O'Neill AMR Review

A massive global public awareness campaign 1.1 With leadership from an appropriate global body, establish an internationally-coordinated public awareness campaign to improve public understanding of the problems of drug resistance and support positive behaviour change regarding antibiotic use. Whilst globally consistent in its overall message, this should be delivered at country or regional level, with the message and the medium (e.g. social media, broadcast advertising, celebrity endorsement) tailored to local and regional norms. 1.2 At a country level, establish robust regulations to prevent the sale of antibiotics and other antimicrobials 'over‑the‑counter' (OTC) without a prescription, and ensure that these are properly enforced. Such policies to be locally‑tailored to recognise instances where OTC sales may be only means of accessing antimicrobials – but where this is the case, provision of proper, clinician-led access should be a priority. 1.3 Global organisations (including the WHO, INTERPOL and World Customs Organization) to ensure a robust and internationally-coordinated effort to prevent cross-border sales of antimicrobials over the internet without prescription. This should be supported by outright bans on non-prescription internet sales at country level.

Build a global coalition for real action – via the G20 and the UN 10.1 The G20 group of countries should take leadership on defined aspects of the global response to AMR, particularly work to develop and implement new incentive models to support the development of new antibiotics, diagnostics and vaccines. This should be complementary to wider discussions on the global response to AMR as part of the UN General Assembly, and the continuing efforts of the WHO, FAO and OIE in their respective sectors. 10.2 Governments and relevant global bodies to initiate rapid work to consider in detail the global coordinated structures which would be required to oversee the development, implementation, and operation of global systems of financial support for antibiotic and diagnostic development and use. 10.3 Governments, industry and relevant global bodies should continue to work together to identify adequate and sustainable global, national and local funding mechanisms for raising the money required to finance a long-term global response to AMR. This should include the exploration of – amongst other options – mechanisms to raise revenue from new sources and on a hypothecated basis, for instance through modest and targeted levies on antibiotic use and/or on the global pharmaceutical, healthcare products, and medical device industries.

Improve hygiene and prevent the spread of infection 2.1 Governments, insurers, regulators and other healthcare system leaders should embed infection prevention and control (IPC) as a top priority at all levels within healthcare systems, using defined healthcare-associated infection (HCAI) reduction goals as the basis for targets, incentives and other performance management measures. 2.2 Public and philanthropic funding bodies to support improvements in funding for studies that demonstrate the effectiveness and cost-effectiveness of novel IPC interventions in health and care settings, and measures to induce positive behaviour change by clinicians and other healthcare workers. 2.3 Governments of low and middle-income countries should ensure that the benefits of improved public health and reduced antimicrobial resistance are properly factored into investment decisions about improved access to water and sanitation infrastructure.

Reduce unnecessary use of antimicrobials in agriculture and their dissemination into the environment 3.1 The G20 and UN, with input from the WHO, FAO and OIE, should lead urgent global efforts to improve the collection and use of surveillance data regarding the use of antibiotics in agriculture, and the emergence and spread of drug-resistant microbes amongst animals. This should be prioritised over the next two years to inform targets to reduce unnecessary use of antibiotics starting in 2018. 3.2 International institutions with the relevant experience should undertake now a detailed economic analysis of the transition costs associated with lowering the use of antibiotics in farming across different regions and countries – particularly those in low and middle-income settings, where less analysis has been done to date 3.3 The WHO, FAO and OIE should, as a matter of urgency, convene a global group of experts, working across the relevant regulatory bodies and international organisations, to agree a single, harmonised list of those antibiotics most critical to human health. This would help to inform those antibiotics that should be banned or restricted from use in agriculture. 3.4 Food producers and retailers to take steps should improve transparency for consumers regarding the use of antibiotics in the meat that we eat, to enable better informed decision-making by customers. As part of this we call on major producers, retailers and regulators to agree standards for 'responsible use', to be used as the basis for an internationally-recognised label, or used by existing certification bodies. 3.5 In 2018, defined targets should be established at the country level to reduce unnecessary use of antibiotics in agriculture. There will not be a one-size-fits-all target, but all countries need to play their part in reducing use. An international panel of experts will be needed to guide the design of these targets and help countries implement them, alongside support from the WHO, FAO and OIE. Our suggestions on how they could be formulated: targets could be set over 10 years, with milestones to ensure regular progress, for reductions in total agricultural usage of antibiotics. These could be defined on the basis of milligrams of antibiotic used per kilogram of meat or fish production, with consideration given to appropriate variation by species. 50 mg/kg would be a reasonable objective for many high-income countries, but each country will need to have and regularly review their own ambitious targets. 3.6 Global bodies/national governments and regulators should establish evidence-based, enforceable targets for maximum levels of antimicrobial active pharmaceutical ingredient (API) discharge associated with the manufacture of pharmaceutical products. 3.7 Pharmaceutical companies should improve monitoring of API emissions from directly-operated manufacturing facilities as well as those of third party suppliers, and support the installation of proper waste processing facilities to reduce or eliminate API discharge. Such efforts should be based in voluntary, transparent and auditable commitments, with a globally-consistent 'quality mark' applied to end products produced on 'environmentally responsible' basis.

