Research in rapidly evolving policy contexts can lead to the following ethical challenges for sponsors and researchers: the study’s standard of care can become different than what patients outside the study receive, there may be political or other pressure to move ahead with unproven interventions, and new findings or revised policies may decrease the relevance of ongoing studies. These ethical challenges are considerable, but not unprecedented. In this article, we review the case of a multinational, randomized, controlled perinatal HIV prevention trial, the “PROMISE” (Promoting Maternal Infant Survival Everywhere) study. PROMISE compared the relative efficacy and safety of interventions to prevent mother to child transmission of HIV. The sponsor engaged an independent international ethics panel to address controversy about the study’s standard of care and relevance as national and international guidelines changed. This ethics panel concluded that continuing the PROMISE trial as designed was ethically permissible because: (1) participants in all arms received interventions that were effective, and there was insufficient evidence about whether one intervention was more effective or safer than the other, and (2) data from PROMISE could be useful for a diverse range of stakeholders. In general, trials designed to inform rapidly evolving policy issues should develop mechanisms to revisit social value while recognizing that the value of research varies for diverse stakeholders with legitimate reasons to weigh evidence differently. We conclude by providing four reasons that trials may depart from the standard of care after a change in policy, while remaining ethically justifiable, and by suggesting how to improve existing trial oversight mechanisms to address evolving social value.

在快速发展的政策背景下进行的研究可能会给申办者和研究人员带来以下伦理挑战：研究的护理标准可能与研究之外的患者接受的不同，可能存在政治或其他压力来推进未经证实的干预措施，以及新的调查结果或修订后的政策可能会降低正在进行的研究的相关性。这些道德挑战是相当大的，但并非史无前例。在本文中，我们回顾了一项跨国、随机、对照围产期 HIV 预防试验的案例，即“PROMISE”（促进母婴生存无处不在）研究。PROMISE 比较了预防母婴传播 HIV 的干预措施的相对有效性和安全性。随着国家和国际指南的变化，申办者聘请了一个独立的国际伦理小组来解决有关该研究的护理标准和相关性的争议。该伦理小组的结论是，按照设计继续进行 PROMISE 试验在伦理上是允许的，因为：(1) 所有组的参与者都接受了有效的干预，并且没有足够的证据表明一种干预是否比另一种更有效或更安全，以及 (2 ) 来自 PROMISE 的数据可能对各种利益相关者有用。一般而言，旨在为快速发展的政策问题提供信息的试验应制定重新审视社会价值的机制，同时认识到研究的价值因不同利益相关者而异，有正当理由对证据进行不同的权衡。