Critical care units present some unique challenges to the researcher, especially when the research topic of interest is related to end-of-life care. The purpose of this article is to address some of the methodological and practical issues related to conducting end-of-life research in the critical care setting. Recruitment barriers include gaining access to a clinical site, gaining access to patients, and prognostic uncertainty. Additional barriers include challenges related to informed consent, data collection, the research team, and ethical considerations. Strategies are described that can be used to guide researchers to conduct end-of-life research successfully in critical care.

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