/10.1056/NEJMp1311479
  • 45. Woolhouse M, Farrar J. Policy: an intergovernmental panel on antimicrobial resistance. Nature. 2014 May 29;509(7502):555-7. http://dx.doi.org/10.1038/509555a PMID:24877180
    » http://dx.doi.org/10.1038/509555a
  • 46. Hoffman SJ, Outterson K, Røttingen J-A, Cars O, Clift C, Rizvi Z, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ . 2015 Feb 1;93(2):66. http://dx.doi.org/10.2471/BLT.15.152710PMID:25883395
    » http://dx.doi.org/10.2471/BLT.15.152710
  • 47. Behdinan A, Hoffman SJ, Pearcey M. Some global policies for antibiotic resistance depend on legally binding and enforceable commitments. J Law Med Ethics. 2015 Jun;43(2) Suppl 3:68-73. PMID:26243246
  • 48. Sandberg K, Hoffman SJ, Pearcey M. Lessons for global health from global environmental governance. London: Chatham House ; 2015. Available from: Available from: http://www.chathamhouse.org/sites/files/chathamhouse/field/field_document/20150119GlobalHealthEnvironmentSandbergHoffmanPearcey.pdf [cited 2014 Jul 16].
    » http://www.chathamhouse.org/sites/files/chathamhouse/field/field_document/20150119GlobalHealthEnvironmentSandbergHoffmanPearcey.pdf
  • 49. Edge JS, Hoffman SJ. Empirical impact evaluation of the WHO global code of practice on the international recruitment of health personnel in Australia, Canada, UK and USA. Global Health. 2013;9(1):60. http://dx.doi.org/10.1186/1744-8603-9-60PMID:24228827
    » http://dx.doi.org/10.1186/1744-8603-9-60
  • 50. Bruno AV, Mackay C. Antimicrobial resistance and the activities of the Codex Alimentarius Commission. Rev Sci Tech. 2012 Apr;31(1):317-23. PMID:22849286
  • 51. Hoffman SJ, Røttingen JA, Frenk J. International law has a role to play in addressing antibiotic resistance. J Law Med Ethics . 2015 Jun;43(2) Suppl 3:65-7. PMID:26243245
  • 52. Clift C. What's the World Health Organization for? London: Chatham House ; 2014. Available from: Available from: http://observgo.uquebec.ca/observgo/fichiers/88303_20140521WHOHealthGovernanceClift.pdf [cited 2014 Jul 9].
    » http://observgo.uquebec.ca/observgo/fichiers/88303_20140521WHOHealthGovernanceClift.pdf

  • Competing interests: SJH is financially supported by the Canadian Institutes of Health Research, the Research Council of Norway and the Trudeau Foundation, and was previously employed by WHO and the UN Secretary-General's Office. GMC works for Médecins Sans Frontières which has documented antimicrobial resistance in its projects. ND previously represented the United States of America on the WHO Executive Board and at other fora. PM currently represents South Africa on the WHO Executive Board and at other fora. ZR interned with WHO. JAR was chair of WHO's Consultative Expert Working Group on Research and Development: Financing and Coordination.

Publication Dates

  • Publication in this collection
    Dec 2015

History

  • Received
    23 Jan 2015
  • Reviewed
    17 Apr 2015
  • Accepted
    25 Aug 2015
Creative Common - by 3.0 igo
This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (http://creativecommons.org/licenses/by/3.0/igo/legalcode), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.
World Health Organization Genebra - Genebra - Switzerland
E-mail: bulletin@who.int