Cited by 401Statistical Methods in Clinical TrialsGenomics and Rare DiseasesEthics in Clinical Research

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Clinical research for rare disease: Opportunities, challenges, and solutions

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Griggs, Robert C., Batshaw, Mark, Dunkle, Mary, Gopal-Srivastava, Rashmi, Kaye, Edward, Krischer, Jeffrey, Nguyen, Tan, Paulus, Kathleen, Merkel, Peter A.·2009·Molecular Genetics and Metabolism

DOI 10.1016/j.ymgme.2008.10.003PMC PMC3134795

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Abstract

Over 7000 rare diseases, each <200,000 US residents, affect nearly 30 million people in the United States. Furthermore, for the 10% of people with a rare disease and for their families, these disorders no longer seem rare. Molecular genetics have characterized the cause of many rare diseases and provide unprecedented opportunities for identifying patients, determining phenotypes, and devising treatments to prevent, stabilize, or improve each disease. Rare disease research poses challenges to investigators requiring specific approaches to: (1) the design of clinical studies; (2) the funding of research programs; (3) the discovery, testing, and approval of new treatments, and (4) the training of clinical scientists. Rigorous, statistically-valid, natural history-controlled, cross-over, and n-of-1 trials can establish efficacy and support regulatory approval of new treatments for rare diseases. The U.S. Orphan Drug Act of the U.S. FDA has stimulated industry investment in clinical trials to develop treatments for rare diseases. For trainees interested in finding a treatment for a rare disease, a commitment to longitudinal care of patients provides a base for the characterization of phenotype and natural history, a stimulus for innovation, a target population for research and helps fund training and research. The scientific methodology, financial resources, and logistics of clinical research for rare diseases have changed dramatically in the past two decades resulting in increased understanding of the pathophysiology of these disorders and direct benefit to patients.

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Authors: Griggs, R. C., Batshaw, M., Dunkle, M., Gopal-Srivastava, R., Kaye, E., Krischer, J., Nguyen, T., Paulus, K., & Merkel, P. A.
Affiliations: University of Rochester Medicine (US)
Children's National (US)
National Organization for Rare Disorders (US)
National Institutes of Health (US)
University of South Florida (US)
United States Food and Drug Administration (US)
Boston University (US)
Corresponding author: Griggs, Robert C.
ORCID: Griggs, Robert C.
Batshaw, Mark
Krischer, Jeffrey
Merkel, Peter A.
Venue: Molecular Genetics and Metabolism
Publisher: Elsevier BV
Published: 2009-01
Volume: 96
Issue: 1
Pages: 20-26
ISSN: 1096-7192 (ISSN-L)
DOI: 10.1016/j.ymgme.2008.10.003
PMC: PMC3134795
OpenAlex: W2132265655
Cited by: 401
References: 21
Citations by year: 2026: 21 · 2025: 22 · 2024: 22 · 2023: 20 · 2022: 38 · 2021: 43 · 2020: 25 · 2019: 26 · 2018: 27 · 2017: 23 · 2016: 18 · 2015: 25 · 2014: 25 · 2013: 22 · 2012: 17
FWCI: 8.50
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular Genetics and Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5u54ns059065-07)
National Heart, Lung, and Blood Institute (U54HL077878)
National Institute of Diabetes and Digestive and Kidney Diseases (U54DK078377)
National Institute of Neurological Disorders and Stroke (U54-NS059065)
National Center for Research Resources (U54RR019478, U54RR019453, U54RR019259, R13RR024337, U54RR019497, U54RR019498, U54RR019480, U54RR019397, U54RR019484)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
Keywords: rare diseases, orphan drugs, Orphan Drug Act, clinical trial design, natural history research, N-of-1 trials, crossover trial, regulatory approval, drug development, clinical research funding, molecular genetics
MeSH terms: Workforce, Clinical Trials as Topic, Financing, Government, Humans, Orphan Drug Production, United States, Drug Design, Rare Diseases, Biomedical Research, Public-Private Sector Partnerships

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