Question and answer sets are the core of clinical research. The [RD] PRISM (Patient Registry Item Specifications and Metadata for Rare Disease) project will provide a library of standardized questions across a broad spectrum of rare diseases that can be used for developing new registries and revising existing ones. Questions will be encoded using well-established clinical terminologies to enable cross-indication and cross-disease analyses, facilitate collaboration, and generate meaningful results for rare disease patients, physicians, and researchers. Encoded question and answer sets will also be indexed to facilitate information retrieval by subject matter, data type, and time interval. This project will outline issues and challenges related to indexing questions for future use and for data sharing; to explore possible metadata and terminological standards for indexing them; and, determine if Dublin Core (DC) is a viable alternative to be explored in a library of standardized rare disease research questions.