Advancing collaborative research for health: why does collaboration matter?

The calls for health research to be collaborative are ubiquitous-even as part of a recent World Health Assembly resolution on clinical trials-yet the arguments in support of collaborative research have been taken for granted and are absent in the literature. This article provides three arguments to justify why health research ought to be collaborative and discusses trade-offs to be considered among the ethical values guiding each argument.

Usefulness of third ventricle volumetry in patients with normal pressure hydrocephalus.

OBJECTIVE: To use third ventricle morphometric variables as a tool for the selection of patients with idiopathic normal pressure hydrocephalus (iNPH) who are candidates for ventriculoperitoneal shunts (VPS). MATERIAL AND METHODS: Retrospective study enrolling patients with iNPH. Katzman infusion test was performed and a Rout > 12 mmHg/mL/min was considered a positive result. The transverse diameter and the volume of the third ventricle were measured in the preoperative MRI. Postoperative improvement was assessed with the NPH score. The results were analysed with SPSS software. RESULTS: 52 patients with a mean age of 76 years were analysed. There was no difference in the diameter of the third ventricle among patients with a positive result and those with a negative result in the infusion test (12.28 vs 11.68 mm; p = 0.14). Neither were difference detected in the ventricle volume of both groups (3.6 vs 3.5cc; p = 0.66). Those patients who improved after VPS had a smaller third ventricle compared to those who did not respond after surgery (11.85 mm vs. 12.96 mm; p = 0.009). Diameter and volume of third ventricle present a significant strong correlation (Pearson correlation coefficient = 0.72; p < 0.0001). CONCLUSION: Morphometric variables of third ventricle may be useful in predicting a good response to VPS in patients with idiopathic normal pressure hydrocephalus.

Preparing ethical review systems for emergencies: next steps.

Ethical review systems need to build on their experiences of COVID-19 research to enhance their preparedness for future pandemics. Recommendations from representatives from over twenty countries include: improving relationships across the research ecosystem; demonstrating willingness to reform and adapt systems and processes; and making the case robustly for better resourcing.

Equitable global allocation of monkeypox vaccines.

With the world grappling with continued spread of monkeypox internationally, vaccines play a crucial role in mitigating the harms from infection and preventing spread. However, countries with the greatest need - particularly historically endemic countries with the highest monkeypox case-fatality rates - are not able to acquire scarce vaccines. This is unjust, and requires rectification through equitable allocation of vaccines globally. We propose applying the Fair Priority Model for such allocation, which emphasizes three key principles: 1) preventing harm; 2) prioritizing the disadvantaged; and 3) treating people with equal moral concern. Post-exposure prophylaxis (PEPV) has the most potential to mitigate harm, and so ensuring countries have sufficient supply for PEPV should be the first priority. And historically endemic countries, which face disadvantages that compound potential harms from monkeypox, should be the first recipients of such vaccines. Once sufficient supply is allocated for countries to apply PEPV, global allocation could move on to pre-exposure prophylaxis (PrEP), again prioritizing historically endemic countries first before distribution to the rest of the global community, based on projected number of cases and vulnerability to harm.

Fair domestic allocation of monkeypox virus countermeasures.

Countermeasures for mpox (formerly known as monkeypox), primarily vaccines, have been in limited supply in many countries during outbreaks. Equitable allocation of scarce resources during public health emergencies is a complex challenge. Identifying the objectives and core values for the allocation of mpox countermeasures, using those values to provide guidance for priority groups and prioritisation tiers, and optimising allocation implementation are important. The fundamental values for the allocation of mpox countermeasures are: preventing death and illness; reducing the association between death or illness and unjust disparities; prioritising those who prevent harm or mitigate disparities; recognising contributions to combating an outbreak; and treating similar individuals similarly. Ethically and equitably marshalling available countermeasures requires articulating these fundamental objectives, identifying priority tiers, and recognising trade-offs between prioritising the people at the highest risk of infection and the people at the highest risk of harm if infected. These five values can provide guidance on preferable priority categories for a more ethically sound response and suggest methods for optimising allocation of countermeasures for mpox and other diseases for which countermeasures are in short supply. Properly marshalling available countermeasures will be crucial for future effective and equitable national responses to outbreaks.

