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Enhancing Equitable Access to Rare Disease Diagnosis and Treatment around the World: A Review of Evidence, Policies, and Challenges
Open accessAbstract
This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. Panelists were selected based on their academic merit, expertise, and knowledge regarding the RD environment. The document is divided into five main sections: (1) methodology and objective; (2) background and context; (3) overview of the current situation and key challenges related to RDs covering six dimensions: burden of disease, patient journey, social impact, disease management, RD-related policies, and research and development; (4) recommendations; and (5) conclusions. The recommendations are derived from the discussion undertaken by the experts on the findings of this review and provide a set of actionable solutions to the challenges and barriers to improving access to RD diagnosis and treatment around the world. The recommendations can support critical decision-making, guiding efforts by a broad range of RDs stakeholders, including governments, international organizations, manufacturers, researchers, and patient advocacy groups.
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“delays in diagnosis lead to delays in treatment and poor prognosis7,8.”
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“Timely diagnosis of rare diseases has always been challenged by a lack of high-quality medical resources in many regions of the world”
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Linertová, R., García‐Pérez, L., & Gorostiza, I. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67144-4_17 · Cited by 26 · cited 1×
“Moreover, cost-of-illness studies of RDs rarely analyze the outcomes or benefits of possible treatments [65].”
BackgroundHealth inequity in workers of Latin America and the Caribbean
Silva-Peñaherrera, M., López-Ruiz, M., Merino-Salazar, P., Gómez-García, A. R., & Benavides, F. G. (2020) · International Journal for Equity in Health · doi:10.1186/s12939-020-01228-x · Cited by 26
Molecular response to imatinib in patients with chronic myeloid leukemia in Tanzania
Nasser, A., Hussein, A. K., Chamba, C. C., Yonazi, M., Mushi, R., Schuh, A., & Luzzatto, L. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020002973 · Cited by 26 · cited 1×
“One example is of a drug made available to patients with chronic myeloid leukemia in some African countries through pharmaceutical and foundation partnerships [104].”
BackgroundShaping national plans and strategies for rare diseases in Europe: past, present, and future
Hedley, V., Bottarelli, V., Weinman, A., & Taruscio, D. (2021) · Journal of Community Genetics · doi:10.1007/s12687-021-00525-4 · Cited by 26
Rosselli, D., Rueda, J. D., & Solano, M. L. (2012) · Journal of Medical Ethics · doi:10.1136/medethics-2011-100204 · Cited by 25 · cited 1×
“This is, for example, the case of patients with mucopolysaccharidosis VI in Colombia, who face the responsibility of costs associated with complications, frequent healthcare encounters, and caregiver dedication [16].”
BackgroundThe Orphan Drug Act at 35: Observations and an Outlook for the Twenty-First Century
Bagley, N., Berger, B., Chandra, A., Garthwaite, C., & Stern, A. D. (2018) · Innovation Policy and the Economy · doi:10.1086/699934 · Cited by 25
Ninomiya, K., & Okura, M. (2022) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-022-02290-0 · Cited by 25 · cited 6×
“While some countries such as Australia, France, Italy, Japan, and the United States have established dedicated RD diagnosis programs to speed up the process of diagnosing patients with RDs [97–101], this is not the case for most countries.”
BackgroundInfluentialGreene, J., & Guanais, F. C. (2018) · Revista Panamericana de Salud Pública · doi:10.26633/rpsp.2018.127 · Cited by 24
Rare diseases, common challenges
(2022) · Nature Genetics · doi:10.1038/s41588-022-01037-8 · Cited by 24
Vieira, T. A., Trapp, F. B., de Souza, C. F. M., Schüler‐Faccini, L., Jardim, L. B., Schwartz, I. V. D., Riegel, M., Vargas, C. R., Burin, M. G., Leistner‐Segal, S., et al. (2019) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2018-0214 · Cited by 20
Human whole genome sequencing in South Africa
Glanzmann, B., Jooste, T., Ghoor, S., Gordon, R. K., Mia, R., Mao, J. X., Li, H., Charls, P., Douman, C., Kotze, M. J., et al. (2021) · Scientific Reports · doi:10.1038/s41598-020-79794-x · Cited by 20
Conradie, E. H., Malherbe, H. L., Hendriksz, C. J., Dercksen, M., & Vorster, B. C. (2021) · Biopreservation and Biobanking · doi:10.1089/bio.2020.0108 · Cited by 20 · cited 11×
“RDs are only recently and progressively becoming a policy priority for the UN and WHO, extending an invitation to increase health policies and initiatives at the regional and country levels.”
