FDA – Natural History Studies Addressing Unmet Needs of Rare Diseases: Orphan Products Research Project Grant (R01)

October 19, 2018 by School of Medicine Webmaster

The FDA Office of Orphan Products Development (OOPD) was created to identify and promote the development of orphan products. Orphan products are drugs, biologics, medical devices, and medical foods that are indicated for a rare disease or condition. Rare diseases, as generally defined in the US Orphan Drug Act (ODA), are diseases or conditions with a prevalence of fewer than 200,000 persons in the US.  Approximately 30 million Americans are affected by 7,000 known rare diseases but only a few hundred of these rare diseases have approved treatments. Unlike common diseases, there is little existing knowledge on the presentation, major limitations on day-to-day function, core unmet needs, and course of most rare diseases which makes drug development challenging.  To address this, it is critical to study the natural history of rare diseases.

The natural history of a disease is traditionally defined as the natural course of a disease from the time immediately prior to its inception, progressing through its pre-symptomatic phase and different clinical stages to the point where the disease has ended without external intervention. A natural history study describes the course of a disease over time, identifying demographic, genetic, environmental, and other variables that correlate with its development and outcomes.  These studies are likely to include patients receiving the current standard of care (e.g., supportive care, unapproved treatment options), which may alter some otherwise natural manifestations or course of the disease.

In a prospective study, data are generated after study initiation. Prospective studies allow implementation of predefined and consistent data collection, utilization of up-to-date medical terminology and standard of care, and the flexibility to collect additional data as the study evolves. However, prospective studies can be resource intensive and time consuming. The outcome of a prospective study hinges on the study design which is dictated by the existing knowledge of the rare disease at study initiation. In a retrospective study, data have already been generated prior to study initiation. Retrospective studies are most commonly reviews of existing medical records. The advantage of retrospective studies is to allow collection of natural history information in a relatively short period. Limitations of retrospective studies may include inconsistent data collection, outdated or non-uniform medical terminology and outdated standard of care.

This FOA is intended to support prospective or retrospective observational/non-interventional natural history studies with a substantial potential to further current or future product development.

Research Objectives

Natural History studies eligible for this funding opportunity will support studies that characterize the natural history of rare diseases/conditions with the goal of providing data by innovative means to facilitate medical product development for patients living with rare diseases where unmet needs exist.  Therefore, natural history studies at various stages of product development and/or disease knowledge are encouraged.  For example, there may already be products in the pipeline that are seeking to develop/validate biomarkers or clinical outcome measures.  Alternatively, where diseases are less well-characterized, there may be need to evaluate the major functional limitations and manifestations of the disease or identify genotypic and phenotypic subpopulations. Higher priority will be given to efficient natural history studies where the study has a potential to exert a broad impact in advancing multiple rare diseases sharing a similar pathophysiology.

Use of innovative models of natural history studies is highly encouraged under this FOA.  Applications that propose simulations and modeling towards the study of safety and effectiveness of a product in conjunction with the natural history study will be a priority.  Modeling and simulation allow for organization of diverse data sets, optimization of product dosing based on individual physiology and genetics, and can provide a vital tool to help evaluate new treatments in rare diseases where patient populations are inherently difficult to study because of their small size.  Innovative methods for data collection as well as data dissemination which can serve as a model for future studies is also highly encouraged.

Inclusion of patient and caregiver perspectives from the rare disease community is highly encouraged. Patients living with a rare disease or a family member who cares for them, have experiences and knowledge that can contribute to generating data about the natural progression of the disease.

Deadline:  December 10, 2018 (letters of intent); January 10, 2019 (full proposals)

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-FD-19-001.html

Filed Under: Funding Opportunities