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Plant breeding plays a crucial role for the EU to live up to its values and promises of sustainability, innovation and diversity and inclusion. The current regulations, however, make it de facto impossible to use new breeding technologies.
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Diversidad Cultural , Fitomejoramiento , Unión Europea , Plantas Modificadas Genéticamente/genéticaRESUMEN
Earlier meetings laid the foundations for Controlled Human Infection Models (CHIMs), also known as human challenge studies and human infection studies, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on CHIM studies being conducted in endemic countries. Over the last ten years we have seen a vast expansion of the number of countries in Africa performing CHIM studies, as well as a growing number of different challenge organisms being used. Community and public engagement with assiduous ethical and regulatory oversight has been central to successful introductions and should be continued, in more community-led or community-driven models. Valuable initiatives for regulation of CHIMs have been undertaken but further capacity building remains essential.
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Many important questions in health professions education require datasets that are built from several sources, in some cases using data collected for a different purpose. In building and maintaining these datasets, project leaders will need to make decisions about the data. While such decisions are often construed as technical, there are several normative concerns, such as who should have access, how the data will be used, how products resulting from the data will be shared, and how to ensure privacy of the individuals the data is about is respected, etc. Establishing a framework for data governance can help project leaders in avoiding problems, related to such matters, that could limit what can be learned from the data or that might put the project (or future projects) at risk. In this paper, we highlight several normative challenges to be addressed when determining a data governance framework. Drawing from lessons in global health, we illustrate three kinds of normative challenges for projects that rely on data from multiple sources or involved partnerships across institutions or jurisdictions: (1) legal and regulatory requirements, (2) consent, and (3) equitable sharing and fair distribution.
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Bio-banking in research elicits numerous ethical issues related to informed consent, privacy and identifiability of samples, return of results, incidental findings, international data exchange, ownership of samples, and benefit sharing etc. In low and middle income (LMICs) countries the challenge of inadequate guidelines and regulations on the proper conduct of research compounds the ethical issues. In addition, failure to pay attention to underlying indigenous worldviews that ought to inform issues, practices and policies in Africa may exacerbate the situation. In this paper we discuss how the African context presents unique and outstanding cultural thought systems regarding the human body and biological materials that can be put into perspective in bio-bank research. We give the example of African ontology of nature presented by John Samwel Mbiti as foundational in adding value to the discourse about enhancing relevance of bio-bank research in the African context. We underline that cultural rites of passage performed on the human body in majority of communities in Africa elicit quintessential perspective on beliefs about handling of human body and human biological tissues. We conclude that acknowledgement and inclusion of African indigenous worldviews regarding the human body is essential in influencing best practices in biobank research in Africa.
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A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.
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Antituberculosos/farmacología , Interpretación Estadística de Datos , Farmacorresistencia Bacteriana Múltiple/genética , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Proteínas Bacterianas/genética , ADN Bacteriano/genética , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Fenotipo , Análisis de Secuencia de ADN , Revisiones Sistemáticas como Asunto , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
Continued progress in addressing challenges associated with detection and management of tuberculosis requires new diagnostic tools. These tools must be able to provide rapid and accurate information for detecting resistance to guide selection of the treatment regimen for each patient. To achieve this goal, globally representative genotypic, phenotypic, and clinical data are needed in a standardized and curated data platform. A global partnership of academic institutions, public health agencies, and nongovernmental organizations has been established to develop a tuberculosis relational sequencing data platform (ReSeqTB) that seeks to increase understanding of the genetic basis of resistance by correlating molecular data with results from drug susceptibility testing and, optimally, associated patient outcomes. These data will inform development of new diagnostics, facilitate clinical decision making, and improve surveillance for drug resistance. ReSeqTB offers an opportunity for collaboration to achieve improved patient outcomes and to advance efforts to prevent and control this devastating disease.