Research ethics systems in Latin America and the Caribbean: a systemic assessment using indicators.

To strengthen research ethics systemically, the Pan American Health Organization (PAHO) devised a strategy that includes objectives and indicators to address core components of research ethics systems. We assessed 22 countries in Latin America and the Caribbean using these indicators. Most countries have adopted legal instruments to govern research with human participants and have implemented national bodies tasked with the oversight of research ethics committees. However, performance with regard to ethics training policies and clinical trial registration was less advanced, and efforts to adopt policies on responsible conduct of research and accelerated ethics review of emergency research did not meet the PAHO objectives in most countries. We discuss the pending challenges and provide recommendations aimed at helping countries from Latin America and the Caribbean to achieve the indicators, and, more generally, to strengthen research ethics with a systemic approach.

[Mapping of research protocols, publications, and collaborations on COVID-19 in Latin America and the CaribbeanMapeamento de protocolos de pesquisa, publicações e colaborações sobre COVID-19 na América Latina e no Caribe]. / Mapeo de protocolos de investigación, publicaciones y colaboraciones sobre la COVID-19 en América Latina y el Caribe.

Objective: To map research protocols, publications, and collaborations on coronavirus disease 2019 (COVID-19) developed in Latin America and the Caribbean (LAC). Methods: Included were research protocols registered in international platforms and research publications containing populations, data, or authors from LAC. The source of information for protocols was primarily the International Clinical Trial Registry Platform (ICTRP) of the World Health Organization; for publications, specific electronic databases and repositories pertaining to COVID-19 were used. The search for publications was conducted up to 11 November; the search for protocols, up to 30 November 2020 (both dates inclusive). Data was extracted from protocols using standardized variables from the ICTRP, and from publications following pre-established criteria. Results: Among the protocols, 63.0% were therapeutic studies, 10% focused on prevention, and 45% were collaborative; 64% of the protocols received no funding from industry; 23% of the publications were not peer-reviewed and 23% were collaborative in nature. The most frequent study designs were systematic reviews and cross-sectional studies; 47.1% of studies were conducted in health facilities and 22% in community settings; 38.0% focused on diagnosis and 27.9% on prognosis. A qualitative synthesis was performed by line of care and approach strategies. Conclusions: There was an increase in the number of collaborative research studies relative to earlier studies and in protocols not funded by industry. The proposed research agenda was covered in large part as the pandemic unfolded.

Objetivo: Mapear protocolos de pesquisa, publicações e colaborações sobre a doença causada pelo coronavírus 2019 (COVID-19, na sigla em inglês) desenvolvidos na América Latina e no Caribe (ALC). Métodos: Foram incluídos protocolos registrados em plataformas internacionais e publicações de pesquisas que consideraram população, dados e autores da ALC. A fonte de informação para os protocolos foi principalmente a Plataforma Internacional de Registros de Ensaios Clínicos (ICTRP, na sigla em inglês) da Organização Mundial da Saúde. Para as publicações, foram utilizadas bases de dados eletrônicas e repositórios específicos sobre COVID-19. As publicações foram pesquisadas até 11 de novembro, e os protocolos, até 30 de novembro de 2020 (inclusive). As informações dos protocolos foram extraídas de acordo com variáveis padronizadas da plataforma ICTRP e das publicações, segundo critérios pré-estabelecidos. Resultados: Dos protocolos, 63% eram estudos sobre terapias, 10% sobre prevenção e 45% eram colaborativos. Em relação ao financiamento, 64% dos protocolos não vieram da indústria. Em relação às publicações, 23% eram sem revisão por pares e 23% eram colaborativas. Os delineamentos mais frequentes foram revisões sistemáticas e estudos transversais; 47,1% foram realizados em serviços de saúde e 22% no âmbito comunitário; 38,0% focaram no diagnóstico e 27,9% no prognóstico. Realizou-se uma síntese qualitativa segundo a linha de cuidado e as estratégias de abordagem. Conclusões: Observou-se um aumento no número de pesquisas colaborativas (em comparação com estudos anteriores) e de protocolos não financiados pela indústria. A agenda de pesquisa proposta foi coberta, em grande parte, à medida que a pandemia progredia.

