Quasi-experimental evaluation of national border closures on COVID-19 transmission.

With over 200 pandemic threats emerging every year, the efficacy of closing national borders to control the transmission of disease in the first months of a pandemic remains a critically important question. Previous studies offer conflicting evidence for the potential effects of these closures on COVID-19 transmission and no study has yet empirically evaluated the global impact of border closures using quasi-experimental methods and real-world data. We triangulate results from interrupted time-series analysis, meta-regression, coarsened exact matching, and an extensive series of robustness checks to evaluate the effect of 166 countries' national border closures on the global transmission of COVID-19. Total border closures banning non-essential travel from all countries and (to a lesser extent) targeted border closures banning travel from specific countries had some effect on temporarily slowing COVID-19 transmission in those countries that implemented them. In contrast to these country-level impacts, the global sum of targeted border closures implemented by February 5, 2020 was not sufficient to slow global COVID-19 transmission, but the sum of total border closures implemented by March 19, 2020 did achieve this effect. Country-level results were highly heterogeneous, with early implementation and border closures so broadly targeted that they resemble total border closures improving the likelihood of slowing the pandemic's spread. Governments that can make productive use of extra preparation time and cannot feasibly implement less restrictive alternatives might consider enacting border closures. However, given their moderate and uncertain impacts and their significant harms, border closures are unlikely to be the best policy response for most countries and should only be deployed in rare circumstances and with great caution. All countries would benefit from global mechanisms to coordinate national decisions on border closures during pandemics.

Exploring Models for an International Legal Agreement on the Global Antimicrobial Commons: Lessons from Climate Agreements.

An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change-both are common pool resource challenges that require massive, long-term political commitments-the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand bargain on AMR. We consider the similarities and differences between the Paris Climate Agreement and current governance structures for AMR, and identify the merits and challenges associated with different international forums for developing a long-term international agreement on AMR. To be effective, fair, and feasible, an enduring legal agreement on AMR will require a combination of universal, differentiated, and individualized requirements, nationally determined contributions that are regularly reviewed and ratcheted up in level of ambition, a regular independent scientific stocktake to support evidence informed policymaking, and a concrete global goal to rally support.

Governing the Global Antimicrobial Commons: Introduction to Special Issue.

Antimicrobial resistance is one of the greatest public health crises of our time. The natural biological process that causes microbes to become resistant to antimicrobial drugs presents a complex social challenge requiring more effective and sustainable management of the global antimicrobial commons-the common pool of effective antimicrobials. This special issue of Health Care Analysis explores the potential of two legal approaches-one long-term and one short-term-for managing the antimicrobial commons. The first article explores the lessons for antimicrobial resistance that can be learned from recent climate change agreements, and the second article explores how existing international laws can be adapted to better support global action in the short-term.

Making Use of Existing International Legal Mechanisms to Manage the Global Antimicrobial Commons: Identifying Legal Hooks and Institutional Mandates.

Antimicrobial resistance (AMR) is an urgent threat to global public health and development. Mitigating this threat requires substantial short-term action on key AMR priorities. While international legal agreements are the strongest mechanism for ensuring collaboration among countries, negotiating new international agreements can be a slow process. In the second article in this special issue, we consider whether harnessing existing international legal agreements offers an opportunity to increase collective action on AMR goals in the short-term. We highlight ten AMR priorities and several strategies for achieving these goals using existing "legal hooks" that draw on elements of international environmental, trade and health laws governing related matters that could be used as they exist or revised to include AMR. We also consider the institutional mandates of international authorities to highlight areas where additional steps could be taken on AMR without constitutional changes. Overall, we identify 37 possible mechanisms to strengthen AMR governance using the International Health Regulations, the Agreement on the Application of Sanitary and Phytosanitary Measures, the Agreement on Trade-Related Aspects of Intellectual Property Rights, the Agreement on Technical Barriers to Trade, the International Convention on the Harmonized Commodity Description and Coding System, and the Basel, Rotterdam, and Stockholm conventions. Although we identify many shorter-term opportunities for addressing AMR using existing legal hooks, none of these options are capable of comprehensively addressing all global governance challenges related to AMR, such that they should be pursued simultaneously with longer-term approaches including a dedicated international legal agreement on AMR.

International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

Principles and methods of global legal epidemiology.

