We are gratified that our paper generated long overdue discussion about the crisis in local IRB function. We hope that the recommendations from the National Bioethics Advisory Commission on human subjects protection and IRB function (1) will promote further discussion and bring about meaningful changes. The Commission clearly recognized the impossible demands on local IRBs in the present system, and their recommendations should improve protection of patient safety while decreasing the inefficiencies in the present system. The Herculean efforts of Dr. Siegel and colleagues to track and interpret the onslaught of adverse event reports from multicenter trials fulfill current reporting requirements but are very unlikely to add to patient safety. The regulations should be changed to clearly place the responsibility for evaluating adverse event reports from multicenter trials on the data center and the data and safety monitoring board.

Dr. Sugar states that our proposals would improve the efficiency of the IRB system but do nothing to improve the protection of research subjects. We counter that these two aspects are closely linked and that improved efficiency is essential if we are to better protect subjects' safety. We agree with his concerns that many consent forms do not effectively communicate with prospective participants (2) and that some of the most worrisome lapses have been in the process of obtaining informed consent (3). However, we suspect that most local IRBs cannot even consider enhanced oversight of informed consent discussions because they are scrambling to keep up with the flood of paperwork from multicenter trials. Ineffective regulations must be eliminated so that local IRBs have the time to monitor the process of obtaining informed consent. Finally, Dr. Sugar appears to propose that IRB members personally obtain informed consent from research participants, a task we believe impossible.

Dr. Nagy-Agren suggests that the resources of local IRBs are monopolized by industry-sponsored trials that do not significantly advance the science of medical care. While we agree that research involving "me too" agents is not revolutionary, we do not dismiss this research, nor would we suggest that central IRBs become the arbiters of clinical relevance. "Me too" agents may not revolutionize medical science, but they do provide the competition that can result in less expensive treatments. Institutional review boards are charged with evaluating whether the risks to participants in a clinical trial are reasonable, not with determining whether the trial's hypothesis is revolutionary.