Merck, Lundbeck and Ionis Pharmaceuticals are seeking more details from the US Food and Drug Administration’s (FDA) draft guidance on natural history studies, including discussions of using third-party disease registries.
The 19-page draft guidance, released in March
, describes the potential uses of a natural history study in all phases of rare disease drug development. It covers the strengths and weaknesses of various types of natural history study designs, common data elements and research plans. The draft also offers a framework for the conduct of such a study, including information on data collection, storage, dissemination and human subject protections.
In comments on the draft, Julie Anne Zawisza, director of global regulatory policy at Merck, explained how the work of organizations and programs outside industry that are conducting natural history studies to better characterize rare diseases should be considered under this guidance.
“Data and data storage methods developed by these organizations and identification of what is acceptable for regulatory submissions (‘regulatory grade’) would greatly facilitate drug development. It would be helpful if FDA were to include discussion in the guidance of the importance of such contributions and emphasize the benefits of collaboration between industry and these outside organizations,” she added.
Lundbeck Chief Medical Officer Doug Williamson also noted how although FDA suggests sponsors should conduct prospective natural history studies, with full control over the study design and data collection, FDA does not acknowledge that many of the existing rare disease registries are controlled by consortia of clinicians and other institutions, making it difficult to create such registries from scratch.
Lundbeck also seeks FDA input on the use of this secondary data and to provide guidance on which “aspects of a study could vary (including how far) and still be acceptable for regulatory purposes.”
FDA in 2017 for the first time awarded six grants
to universities and hospitals to conduct natural history studies.
The draft guidance also briefly covers when natural history data can be used as an external control. Merck said it would be worth mentioning that a statistical analysis plan for incorporating natural history study data as the external control would be required. “The analysis plan is to pre-specify patient population, i.e., algorithm of patient selection from the natural history studies, time point, endpoints, and analysis models,” Zawisza wrote.
Tiffany Baumann, director of regulatory affairs at Ionis Pharmaceuticals, also called for subject-level data to be shared in addition to any peer-reviewed publications.
As it is often not feasible for each sponsor to conduct its own natural history study, sponsors “should be strongly encouraged to share not only methods, practical aspects and results, but also subject-level data in a timely fashion. The dissemination of raw, subject-level data to the public and community is a critical necessity and should be strongly encouraged within Industry,” she wrote.