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ADN Bacteriano/genética , Bases de Datos de Ácidos Nucleicos , Cooperación Internacional , Mycobacterium tuberculosis/genética , Análisis de Secuencia de ADN , Antituberculosos , Farmacorresistencia Bacteriana/genética , Genotipo , Humanos , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/diagnósticoRESUMEN
BACKGROUND: In the current information age, the use of data has become essential for decision making in public health at the local, national, and global level. Despite a global commitment to the use and sharing of public health data, this can be challenging in reality. No systematic framework or global operational guidelines have been created for data sharing in public health. Barriers at different levels have limited data sharing but have only been anecdotally discussed or in the context of specific case studies. Incomplete systematic evidence on the scope and variety of these barriers has limited opportunities to maximize the value and use of public health data for science and policy. METHODS: We conducted a systematic literature review of potential barriers to public health data sharing. Documents that described barriers to sharing of routinely collected public health data were eligible for inclusion and reviewed independently by a team of experts. We grouped identified barriers in a taxonomy for a focused international dialogue on solutions. RESULTS: Twenty potential barriers were identified and classified in six categories: technical, motivational, economic, political, legal and ethical. The first three categories are deeply rooted in well-known challenges of health information systems for which structural solutions have yet to be found; the last three have solutions that lie in an international dialogue aimed at generating consensus on policies and instruments for data sharing. CONCLUSIONS: The simultaneous effect of multiple interacting barriers ranging from technical to intangible issues has greatly complicated advances in public health data sharing. A systematic framework of barriers to data sharing in public health will be essential to accelerate the use of valuable information for the global good.
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Barreras de Comunicación , Difusión de la Información , Salud Pública , Salud Global , HumanosRESUMEN
BACKGROUND: The generation of evidence is integral to the work of public health and health service providers. Traditionally, ethics has been addressed differently in research projects, compared with other forms of evidence generation, such as quality improvement, program evaluation, and surveillance, with review of non-research activities falling outside the purview of the research ethics board. However, the boundaries between research and these other evaluative activities are not distinct. Efforts to delineate a boundary - whether on grounds of primary purpose, temporality, underlying legal authority, departure from usual practice, or direct benefits to participants - have been unsatisfactory.Public Health Ontario has eschewed this distinction between research and other evaluative activities, choosing to adopt a common framework and process to guide ethical reflection on all public health evaluative projects throughout their lifecycle - from initial planning through to knowledge exchange. DISCUSSION: The Public Health Ontario framework was developed by a working group of public health and ethics professionals and scholars, in consultation with individuals representing a wide range of public health roles. The first part of the framework interprets the existing Canadian research ethics policy statement (commonly known as the TCPS 2) through a public health lens. The second part consists of ten questions that guide the investigator in the application of the core ethical principles to public health initiatives.The framework is intended for use by those designing and executing public health evaluations, as well as those charged with ethics review of projects. The goal is to move toward a culture of ethical integrity among investigators, reviewers and decision-makers, rather than mere compliance with rules. The framework is consonant with the perspective of the learning organization and is generalizable to other public health organizations, to health services organizations, and beyond. SUMMARY: Public Health Ontario has developed an ethics framework that is applicable to any evidence-generating activity, regardless of whether it is labelled research. While developed in a public health context, it is readily adaptable to other health services organizations and beyond.
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Bioética , Investigación Biomédica/ética , Revisión Ética , Obligaciones Morales , Evaluación de Programas y Proyectos de Salud , Salud Pública/ética , Canadá , Humanos , Ontario , Proyectos de Investigación , InvestigadoresRESUMEN
Although several countries have adopted a single-dose human papillomavirus (HPV) vaccination strategy, many other countries continue to include multiple doses in their vaccination programmes. There are ethical reasons to transition to a single-dose strategy. We discuss how a single-dose HPV vaccination strategy advances equity in three dimensions: vaccine equity, health equity, and gender equity. Adopting a single-dose strategy eases pressure on vaccine supply, lowers programme costs, and is easier to distribute. This change facilitates vaccine procurement and implementation programmes (contributing to vaccine equity) and reaching hard to reach people or populations (contributing to health equity). A lower number of cases of HPV-related diseases that stem from greater vaccine distribution reduces the burden on women, who are at a higher risk of HPV-related disease or who act as caregivers, which prevents them from accessing opportunities that contribute to their empowerment (contributing to gender equity). Thus, pursuing the single-dose HPV vaccination programme strategy is ethically desirable.
