The Granting of Emergency Use Designation to COVID-19 Candidate Vaccines : Implications for COVID-19 Vaccine Trials

An efficacious COVID-19 vaccine is currently the world's leading research priority. Several nations have indicated that if there is a compelling case for use of a vaccine before it is licensed, they would be prepared to authorise its emergency use or conditional approval on public health grounds. As of Dec 1, 2020, several developers of leading COVID-19 candidate vaccines have indicated that they have applied, or intend to apply, for emergency authorisation for their vaccines. Should candidate vaccines attain emergency use designation and be programmatically deployed before their phase 3 trials conclude, such a strategy could have far reaching consequences for COVID-19 vaccine research and the effective control of the COVID-19 pandemic. These issues merit careful consideration.

WHO guidance on COVID-19 vaccine trial designs in the context of authorized COVID-19 vaccines and expanding global access: Ethical considerations.

While the degree of COVID-19 vaccine accessibility and uptake varies at both national and global levels, increasing vaccination coverage raises questions regarding the standard of prevention that ought to apply to different settings where COVID-19 vaccine trials are hosted. A WHO Expert Group has developed guidance on the ethical implications of conducting placebo-controlled trials in the context of expanding global COVID-19 vaccine coverage. The guidance also considers alternative trial designs to placebo controlled trials in the context of prototype vaccines, modified vaccines, and next generation vaccines.

Governing the Access to COVID-19 Tools Accelerator: towards greater participation, transparency, and accountability.

The Access to COVID-19 Tools Accelerator (ACT-A) is a multistakeholder initiative quickly constructed in the early months of the COVID-19 pandemic to respond to a catastrophic breakdown in global cooperation. ACT-A is now the largest international effort to achieve equitable access to COVID-19 health technologies, and its governance is a matter of broad public importance. We traced the evolution of ACT-A's governance through publicly available documents and analysed it against three principles embedded in the founding mission statement of ACT-A: participation, transparency, and accountability. We found three challenges to realising these principles. First, the roles of the various organisations in ACT-A decision making are unclear, obscuring who might be accountable to whom and for what. Second, the absence of a clearly defined decision making body; ACT-A instead has multiple centres of legally binding decision making and uneven arrangements for information transparency, inhibiting meaningful participation. Third, the nearly indiscernible role of governments in ACT-A, raising key questions about political legitimacy and channels for public accountability. With global public health and billions in public funding at stake, short-term improvements to governance arrangements can and should now be made. Efforts to strengthen pandemic preparedness for the future require attention to ethical, legitimate arrangements for governance.

Ending the evidence gap for pregnancy, HIV and co-infections: ethics guidance from the PHASES project.

INTRODUCTION: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co-infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy-specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next-generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co-infections research. DISCUSSION: The 26-member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics-centred guidance for advancing timely, responsible HIV/co-infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug-related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post-approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co-infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. CONCLUSIONS: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for - and the promise of - advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and wellbeing of pregnant people and their children.

Preprints in times of COVID19: the time is ripe for agreeing on terminology and good practices.

Over recent years, the research community has been increasingly using preprint servers to share manuscripts that are not yet peer-reviewed. Even if it enables quick dissemination of research findings, this practice raises several challenges in publication ethics and integrity. In particular, preprints have become an important source of information for stakeholders interested in COVID19 research developments, including traditional media, social media, and policy makers. Despite caveats about their nature, many users can still confuse pre-prints with peer-reviewed manuscripts. If unconfirmed but already widely shared first-draft results later prove wrong or misinterpreted, it can be very difficult to "unlearn" what we thought was true. Complexity further increases if unconfirmed findings have been used to inform guidelines. To help achieve a balance between early access to research findings and its negative consequences, we formulated five recommendations: (a) consensus should be sought on a term clearer than 'pre-print', such as 'Unrefereed manuscript', "Manuscript awaiting peer review" or ''Non-reviewed manuscript"; (b) Caveats about unrefereed manuscripts should be prominent on their first page, and each page should include a red watermark stating 'Caution-Not Peer Reviewed'; (c) pre-print authors should certify that their manuscript will be submitted to a peer-review journal, and should regularly update the manuscript status; (d) high level consultations should be convened, to formulate clear principles and policies for the publication and dissemination of non-peer reviewed research results; (e) in the longer term, an international initiative to certify servers that comply with good practices could be envisaged.

The impact of the COVID-19 pandemic response on other health research.

While governments have been focusing on the unprecedented disruption to the global economy caused by coronavirus disease 2019 (COVID-19) and the urgent need for COVID-19 research, other health research has become a casualty of the pandemic. Major research operations that are unrelated to COVID-19 have been significantly diminished or suspended entirely because of either COVID-19-related legal restrictions or logistical, staffing or operational concerns. Billions of people globally are currently affected by lockdowns or curfews. Since the timescale of such restrictive measures is unknown and subject to change, many studies are now in limbo and the welfare of tens of thousands of study participants is at risk. These circumstances have introduced complex ethical challenges that merit urgent attention from international sponsors, researchers and regulators. Certain sponsors and regulators have published guidelines on how the COVID-19-related disruptions to clinical research should be managed. Although these guidelines provide a good starting point in navigating the challenges of the evolving pandemic, they only apply to those researchers funded or governed by these bodies. Here, we provide guidelines on managing such disruptions that apply beyond these specific settings. We highlight some of the effects of the COVID-19 pandemic on other ongoing research projects that are unrelated to COVID-19 and provide practical guidance on how the welfare of affected study participants should be managed. We conclude that policy-makers, sponsors, researchers and regulators must adopt a more flexible approach to ensure participant safety, while maintaining data integrity and complying with good clinical practices.