Evaluating the optimal number of burr-holes for treating chronic subdural haematomas: good results from a single burr-hole?

INTRODUCTION: Chronic subdural haematomas (cSDH) are one of the most common types of traumatic intracranial lesion. Burr-hole craniostomy followed by closed-system drainage has become the treatment of choice. However, there is no definitive indication as to the number of burr-holes needed. Our aim was to to assess clinical and radiological outcomes taking into account the number of burr-holes made. MATERIAL AND METHODS: A retrospective single-centre-study was performed including patients treated for cSDH by performing burr-hole craniostomy from 2012 to 2018. After collecting data regarding demographics, comorbidities, and clinical and radiological records, haematomas were grouped depending on the number of burr-holes made (Group 1: single burr-hole; Group 2: double burr-holes). Clinical and radiological outcomes were statistically compared between groups, as well as the main complications. RESULTS: After collecting 171 patients, 205 cSDHs were analysed. 173 were treated with a single burr-hole (we called these Group 1) and 32 with double burr-holes (Group 2). No differences in preoperative characteristics were found between the groups, except for diabetes mellitus and previous antiplatelet/anticoagulation treatment. No radiological differences were found regarding haematoma volume (p = 0.7) or thickness (p = 0.3). Surgical site infection (p = 0.13), recurrence (p = 0.6), acute rebleeding (p = 0.25) and mortality (p = 0.94) were assessed without evidencing statistically significant differences. At the time of hospital discharge, most patients showed a remarkable clinical improvement, regardless of the number of burr-holes made (p = 0.7). CONCLUSIONS: This study suggests that cSDH can be efficiently evacuated by a single burr-hole craniostomy, a less invasive and shorter surgical procedure with quite good clinical outcomes and a low rate of complications.

Ethics review of COVID-19 human challenge studies: A joint HRA/WHO workshop.

This report of a joint World Health Organization (WHO) and United Kingdom (UK) Health Research Authority (HRA) workshop discusses the ethics review of the first COVID-19 human challenge studies, undertaken in the midst of the pandemic. It reviews the early efforts of international and national institutions to define the ethical standards required for COVID-19 human challenge studies and create the frameworks to ensure rigorous and timely review of these studies. This report evaluates the utility of the WHO's international guidance document Key criteria for the ethical acceptability of COVID-19 human challenge studies (WHO Key Criteria) as a practical resource for the ethics review of COVID-19 human challenge studies. It also assesses the UK HRA's approach to these complex ethics reviews, including the formation of a Specialist Ad-Hoc Research Ethics Committee (REC) for COVID-19 Human Challenge Studies to review all current and future COVID-19 human challenge studies. In addition, the report outlines the reflections of REC members and researchers regarding the ethics review process of the first COVID-19 human challenge studies. Finally, it considers the potential ongoing scientific justification for COVID-19 human challenge studies, particularly in relation to next-generation vaccines and optimisation of vaccination schedules. Overall, there was broad agreement that the WHO Key Criteria represented an international consensus document that played a powerful role in setting norms and delineating the necessary conditions for the ethical acceptability of COVID-19 human challenge studies. Workshop members suggested that the WHO Key Criteria could be practically implemented to support researchers and ethics reviewers, including in the training of ethics committee members. In future, a wider audience may be engaged by the original document and potential additional materials, informed by the experiences of those involved in the first COVID-19 human challenge studies outlined in this document.

