OBJECTIVES: An appraisal of patient-reported outcome (PRO) endpoints and existing instruments to measure such endpoints was conducted to identify and critically review potentially relevant and appropriate instruments for use in clinical trials of cancer-related anemia (CRA). The purpose of the study was to determine what PRO endpoints and instruments have been used to assess the impact of treatment in reducing CRA symptoms, and whether the instruments identified were likely to be of the standard acceptable by regulatory authorities to support a label claim. METHODS: A systematic search and review of 1486 published scientific abstracts was conducted using MEDLINE and EMBASE, as well as the supporting statements in regulatory agency labels for drugs used in the treatment of anemia. Consistency of the identified PRO measures and their psychometric properties with the current Food and Drug Administration (FDA) draft guidance on PROs supporting a labeling claim was also evaluated. RESULTS: A total of 29 instruments were identified. Four instruments were found to support a label claim or used specifically in the CRA population (FACT-F, FACT-An, CLAS/LASA, EORTC QLQ-C30); these were assessed further. Twenty-five were excluded from further assessment because they were specific to a particular disease other than cancer and covered aspects specific to these diseases which were not relevant to the CRA population. Other exclusion reasons included measurement of general health or health-related quality of life (HRQOL) and other symptoms that were neither specific to cancer nor anemia. CONCLUSIONS: None of the four instruments assessed were found to meet all the criteria in the FDA draft guidance; however, the findings help inform the design of new PRO instruments for CRA.