The FDA PRO Guidance, over a decade in development and more than a decade after approval, set standards for incorporating the patient voice into medical product labeling. The regulatory context necessitates substantial evidence of effectiveness and well-defined and reliable assessments of patients’ views. Built on existing standards for psychological assessment, the Guidance advanced regulatory science of PRO measures (PROMS) with an emphasis on establishing the validity of content through qualitative research and the separation of the measurement of change from the assignment of meaning to that change. In other words, are we measuring what matters most to people using the products and can we conclude from the evidence presented that the changes reported are indeed important at the level of the population? The Roadmap accompanying the Guidance and division-specific recommendations help to evaluate the assertion that the product “works” as well as the evidence suggests. These principles, now integrated into regulatory decision-making throughout the FDA, impact how MRTP are evaluated and approved. Developers of MRTP must demonstrate that they will significantly reduce harm to individual tobacco users and benefit population health, taking into account both users of the products and persons who do not currently use tobacco. CROMs supplement toxicological evidence with consumer perceptions of information, benefits, and harms. Studies must assess consumer understanding of the claims that reducing exposure to harmful chemicals is relative to smoking, requiring exclusive use of MRTP. Building content-valid CROMs that can assess if meaningful change has occurred requires long-term development of an individual assessment strategy as well as a population impact model. Required are rigorous cross-cultural investigation of what MRTP mean to consumers, how consumers evaluate risks and benefits, and how these translate into stopping smoking tobacco. Particular attention has to be paid to youthful smokers. Painstaking studies with novel instruments are in development to assess how replicable findings will be across different populations and how much change in attitude and use we expect and observe. Consumer reported outcomes provide important and necessary evidence to evaluate reduced harm in using tobacco and/or nicotine-containing products more safely.