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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.

Summary 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.

Over recent years, the research community has been increasingly using preprint servers to share manuscripts that are not yet peer-reviewed.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manuscripts should be prominent on their first page, and each page should include a red watermark stating ‘Caution—Not Peer Reviewed’; (c) pre-print authors should certify that their manuscript will be submitted to a peer-review journal, and should regularly update the manuscript status; (d)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.

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.

Adaptive Clinical Trials (ACT) differ from conventional clinical trials because they permit continual modifications to key components of trial design during the trial. ACTs have grown in prevalence in recent years, with Adaptive Platform Trials (APTs), in particular, having demonstrated their significant scientific, clinical, and public health utility in relation to the COVID-19 pandemic. There has been a steady increase in the number of regulations and guidelines aimed at guiding the conduct of clinical trials. However, despite the potential of APTs to expedite the testing of new interventions in emergency situations, there is a relative dearth of published literature on why and how such trials should be governed. This work attempts to address this knowledge gap.

While Adaptive Clinical Trials (ACTs) have grown in prevalence, prominence, and impact, the ethical issues implicit in such trial designs, particularly in the context of public health emergencies, have been afforded relatively scant attention. This work argues that the ethical dimensions of ACTs should be considered at trial conception, factored into the trial’s design, and subject to ongoing evaluation during the trial’s conduct.

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.

Jerome Amir Singh's affiliation was erroneously given as: Centre for Medical Ethics and Law, Stellenbosch University, Stellenbosch, South Africa. Thecorrect affiliation is: School of Law, Howard College, University of KwaZulu-Natal, Durban, South Africa. The error appears in the Discussion Document by Adams et al. [https://doi.org/10.17159/sajs.2021/10933] on Page 1 under Affiliations (no. 22) and on Page 11 in the table under Authors' information, as well as in the accompanying Commentary by Adams et al. [https://doi.org/10.17159/sajs.2021/10935] in Table 1 on Page 3.

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.

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.

Artificial Intelligence (AI) offers unprecedented opportunities and challenges for humanity. If AI can be positioned and leveraged correctly, it can rapidly accelerate progress on achieving the United Nations’ Sustainable Development Goals (SDGs), including SDG #3: ‘Ensure healthy lives and promote wellbeing for all at all ages’. Achieving this goal could have a transformative impact on global health. An ethical, transparent and responsible approach to AI development will result in AI translating data into contextually relevant knowledge, conclusions, and impactful actions.

The POPIA Code of Conduct for Research, as it is currently being considered, pertains to research conducted in South Africa, which, as part of the research process, uses personal information as defined under POPIA. This Discussion Document outlines the main areas relating to the processing of personal information for research purposes which the proposed Code will address, including what consent models would be permissible under POPIA; the issues in relation to genetic research and the processing of personal information contained in inherited characteristics; the use of information matching programmes by researchers; and the use of personal information obtained from social media platforms for research. With ongoing and wide consultation with the scientific community in South Africa and all relevant stakeholders, it is hoped that the Code will provide guidance in supporting the lawful and responsible use of personal information while conducting scientific research in South Africa. The purpose and scope of the Code of Conduct for Research are set out in the accompanying Commentary available at https://doi.org/10.17159/sajs.2021/10935

Summary box As a growing number of vaccines for COVID-19 gain emergency use designation, including emergency use authorisation and conditional marketing authorisation under different jurisdictions, the WHO Strategic Advisory Group of Experts on Immunization (SAGE)1 has issued a number of …

This discussion paper addresses the safety of HIV cure studies, particularly those involving stopping antiretroviral therapy, known as an analytic treatment interruption (ATI) in the context of the SARS-CoV-2 pandemic. More than 30 studies listed on ClinicalTrials.gov include an ATI and many others were planned to begin over the next 12 months but most were halted due to the COVID-19 pandemic. We consider the ethics, risks and practical considerations to be taken into account before re-opening HIV cure clinical trials, noting the specific risks of ATI in the context of circulating SARS-CoV-2.

