Department of Philosophy, Oakland University, Rochester, MI, USA.
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA; Center for Bioethics and Social Sciences in Medicine, University of Michigan, Ann Arbor, MI, USA.
Vaccine. 2023 Feb 24;41(9):1584-1588. doi: 10.1016/j.vaccine.2023.01.055. Epub 2023 Jan 27.
In the development of new vaccines, many trials use age de-escalation: after establishing safety and efficacy in adult populations, progressively younger cohorts are enrolled and studied. Age de-escalation promotes many values. The responsibility to protect children from potential risks of experimental vaccines is significant, not only given increased risks of adverse effects but also because parents and medical professionals have a moral responsibility to protect children from harms associated with novel, uncertain interventions. Further, given that young children cannot provide informed consent, acceptable risks for research requiring proxy consent are lower than for adults making decisions for themselves. Although age de-escalation approaches are widely used in vaccine trials, including notably in the recent development of pediatric COVID-19 vaccines, ethicists have not addressed the benefits and risks of these approaches. Their benefits are largely assumed and unstated, while their potential risks are usually overlooked. There are no official ethics guidelines for the use of age de-escalation in clinical research. In this paper, we provide a systematic account of key moral factors to consider when employing age de-escalation. Analyzing pediatric COVID-19 vaccine development as our key case study, we clarify the benefits, risks, and trade-offs involved in age de-escalation approaches and call for the development of evidence-based best practice guidelines to identify when age de-escalation is likely to be an ethical strategy in vaccine development.
在新疫苗的开发中，许多试验采用年龄降阶策略：在成人人群中确立安全性和有效性后，逐渐纳入和研究更年轻的队列。年龄降阶策略促进了许多价值。保护儿童免受实验疫苗潜在风险的责任重大，不仅因为儿童面临更高的不良反应风险，还因为父母和医疗专业人员有道德责任保护儿童免受与新的、不确定的干预措施相关的伤害。此外，由于幼儿无法提供知情同意，需要代理同意的研究的可接受风险低于成年人自行做出决定的风险。尽管年龄降阶方法在疫苗试验中被广泛应用，包括在最近开发儿科 COVID-19 疫苗方面，伦理学家尚未讨论这些方法的益处和风险。它们的益处在很大程度上是假设的，没有明确说明，而它们的潜在风险通常被忽视。在临床研究中使用年龄降阶方法没有官方的伦理准则。在本文中，我们提供了一个系统的论述，说明在采用年龄降阶方法时需要考虑的关键道德因素。我们将儿科 COVID-19 疫苗开发作为我们的关键案例研究，阐明了年龄降阶方法所涉及的益处、风险和权衡，并呼吁制定基于证据的最佳实践指南，以确定在疫苗开发中年龄降阶策略何时可能成为一种伦理策略。