Mapeo de protocolos de investigación, publicaciones y colaboraciones sobre la COVID-19 en América Latina y el Caribe / Mapping of research protocols, publications, and collaborations on COVID-19 in Latin America and the Caribbean / Mapeamento de protocolos de pesquisa, publicações e colaborações sobre COVID-19 na América Latina e no Caribe

RESUMEN Objetivo. Mapear protocolos de investigación, publicaciones y colaboraciones sobre la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés) desarrollados en América Latina y el Caribe (ALC). Métodos. Se incluyeron protocolos registrados en plataformas internacionales y publicaciones de investigaciones que consideraron población, datos y autores de ALC. La fuente de información para los protocolos fue principalmente la Plataforma Internacional de Registro de Ensayos Clínicos (ICTRP, por su sigla en inglés) de la Organización Mundial de la Salud; para las publicaciones se utilizaron bases electrónicas y repositorios específicos sobre la COVID-19. Se realizaron búsquedas de las publicaciones hasta el 11 de noviembre y de los protocolos hasta el día 30 de noviembre de 2020, inclusive. La información de los protocolos se extrajo según variables estandarizadas de la plataforma ICTRP y la de las publicaciones, según criterios preestablecidos. Resultados. De los protocolos, 63,0% fueron estudios sobre terapias, 10% de prevención y 45% fueron colaborativos. Con respecto al financiamiento, 64% de los protocolos no provino de la industria. En cuanto a las publicaciones, 23% fueron sin revisión de pares y 23% fueron colaborativas. Los diseños más frecuentes fueron las revisiones sistemáticas y estudios de corte transversal; 47,1% fueron realizados en servicios de salud y 22% en el ámbito comunitario; 38,0% se enfocaron en el diagnóstico y 27,9% en el pronóstico. Se realizó una síntesis cualitativa según la línea de cuidado y las estrategias de abordaje. Conclusiones. Se observó un aumento del número de investigaciones colaborativas en comparación con estudios anteriores y de protocolos no financiados por la industria. La agenda de investigación propuesta se cubrió en gran parte conforme al avance de la pandemia.

ABSTRACT Objective. To map research protocols, publications, and collaborations on coronavirus disease 2019 (COVID-19) developed in Latin America and the Caribbean (LAC). Methods. Included were research protocols registered in international platforms and research publications containing populations, data, or authors from LAC. The source of information for protocols was primarily the International Clinical Trial Registry Platform (ICTRP) of the World Health Organization; for publications, specific electronic databases and repositories pertaining to COVID-19 were used. The search for publications was conducted up to 11 November; the search for protocols, up to 30 November 2020 (both dates inclusive). Data was extracted from protocols using standardized variables from the ICTRP, and from publications following pre-established criteria. Results. Among the protocols, 63.0% were therapeutic studies, 10% focused on prevention, and 45% were collaborative; 64% of the protocols received no funding from industry; 23% of the publications were not peer-reviewed and 23% were collaborative in nature. The most frequent study designs were systematic reviews and cross-sectional studies; 47.1% of studies were conducted in health facilities and 22% in community settings; 38.0% focused on diagnosis and 27.9% on prognosis. A qualitative synthesis was performed by line of care and approach strategies. Conclusions. There was an increase in the number of collaborative research studies relative to earlier studies and in protocols not funded by industry. The proposed research agenda was covered in large part as the pandemic unfolded.

