This guidance outlines how the FDA evaluates patient-reported outcome (PRO) instruments used as effectiveness endpoints in clinical trials. It provides guidance on how sponsors can develop and use study results measured by PRO instruments to support claims in approved product labeling. The guidance does not address the use of PRO instruments for purposes beyond evaluating claims made about a drug or medical product in its labeling. By addressing the review issues identified in this guidance, sponsors can increase the efficiency of their endpoint discussions with the FDA during the product development process, streamline the FDA's review of PRO endpoint adequacy, and provide optimal information about the patient's perspective of treatment benefit at the time of product approval. A PRO is a measurement of any aspect of a patient's health status that comes directly from the patient, without interpretation by a physician or anyone else. In clinical trials, a PRO instrument can be used to measure the impact of an intervention on one or more aspects of patients' health status, referred to as PRO concepts. These concepts range from the purely symptomatic (e.g., response of a headache) to more complex concepts (e.g., ability to carry out activities of daily living), to extremely complex concepts such as quality of life, which is a multidomain concept with physical, psychological, and social components. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient perspective. For this data to be meaningful, there should be evidence that the PRO instrument effectively measures the particular concept that is studied. The guidance defines many terms used in this document. The term "instrument" refers to the actual questions or items contained in a questionnaire or interview schedule along with all the additional information and documentation that supports the use of these items in producing a PRO measure. The term "conceptual framework" refers to how items are grouped according to subconcepts or domains. The FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance documents describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The guidance discusses the use of PRO instruments in medical product development, including the reasons for using them, the types of PRO instruments, and the evaluation of their measurement properties. It also outlines the steps involved in the development of PRO instruments, including the identification of concepts and domains, the creation of the instrument, the assessment of measurement properties, and the modification of existing instruments. The guidance emphasizes the importance of ensuring that PRO instruments are appropriate and adequate to support the study objectives, and that they are validated to measure the intended concepts. The guidance also discusses the challenges of developing PRO instruments for specific populations, such as children and patients with cognitive impairment, and the importance of considering these factors when developing and validating PRO instruments. The guidance concludes with a discussion of study design considerations, including the importance of blinding and randomization in clinical trials involving PRO instruments.This guidance outlines how the FDA evaluates patient-reported outcome (PRO) instruments used as effectiveness endpoints in clinical trials. It provides guidance on how sponsors can develop and use study results measured by PRO instruments to support claims in approved product labeling. The guidance does not address the use of PRO instruments for purposes beyond evaluating claims made about a drug or medical product in its labeling. By addressing the review issues identified in this guidance, sponsors can increase the efficiency of their endpoint discussions with the FDA during the product development process, streamline the FDA's review of PRO endpoint adequacy, and provide optimal information about the patient's perspective of treatment benefit at the time of product approval. A PRO is a measurement of any aspect of a patient's health status that comes directly from the patient, without interpretation by a physician or anyone else. In clinical trials, a PRO instrument can be used to measure the impact of an intervention on one or more aspects of patients' health status, referred to as PRO concepts. These concepts range from the purely symptomatic (e.g., response of a headache) to more complex concepts (e.g., ability to carry out activities of daily living), to extremely complex concepts such as quality of life, which is a multidomain concept with physical, psychological, and social components. Data generated by a PRO instrument can provide evidence of a treatment benefit from the patient perspective. For this data to be meaningful, there should be evidence that the PRO instrument effectively measures the particular concept that is studied. The guidance defines many terms used in this document. The term "instrument" refers to the actual questions or items contained in a questionnaire or interview schedule along with all the additional information and documentation that supports the use of these items in producing a PRO measure. The term "conceptual framework" refers to how items are grouped according to subconcepts or domains. The FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance documents describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The guidance discusses the use of PRO instruments in medical product development, including the reasons for using them, the types of PRO instruments, and the evaluation of their measurement properties. It also outlines the steps involved in the development of PRO instruments, including the identification of concepts and domains, the creation of the instrument, the assessment of measurement properties, and the modification of existing instruments. The guidance emphasizes the importance of ensuring that PRO instruments are appropriate and adequate to support the study objectives, and that they are validated to measure the intended concepts. The guidance also discusses the challenges of developing PRO instruments for specific populations, such as children and patients with cognitive impairment, and the importance of considering these factors when developing and validating PRO instruments. The guidance concludes with a discussion of study design considerations, including the importance of blinding and randomization in clinical trials involving PRO instruments.