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Gene drive technology has been recognized for its potential to provide durable and cost-effective solutions for previously intractable problems in public health, conservation, and agriculture. In recognition of the rapid advances in this field, in 2016 the U.S. National Academies of Sciences, Engineering, and Medicine issued a report making several recommendations aimed at researchers, funders, and policymakers for the safe and responsible research and development of gene drive technology. Subsequently, in 2017 sixteen global organizations self-identifying as sponsors and supporters of gene drive research became public signatories committed to the 'Principles for Gene Drive Research' which were inspired by the report's recommendations. Herein we reflect on the progress of gene drive research in relation to the ethical principles laid out and committed to by the signatories to the Principles. Our analysis indicates high levels of alignment with the Principles in the field of gene drive research. The manuscript also discusses the Gene Drive Research Forum, which had its genesis in the publication of the Principles. Discussions between participants at the latest meeting of the Forum point to the work that lies ahead for gene drive research in line with the Principles. Going forward the gene drive research community can productively focus on: i) safety and efficacy criteria for open release, ii) risk assessment frameworks and methods, iii) more downstream technical, regulatory and policy considerations for field evaluations and implementation, iv) continued transparency and developing mechanisms of accountability, and v) strengthening capacity in locales of potential release and expected drive spread.
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Tecnología de Genética Dirigida , Humanos , Tecnología de Genética Dirigida/métodos , Investigación Biomédica/éticaRESUMEN
Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come. The development and licensing of an affordable, accessible therapeutic HPV vaccine, designed to clear or control carcinogenic HPV and/or to induce regression precancer could significantly contribute to the elimination efforts, particularly benefiting those who missed out on the prophylactic vaccine. One barrier to development of such vaccines is clarity around the regulatory pathway for licensure. In Washington, D.C. on September 12-13, 2023, a meeting was convened to provide input and guidance on trial design with associated ethical and regulatory considerations. This report summarizes the discussion and conclusions from the meeting. Expert presentation topics included the current state of research, potential regulatory challenges, WHO preferred product characteristics, modeling results of impact of vaccine implementation, epidemiology and natural history of HPV infection, immune responses related to viral clearance and/or precancer regression including potential biomarkers, and ethical considerations. Panel discussions were held to explore specific trial design recommendations to support the licensure process for two vaccine indications: (1) treatment of prevalent HPV infection or (2) treatment of cervical precancers. Discussion covered inclusion/exclusion criteria, study endpoints, sample size and power, safety, study length, and additional data needed, which are reported here. Further research of HPV natural history is needed to address identified gaps in regulatory guidance, especially for therapeutic vaccines intended to treat existing HPV infections.
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Addressing global health crises requires a receptive and expedient policy environment to minimise delays in making available potentially life-saving technologies. Over time, the policy environment has adapted to ensure that communities have expedited access to promising technologies, such as vaccines, that can mitigate morbidity and mortality. Emergency authorisations are one such policy mechanism. While these have been employed successfully for several diseases, such as influenza, Ebola and COVID-19, the policy mechanism is tied to contexts where key bodies have designated the disease an 'emergency', whereas no equivalent mechanism exists for those failing to acquire the designation (eg, malaria and tuberculosis). In this paper, we examine ethical issues associated with emergency authorisations. We argue that there is no moral difference between those diseases considered emergencies and many that fail to be designated as such with respect to impact on affected communities. Thus, tying access to an expedient policy mechanism for approval to an emergency designation is ethically unjustified-it should be based on considerations of risks and benefits, the disease burden and the values of the communities that carry those risks and not contingent on if the disease is designated an emergency. We suggest the need to further enhance the policy environment to ensure access to similar expedited approval programmes irrespective of if a disease is an emergency. Levelling the field for access to expedited approval programmes across diseases can help in moving towards achieving global health equity but is not a panacea.
