The Food and Drug Administration (FDA or Agency) has announced (27 March 2019) the availability of a draft guidance for industry entitled “Rare Diseases: Natural History Studies for Drug Development.” FDA is publishing this draft guidance to help inform the design and implementation of natural history studies that can be used to support the development of safe and effective drugs and biological products for rare diseases. A natural history study collects information about the natural history of a disease in the absence of an intervention, from the disease’s onset until either its resolution or the individual’s death. Although knowledge of a disease’s natural history can benefit drug development for many disorders and conditions, natural history information is usually not available or is incomplete for most rare diseases; therefore, natural history information is particularly needed for these diseases.

Although existing FDA guidance considers common issues encountered in drug development for rare diseases, this draft guidance expands on the subject of natural history studies specifically. The focus of this guidance is rare diseases; however, the recommendations in the guidance may be applicable to drug development for non-rare diseases. For applicability to non-rare diseases, discuss with the FDA review division or office responsible for the review of the drug

This guidance describes the broad potential uses of a natural history study in all phases of drug development for rare diseases, the strengths and weaknesses of various types of natural history studies, data elements and research plans, and a practical framework for the conduct of a natural history study. This guidance also discusses some considerations for aligning the study design with study objectives and for enhancing the interpretability of study results; patient confidentiality and data protection issues in natural history studies; and potential interactions with FDA related to these studies.