Although the theory and methods of legal epidemiology-the scientific study and deployment of law as a factor in the cause, distribution, and prevention of disease and injury in a population-have been well developed in the context of domestic law, the challenges posed by shifting the frame of analysis to the global legal space have not yet been fully explored. While legal epidemiology rests on the foundational principles that law acts as an intervention, that law can be an object of scientific study and that law has impacts that should be evaluated, its application to the global level requires the recognition that international laws, policies and norms can cause effects independently from their legal implementation within countries. The global legal space blurs distinctions between 'hard' and 'soft' law, often operating through pathways of global agenda setting, legal language, political pressures, social mobilisation and trade pressures to have direct impacts on people, places and products. Despite these complexities, international law has been overwhelmingly studied as operating solely through national policy change, with only one global quasi-experimental evaluation of an international law's impact on health published to date. To promote greater adoption of global legal epidemiology, we expand on an existing typology of public health law studies with examples of policymaking, mapping, implementation, intervention and mechanism studies. Global legal epidemiology holds great promise as a way to produce rigorous and impactful research on the international laws, policies and norms that shape our collective health, equity and well-being.

Taking stock of global commitments on antimicrobial resistance.

Over the last six years, antimicrobial resistance (AMR) has generated an unprecedented amount of global attention. This global attention has coincided with an increase in discussion around AMR at various multilateral organisations and international fora. This study catalogues and analyses AMR-related commitments made by the global community following the implementation of the AMR Tripartite's Global Action Plan (GAP) in 2015. In examining these commitments, we elucidated emergent themes and gaps in AMR discourse through a qualitative content analysis of global political resolutions, declarations and statements made by members of the United Nations, the World Health Assembly, Food and Agriculture Organization Conferences, World Organisation for Animal Health General Sessions, and the G7 and G20 summits and ministerial meetings between the years 2015 and 2021. Emergent themes included AMR research, surveillance and stewardship. Across sectors, fewer commitments were made for specific action on AMR in the environment. The themes and types of commitments were found to be consistent across time and fora but did not evolve into more concrete or nuanced pledges to action between 2015 and 2021. GAP objectives relating to infection prevention and efforts to address the root drivers of AMR appeared the least frequently in our analysis, indicating a lack of global commitment to take a proactive prevention-focused approach to AMR.

Waves of attention: patterns and themes of international antimicrobial resistance reports, 1945-2020.

This article uses quantitative and qualitative approaches to review 75 years of international policy reports on antimicrobial resistance (AMR). Our review of 248 policy reports and expert consultation revealed waves of political attention and repeated reframings of AMR as a policy object. AMR emerged as an object of international policy-making during the 1990s. Until then, AMR was primarily defined as a challenge of human and agricultural domains within the Global North that could be overcome via 'rational' drug use and selective restrictions. While a growing number of reports jointly addressed human and agricultural AMR selection, international organisations (IOs) initially focused on whistleblowing and reviewing data. Since 2000, there has been a marked shift in the ecological and geographic focus of AMR risk scenarios. The Global South and One Health (OH) emerged as foci of AMR reports. Using the deterritorialised language of OH to frame AMR as a Southern risk made global stewardship meaningful to donors and legitimised pressure on low-income and middle-income countries to adopt Northern stewardship and surveillance frameworks. It also enabled IOs to move from whistleblowing to managing governance frameworks for antibiotic stewardship. Although the environmental OH domain remains neglected, realisation of the complexity of necessary interventions has increased the range of topics targeted by international action plans. Investment nonetheless continues to focus on biomedical innovation and tends to leave aside broader socioeconomic issues. Better knowledge of how AMR framings have evolved is key to broadening participation in international stewardship going forward.

Lessons learned from COVID-19 for the post-antibiotic future.

INTRODUCTION: COVID-19 has rapidly and radically changed the face of human health and social interaction. As was the case with COVID-19, the world is similarly unprepared to respond to antimicrobial resistance (AMR) and the challenges it will produce. COVID-19 presents an opportunity to examine how the international community might better respond to the growing AMR threat. MAIN BODY: The impacts of COVID-19 have manifested in health system, economic, social, and global political implications. Increasing AMR will also present challenges in these domains. As seen with COVID-19, increasing healthcare usage and resource scarcity may lead to ethical dilemmas about prioritization of care; unemployment and economic downturn may disproportionately impact people in industries reliant on human interaction (especially women); and international cooperation may be compromised as nations strive to minimize outbreaks within their own borders. CONCLUSION: AMR represents a slow-moving disaster that offers a unique opportunity to proactively develop interventions to mitigate its impact. The world's attention is currently rightfully focused on responding to COVID-19, but there is a moral imperative to take stock of lessons learned and opportunities to prepare for the next global health emergency.

Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy.

There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an 'implementation gap'. At a policy level, the design of internationally salient solutions that are able to address AMR's interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise 'good' antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scales.

Using a rapid environmental scan methodology to map country-level global health research expertise in Canada.

