The World Health Organization (WHO) defines Rare disease as a disorder which affects less than 6.5 to 10 per 10,000 people (Rabiei). In the European Union, the definition narrows down to 5 in 10,000 people, while in the United States, a rare disease is defined as a condition that affects fewer than 200,000 people. By these definitions there are more than 6800 (“Rare Diseases”) rare diseases.  While the exact cause for most rare diseases are not known, several of these are usually traced to mutations in a single gene, which would essentially be passed down from one generation to the next.  That is the reason we see these rare diseases running in families.

Diagnosis and treatment of rare diseases have come a long way in the last two decades.  However, rare disease research and treatment still faces certain challenges:

  1. Lack of awareness – Several physicians and medical researchers have limited knowledge of rare diseases. Patients and the general public lack information as well, which can lead to delays in seeking medical advice and treatment.
  2. Diagnosis – Non-specific symptoms and lack of specialized diagnostic tools and tests to identify rare diseases can lead to delayed diagnosis and treatment.
  3. Limited number of patients – Rare diseases affect a small number of people. The patient population is also fragmented and distributed globally. This makes patient recruitment for research studies challenging.
  4. Funding – Limited resources and funding have certainly not helped the cause for rare diseases research. As the beneficiary population is small, securing funding for rare disease research can be less than straightforward. Pharmaceutical companies may not view investing in rare disease research as commercially viable. As a result, developing treatments or therapeutics can be delayed
  5. Regulatory – Regulatory challenges associated with the clinical trials for rare diseases can also be difficult to navigate. With the narrow patient base, demonstrating treatment efficacy and safety can be cumbersome.
  6. Affordability – Even if drugs are developed for rare diseases, affordability for the patient is a major hurdle both in terms of limited or no reimbursement from health care plans to unaffordable out of pocket expenses.
  7. Long-term care and support – Rare diseases often require special long-term care management and follow up. This could mean follow up with patients can be difficult.

Given all these challenges, a Patient registry can be a game changer for rare disease research.

Patient registries have been defined as “an organized system that uses observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves a predetermined scientific, clinical, or policy purpose” (“Defining Patient Registries and Research Networks – Engaging Patients in Information Sharing and Data Collection”). Effectively, a patient registry is just that, a collection of patient data.

Patient registries can be instrumental for rare disease research in more ways than one:

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  1. Sample size – With the help of a pool of data from rare disease patient registries globally, researchers have a larger sample size to conduct studies.
  2. Natural progression of disease – Patient registries can include apart from demographic information, data relating to prevalence, distribution of the patients, familial characteristics and progression of symptoms, age of onset, and progression of the disease. This information can help researchers in identifying patterns and prognosis of diseases. This could help in designing clinical trials and developing therapeutic interventions.
  3. Shorter recruitment time – Patient registries can be a source for patient recruitment. It can be easily facilitated through collaborations between different patient registries. This can lead to easier recruitment for clinical trials.
  4. Study disease patterns Patient registries can help researchers to study correlations between various genetic mutations and symptoms associated with it. This could enhance better understanding of the disease.
  5. Safety and efficacy studies – Patient registries can track real world patient reported outcomes, side effects of various treatments. This can help in studies relating to safety and efficacy of various interventions.
  6. Public policy – Patient registries can help with public policy, resource allocation as they give a birds eye view of the geographic distribution of patients, demography, disease prevalence and the quality and access to health care.
  7. Support system – Patient registries can foster care and support amongst patients and caregivers by connecting them and forming a platform for exchange of information regarding disease progression, new therapies, finding specialists and clinical trials.

There has been government-led action in rare disease research. The orphan drug act was passed in 1983 in an effort to encourage research and development of therapies for rare diseases through tax incentives, market exclusivity and user fee exemptions to industries.  Although this resulted in a marked increase in rare disease research, several hurdles for commercialization remain due to an incomplete understanding of underlying disease mechanism, clinical end points and a small patient base for clinical trials.

