Equity in the Pandemic Treaty: Access and Benefit-Sharing as a Policy Device or a Rhetorical Device?

Equity is a foundational concept for the new World Health Organization (WHO) Pandemic Treaty. WHO Member States are currently negotiating to turn this undefined concept into tangible outcomes by borrowing a policy mechanism from international environmental law: "access and benefit-sharing" (ABS).

Collaboration in neonatal and paediatric clinical pharmacology: creating a peer-based mentoring platform in a pan-European clinical trial network

IntroductionIn recent years, substantial improvements in clinical trial facilitation have been made through a pan-European network conect4children (c4c), funded by the Innovative Medicines Initiative 2. Within c4c, collaboration and experience-based teaching were attainable due to live meetings and structured social interactions. Since the COVID-19 pandemic, meeting platforms were limited and strictly virtual, creating an artificial communication environment and a gap for young talent to interact and learn.MethodsIn light of c4c's main objective to build strong collaborations and connections between different national clinical trial networks, the younger generation was in need of support. In May 2021, the young investigators community (YIC) platform was launched to facilitate an informal teaching and connecting vehicle. However, interaction with the experienced and leading generation was lacking, in order to mentor the ‘starters' for a durable network.ResultsWithin the first year, the YIC created an open platform in which the 32 members could interact on a regular basis. Topics included involving medical students, how to build and prepare sustainable business plans and working and interacting with industry partners. Inspired by Erasmus+ funded Pathway project and McBride at al (2017) Mentorship profiling, a 4-page intake questionnaire for both mentor and mentee has been designed, that focuses on specific skills and a plan-of-action for the mentorship session, maximizing efficiency of the interaction.ConclusionWithin YIC, a questionnaire was designed to approach mentor and mentee selection, to be used to minimize the gap between young talent and the established community. The method could be beneficial to other national and international network

Implementation of a centralized pharmacovigilance system in academic pan-European clinical trials: Experience from EU-Response and conect4children consortia.

Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors.

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

European research networks to facilitate drug research in children.

Paediatric drug development faces several barriers. These include fragmentation of stakeholders and inconsistent processes during the conduct of research. This review summarises recent efforts to overcome these barriers in Europe. Two exemplar initiatives are described. The European Paediatric Translational Research Infrastructure facilitates preclinical research and other work that underpins clinical trials. conect4children facilitates the design and implementation of clinical trials. Both these initiatives listen to the voices of children and their advocates. Coordination of research needs specific effort that supplements work on science, resources and the policy context.

State Effectiveness and Crises in East and Southeast Asia: The Case of COVID-19

East and Southeast Asian countries have recorded significant success in dealing with the COVID-19 pandemic. They have employed more effective crisis management strategies than countries in many other parts of the world. This article examines in detail the experiences of two of Asia’s pandemic success stories—South Korea and Vietnam—to identify the ways in which they responded to COVID-19 and how they related to state effectiveness. The lessons learned from the analysis of South Korean and Vietnamese crisis management include: the importance of preparedness and decisive action;the need for flexibility to cope with changing circumstances;that there are alternative crisis management strategies to reach the same desired outcomes;and that crisis management is best served by securing unity of purpose among government, citizens, civil society and the private sector. State effectiveness is a foundation for such features of successful crisis management.

Exploring the changes and challenges of COVID-19 in adult safeguarding practice: qualitative findings from a mixed-methods project

Purpose The purpose of this paper is to present findings from a mixed-methods study on the impact that COVID-19 has had on adult safeguarding. The research sought to explore the challenges and opportunities presented by COVID-19 to both frontline and non-frontline professionals working in adult safeguarding. Design/methodology/approach A mixed-methods project was undertaken comprising a literature review, survey, semi-structured interviews and a small number of freedom of information requests. This paper presents the findings predominantly from the survey and interviews. Findings Unsurprisingly, COVID-19 has presented a variety of challenges for professionals working in adult safeguarding. The themes that occurred most often were the day-to-day changes and challenges, relationships across sectors, information and navigating the ethical questions in safeguarding. Originality/value To the best of the authors' knowledge, the findings represent the first focused qualitative mixed-method study aimed at understanding more about the impact the pandemic has had on adult safeguarding through the eyes of those professionals working in that field.

Governing Global Antimicrobial Resistance: 6 Key Lessons Fromthe Paris Climate Agreement

[...]mitigating the threat posed by AMR requires a recognition of how embedded social structures and incentives drive antimicrobial use across sectors. [...]escalating commitments through national AMR action plans, which outline each country's AMR goals and planned actions, will likely increase the effectiveness of global AMR efforts. Fifth, like the Intergovernmental Panel on Climate Change guiding the Paris Agreement, ongoing AMR action would be best informed by a regular and independent stock-taking to evaluate existing measures and advise on evidence-informed adjustments.11,12 This endeavor must (1) recognize that different ways of knowing constitute the global knowledge base, (2) ensure that using evidence to inform adjustments that work does not detract from the inherently political questions of works for what purpose and for whose benefit, and (3) come with a commitment to equitable evidence generation and prioritization. Striking a panel to assess the global knowledge base on these terms will ensure that global, regional, and national goals and policies are continually informed by the best available evidence and are in line with leading practices.12 Finally, an enduring international legal agreement could institutionalize requires new legal mechanisms beyond those available through the World Health Organization, the Food and Agriculture Organization of the United Nations, the World Organization for Animal Health, and the United Nations Environment Program, which are limited to the area-specific mandates of each institution.

