Research surrounding social media's impact on patient-reported health outcomes continues to emerge. However, an ongoing challenge for researchers is generating valid and reliable evidence that draws upon rigorous frameworks. This manuscript details the development and refinement of a framework that defines criteria and methods for generating and evaluating evidence about social media use in chronic disease management; the Therapeutic Affordances of Social Media (TASoMe) framework. TASoMe was built through the considered combination of mixed research methods and data collection instruments. It represents a systematic methodology for conducting research that brings together the key concepts of: therapeutic affordances, patient-reported outcomes, and evidence-based practice to generate evidence about health outcomes from social media use. Its key building blocks include: the key research concepts, research methods, and stakeholders standing to benefit from outcomes. TASoMe contributes to the field of participatory health informatics by offering a stringent and reliable model for advancing research and practice. It has begun to be independently validated across a range of health conditions, and has the potential to be applied to a range of participatory health informatics technologies.