Pendant que les gouvernements se concentrent sur les profonds bouleversements que la maladie à coronavirus 2019 (COVID-19) engendre pour l'économie mondiale ainsi que sur l'urgence des recherches qui y sont consacrées, d'autres études sont touchées de plein fouet par la pandémie. Plusieurs travaux de recherche d'importance majeure, sans lien avec la COVID-19, ont considérablement ralenti ou ont été totalement interrompus. Soit en raison des restrictions légales relatives à la COVID-19, soit à cause de problèmes logistiques, opérationnels ou d'effectifs. En ce moment, des milliards de personnes à travers le monde sont soumises à un confinement ou un couvre-feu. Comme la durée de telles mesures restrictives est inconnue et susceptible de changer, de nombreuses études sont actuellement en suspens et le bien-être de dizaines de milliers de participants est menacé. Ces circonstances particulières ont entraîné des défis éthiques complexes, qui requièrent une attention immédiate de la part des promoteurs, chercheurs et organismes de réglementation internationaux. Certains promoteurs et organismes de réglementation ont publié des directives sur la manière de gérer les interruptions de recherches cliniques dues à la COVID-19. Elles offrent un bon point de départ pour négocier les écueils au fil de l'évolution de la pandémie, mais elles ne s'appliquent qu'aux chercheurs financés ou administrés par ces instances. Dans le présent document, nous proposons donc des directives destinées à mieux gérer de telles interruptions, au-delà de ce cadre spécifique. Nous soulignons quelques-uns des effets de la pandémie de COVID-19 sur d'autres projets de recherche en cours qui n'ont aucun rapport avec la maladie, et nous donnons des conseils pratiques sur la manière de garantir le bien-être des participants aux études concernées. Enfin, nous parvenons à la conclusion que les législateurs, promoteurs, chercheurs et organismes de réglementation doivent adopter une approche plus souple, afin d'assurer la sécurité des participants tout en préservant l'intégrité des données et en respectant les bonnes pratiques cliniques.

Mientras que los gobiernos se han centrado en la perturbación sin precedentes de la economía global que la enfermedad del coronavirus 2019 (COVID-19) ha causado y en la urgente necesidad de investigar sobre esta enfermedad, otras investigaciones sanitarias se han convertido en víctimas de la pandemia. Las principales actividades de investigación que no están relacionadas con la COVID-19 se han reducido de manera significativa o se han suspendido por completo debido a las restricciones legales relacionadas con la COVID-19 o a los problemas logísticos, de personal u operativos. En la actualidad, el confinamiento o los toques de queda afectan a miles de millones de personas en todo el mundo. Muchos estudios se encuentran ahora en el limbo y el bienestar de decenas de miles de sus participantes está en peligro debido a que se desconoce el calendario de esas medidas restrictivas y está sujeto a cambios. Estas circunstancias han planteado desafíos éticos complejos que merecen una atención urgente por parte de los patrocinadores, los investigadores y los organismos reguladores internacionales. Algunos patrocinadores y organismos reguladores han publicado pautas sobre cómo se deben gestionar las perturbaciones relacionadas con la COVID-19 en la investigación clínica. Aunque estas pautas constituyen un buen punto de partida para hacer frente a los desafíos de la pandemia que está evolucionando, solo se aplican a los investigadores que son financiados o gestionados por estos organismos. En este documento, se ofrecen pautas para gestionar esas perturbaciones que se extienden más allá de estos entornos específicos. Se resaltan algunos de los efectos de la pandemia de la COVID-19 en otros proyectos de investigación en curso que no están relacionados con esta enfermedad y se proporcionan pautas prácticas sobre cómo se debe gestionar el bienestar de los participantes afectados en el estudio. Se concluye que los responsables de formular las políticas, los patrocinadores, los investigadores y los organismos reguladores deben adoptar un enfoque más flexible para garantizar la seguridad de los participantes, al tiempo que se mantiene la integridad de los datos y se cumplen las buenas prácticas clínicas.

COVID-19 therapeutics: how to sow confusion and break public trust during international public health emergencies.

Since SARS-CoV2 was declared a Public Health Emergency of International Concern, those tasked with the stewardship of public health at a global, regional, and local level-policymakers, politicians, scientists, drug regulators, health officials, professional associations, journal editors, publishers, and clinicians-have displayed rushed decisions and lapses in judgment in their handling of chloroquine and hydroxychloroquine as potential COVID-19 therapeutics and prophylactics. These lapses merit noting as they hold lessons for how the guardians of medicines regulation and public health can inadvertently sow confusion and damage public trust.

The Case for Why Africa Should Host COVID-19 Candidate Vaccine Trials.

In response to provocative comments by 2 European clinicians and scientists, the World Health Organization Director General has declared that Africa will not host COVID-19 vaccine trials. Such a stance risks stigmatizing COVID-19 vaccine trials in Africa and depriving Africa of critical research. To the contrary, there is a critical need for Africa to host COVID-19 vaccine trials on public health, scientific, and ethics grounds.