BackgroundInfluentialAnalysis of patient access to orphan drugs in Turkey
Kockaya, G., Atalay, S., Oğuzhan, G. E., KURNAZ, M., Ökçün, S., Gedik, C. S., Şaylan, M., & Şencan, N. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01718-3 · Cited by 16
Cost of hemophilia A in Turkey: an economic disease burden analysis
Malhan, S., Öksüz, E., Antmen, B., Ar, M. C., Balkan, C., & Kavaklı, K. (2021) · Journal of Medical Economics · doi:10.1080/13696998.2021.1965388 · Cited by 16 · cited 1×
“• Lack of reimbursement of orphan drugs [7,83].”
BackgroundVilla, F., Filippo, A. D., Pierantozzi, A., Genazzani, A. A., Addis, A., Trifirò, G., Cangini, A., Tafuri, G., Settesoldi, D., & Trotta, F. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.820757 · Cited by 16 · cited 1×
“Orphan drugs cost roughly five times more than non-orphan drugs [22], which poses challenges and concerns in terms of the sustainability of health systems [23].”
BackgroundDrivers of Orphan Drug Development
Mingorance, A. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00438 · Cited by 12
Adachi, T., Imanishi, N., Ogawa, Y., Furusawa, Y., Izumida, Y., Izumi, Y., & Suematsu, M. (2018) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-018-0943-y · Cited by 11
Self-citationRare Diseases in India:Time for Cure-Driven Policy Initiatives and Action
Taneja, A., Shashidhara, L. S., & Bhattacharya, A. (2020) · Current Science · doi:10.18520/cs/v118/i10/1500-1506 · Cited by 9
An Analysis of Medical Care Services for Children With Rare Diseases in the Russian Federation
Volgina, S. Y., & Sokolov, A. A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.754073 · Cited by 9
Garrison, S. R., Kennedy, A., Manetto, N., Pariser, A., Rutter, J. L., & Yang, G. (2022) · Forefront Group · doi:10.1377/forefront.20220128.987667 · Cited by 9 · cited 2×
“The limited availability of medical history and epidemiologic data regarding RDs, as well as a standardized methodological approach to calculate cost-of-illness, constrains the possibility to estimate direct and indirect costs associated with RDs and, consequently, the estimation of potential economic benefits of trea…”
BackgroundWhy children do not receive treatment
Choonara, I. (2014) · Archives of Disease in Childhood · doi:10.1136/archdischild-2013-305257 · Cited by 8 · cited 1×
“younger and the poorer segments of populations, similar to what happens regarding the treatment of other diseases [87,88].”
Butti, N., Castagna, A., & Montirosso, R. (2022) · Children · doi:10.3390/children9040551 · Cited by 7
An Overview About Rare Diseases in Saudi Arabia and Reimbursement of Orphan Drugs
Alsaqa’aby, M., & Ibrahim, N. A. R. (2019) · Global Journal of Medical Therapeutics · doi:10.46982/gjmt.2019.105 · Cited by 6
Access to Affordable Orphan Medicines in Europe: An EHA Position Paper
Merlini, G., Gribben, J. G., Macintyre, E. A., Piggin, M., & Doeswijk, R. (2020) · HemaSphere · doi:10.1097/hs9.0000000000000477 · Cited by 6 · cited 1×
“This, in turn, affects the quality of care and treatment that RD patients receive [51,52].”
BackgroundGlobal Data Access for Solving Rare Disease, A Health Economics Value Framework.
Belsey, J., Chaihorsky, L., Chediak, L., Currie, G. R., Goranitis, I., & Marshall, D. A. (2020) · Minerva Access (University of Melbourne) · Cited by 5
PRO11 COSTS OF TREATMENT OF ATYPICAL HEMOLYTIC UREMIC SYNDROME IN POOR POPULATION OF COLOMBIA.
Zakzuk, J. A., Gamero, K., Mercado, J. C. F., Alvis‐Guzmán, N., & Wilchez, J. P. (2020) · Value in Health · doi:10.1016/j.jval.2020.04.1242 · Cited by 3
Impacto económico de los inhibidores en hemofilia tipo A pediátrica
Facundo, N. A. L., Rodríguez‐Castillejos, C., Romero, Y., Gay, J. G., & Prada, D. (2019) · Gaceta Médica de México · doi:10.24875/gmm.19004674 · Cited by 2
Gilardino, R. E., Cabra, H., & Zanela, O. O. (2016) · Value in Health · doi:10.1016/j.jval.2016.03.775 · Cited by 1 · cited 1×
“In Argentina, around 50% of patients consult three or more centers, many of which require traveling to other towns or provinces [70] since the large urban centers contain most of the healthcare facilities in the country [90].”
