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Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.

[...]antibiotic candidates that have the greatest potential public health value must be selected, and trials should be conducted in the countries most affected, recruiting people most at risk, including women, children, and people living with HIV, who are often not prioritised in clinical trials. 7 This approach also requires investment in manufacturing, including the use and support of technology transfers and licensing agreements, and in market shaping, such as through pooled procurement and demand forecasting, to create regional supply security and affordability. Calls for push and pull incentives to help stimulate antibiotic R&D and support private sector efforts, respectively, are leading to change. 8 There has also been notable progress towards embedding public health needs and access into antibiotics R&D—something our three organisations (the Global Antibiotic Research & Development Partnership [GARDP], the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator [CARB-X], and Wellcome) have helped lead on. By working with industry and global stakeholders, not-for-profit organisations such as ours are supporting the development of much-needed new antibiotics for underserved settings, with early investments made through CARB-X and GARDP that we hope will deliver benefits decades into the future. 8 For such efforts to ultimately succeed, a change in mindset among policy makers is also needed.

Rising antimicrobial resistance (AMR) is a global health crisis for countries of all economic levels, alongside the broader challenge of access to antibiotics. As a result, development goals for child survival, healthy ageing, poverty reduction, and food security are at risk. Preserving antimicrobial effectiveness, a global public good, requires political will, targets, accountability frameworks, and funding. The upcoming second high-level meeting on AMR at the UN General Assembly (UNGA) in September, 2024, is evidence of political interest in addressing the problem of AMR, but action on targets, accountability, and funding, absent from the 2016 UNGA resolution, is needed. We propose ambitious yet achievable global targets for 2030 (relative to a prepandemic 2019 baseline): a 10% reduction in mortality from AMR; a 20% reduction in inappropriate human antibiotic use; and a 30% reduction in inappropriate animal antibiotic use. Given national variation in current levels of antibiotic use, these goals (termed the 10–20–30 by 2030) should be met within a framework of universal access to effective antibiotics. The WHO Access, Watch, Reserve (AWARE) system can be used to define, monitor, and evaluate appropriate levels of antibiotic use and access. Some countries should increase access to narrow-spectrum, safe, and affordable (Access) antibiotics, whereas others should discourage the inappropriate use of broader-spectrum (Watch) and last-resort (Reserve) antibiotics; AWARE targets should use a risk-based, burden-adjusted approach. Improved infection prevention and control, access to clean water and sanitation, and vaccination coverage can offset the selection effects of increased antibiotic use in low-income settings. To ensure accountability and global scientific guidance and consensus, we call for the establishment of the Independent Panel on Antimicrobial Access and Resistance and the support of leaders from low-income and middle-income countries.

Quasi-experimental studies are increasingly used to establish causal relationships in epidemiology and health systems research. Quasi-experimental studies offer important opportunities to increase and improve evidence on causal effects: (1) they can generate causal evidence when randomized controlled trials are impossible; (2) they typically generate causal evidence with a high degree of external validity; (3) they avoid the threats to internal validity that arise when participants in nonblinded experiments change their behavior in response to the experimental assignment to either intervention or control arm (such as compensatory rivalry or resentful demoralization); (4) they are often well suited to generate causal evidence on long-term health outcomes of an intervention, as well as nonhealth outcomes such as economic and social consequences; and (5) they can often generate evidence faster and at lower cost than experiments and other intervention studies.

The pipeline of new antibiotics is insufficient to keep pace with the growing global burden of drug-resistant infections. Substantial economic challenges discourage private investment in antibiotic research and development (R&D), with a decline in the number of companies and researchers working in the field. Compounding these issues, many countries (from low income to high income) face a growing crisis of antibiotic shortages and inequitable access to existing and emerging treatments. This has led to an increasing role for public and philanthropic funding in supporting antibiotic R&D via the creation of nonprofit public–private partnerships, including Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and the Global Antibiotic Research and Development Partnership (GARDP), industry support for the AMR Action Fund, and pilot schemes to evaluate and reimburse antibiotics in innovative ways. Now is the time to raise the urgency, ambition and commitments of the world’s leaders to fully support the antibiotic R&D ecosystem, incentivizing all sectors to conduct public health-driven antibiotic R&D and make effective antibiotics accessible to all who need them. Tackling antimicrobial resistance will require a sustainable research and development ecosystem for antibiotic development, alongside strategies for responsible use and global access.

The objective of this study was to contrast the historical development of experiments and quasi-experiments and provide the motivation for a journal series on quasi-experimental designs in health research. A short historical narrative, with concrete examples, and arguments based on an understanding of the practice of health research and evidence synthesis. Health research has played a key role in developing today's gold standard for causal inference—the randomized controlled multiply blinded trial. Historically, allocation approaches developed from convenience and purposive allocation to alternate and, finally, to random allocation. This development was motivated both by concerns for manipulation in allocation as well as statistical and theoretical developments demonstrating the power of randomization in creating counterfactuals for causal inference. In contrast to the sequential development of experiments, quasi-experiments originated at very different points in time, from very different scientific perspectives, and with frequent and long interruptions in their methodological development. Health researchers have only recently started to recognize the value of quasi-experiments for generating novel insights on causal relationships. While quasi-experiments are unlikely to replace experiments in generating the efficacy and safety evidence required for clinical guidelines and regulatory approval of medical technologies, quasi-experiments can play an important role in establishing the effectiveness of health care practice, programs, and policies. The papers in this series describe and discuss a range of important issues in utilizing quasi-experimental designs for primary research and quasi-experimental results for evidence synthesis.

The newly formed international Coalition for Epidemic Preparedness Innovations aims to stimulate, finance, and coordinate the development of vaccines against epidemic infectious diseases, especially in cases in which market incentives alone are insufficient. The vaccine-development response to the 2014 Ebola epidemic in West Africa, though a valiant effort, was too little, too late. Three vaccine candidates were tested successfully under challenging conditions. 1 – 3 Governments and foundations mobilized funds quickly. Companies and research-and-development institutions brought vaccine candidates into the field. Collaborations among the World Health Organization (WHO), funders, academia, civil society, and industry saw vaccines advancing through more than 15 accelerated clinical trials in a year. But the testing of Ebola vaccine candidates had previously stalled, though several candidates could have been ready for efficacy testing before the epidemic if the necessary investments had . . .

[...]the amount and quality of relevant data on AMR from local, national, or regional centers for disease control have been enhanced. [...]as for many problems of international cooperation in which countries can free ride on the efforts of others, improved monitoring will reduce information uncertainty about the current situation and responses and create better conditions for cooperation through joint effort to produce global public goods [12]. How to expand monitoring? Because AMR control is complex, the goal should be to measure the problem and progress across its multiple dimensions while at the same time making it more tractable to policy makers and the public. [...]measurements of structures are about the “responses,” which include the adoption of a national action plan and the enactment of regulations in human medicine and agriculture.

Following the recommendations of the HLIP, the G20 catalysed the creation of the Pandemic Fund at the World Bank in 2022, but the Fund has only mobilised pledges for approximately $3 billion of its envisioned annual $10 billion scale. 2 The G20 Joint Finance–Health Task Force (JFHTF) was launched in 2021 to bridge finance and health policy. [...]low-income and middle-income countries (LMICs) must be able to act early when biological threats emerge. [...]the Pandemic Fund must become the world's premier facility for external support for preparedness financing. The HLIP calls on the World Bank and other development banks to commit to establishing standing, renewable allocations to ensure sustained support for the Pandemic Fund and its work.