Research and clinical care without informed consent

研究：我的研究集中在三个主要领域：1）儿科研究;和2）研究中的风险/效益评估。 1.儿科研究：我系统地评估了现有的儿科研究指南，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。 美国法规评估儿科研究的风险与日常生活的风险相比。然而，我们收集的数据显示，这一标准在某些情况下有可能使儿童面临过度风险。为了解决这一问题，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的风险进行比较，这些风险在旨在造福他人的活动中被认为是适合儿童的。该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/获益评估：目前，IRB依靠直觉评估研究风险。然而，大量的数据表明，直观的评价受到系统性偏见。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）比较不同类型的风险。这种方法导致了第一个经验数据，即IRB对儿科研究的风险进行了错误分类。 我和一位同事进一步开发了SERR，让IRB能够比较研究风险与日常生活风险的可能性和程度。目前的工作包括与Denny Porter（NICHD）及其团队合作，使用SERR来确定腰椎穿刺是否构成最小或大于最小风险。我们也开始致力于一个简化SERR方法的项目，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，当风险是合理的潜在的直接利益。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，IRB不应该允许研究的一个组成部分的潜在利益抵消或证明另一个组成部分的风险。在这种方法下，接受正在测试的干预的潜在益处不能证明研究中其他程序或干预的风险是合理的。我组织了一个伦理圆桌会议的情况下，发表在儿科，批判性地评估这种方法。在这篇文章中，我认为实验性治疗的潜在益处可以证明管理它所需的干预措施的风险，确保其安全性或评估其有效性。 大多数关注保护研究中的弱势参与者的重点是尽量减少风险。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，参与者的入组是否可以接受取决于入组的潜在益处是否与风险相称。是否如此不仅取决于风险的程度，还取决于入组是否以及在多大程度上为参与者提供了潜在的临床获益。第二，除了保护研究参与者免受风险之外，保护他们免受剥削也很重要。这一点很重要，因为剥削是参与者面临的风险和其他人从他们的参与中获益的程度的函数。这表明，关注参与者获得的潜在利益也是适当保护他们的核心。

Research: My research has focused on three primary areas: 1) Pediatric research; and 2) Risk/benefit evaluation in research. 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.