BACKGROUND: Many countries are currently rethinking their global health research funding priorities. When resources are limited, it is important to understand and use information about existing research strengths to inform research strategies and investments and to drive impact. This study describes a method to rapidly assess a country's global health research expertise and applies this method in the Canadian context. METHODS: We developed a three-pronged rapid environmental scan to evaluate Canadian global health research expertise that focused on research funding inputs, research activities and research outputs. We assessed research funding inputs from Canada's national health research funding agency and identified the 30 Canadian universities that received the most global health research funding. We systematically searched university websites and secondary databases to identify research activities, including research centres, research chairs and research training programmes. To evaluate research outputs, we searched PubMed to identify global health research publications by Canadian university-affiliated researchers. We used these three perspectives to develop a more nuanced understanding of Canadian strengths in global health research from different perspectives. RESULTS: Canada's main global health research funder, the Canadian Institutes of Health Research, invested a total of $314 M from 2000 to 2016 on global health research grants. This investment has contributed to Canada's wealth of global health research expertise, including 12 training programmes, 27 Canada Research Chairs, 6 research centres and 30 WHO Collaborating Centres across 27 universities. Research activities were concentrated in Canada's biggest cities and most commonly focused on health equity and globalisation issues. Canadian-affiliated researchers have contributed to a research output of 822 unique publications on PubMed. There is an opportunity to build global health expertise in regions not already concentrated with research activity, focusing on transnational risks and neglected conditions research. CONCLUSIONS: Our three-pronged approach allowed us to rapidly identify clear geographic and substantive areas of strength in Canadian global health research, including urban regions and research focused on health equity and globalisation topics. This information can be used to support research policy directives, including to inform a Canadian global health research strategy, and to allow relevant academic institutions and funding organisations to make more strategic decisions regarding their future investments.

A behavioural approach to specifying interventions: what insights can be gained for the reporting and implementation of interventions to reduce antibiotic use in hospitals?

BACKGROUND: Reducing unnecessary antibiotic exposure is a key strategy in reducing the development and selection of antibiotic-resistant bacteria. Hospital antimicrobial stewardship (AMS) interventions are inherently complex, often requiring multiple healthcare professionals to change multiple behaviours at multiple timepoints along the care pathway. Inaction can arise when roles and responsibilities are unclear. A behavioural perspective can offer insights to maximize the chances of successful implementation. OBJECTIVES: To apply a behavioural framework [the Target Action Context Timing Actors (TACTA) framework] to existing evidence about hospital AMS interventions to specify which key behavioural aspects of interventions are detailed. METHODS: Randomized controlled trials (RCTs) and interrupted time series (ITS) studies with a focus on reducing unnecessary exposure to antibiotics were identified from the most recent Cochrane review of interventions to improve hospital AMS. The TACTA framework was applied to published intervention reports to assess the extent to which key details were reported about what behaviour should be performed, who is responsible for doing it and when, where, how often and with whom it should be performed. RESULTS: The included studies (n = 45; 31 RCTs and 14 ITS studies with 49 outcome measures) reported what should be done, where and to whom. However, key details were missing about who should act (45%) and when (22%). Specification of who should act was missing in 79% of 15 interventions to reduce duration of treatment in continuing-care wards. CONCLUSIONS: The lack of precise specification within AMS interventions limits the generalizability and reproducibility of evidence, hampering efforts to implement AMS interventions in practice.

Systematic analysis of global health research funding in Canada, 2000-2016.

OBJECTIVES: Considering recent shifts in global funding landscapes, this study analyzes Canada's long-term global health research funding trends in the hope of informing a new Canadian global health research strategy. Examining past investments can help prioritize limited future resources to either build on Canada's existing strengths or fill gaps where needed, while simultaneously informing the investments of research funders in other countries. METHODS: Administrative data were analyzed covering all 1584 global health research grants awarded by the Canadian Institutes of Health Research (CIHR) to 927 unique principal investigators from 2000 to 2016, totalling C$341 million. Existing metadata associated with each grant was supplemented by additional qualitative coding. Descriptive time-series analyses of global health research grant data were conducted using various measures related to each grant's recipient (e.g., province, university, sex, distribution) and subject matter (e.g., research theme, area, focus). RESULTS: CIHR's total annual global health research funding increased sharply from $3.6 million in FY2000/2001 to $30.3 million in FY2015/2016, with the largest share of research funding now focused on health equity-representing nearly 50% of CIHR's global health research funding. Past grants have concentrated on infectious disease and public health research. One third of CIHR's global health grant funding went to 20 principal investigators. Only 42.2% of global health research funding came from CIHR's open investigator-driven competitions, with the rest coming from strategic priority-driven competitions. CONCLUSION: Global health research has seen steady increases in funding from CIHR's open competitions when preceded by investment in strategic competitions, which suggests the level of a national research funding agency's strategic investments in global health research may determine the size of the field in their country. The greatest concentration of past investment lies in health equity research, followed by infectious disease research. Future analyses of research funding would benefit from an internationally accepted keyword classification scheme and more granular administrative data.

