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Three pillars support the current system for protecting the rights and interests of human subjects in research: responsible investigators and funders, oversight by Institutional Review Boards (IRBs), and informed consent. However, experience using this system of pillars and changes in the research enterprise suggest that the current system is inadequate. For example, investigators and funders may face conflicts of interests that can challenge their fiduciary obligations to participants; some empirical information suggests that IRBs may not be functioning in a uniform and optimum manner; and data indicate that informed consent needs improvement. Given these problems, a variety of solutions have been offered, including disclosing conflicts of interests to potential research subjects, centralizing and accrediting IRBs, and abbreviating consent documents. Nevertheless, since it is unclear whether these measures work, efforts should be taken to test them in controlled settings before making major policy changes.