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Equidad en Salud , Fiebre Hemorrágica Ebola , Contramedidas Médicas , Vacunas , Humanos , Salud GlobalRESUMEN
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.
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COVID-19 , Revisión Ética , COVID-19/prevención & control , Comités de Ética en Investigación , Humanos , Pandemias/prevención & control , Organización Mundial de la SaludRESUMEN
BACKGROUND: Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries. DISCUSSION: To a considerable extent, the failure to adequately engage host communities, the opacity of informed consent, and the lack of fair benefit-sharing have played a significant role in eroding trust. These ethical considerations are central to biomedical research in low to middle income countries and failure to attend to them can inadvertently contribute to exploitation and erode trust. A 'tissue trust' may be a plausible means for enabling access to human tissues for research in a manner that is responsive to the ethical challenges considered. SUMMARY: Preventing exploitation and restoring trust while simultaneously promoting global health research calls for innovative approaches to human tissues research. A tissue trust can reduce the risk of exploitation and promote host capacity as a key benefit.
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Investigación Biomédica/ética , Investigación Participativa Basada en la Comunidad , Países en Desarrollo , Consentimiento Informado , Bancos de Tejidos , Investigación Participativa Basada en la Comunidad/ética , Humanos , Consentimiento Informado/ética , Bancos de Tejidos/ética , ConfianzaRESUMEN
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.
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Investigación Biomédica/ética , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Experimentación Humana/ética , Consentimiento Informado/ética , SARS-CoV-2/patogenicidad , Antivirales/administración & dosificación , COVID-19/inmunología , COVID-19/virología , Comités de Ética en Investigación/organización & administración , Voluntarios Sanos , Experimentación Humana/legislación & jurisprudencia , Humanos , Selección de Paciente/ética , SARS-CoV-2/efectos de los fármacos , Vacunación/ética , Organización Mundial de la Salud , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: The amount of research utilizing health information has increased dramatically over the last ten years. Many institutions have extensive biobank holdings collected over a number of years for clinical and teaching purposes, but are uncertain as to the proper circumstances in which to permit research uses of these samples. Research Ethics Boards (REBs) in Canada and elsewhere in the world are grappling with these issues, but lack clear guidance regarding their role in the creation of and access to registries and biobanks. METHODS: Chairs of 34 REBS and/or REB Administrators affiliated with Faculties of Medicine in Canadian universities were interviewed. Interviews consisted of structured questions dealing with diabetes-related scenarios, with open-ended responses and probing for rationales. The two scenarios involved the development of a diabetes registry using clinical encounter data across several physicians' practices, and the addition of biological samples to the registry to create a biobank. RESULTS: There was a wide range of responses given for the questions raised in the scenarios, indicating a lack of clarity about the role of REBs in registries and biobanks. With respect to the creation of a registry, a minority of sites felt that consent was not required for the information to be entered into the registry. Whether patient consent was required for information to be entered into the registry and the duration for which the consent would be operative differed across sites. With respect to the creation of a biobank linked to the registry, a majority of sites viewed biobank information as qualitatively different from other types of personal health information. All respondents agreed that patient consent was needed for blood samples to be placed in the biobank but the duration of consent again varied. CONCLUSION: Participants were more attuned to issues surrounding biobanks as compared to registries and demonstrated a higher level of concern regarding biobanks. As registries and biobanks expand, there is a need for critical analysis of suitable roles for REBs and subsequent guidance on these topics. The authors conclude by recommending REB participation in the creation of registries and biobanks and the eventual drafting of comprehensive legislation.
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Investigación Biomédica/ética , Comités de Ética en Investigación , Sistema de Registros/ética , Bancos de Tejidos/ética , Canadá , Factores de Confusión Epidemiológicos , Ética en Investigación , Humanos , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.