OBJECTIVES: The linguistic validation and cognitive debriefing of PROs are now well documented and routinely used within the pharmaceutical industry to ensure that the translated instruments are conceptually equivalent to their sources.  Increasingly, new adjustments are being developed to further customize these processes according to the special needs of the instrument and target culture.  This paper seeks to enumerate the challenges faced when debriefing questionnaires of an embarrassing, and potentially offensive, nature and recommends the use of a specialized methodology to make respondents more comfortable during this process. METHODS: To establish guidelines for debriefing PROs of a sensitive nature, subject feedback from previous ED questionnaire debriefing reports was examined.  The subjects that expressed the most discomfort during the debriefing process resided in India, Africa, and the Middle East. Additionally, older subjects and subjects with lower levels of education were more likely to express reservations.  For this study, we collaborated with translators from each of these regions to determine a list of measures that can be taken to help ensure that subjects feel comfortable enough to provide reliable feedback within the interview setting. RESULTS: The goal of any cognitive debriefing session is to adequately test the translated questionnaire while maintaining the cultural sensitivities of the target country.  Recommended considerations include:  assigning an interviewer of the same sex as the subject, performing a specialized training session with interviewers that reviews subjects' boundaries and strategies for effective probing, sending subjects an introductory note that emphasizes confidentiality prior to the interview, conducting interviews via telephone rather than in-person, and debriefing questionnaires via a web-based device. CONCLUSIONS: For some cultures, cognitively debriefing PRO questionnaires of a sensitive nature places added burden on respondents.  Evidence suggests that additional considerations should be exercised during debriefing to respect subjects’ cultural boundaries.