Ever since the emergence of the coronavirus disease 2019 (COVID-19), global public health infrastructures and systems, along with community-wide collaboration and service, have risen to an unprecedented challenge. Vaccine development was immediately propelled to the centre of all our scientific, public health and community efforts. Despite the development of SARS-CoV-2 vaccines arguably being the greatest and most palpable achievements of the past 12 months, they have also been one of the most contentious and debated issues during the pandemic. However, what uniquely differentiates vaccine development is its intimate relationship with the community it seeks to serve; both in its clinical trial testing as an efficacious and safe prophylactic, and its post-developmental ‘roll-out’ success, as an effective public health tool. These relationships have birthed a myriad of complexities, from community-based mistrust, to academically contended ethical dilemmas. Indeed, the accelerated advances in the COVID-19 vaccine race have further exacerbated this phenomenon, bringing with it new ethical dilemmas that need to be examined to ensure the continued clinical success of these therapeutics and a renewed societal trust in clinical medicine. In this paper, we discuss two major ethical dilemmas: (1) the equipoise of continuing new vaccine trials in the advent of successful candidates and (2) the maleficence of blinded placebo arms. Accordingly, we discuss six different potential approaches to these ethical dilemmas: (1) continuing with placebo-controlled trials, (2) transitioning from placebo-controlled to open-label, (3) unblinding at-risk priority groups only, (4) transitioning to a blinded stepped-wedge cross-over design, (5) progressing to a blinded active-controlled stepped-wedge cross-over trial, and (6) conducting randomised stepped-wedge community trials. We also propose a decision-making algorithm for relevant stakeholders in advanced stages of vaccine trials. It is important to remember that the emergent nature of the COVID-19 situation does not justify a compromise on core ethical values. In fact, the discourse surrounding this topic and the decisions made will remain a potent case study and a continuously referenced example for all such future scenarios.

中文翻译：

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大流行期间的疫苗试验：解决道德困境的潜在方法

自2019年冠状病毒病（COVID-19）出现以来，全球公共卫生基础设施和系统以及社区范围内的协作和服务面临着前所未有的挑战。疫苗开发立即成为我们所有科学、公共卫生和社区努力的中心。尽管 SARS-CoV-2 疫苗的开发可以说是过去 12 个月中最伟大、最明显的成就，但它们也是大流行期间最有争议和争论的问题之一。然而，疫苗开发的独特之处在于它与其所服务的社区的密切关系。无论是作为一种有效且安全的预防剂的临床试验测试，还是作为一种有效的公共卫生工具的开发后“推广”成功。这些关系带来了无数的复杂性，从社区的不信任到学术上争论的道德困境。事实上，COVID-19 疫苗竞赛的加速进展进一步加剧了这一现象，带来了新的伦理困境，需要进行审查，以确保这些疗法在临床上持续取得成功，并重新获得社会对临床医学的信任。在本文中，我们讨论了两个主要的伦理困境：（1）成功候选疫苗出现后继续进行新疫苗试验的平衡；（2）盲目安慰剂组的危害。因此，我们讨论了解决这些道德困境的六种不同的潜在方法：（1）继续安慰剂对照试验，（2）从安慰剂对照过渡到开放标签，（3）仅对高危优先群体进行揭盲，（4）过渡到盲法阶梯楔形交叉试验，(5) 进行盲法主动对照阶梯楔形交叉试验，(6) 进行随机阶梯楔形社区试验。我们还为疫苗试验后期的相关利益相关者提出了一种决策算法。重要的是要记住，新冠肺炎 (COVID-19) 疫情的突发性质并不意味着我们有必要在核心道德价值观上做出妥协。事实上，围绕这一主题的讨论和做出的决定将仍然是一个有效的案例研究，并为所有此类未来场景不断引用的例子。