OBJECTIVES: The FDA Guidance on the development and use of Patient Reported Outcome (PRO) instruments emphasizes the need to establish content validity for the concepts addressed by the PRO items.  Content validity is the relationship between an instrument’s content and the construct it intends to measure. This paper presents eight key points of criteria for supporting evidences of content validity for PRO instruments. METHODS: Language is the primary means of patient recognition and expression of concepts.  Concept relevance is assessed by qualitative analysis. A Concept Elicitation process is used to describe the relationship between concepts and patient experience. Patient comprehension of a concept is evaluated through cognitive interviews.  The design of interviews and treatment of results must focus on specific criteria in order to support content validity of the PRO. RESULTS: The eight key criteria required to support PRO content validity are:  (1) concepts are relevant to the patient experience with their condition; (2) qualitative data collection has been conducted to the point of “saturation of concept” (3) concepts are presented in the language of the patients; (4) the appropriate aspect of the concept is being evaluated; (5) the presentation of the concept in a PRO can be properly comprehended by patients; (6) response options are meaningful and clear; (7) the recall period is appropriate to the patient experience of their condition; and (8)  the concepts and language used in the PRO are adaptable for use in global trials. This paper presents examples of data collection, and documentation for each criterion. CONCLUSIONS: Evidences of content validity are can only be provided by qualitative data. The qualitative interview process may vary in specific methods but should adhere to consistent objectives, and should cover at least eight key evidences in order to provide adequate support for content validity of a PRO.