How law can help solve the collective action problem of antimicrobial resistance.

Antimicrobial resistance is a global collective action problem with dire consequences for human health. This article considers how domestic and international legal mechanisms can be used to address antimicrobial resistance and overcome the governance and political economy challenges that accelerate it.

Government policy interventions to reduce human antimicrobial use: A systematic review and evidence map.

BACKGROUND: Growing political attention to antimicrobial resistance (AMR) offers a rare opportunity for achieving meaningful action. Many governments have developed national AMR action plans, but most have not yet implemented policy interventions to reduce antimicrobial overuse. A systematic evidence map can support governments in making evidence-informed decisions about implementing programs to reduce AMR, by identifying, describing, and assessing the full range of evaluated government policy options to reduce antimicrobial use in humans. METHODS AND FINDINGS: Seven databases were searched from inception to January 28, 2019, (MEDLINE, CINAHL, EMBASE, PAIS Index, Cochrane Central Register of Controlled Trials, Web of Science, and PubMed). We identified studies that (1) clearly described a government policy intervention aimed at reducing human antimicrobial use, and (2) applied a quantitative design to measure the impact. We found 69 unique evaluations of government policy interventions carried out across 4 of the 6 WHO regions. These evaluations included randomized controlled trials (n = 4), non-randomized controlled trials (n = 3), controlled before-and-after designs (n = 7), interrupted time series designs (n = 25), uncontrolled before-and-after designs (n = 18), descriptive designs (n = 10), and cohort designs (n = 2). From these we identified 17 unique policy options for governments to reduce the human use of antimicrobials. Many studies evaluated public awareness campaigns (n = 17) and antimicrobial guidelines (n = 13); however, others offered different policy options such as professional regulation, restricted reimbursement, pay for performance, and prescription requirements. Identifying these policies can inform the development of future policies and evaluations in different contexts and health systems. Limitations of our study include the possible omission of unpublished initiatives, and that policies not evaluated with respect to antimicrobial use have not been captured in this review. CONCLUSIONS: To our knowledge this is the first study to provide policy makers with synthesized evidence on specific government policy interventions addressing AMR. In the future, governments should ensure that AMR policy interventions are evaluated using rigorous study designs and that study results are published. PROTOCOL REGISTRATION: PROSPERO CRD42017067514.

Impact of the WHO Framework Convention on Tobacco Control on global cigarette consumption: quasi-experimental evaluations using interrupted time series analysis and in-sample forecast event modelling.

OBJECTIVE: To evaluate the impact of the WHO Framework Convention on Tobacco Control (FCTC) on global cigarette consumption. DESIGN: Two quasi-experimental impact evaluations, using interrupted time series analysis (ITS) and in-sample forecast event modelling. SETTING AND POPULATION: 71 countries for which verified national estimates of cigarette consumption from 1970 to 2015 were available, representing over 95% of the world's cigarette consumption and 85% of the world's population. MAIN OUTCOME MEASURES: The FCTC is an international treaty adopted in 2003 that aims to reduce harmful tobacco consumption and is legally binding on the 181 countries that have ratified it. Main outcomes were annual national estimates of cigarette consumption per adult from 71 countries since 1970, allowing global, regional, and country comparisons of consumption levels and trends before and after 2003, with counterfactual control groups modelled using pre-intervention linear time trends (for ITS) and in-sample forecasts (for event modelling). RESULTS: No significant change was found in the rate at which global cigarette consumption had been decreasing after the FCTC's adoption in 2003, using either ITS or event modelling. Results were robust after realigning data to the year FCTC negotiations commenced (1999), or to the year when the FCTC first became legally binding in each country. By contrast to global consumption, high income and European countries showed a decrease in annual consumption by over 1000 cigarettes per adult after 2003, whereas low and middle income and Asian countries showed an increased annual consumption by over 500 cigarettes per adult when compared with a counterfactual event model. CONCLUSIONS: This study finds no evidence to indicate that global progress in reducing cigarette consumption has been accelerated by the FCTC treaty mechanism. This null finding, combined with regional differences, should caution against complacency in the global tobacco control community, motivate greater implementation of proven tobacco control policies, encourage assertive responses to tobacco industry activities, and inform the design of more effective health treaties.