Stakeholders on Natural History Study Guidance
The Biotechnology Innovation Organization (BIO) says FDA should highlight and recognize that its draft guidance on natural history studies for rare disease drug development can apply to a wider range of stakeholders, such as advocacy and patient organizations. It says the guidance should encourage patient organizations to consider the guidance when developing their natural history studies so that the data are robust and can be considered by the agency for regulatory decision-making.
The BIO comment letter also says FDA should accept and encourage use of appropriate retrospective natural history study data and alignment across guidance pertaining to rare disease drug development, should leverage existing natural history data when a new treatment is approved, and should provide more flexibility and clarify considerations for the statistical analysis plan.
In its letter, Roche/Genentech says the draft compares in detail the relative merits of retrospective versus prospective natural history studies, as well as cross-sectional studies versus longitudinal natural history studies. “While we largely agree with the agency,” the letter says, “we also note that every approach has both limitations and utility. We, therefore, ask the agency to provide guidance on practical means of combining different methods such that data can be leveraged to develop robust natural history of diseases.”
Ionis Pharmaceuticals offers suggestions on rare disease and ultra-rare disease definitions, additional uses for natural history studies, encouragement and increased recognition of the importance of interim analyses, and the need for subject-level data dissemination.
Merck writes that changes it would like to see more information on the role of outside organizations, protocol elements, statistical analysis plan, and data submission.
Finally, Novartis says it believes natural history studies might include interventional elements if non-standard investigations are necessary to understand the disease. It also says the guidance readability may be enhanced if it included a separate section for studies with secondary use of data for which some sections do not apply.