Comment Now! Rare Disease: Natural History Studies for Drug Development (FDA Draft Guidance)



The Food and Drug Administration (FDA) has released a draft guidance, “Rare Diseases: Natural History Studies for Drug Development”. We discussed another draft guidance released in January, “Rare Diseases: Common Issues in Drug Development” in our blog. The new draft guidance describes how natural history studies may be best used for drug development for rare diseases.


What is a rare disease?

There are around 7000 rare diseases, and they affect fewer than 200,000 individuals in the United States. They frequently do not have approved treatments.

What is the importance of a rare disease’s natural history?

The natural history of a disease is the progression of a disease from the start through to the conclusion of the disease, either a resolution or death. A natural history study is a planned observational study of the course of the disease. Understanding the natural history of a disease aids in the drug development process, including drug discovery, study design, and postmarket surveillance. Since rare diseases are less understood, the draft guidance hopes to aid in the design of rare disease natural history studies, including how to map the design to the study objectives, protect subject confidentiality, and improve study results.

Elements of the draft guidance:

The following are important contributors from a natural history study to the drug development process:

  • Identification of the patient population

  • Identification or development of clinical outcome assessments

  • Identification or development of biomarkers

  • Design of externally controlled studies using natural history study data

The draft guidance also discusses:

  • Strengths and weaknesses of different types of natural history studies such as:

    • Retrospective and prospective natural history studies

    • Cross-sectional studies and longitudinal natural history studies

  • Important considerations in study design, including:

    • Study protocol

    • Data elements

    • Elements needed in the protocol

    • Plan for data analysis

  • Practical considerations, such as:

    • Plans for monitoring study conduct

    • Timing of study start

    • How to find the patient population

    • Plans for retention of subjects

    • Finding the right study site

    • Data collection

  • Human subject protection, including:

    • Confidentiality

    • IRB review

    • Informed consent

Do you think the detailed guidance on how to best conduct a natural history study will help support the development of safe and effective drugs and biologics for rare diseases? Comment on the draft guidance here, now through May 24, 2019.

- The Clinical Pathways Team

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