Sovereignty, sanctions, and data sharing under international law.

Pathogen samples and scientific data are bargaining chips in a global argument about who gets what in a pandemic.

ARGUMENTS AGAINST THE INEQUITABLE DISTRIBUTION OF VACCINES USING THE ACCESS AND BENEFIT SHARING TRANSACTION

Access and benefit sharing (ABS) is a transactional mechanism designed to allow countries to trade access to their sovereign genetic resources for monetary and non-monetary benefits, with the ultimate goal of channelling those benefits into sustainable development and environmental conservation. Arguments about how pathogens are not the sort of genetic resources the world ought to conserve eventually gave way to a recognition that pathogens are indeed sovereign genetic resources under the Convention on Biological Diversity and its Nagoya Protocol, and that the ABS transaction may be an effective way to deliver scarce vaccines to developing nations as benefits received in exchange for shared pathogen samples. This article argues that categorising vaccines as benefits given in exchange for access to pathogen samples creates opposing incentives for providers and users of virus samples and undermines the human right to health because it makes that right a commodity to be bought. The provision of pathogen samples to the global research commons and the fair and equitable distribution of medicines should be two parallel public goods to be pursued as goals in and of themselves. We conclude that the linking of these goals through the ABS transaction should be reassessed.

Early Impact of Severe Acute Respiratory Syndrome Coronavirus 2 on Pediatric Clinical Research: A Pan-European and Canadian Snapshot in Time.

OBJECTIVE: To capture the early effects of the coronavirus disease 2019 (COVID-19) pandemic on pediatric clinical research. STUDY DESIGN: Pediatric clinical research networks from 20 countries and 50 of their affiliated research sites completed two surveys over one month from early May to early June 2020. Networks liaised with their affiliated sites and contributed to the interpretation of results through pan-European group discussions. Based on first detection dates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), countries formed 1 early detecting and 1 late detecting cluster. We tested the hypothesis that this clustering influenced clinical research. RESULTS: Research sites were first impacted by the pandemic in mid-March 2020 (March 16 ± 10 days, the same date as lockdown initiation; P = .99). From first impact up until early June, site initiation and feasibility analysis processes were affected for >50% of the sites. Staff were redirected to COVID-19 research for 44% of the sites, and 75.5% of sites were involved in pediatric COVID-19 research (only 6.3% reported COVID-19 cases in their other pediatric trials). Mitigation strategies were used differently between the early and late detecting country clusters and between countries with and without a pediatric COVID-19 research taskforce. Positive effects include the development of teleworking capacities. CONCLUSIONS: Through this collaborative effort from pediatric research networks, we found that pediatric trials were affected and conducted with a range of unequally applied mitigations across countries during the pandemic. The global impact might be greater than captured. In a context where clinical research is increasingly multinational, this report reveals the importance of collaboration between national networks.

Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial.

INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss. METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice. ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study. TRIAL REGISTRATION NUMBER: ISRCTN13704894. PROTOCOL VERSION: V 1.3.

International Collaboration to Ensure Equitable Access to Vaccines for COVID-19: The ACT-Accelerator and the COVAX Facility.

Policy Points Equitable access to a COVID-19 vaccine in all countries remains a key policy objective, but experience of previous pandemics suggests access will be limited in developing countries, despite the rapid development of three successful vaccine candidates. The COVAX Facility seeks to address this important issue, but the prevalence of vaccine nationalism threatens to limit the ability of the facility to meet both its funding targets and its ambitious goals for vaccine procurement. A failure to adequately address the underlying lack of infrastructure in developing countries threatens to further limit the success of the COVAX Facility. CONTEXT: Significant effort has been directed toward developing a COVID-19 vaccine, which is viewed as the route out of the pandemic. Much of this effort has coalesced around COVAX, the multilateral initiative aimed at accelerating the development of COVID-19 vaccines, and ensuring they are equitably available in low- and middle-income countries (LMICs). This paper represents the first significant analysis of COVAX, and the extent to which it can be said to have successfully met these aims. METHODS: This paper draws on the publicly available policy documents made available by the COVAX initiatives, as well as position papers and public statements from governments around the world with respect to COVID-19 vaccines and equitable access. We analyze the academic literature regarding access to vaccines during the H1N1 pandemic. Finally, we consider the WHO Global Allocation System, and its principles, which are intended to guide COVAX vaccine deployment. FINDINGS: We argue that the funding mechanism deployed by the COVAX Pillar appears to be effective at fostering at-risk investments in research and development and the production of doses in advance of confirmation of clinical efficacy, but caution that this represents a win-win situation for vaccine manufacturers, providing them with opportunity to benefit regardless of whether their vaccine candidate ever goes on to gain regulatory approval. We also argue that the success of the COVAX Facility with respect to equitable access to vaccine is likely to be limited, primarily as a result of the prevalence of vaccine nationalism, whereby countries adopt policies which heavily prioritize their own public health needs at the expense of others. CONCLUSIONS: Current efforts through COVAX have greatly accelerated the development of vaccines against COVID-19, but these benefits are unlikely to flow to LMICs, largely due to the threat of vaccine nationalism.