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Page 2 of 14 Brooks et al. Rare Dis Orphan Drugs J 2024;3:15 https://dx.doi.org/10.20517/rdodj.2023.27

diseases. These include the support of “basket trials” based on shared molecular etiologies across multiple rare
diseases, as well as therapeutic platforms for the treatment of monogenic diseases, such as gene therapy and
genome editing. This Perspective will provide an overview and summary of these various activities, noting where
relevant our collaborative partnerships within the U.S. and internationally.

Keywords: Clinical research readiness, genetic disease, diagnostic odyssey, translational research, research
funding

DRDRI, A HISTORICAL PERSPECTIVE
Following the completion of the report from the National Commission on Orphan Diseases in 1989, NIH
established the rare diseases initiative to implement the recommendations provided by the Commission. In
1993, NIH established the Office of Rare Diseases (ORD) and later changed the name to include Office of
Rare Diseases Research (ORDR) to reflect the expansion of activities to focus on research needs and
opportunities. Activities included the development of the Genetic and Rare Diseases Information Center
(GARD), providing support for the Bench-to-Bedside Awards program at the Clinical Center Hospital with
other NIH Research Institutes and Centers, contributions of information to clinical.trials.gov information
system provided by NIH’s National Library of Medicine, the International Rare Diseases Research
Consortium (IRDiRC), the International Collaboration on Rare Diseases and Orphan Products (ICORD),
the Rare Diseases Clinical Research Network (RDCRN), and assistance with the development of NIH’s
Undiagnosed Diseases Program with the expansion to the Undiagnosed Diseases Network (UDN), and the
International expansion (UDNI).

On November 6, 2002, the United States enacted Public Law 107-280, the Rare Diseases Act of 2002. This
legislative mandate requested NIH to establish and directed ORD to support regional centers of excellence
for training and clinical research into rare diseases, and demonstration of prevention, diagnosis, and
treatment methods for rare diseases, and to address the needs of rare disease clinical research. The
legislation also directed ORD to increase the national investment in the development of treatments and
diagnostics for rare disease patients. The legislation suggested a broad range of research and education
activities to assist in developing a research agenda for conducting and supporting research on rare diseases.
One effective tool used extensively is support for scientific workshops and symposia to identify research
opportunities and establish research priorities and a research agenda for rare diseases. ORD established the
Genetic and Rare Diseases (GARD) Information Center to provide understandable information about these
diseases to the public, medical professionals, and patients and their families.

The National Center for Advancing Translational Sciences (NCATS), one of 27 Institutes and Centers at
NIH, was established in 2011 with the goal of transforming the translational process so that new treatments
and cures for diseases could be delivered to patients faster. At that time, ORDR was transitioned from
within the Office of the NIH Director to become one of the founding programs within the new Center.
Finally, in 2022, ORDR became the Division of Rare Diseases Research Innovation (DRDRI), further
emphasizing the importance of rare diseases research within NCATS.

DRDRI’s portfolio encompasses a broad range of resources [Table 1]. Since becoming part of NCATS,
DRDRI has maintained its role in promoting coordination and cooperation among the NIH research
institutes and centers that support rare disease research. DRDRI also collaborates with national and
international patient organizations, global research investigators, the biopharmaceutical and medical devices
industries, and health and scientific organizations with an emphasis on rare diseases. More recently, DRDRI