OBJECTIVES: Conceptual models, endpoint models, and conceptual frameworks are research tools used by patient reported outcome (PRO) researchers. The objective of this study was to understand and clarify the role of each tool and to understand the relationships between them in relation to making treatment benefit claims to the FDA. METHODS: Published literature and expert consultation were used to explore definitions, development strategies, and use of each tool. RESULTS: A conceptual model is a representation of proposed causal linkages among a set of concepts. It can be developed from reviewing the literature, and interviewing patients and clinicians. An endpoint model is a representation of the relationships between all measures that may be defined as endpoints (primary or supportive) in a clinical trial. It is developed from a systematic/comprehensive review of disease literature and/or a conceptual model, the Target Product Profile (TPP), clinical experts, and the clinical development team. A conceptual framework is a representation of the expected relationships of items within a domain and of domains within a PRO concept. It is developed during the development of a PRO and is validated during the process of psychometric validation. Each of these tools fit together to take researchers from early drug development through to eventual treatment benefit claim. CONCLUSION: Each of the models discussed are useful research tools and the endpoint model and conceptual frameworks are essential for treatment benefit claims to be made to the FDA. They can be easily differentiated and their inter-relationships within the timescale of the drug development and treatment benefit claim process can be modelled.