RESUMO Objetivo. Mapear protocolos de pesquisa, publicações e colaborações sobre a doença causada pelo coronavírus 2019 (COVID-19, na sigla em inglês) desenvolvidos na América Latina e no Caribe (ALC). Métodos. Foram incluídos protocolos registrados em plataformas internacionais e publicações de pesquisas que consideraram população, dados e autores da ALC. A fonte de informação para os protocolos foi principalmente a Plataforma Internacional de Registros de Ensaios Clínicos (ICTRP, na sigla em inglês) da Organização Mundial da Saúde. Para as publicações, foram utilizadas bases de dados eletrônicas e repositórios específicos sobre COVID-19. As publicações foram pesquisadas até 11 de novembro, e os protocolos, até 30 de novembro de 2020 (inclusive). As informações dos protocolos foram extraídas de acordo com variáveis padronizadas da plataforma ICTRP e das publicações, segundo critérios pré-estabelecidos. Resultados. Dos protocolos, 63% eram estudos sobre terapias, 10% sobre prevenção e 45% eram colaborativos. Em relação ao financiamento, 64% dos protocolos não vieram da indústria. Em relação às publicações, 23% eram sem revisão por pares e 23% eram colaborativas. Os delineamentos mais frequentes foram revisões sistemáticas e estudos transversais; 47,1% foram realizados em serviços de saúde e 22% no âmbito comunitário; 38,0% focaram no diagnóstico e 27,9% no prognóstico. Realizou-se uma síntese qualitativa segundo a linha de cuidado e as estratégias de abordagem. Conclusões. Observou-se um aumento no número de pesquisas colaborativas (em comparação com estudos anteriores) e de protocolos não financiados pela indústria. A agenda de pesquisa proposta foi coberta, em grande parte, à medida que a pandemia progredia.

[The landscape of COVID-19 clinical trials in Latin America and the Caribbean: assessment and challenges]. / El panorama de los ensayos clínicos sobre COVID-19 en América Latina y el Caribe: evaluación y desafíos.

A considerable number of clinical trials is being conducted globally in response to the COVID-19 pandemic, including in low- and middle-income countries such as those in the Latin America and Caribbean region (LAC). Yet, an abundance of studies does not necessarily shorten the path to find safe and efficacious interventions for COVID-19. We analyze the trials for COVID-19 treatment and prevention that are registered from LAC countries in the International Clinical Trials Registry Platform, and identify a trend towards small repetitive non-rigorous studies that duplicate efforts and drain limited resources without producing meaningful conclusions on the safety and efficacy of the interventions being tested. We further assess the challenges to conducting scientifically sound and socially valuable research in the LAC region in order to inform recommendations to encourage clinical trials that are most likely to produce robust evidence during the pandemic.

Top five ethical lessons of COVID-19 that the world must learn.

As the world reflects upon one year since the first cases of coronavirus disease 2019 (COVID-19) and prepare for and experience surges in cases, it is important to identify the most crucial ethical issues that might lie ahead so that countries are able to plan accordingly. Some ethical issues are rather obvious to predict, such as the ethical issues surrounding the use of immunity certificates, contact tracing, and the fair allocation of vaccines globally. Yet, the most significant ethical challenge that the world must address in the next year and beyond is to ensure that we learn the ethical lessons of the first year of this pandemic. Learning from our collective experiences thus far constitutes our greatest moral obligation. Appreciating that decision-making in the context of a pandemic is constrained by unprecedented complexity and uncertainty, beginning in June 2020, an international group of 17 experts in bioethics spanning 15 countries (including low-, middle-, and high-income countries) met virtually to identify what we considered to be the most significant ethical challenges and accompanying lessons faced thus far in the COVID-19 pandemic. Once collected, the group met over the course of several virtual meetings to identify challenges and lessons that are analytically distinct in order to identify common ethical themes under which different challenges and lessons could be grouped. The result, described in this paper, is what this expert group consider to be the top five ethical lessons from the initial experience with COVID-19 that must be learned.

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response.

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely - and at times uniquely - affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group - a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy - in consultation with a variety of external experts and stakeholders.

Key criteria for the ethical acceptability of COVID-19 human challenge studies: Report of a WHO Working Group.

This report of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19 outlines ethical standards for COVID-19 challenge studies. It includes eight Key Criteria related to scientific justification, risk-benefit assessment, consultation and engagement, co-ordination of research, site selection, participant selection, expert review, and informed consent. The document aims to provide comprehensive guidance to scientists, research ethics committees, funders, policymakers, and regulators in deliberations regarding SARS-CoV-2 challenge studies by outlining criteria that would need to be satisfied in order for such studies to be ethically acceptable.