Improve global surveillance of drug resistance in humans and animals 4.1 WHO to provide global leadership and coordination to efforts – supported from governments, regional organisations, and philanthropic organisations – to establish a global surveillance system to monitor the emergence and spread of drug-resistant infections. 4.2 National governments/regulators and globally-representative bodies to initiate work to incentivise and remove barriers to the safe, secure and appropriate sharing of data of use to global surveillance efforts between public and private organisations on a large scale, with a particular view to unleashing the potential of advances in 'big data', cloud computing and machine learning in the coming years.

Promote new, rapid diagnostics to cut unnecessary use of antibiotics 5.1 In high-income countries, governments, regulators and other health system leaders to support the uptake and use of rapid point-of-care diagnostics in primary and secondary care. Incentives should be considered in high-income countries to facilitate the mandatory use of such tests to support clinical decision-making, where they are available, or the use of up-to-date epidemiological data where they are not, by 2020. 5.2 In low and middle-income countries, the uptake and use of rapid point-of-care diagnostics to guide the use of antimicrobials should be supported via a globally-administered 'diagnostic market stimulus' system, providing a direct per unit subsidy to diagnostic test manufacturers upon evidence of their product's purchase or use.

Promote the development and use of vaccines and alternatives 6.1 Promote the uptake and use of existing vaccines more widely in humans and animals to save lives and reduce unnecessary antibiotic use, including through the work of Gavi or by initiating comparable new initiatives. 6.2 Sustain a viable market for vaccines with the greatest potential in tackling drug resistance. Depending on the characteristics of the vaccines in question, this might be through 'pull' funding using a similar form to existing Advanced Market Commitments (to promote broad uptake in mid to large-sized populations), or as market entry rewards (to ensure availability for smaller populations at high risk). 6.3 Some alternatives aim to prevent infection, as vaccines do, others to replace antibiotics as treatment, and still others to make antibiotics more effective or reduce the likelihood of resistance arising by being taken alongside them. We believe that alternatives should be eligible for the same incentives as vaccines or antibiotics, where they fulfill the same role in combating AMR.

Improve the numbers, pay and recognition of people working in infectious disease 7.1 Governments, healthcare system leaders and private actors (such as clinical professional bodies and academic institutions), should work together to expand funding and training opportunities to increase the number and capacity of healthcare workers on the frontline of fighting resistance, and of academic scientists working in the field. These efforts should extend to considering the pay, recognition and standing of professionals working in fields relevant to AMR within the healthcare, academic, and commercial communities.

Establish a Global Innovation Fund for early-stage and non-commercial research 8.1 Governments, and public and philanthropic research funding organisations, to collaborate on a global basis to develop a Global Innovation Fund for R&D into new antimicrobials and other related products (including vaccines and diagnostics.) This fund should build on existing bilateral and multilateral arrangements for pooling and coordinating the spending of research funds, but do more to ensure that AMR-related research is properly funded and more proactively targeted towards neglected areas (e.g. re-purposing of older products.)

Better incentives to promote investment for new drugs and improving existing ones 9.1 Institute a system of 'market entry rewards' to provide lump-sum payments to the successful developers of new antibiotics that meet a specified unmet medical need. In principle, this should be administered and funded on a supra‑national basis, with support for global, affordable, and responsible access to antibiotics at its heart. Detailed work on the design and implementation of such a system should be picked up as a matter of urgency by the appropriate international partners. 9.2 Consider the role that such a system of market entry rewards can play in supporting the development of complete treatment regimens for tuberculosis (TB), as a means of 'supercharging' systems of support for TB product development. 9.3 Key regulatory agencies should work together to improve the global harmonisation of regulatory pathways for new antibiotics, and explore the possibilities for mutual recognition of regulatory approval across multiple jurisdictions. 9.4 Pharmaceutical companies, regulators and healthcare system leaders to work together to institute national and regional 'clinical trial networks' for antibiotics, to streamline the clinical trial process and reduce the costs and duration of antibiotic development.