Background
Flagged first, then by citations
Research works printed but not linked: 5
- American Association for the Advancement of Science (2022, August 04). 7000 Challenges: The Basis and Burden of Rare Diseases [Internet]. Available online: https://www.science.org/content/webinar/7000-challenges-basis-and-burden-rare-diseases.
- Linertová, R., García-Pérez, L., and Gorostiza, I. (2017). Rare Diseases Epidemiology: Update and Overview, Springer.
- Adamek, M.E., Chane, S., and Kotecho, M.G. (2020). Health and Care in Old Age in Africa, Routledge.
- Office of the United Nations High Commissioner for Human Rights (2023, January 30). Experts of the Committee on the Rights of Persons with Disabilities Commend China on Reforms Made since the Initial Review, Ask Questions on the Independence of Persons with Disabilities in the Community and on Home Schooling [Internet]. Available online: https://www.ohchr.org/en/news/2022/08/experts-committee-rights-persons-disabilities-commend-china-reforms-made-initial.
- Vickers, 2013, Challenges and Opportunities in the Treatment of Rare Diseases, Drug Discov. World, 14, 9
Cited by
Sorted by citations
Enhancing diagnostic capability with multi-agents conversational large language models
Chen, X., Yi, H., You, M., Liu, W., Wang, L., Li, H., Zhang, X., Guo, Y., Fan, L., Chen, G., et al. (2025) · npj Digital Medicine · doi:10.1038/s41746-025-01550-0 · Cited by 147
“Timely diagnosis of rare diseases has always been challenged by a lack of high-quality medical resources in many regions of the world, and delays in diagnosis lead to delays in treatment and poor prognosis 7,8 .”
The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap
Jonker, A. H., Tãtaru, E.-A., Graeßner, H., Dimmock, D., Jaffé, A., Baynam, G. S., Davies, J. O. J., Mitkus, S., Iliach, O., Horgan, R., et al. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01059-3 · Cited by 48
“For example, these inequities are due to the lack of detailed standardized diagnostic criteria, for which availability varies from region to region 91 , or due to the costs of obtaining a diagnosis 92 .”
The impact of rare diseases on the quality of life in paediatric patients: current status
Dumbuya, J. S., Zeng, C., Deng, L., Li, Y., Chen, X., Ahmad, B., & Lü, J. (2025) · Frontiers in Public Health · doi:10.3389/fpubh.2025.1531583 · Cited by 45
Global insight into rare disease and orphan drug definitions: a systematic literature review
Abo-Zaid, G., Kerr, K., Alomary, H., Al‐Omar, H. A., & McKnight, A. J. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-086527 · Cited by 19
Khaskheli, M. A., Nizamani, M. M., Tarafder, E., Das, D., Nosheen, S., Muhae‐Ud‐Din, G., Khaskheli, R. A., Ren, M.-J., Wang, Y., & Yang, S. (2025) · Journal of Fungi · doi:10.3390/jof11030207 · Cited by 18
“The following are some key policy recommendations [319].”
Metadata
- Authors
- Adachi, T., El-Hattab, A. W., Jain, R., Nogales Crespo, K. A., Quirland Lazo, C. I., Scarpa, M., Summar, M., & Wattanasirichaigoon, D.
- Affiliations
- Keio University (JP)
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Nanyang Technological University (SG)
- Policy Wisdom LLC, Quebradillas 00678-2705, Puerto Rico
- Health Technology Assessment Unit, Cancer Research Department, Arturo López Perez Foundation, Santiago 7500921, Chile
- University of Udine (IT)
- National Institutes of Health (US)
- Mahidol University (TH)
- ORCID
- Venue
- International Journal of Environmental Research and Public Health
- Publisher
- MDPI AG
- Published
- 2023-03-08
- Volume
- 20
- Issue
- 6
- Pages
- 4732
- ISSN
- 1660-4601 (ISSN-L)
- PMC
- PMC10049067
- OpenAlex
- W4323568260
- Cited by
- 168
- References
- 103
- Citations by year
- 2026: 47 · 2025: 70 · 2024: 42 · 2023: 9
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Environmental Research and Public Health (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
- Funders
- Takeda Pharmaceutical Company Limited
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
- Keywords
- rare diseases, access to treatment, health policy, regulatory framework, disease burden, patient journey, disease management, barriers to care, patient advocacy
- MeSH terms
- Health Policy, Humans, Rare Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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