Research and clinical care with individuals unable to consent

调研：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/获益评估; 3）无行为能力患者的决策。 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。 我进行了第一次关于父母和孩子对非有益儿科研究的看法的调查。这项研究提供了支持非有益的研究，发现受访者愿意让孩子参加慈善活动的研究。 最低风险标准通常被理解为建立一个风险阈值。然而，根据青少年能够自己做决定的经验数据，我认为有两个风险阈值，一个是年幼的孩子，一个是年长的孩子。 和一个研究员，我评估了与国家病房研究的规定。这项分析确定了一些保障措施，以更好地保护这些特别脆弱的个人。 我和一位同事一起，对受试者的条件要求进行了第一次系统评估，这引起了大量的混乱。这一分析表明，这一要求允许迄今为止被排除在外的群体参加。 一些评论家认为，为了他人的利益而使儿童面临研究风险是不道德的。这一观点得到了美国法院的支持，可能会阻止改善儿科临床护理的重要尝试。作为回应，我发表了第一篇关于非有益儿科研究的全面论证。 2.临床研究中的风险/获益评估：目前，IRB仅使用直觉评估研究风险。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IRB错误地分类了儿科研究的风险。 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。自从它发表以来，两个最大的临床研究小组，西方IRB和昆泰，都对使用这种方法感兴趣。 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。我们进行了一项分析，发现现有的对直接益处的解释过于狭隘，并支持一种阻碍适当研究的风险较小的解释。 3.无行为能力的个人的决策：虽然目前强调尊重个人自主权尊重有能力的成年人，但它对治疗无行为能力的成年人构成了一个重大的困境。我在这一领域的工作主要集中在评估对代理人的依赖如何促进决策目标的实现和开发改进的方法。 在之前的系统性综述中，我们表明，代理人无法促进提供与患者偏好一致的治疗的目标。作为回应，我描述并捍卫了一种新的方法，患者偏好预测器，它根据相似个体的偏好预测给定患者想要的治疗， 我们刚刚完成了有史以来最大的关于代理决策的调查之一。这项对近1200名患者的调查是有史以来第一次收集关于患者自己优先考虑替代决策目标的系统数据。它还将提供关于患者偏好预测的患者态度的经验数据。 许多人认为，对代理人的依赖促进了帮助家庭的目标。为了评估这一说法，我和一位研究员完成了第一次对无行为能力患者做出治疗决定的影响进行系统评价。这项审查发现，做出这些决定对许多代理人构成了重大负担。这些数据强调需要考虑新的方法来做出这些决定。

Research: My research has focused on three primary areas: 1) Pediatric research; 2) Risk/benefit evaluation in research; and 3) Decision making for incapacitated patients. 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. I conducted the first survey of the views of parents and children regarding non-beneficial pediatric research. This study provides support non-beneficial research, finding that respondents were as willing to have the children participate in research as charitable activities. The minimal risk standard typically is understood as establishing one risk threshold. However, based on empirical data that teenagers are able to make their own decisions, I argued for two risk thresholds, one for younger children and a somewhat higher one for older children. With a fellow, I evaluated the regulations for research with wards of the state. This analysis identified several safeguards to better protect these especially vulnerable individuals. With a colleague, I conducted the first systematic evaluation of the subjects condition requirement which has caused a good deal of confusion. This analysis reveals that the requirement allows the enrollment of groups that to date have been excluded. A number of commentators argue that it is unethical to expose children to research risks for the benefit of others. This view, which has been supported by U.S. courts, could halt vital attempts to improve pediatric clinical care. In response, I published the first comprehensive justification for non-beneficial pediatric research. 2. Risk/Benefit Evaluation in Clinical Research: Currently, IRBs evaluate the risks of research using only 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, I developed a method (SERR) for comparing risks of different types. This method led to the first empirical data that IRBs are miscategorizing 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. Since it was published, I have been contacted by two of the largest clinical research groups, Western IRB and Quintiles, who are interested in using the approach. Most regulations allow vulnerable individuals to be enrolled in riskier research only when the risks are justified by the potential for direct benefit. We conducted an analysis which reveals that existing interpretations of direct benefits are overly narrow and supports an interpretation which has less risk of blocking appropriate research. 3. Decision making for incapacitated individuals: While current emphasis on respecting individual autonomy respects competent adults, it poses a significant dilemma for treating incapacitated adults. My work in this area has focused on evaluating how well reliance on surrogates promotes the goals of decision making and developing improved methods. In a prior systematic review, we showed that surrogates are not able to promote the goal of providing treatment consistent with patient preferences. In response, I described and defended a new approach, the Patient Preference Predictor, which predicts which treatments a given patient would want based on the preferences of similar individuals, We just completed one of the largest surveys ever conducted on surrogate decision making. This survey of almost 1200 patients was the first ever to gather systematic data on patients own priorities regarding the goals for surrogate decision making. It also will provide empirical data on patients attitudes regarding the Patient Preference Predictor. Many argue that reliance on surrogates promotes the goal of helping the family. To evaluate this claim, a fellow and I completed the first systematic review of the impact of making treatment decisions for incapacitated patients. This review found that making these decisions poses a significant burden on many surrogates. These data underscore the need to consider new methods to make these decisions.