To analyze the ethical challenges dealing with clinical research, we carried out a systematic review of the literature and qualitative research, determining facilitators, barriers, and ethical paradigms perceived by Chilean clinical researchers. Through the analysis of the literature, we identified the main ethical challenges involved "in" clinical research (hic et nunc) and those that arise "from" clinical research itself (ex post). Semi-structured interviews showed four critical knots

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... ed with clinical research (founding, legislation, multi-center research, and the relationship with regulatory entities), together with facilitating aspects and barriers when implementing researches.