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.

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., African sites should be central to COVID-19 vaccine trial site mapping. Such an approach is in the interests of public health, scientifically responsible, and realizes key ethics values.

Less than 3 months after the World Health Organization (WHO) declared COVID-19 a Public Health Emergency of International Concern, and within a month of the WHO declaring COVID19 a global pandemic, COVID-19 infections and fatalities have grown exponentially, globally. Now, more than ever, the world needs responsible political leadership, evidence-based decision-making, and co-ordinated global health action.

Since community transmission of COVID-19 became established in South Africa, individuals who test positive for COVID-19 and who do not require hospitalisation have been permitted to self-isolate in their homes to reduce the burden on the health system. The Premier of KwaZulu-Natal Province has since announced that self-isolation will no longer be permitted in the province. Instead, mandatory isolation in state-designated isolation sites would apply. This policy change marks a dangerous departure from the country's prevailing position on home-based self-isolation and should not be replicated elsewhere.

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.بينما كانت الحكومات تركز على الاضطراب غير المسبوق في الاقتصاد العالمي والذي نتج عن مرض فيروس كورونا 2019 (كوفيد-19)، والحاجة الملحة للأبحاث حول كوفيد-19، تأثرت الأبحاث الصحية الأخرى نتيجة للوباء. كما تقلصت بشكل كبير عمليات البحث الرئيسية غير المتعلقة بكوفيد-19، أو توقفت بشكل تام نظراً للقيود القانونية، أو المخاوف اللوجستية أو التشغيلية، أو تلك الخاصة بفرق العمل، والمتعلقة بكوفيد-19. يقع مليارات الأشخاص حول العالم حالياً تحت تأثير عمليات الإغلاق أو حظر التجول. نظراً لأن النطاق الزمني لمثل هذه التدابير التقييدية غير معروف، كما أنه عُرضة للتغيير، فإن العديد من الدراسات أصبحت الآن في غياهب النسيان، كما أن عشرات الآلاف من المشاركين في الدراسة معرضين للخطر. طرحت هذه الظروف تحديات أخلاقية معقدة تستحق الاهتمام العاجل من الرعاة والباحثين والمراقبين الدوليين. قامت جهات راعية وجهات رقابية معينة بنشر توجيهات حول كيفية إدارة الاضطرابات في الأبحاث السريرية، والمتعلقة بكوفيد-19. على الرغم من أن هذه التوجيهات توفر نقطة انطلاق جيدة لاستعراض تحديات الوباء المتزايدة، إلا أنها تنطبق فقط على الباحثين الممولين من جانب هذه الهيئات، أو الخاضعين لإدارتها. نحن نقدم هنا توجيهات حول إدارة مثل هذه الاضطرابات التي تسري خارج إطار هذه الظروف المحددة. نحن نسلط الضوء على بعض آثار وباء كوفيد-19 على المشاريع البحثية الجارية الأخرى، والتي لا علاقة لها بكوفيد-19، كما نقدم إرشادات عملية حول كيفية إدارة رفاهية المشاركين في الدراسة. نحن نستنتج أنه يجب على واضعي السياسات والرعاة والباحثين والمراقبين انتهاج أسلوب أكثر مرونة لضمان سلامة المشاركين، إلى جانب الحفاظ على تكامل البيانات والالتزام بالممارسات السريرية الجيدة.