Research and clinical care without informed consent

Clinical Center

Investigators

Linked publications & trials

Abstract

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.