GARD is a program of the National Institutes of Health (NIH) that provides free access to reliable, easy to understand information about genetic and rare diseases. Public awareness campaigns like Rare disease day (“Rare Disease Day at NIH 2023”) which takes place worldwide, typically on or near the last day of February each year, to raise awareness among policymakers and the public about rare diseases and their impact on patients’ lives.

International rare disease research consortium with 60 member organizations from all continents, with funders, researchers, companies and patient advocacy groups all under one umbrella, is collaborating with international experts nominated into the diagnostics, therapies and Interdisciplinary Scientific committees (“Who we are – IRDiRC”).

How can government organizations and nonprofits collaborate for successful clinical trials?

 Funding and standardization – Government can and should fund the development of patient registries, establish standardization so data sharing can happen between various patient registries and research groups. This collaboration can enable access to a larger pool of patient data.

Recruitment of patients – Through outreach programs, nonprofits and patient advocacy groups can help populate patient registries. They can work with governments to streamline the regulatory process for clinical trials of orphan drugs or research designed for rare diseases by establishing clear guidelines and expedited reviews.

Patient engagement – Patients need constant support and engagement. Nonprofits can continue to engage with patients, address their concerns, create and promote information collaterals, conduct seminars and keep them abreast of clinical trials. This can help in decreasing patient dropout rates.

Rare disease research has come a long way, but it still has a long way to go and Patient registries can act as a platform to bring together different stakeholders – patients, clinicians, researchers and pharma industry for knowledge sharing, learning from best practices and building connections. This collaboration can ultimately benefit individuals affected by rare diseases.

[1] Derayeh S, Kazemi A, Rabiei R, Hosseini A, Moghaddasi H. National information system for rare diseases with an approach to data architecture: A systematic review. Intractable Rare Dis Res. 2018 Aug;7(3):156-163. doi: 10.5582/irdr.2018.01065. PMID: 30181934; PMCID: PMC6119672. [Article] Last accessed on June 15, 2023.
[2] Rare Diseases FAQ. National Human Genome Research Institute, January 10, 2020. [Article]. Last accessed on June 15, 2023.
[3] Gliklich RE, Dreyer NA, Leavy MB, editors. Registries for Evaluating Patient Outcomes: A User’s Guide [Internet]. 3rd edition. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Apr. 20, Rare Disease Registries. Online  Last accessed on June 15, 2023.
[4] Workman TA. Engaging Patients in Information Sharing and Data Collection: The Role of Patient-Powered Registries and Research Networks [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Sep. Defining Patient Registries and Research Networks. Online. Last accessed on June 15, 2023.
[5] Rare Disease Day at NIH 2023 | National Center for Advancing Translational Sciences.” National Center for Advancing Translational Sciences | 22 March 2023, Last accessed on June 15, 2023.
[6] Who we are – IRDiRC. IRDiRC, Last accessed on June 15, 2023.
[7] Augustine EF, Adams HR, Mink JW. Clinical trials in rare disease: challenges and opportunities. J Child Neurol. 2013 Sep;28(9):1142-50. doi: 10.1177/0883073813495959. PMID: 24014509; PMCID: PMC3964003. Last accessed on June 15, 2023.
[8] Julkowska D, Austin CP, Cutillo CM, Gancberg D, Hager C, Halftermeyer J, Jonker AH, Lau LPL, Norstedt I, Rath A, Schuster R, Simelyte E, van Weely S. The importance of international collaboration for rare diseases research: a European perspective. Gene Ther. 2017 Sep;24(9):562-571. doi: 10.1038/gt.2017.29. Epub 2017 Jul 27. PMID: 28440796; PMCID: PMC5628265. [Article] Last accessed on June 15, 2023.

Featured image by National Cancer Institute on Unsplash. used with permission.

How to Cite


Padma Rammoorthy, MD 1
Why are Patient Registries Key to Accelerating Rare Disease Research? – Onco Zine – The International Oncology Network, July 28, 2023.
DOI: 10.14229/onco.2023.07.28.002
1 IndoUSrare


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