由于各国政府一直在关注 2019 冠状病毒病（新型冠状病毒肺炎）对全球经济造成的前所未有的破坏，以及对新型冠状病毒肺炎研究的迫切需求，因此导致其他健康研究成为这场大流行下的牺牲品。与新型冠状病毒肺炎无关的重大研究活动要么因为新冠肺炎相关的法律限制，要么出于后勤、人员配备或运营方面的考虑，都被大幅减少或完全暂停。目前全球有数十亿人受到封城或宵禁的影响。由于这种限制性措施的时间范围尚不清楚，而且随时可能会变化，许多研究现在处于停滞状态，数万名研究参与者的福利得不到保障。这些情况引起了复杂的道德挑战，急需国际赞助商、研究人员和监管机构的高度关注。某些赞助商和监管机构已经发布了关于如何管理由新型冠状病毒肺炎导致的临床研究中断事件的指导方针。虽然这些指导方针为应对不断演变的大流行带来的挑战提供了一个很好的起点，但它们只适用于由这些机构资助或管理的研究人员。在本文中，我们提供了管理此类中断事件的指导方针，这些指导方针不止适用于上述特定状况。我们强调了新型冠状病毒肺炎大流行对其他正在进行的与新型冠状病毒肺炎无关的研究项目造成的影响，并就如何管理受影响的研究参与者的福利提供了实用指导。我们的结论是，政策制定者、赞助商、研究人员和监管机构必须采取更灵活的方法，以确保参与者的安全，同时保持数据完整性，并遵守药品临床管理规范。.В то время как внимание правительств стран приковано к беспрецедентной дестабилизации мировой экономики, вызванной коронавирусным заболеванием 2019 года (COVID-19), и к насущной необходимости проведения исследований вируса COVID-19, другие научные исследования в области здравоохранения отошли на второй план из-за пандемии. Крупные научные исследования, не связанные с COVID-19, были значительно сокращены или полностью приостановлены по причине связанных с COVID-19 правовых ограничений или в результате проблем с логистикой, отсутствия специалистов или по соображениям, связанным с текущей деятельностью. Миллиарды людей во всем мире в настоящее время страдают от введенных режимов самоизоляции или комендантского часа. Поскольку сроки таких ограничительных мер неизвестны и могут изменяться, многие исследования в настоящее время находятся в состоянии неопределенности, а благополучие десятков тысяч участников исследований находится под угрозой. Данные обстоятельства привели к возникновению сложных этических проблем, требующих неотложного внимания со стороны международных спонсоров, исследователей и регулирующих государственных органов. Некоторые спонсоры и регулирующие государственные органы опубликовали рекомендации по управлению непредвиденными изменениями в ходе клинических исследований, вызванными COVID-19. Несмотря на то что такие рекомендации являются отличной отправной точкой для решения проблем, связанных с распространением пандемии, они полезны только тем исследователям, которые финансируются или контролируются этими органами. Авторы приводят руководящие принципы по управлению такими непредвиденными изменениями, которые могут применяться к более широкому набору конкретных условий и обстоятельств. Авторы перечисляют некоторые из последствий пандемии COVID-19 для других текущих исследовательских проектов, не связанных с COVID-19, и дают практические рекомендации по управлению благополучием затронутых участников исследований. Авторы приходят к выводу о том, что органы, отвечающие за формирование политики, спонсоры, исследователи и регулирующие государственные органы должны применять более гибкий подход для обеспечения безопасности участников, сохраняя при этом целостность данных и соблюдая передовые клинические практики.

