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.

Ethics, climate change and health - a landscape review.

Anthropogenic climate change is unequivocal, and many of its physical health impacts have been identified, although further research is required into the mental health and wellbeing effects of climate change. There is a lack of understanding of the importance of ethics in policy-responses to health and climate change which is also linked to the lack of specific action-guiding ethical resources for researchers and practitioners. There is a marked paucity of ethically-informed health input into economic policy-responses to climate change-an area of important future work. The interaction between health, climate change and ethics is technically and theoretically complex and work in this area is fragmentary, unfocussed, and underdeveloped. Research and reflection on climate and health is fragmented and plagued by disciplinary silos and exponentially increasing literature means that the field cannot be synthesised using conventional methods. Reviewing the literature in these fields is therefore methodologically challenging. Although many of the normative challenges in responding to climate change have been identified, available theoretical approaches are insufficiently robust, and this may be linked to the lack of action-guiding support for practitioners. There is a lack of ethical reflection on research into climate change responses. Low-HDI (Human Development Index) countries are under-represented in research and publication both in the health-impacts of climate change, and normative reflection on health and climate change policy. There is a noticeable lack of ethical commentary on a range of key topics in the environmental health literature including population, pollution, transport, energy, food, and water use. Serious work is required to synthesise the principles governing policy responses to health and climate change, particularly in relation to value conflicts between the human and non-human world and the challenges presented by questions of intergenerational justice.

Ethical research when abortion access is legally restricted.

Risks and benefits of some clinical research may be altered.

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.

Ethical implications of economic compensation for voluntary medical male circumcision for HIV prevention and epidemic control.

Despite tremendous efforts in fighting HIV over the last decades, the estimated annual number of new infections is still a staggering 1.5 million. There is evidence that voluntary medical male circumcision (VMMC) provides protection against men's heterosexual acquisition of HIV-1 infection. Despite good progress, most countries implementing VMMC for HIV prevention programmes are challenged to reach VMMC coverage rates of 90%. Particularly for men older than 25 years, a low uptake has been reported. Consequently, there is a need to identify, study and implement interventions that could increase the uptake of VMMC. Loss of income and incurred transportation costs have been reported as major barriers to uptake of VMMC. In response, it has been suggested to use economic compensation in order to increase VMMC uptake. In this discussion paper, we present and review relevant arguments and concerns to inform decision-makers about the ethical implications of using economic compensation, and to provide a comprehensive basis for policy and project-related discussions and decisions.

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.

SARS-CoV-2 Variants and Vaccines.

Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.

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.

High incidence and persistence of hepatitis B virus infection in individuals receiving HIV care in KwaZulu-Natal, South Africa.

BACKGROUND: Hepatitis B virus (HBV), Human Immunodeficiency virus (HIV) and Tuberculosis (TB) are common infections in South Africa. We utilized the opportunity of care provision for HIV-TB co-infected patients to better understand the relationship between these coinfections, determine the magnitude of the problem, and identify risk factors for HBV infection in HIV infected patients with and without TB in KwaZulu-Natal, South Africa. METHODS: This retrospective cohort analysis was undertaken in 2018. In-care HIV infected patients were included in the analysis. Results from clinical records were analysed to determine the prevalence, incidence, persistence and factors associated with HBsAg positivity in HIV-infected patients with or without TB co-infection. RESULTS: A total of 4292 HIV-infected patients with a mean age of 34.7 years (SD: 8.8) were included. Based on HBsAg positivity, the prevalence of HBV was 8.5% (363/4292) [95% confidence interval (CI): 7.7-9.3] at baseline and 9.4% (95%CI: 8.6-10.3%) at end of follow-up. The HBV incidence rate was 2.1/100 person-years (p-y). Risk of incident HBV infection was two-fold higher among male patients (HR 2.11; 95% CI: 1.14-3.92), while severe immunosuppression was associated with a greater than two-fold higher risk of persistent infection (adjusted risk ratio (RR) 2.54; 95% CI 1.06-6.14; p = 0.004. Additionally, active TB at enrolment was associated with a two-fold higher risk of incident HBV infection (aHR 2.38; 95% CI: 0.77-7.35). CONCLUSION: The provision of HIV care and treatment in high HBV burden settings provide a missed opportunity for HBV screening, immunization and care provision.