Research and clinical care with individuals unable to consent

研究：我的研究集中在三个主要领域：1)儿科研究；2)研究中的风险/收益评估；3)欺骗 1.儿科研究：我系统地评估了儿科研究的现有指南，并试图描述现有要求不能提供足够保护或有可能阻碍适当研究的替代方案。 美国的法规将儿科研究的风险与日常生活的风险进行比较。然而，我们收集的数据显示，在某些情况下，这一标准有可能使儿童面临过度风险。为了解决这一关切，我制定并捍卫了慈善参与标准，根据该标准，儿科研究的风险应与日常生活中被认为适合儿童在旨在造福他人的活动中的风险进行比较。这一标准提供了一种保护儿童免受过度风险的方法。 2.临床研究中的风险/收益评估：目前，IRBs依靠直觉来评估研究的风险。然而，大量数据显示，直观的评估容易受到系统性偏差的影响。为了更好地保护研究对象，我一直在开发一种评估研究风险的系统方法。 认识到研究和日常生活的风险是不同类型的，我们开发了一种方法(SERR)来比较不同类型的风险。这种方法导致了第一个经验数据，即IRBs错误地对儿科研究的风险进行了分类。 我和一位同事进一步开发了SERR，使IRBs能够将研究风险的可能性和大小与日常生活的风险进行比较。目前的工作包括与Denny Porter(NICHD)和他的团队合作，使用SERR来确定腰椎穿刺术造成的风险是最小还是更高。我们还开始着手一个项目，以简化SERR方法，最终目标是使其基于计算机。 大多数法规只允许脆弱的个人参加风险更高的研究，只有当风险被直接受益的可能性证明是合理的时。这种方法提出了一个问题，即哪些潜在的好处可以证明研究的风险是合理的。现有的方法支持所谓的“一揽子交易的谬误”。这种方法认为，研究所不应允许研究的一个组成部分的潜在益处抵消或证明另一个组成部分带来的风险是合理的。在这种方法下，接受接受测试的干预措施的潜在好处不能证明研究中其他程序或干预措施的风险是合理的。我组织了一个伦理巡回案例，发表在《儿科学》上，对这种方法进行了批判性的评估。在书中，我认为试验性治疗的潜在好处可以证明实施治疗、确保其安全性或评估其有效性所需的干预措施的风险是合理的。 在研究中，大多数关注保护脆弱参与者的重点是将风险降至最低。我认为，这种方法虽然重要，但在两个方面是不够的。首先，在许多情况下，参与者的注册是否可接受取决于注册的潜在好处是否值得冒风险。情况是否如此不仅取决于风险的程度，还取决于登记是否以及在多大程度上为参与者提供了潜在的临床益处。其次，除了保护研究参与者免受风险外，保护他们免受剥削也很重要。这一点很重要，因为剥削既是参与者面临的风险的函数，也是其他人从他们的参与中受益的程度的函数。这表明，关注参与者获得的潜在好处也是适当保护他们的核心。 3.欺骗：在总体风险大于最低限度的研究中，通常禁止使用欺骗。这种方法防止研究人员使用欺骗手段来隐瞒重大风险，或在研究的目的、潜在利益或与决定是否接受此类风险相关的其他方面欺骗参与者。然而，这种方法也错误地阻碍了适当的研究。特别是，它防止研究人员在风险大于最小风险的研究中使用欺骗手段，即使参与者被准确地告知了研究的风险和与是否参与的决定相关的其他方面。我认为，当整体研究构成的风险大于最小风险时，政策应该禁止欺骗，而不是在研究中哪些参与者被欺骗的方面构成大于最小风险的情况下禁止欺骗。这种方法为参与者提供了相同水平的保护，同时允许进行更多的研究。

Research: My research has focused on three primary areas: 1) Pediatric research; 2) Risk/benefit evaluation in research; and 3) Deception 1. Pediatric research: I have systematically evaluated the existing guidelines for pediatric research, and attempted to describe alternatives where existing requirements do not provide sufficient protection, or have the potential to block appropriate research. The U.S. regulations evaluate the risks of pediatric research in comparison to the risks of daily life. However, data we collected reveal that this standard has the potential to expose children to excessive risks in some cases. To address this concern, I have developed and defended the charitable participation standard, according to which the risks of pediatric research should be compared to the risks in daily life that are considered appropriate for children in the context of activities designed to benefit others. This standard offers a way to protect children from being exposed to excessive risks. 2. Risk/Benefit Evaluation in Clinical Research: Currently, IRBs evaluate the risks of research by relying on their intuition. Yet, extensive data reveal that intuitive evaluation is subject to systematic biases. To better protect research subjects, I have been developing a systematic method for evaluating research risks. Recognizing that the risks of research and daily life are of different types, we developed a method (SERR) for comparing risks of different types. This method led to the first empirical data that IRBs are mis-categorizing the risks of pediatric studies. With a fellow, I further developed SERR to allow IRBs to compare the likelihood and magnitude of the risks of research to the risks of daily life. Current work involves collaborating with Denny Porter (NICHD) and his group to use SERR to determine whether lumbar puncture poses minimal or greater than minimal risk. We are also beginning to work on a project to simplify the SERR method with the ultimate goal of making it computer based. Most regulations allow vulnerable individuals to be enrolled in riskier research only when the risks are justified by the potential for direct benefit. This approach raises the question of which potential benefits can justify the risks of research. The existing approach endorses what is called the "Fallacy of the Package Deal." This approach maintains that IRBs should not allow the potential benefits from one component of the research to offset or justify the risks presented by another. Under this approach, the potential benefits of receiving the intervention being tested cannot justify the risks of other procedures or interventions in the study. I organized an Ethics Rounds case which was published in Pediatrics which critically evaluates this approach. In it, I argue that the potential benefits of experimental treatments can justify the risks of interventions that are needed to administer it, ensure its safety, or assess its efficacy. Most of the focus on protecting vulnerable participants in research focuses on minimizing risks. I have argued that this approach, while important, is insufficient in two ways. First, in many cases, whether enrollment of participants is acceptable depends on whether the potential benefits of enrollment justify the risks. Whether this is the case depends, not just on the extent of the risks, but also whether and to what extent enrollment offers participants the potential for clinical benefit. Second, in addition to protecting research participants from risks, it is also important to protect them from exploitation. This is important because exploitation is a function of both the risks to participants and also the extent to which others benefit from their involvement. This suggests that attention to the potential benefits that participants receive is also central to appropriately protecting them. 3. Deception: The use of deception is typically prohibited in studies that pose greater than minimal risk overall. This approach prevents researchers from using deception to conceal significant risks or to deceive participants about the purpose, potential benefits, or other aspects of a study that are relevant to deciding whether to accept such risks. Yet this approach also mistakenly blocks appropriate research. In particular, it keeps researchers from using deception in studies that pose greater than minimal risk, even when participants are informed accurately about the risks and other aspects of the study that are relevant to deciding whether to participate. Rather than prohibiting deception when the overall study poses greater than minimal risk, I have argued that policies should prohibit deception when the aspect of the study about which participants are deceived poses greater than minimal risk. This approach offers the same level of protection to participants while permitting more research.