South Africa’s Children’s Act 38 of 2005 requires health professionals to determine whether a child possesses ‘sufficient maturity’ and ‘mental capacity’ to make decisions about themselves in relation to surgery, treatment, and HIV testing. Similarly, the National Health Act 61 of 2003 requires a child to be ‘capable of understanding’ to provide informed consent in research. However, neither the Children’s Act nor the National Health Act defines these terms. Moreover, there is no common definition of ‘sufficient maturity’ among healthcare professionals in South Africa. Appreciating how foreign law interprets ‘mental capacity’ and how different healthcare professionals evaluate ‘maturity’ could prove illuminative in respect to how these terms could be interpreted by health professionals in South Africa, and elsewhere.

Background The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene drive constructs to reduce or suppress mosquito populations to levels that do not support disease transmission. Despite this prospect, social resistance to genetically modified organisms remains high. Gene drive open field research thus raises important questions regarding what is owed to those who may not consent to such research, or those could be affected by the proposed research, but whose consent is not solicited. The precise circumstances under which informed consent must be obtained, and from whom, requires careful consideration. Furthermore, appropriate engagement processes should be central to any introduction of genetically modified mosquitos in proposed target settings. Discussion In this work, international guidance documents on informed consent and engagement are reviewed and applied to the genetically modified mosquito research context. Five analogous research endeavours that involve area-wide / open field experiments are reviewed. The approach of each in respect to the solicitation of individual informed consent and community engagement are highlighted. Conclusions While the solicitation of individual informed consent in host settings of gene drive field trials may not be possible or feasible in some instances, local community and stakeholder engagement will be key to building trust towards the proposed conduct of such research. In this regard, the approaches taken by investigators and sponsors of political science field research and weather modification field research should be avoided. Rather, proponents of gene drive field research should look to the Eliminate Dengue field trials, cluster randomised trials, and pragmatic clinical trials for guidance regarding how the solicitation of individual informed consent of host communities ought to be managed, and how these communities ought to be engaged.

These recommendations on practices for stakeholder engagement build on the knowledge and experience of practitioners and subject-matter experts from a large variety of fields. They aim to provide teams involved in the development of area-wide vector control methods with guidance on how to design community and stakeholder engagement programmes as part of their development pathway. Area-wide vector control methods are not new in concept [1]. For example, the use of natural predators for biocontrol of agricultural pests or public intervention for the treatment of water bodies with larvicides are current area-wide applications. Thus, new approaches under development—such as those using sterile-male techniques, Wolbachia, or gene drive—can build upon well-established development pathways. These methods offer the benefit of providing vector control for all inhabitants of a specific treated area without individual or group biases related to economic means, level of education, etc. Although this benefit can be a great advantage, multiperson or community-applied interventions may not offer individuals the chance to ‘opt out’ of a home or area receiving the intervention [2]. There may be aspects of the research in which individuals can choose to participate or not (for example, during the collection of mosquitoes or other insects from houses), but the research or technique developed will, at some stage, require the deployment of the tools in selected sites, and residents of those sites may not be able to ‘opt out’ of these phases in the same way that individuals can decline to be part of a vaccine field trial. Therefore, although these methods may differ greatly in scope and impact, the processes for their development and use share commonalities that provide a basis for asserting a broadly applicable framework for engagement. The framework set out below attempts to leverage these commonalities to provide a starting point that may be useful to a very wide variety of projects working in this field while retaining sufficient flexibility to be tailored as appropriate to local circumstances Some methods, such as gene drives and environmentally persistent Wolbachia methods, involve modifications to vector species that could persist and disseminate through a population over time and space. This means that the scale of the human communities affected can be quite large fairly early on in the development process and may persist or increase over time. Thus, testing of area-wide vector control methods does not conform to the familiar clinical trial model employing individual informed consent [3], and a different set of research ethics considerations is required. Trial authorisation by the hosting community and, potentially, peripheral communities that may be affected may be necessary. Therefore, identification of key stakeholders and community representatives is vital, and early and ongoing engagement with them is essential. This type of engagement can enable the sharing of knowledge, experience, and perceptions between the project and its stakeholders to help ensure that the pathways for development respond to the expectations of communities and other stakeholders, that the tools developed are ultimately effective and appropriate and meet the needs and preferences of users and other potential beneficiaries, and that accountability is established for trial outcomes and eventual disease mitigation. The recommendations may serve not only for projects involved in the development of new area-wide vector control methods but also as a benchmark to shape the expectations of a wider range of stakeholders, including project funders, communities, the media, and policy makers and regulators, about what projects will and should deliver. More broadly, shared recommendations can help facilitate the alignment of approaches of different projects and provide a clear pathway for other projects entering the field. These recommendations also describe ways in which projects can engage with stakeholders to meet other requirements for their research, including community acceptance for specific activities or phases of the research that may be necessary for the research to be able to proceed. However, the ability to implement these recommendations hinges on the availability of appropriate funding. Many of the suggested activities and approaches will be resource intensive. Therefore, funders are encouraged to make adequate supplies available for stakeholder engagement at every stage of the development process.