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 for non-beneficial research, finding that respondents were as willing to have the children participate in research as charitable activities, when the risks were specified as constant across the two domains. 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 have 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 and subsequently defended the proposal against criticisms that it fails to justify the enrollment of children in studies that are prospectively valuable, but end up being valueless or harmful. 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, I 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. 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. We are currently working on a project to simplify and expand the SERR approach, with the ultimate goal of developing a computer based version. 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 support an interpretation which has less potential to block appropriate research. The standard approach to evaluating the risks of research is guided by what is called the Fallacy of the Package Deal. Specifically, 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 to be published in Pediatrics which critically evaluates the 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. 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 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 provides empirical data on patients' attitudes regarding the Patient Preference Predictor, finding that the majority of patients supports its use as either informational or as a weak default. In current research, we are expanding on this work by evaluating surrogates' views 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.
