Authored by Dr. Harsha Rajasimha, Founder and Executive Chairman, IndoUSrare. Co-Authored by Dr. Padma Rammoorthy, Medical Consultant, IndoUSrare.

The diagnostic journey for patients with rare diseases often becomes a prolonged odyssey, with an average of 7.3 physicians being consulted before receiving a definitive diagnosis. (Can a decision support system accelerate rare disease diagnosis?). Rare diseases affect approximately 8 to 10% of the world’s population. Due to the limited prevalence of rare diseases, the medical community often lacks awareness about the majority of these conditions and their corresponding treatments. Consequently, many patients find themselves in a situation where they must undertake the diagnostic process independently, which can significantly impact the physical and mental well-being of both the patients and their caregivers.

What is a rare disease?

The definition of rare disease differs from one country to another. In the United States, a rare disease, also known as an orphan disease, is a medical condition that affects fewer than 200,000 people. The World Health Organisation defines a rare disease as a disorder that 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. 80% of rare diseases have a genetic origin. (“A guide for the diagnosis of rare and undiagnosed disease: beyond the exome”).

These diseases are often complex, chronic, and life-threatening, and they pose significant challenges for patients, caregivers, and the medical community.

Rare disease patients face obstacles such as lack of awareness, difficulty finding specialists, delayed diagnosis, limited treatment options, financial burden, and isolation. Limited research also impact their lives significantly. This is due to the lack of sufficient funding for research. Pharmaceutical companies may not be very keen to develop therapies for rare diseases due to the high investments required with low profitability, given the small patient base.

Apart from funding, rare disease researchers face challenges in collaborating and sharing knowledge due to their global distribution. Coordinating efforts and exchanging findings becomes daunting, impeding progress in this field of research. Furthermore, navigating the complex regulatory processes for rare disease treatments can result in delays in approvals and hinder access to the market.

Patient registries can be a transformative tool in addressing most of these challenges in rare disease research.

 What is a Patient Registry?

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”). A patient registry is thus a centralised and organised database that collects comprehensive information about individuals with a specific medical condition, aiding research and improving patient care.

The primary purpose of patient registries is to create a valuable resource for patients, researchers, healthcare professionals, and policymakers to better understand specific diseases or conditions.

Patient registries and patients:

• Through patient registries, patients and their care givers can access valuable information about their condition, treatment options, disease management strategies and ongoing research.
• Patient registries can connect patients with others who share similar conditions, fostering a sense of community and support among individuals facing similar challenges.
• Registries can match eligible patients with clinical trials and research studies, offering patients the chance to participate in cutting-edge research and potentially access new treatments.
• Research on rare diseases remains insufficient, and healthcare professionals are continually acquiring knowledge about novel symptoms, disease indicators, and the progression of these conditions. By contributing their experiences living with the disease to the patient registries, patients can be active participants in the healthcare journey helping in research and advancement of knowledge of their disease condition.

Patient registries – Researchers and Healthcare Professionals

• Valuable information stored in patient registries, such as patient demographics, familial characteristics, age of onset, and disease progression, helps identify patterns and prognosis, aiding in better understanding and management of the disease by the physicians caring for rare disease patients.
• Collaboration between different patient registries facilitates easier patient recruitment, due to access to a larger and more diverse patient pool, which in turn can enable more robust and comprehensive studies.
• Registries can facilitate better coordination of care among healthcare providers, leading to more efficient and effective treatment plans for patients.
• Registries can also provide valuable insights to healthcare professional through long term monitoring of health outcomes.

Policymakers

• Support for regulatory decisions: Regulators typically favor randomized controlled trial (RCT) data when evaluating medicinal products for marketing authorization. Nonetheless, there are instances where RCT data might be scarce, unethical, or impractical, especially in the context of rare diseases. In such cases, patient registry data can play a vital role in supporting regulatory decision-making. For instance, the updated guideline on Factor VIII products in haemophilia eliminates the need for clinical trials in previously untreated patients but stipulates the collection of core data elements through patient registries for post-authorization studies. This approach ensures that valuable real-world data from registries are utilized to inform regulatory decisions when traditional RCTs are not feasible or appropriate. (Patient Registries: An Underused Resource for Medicines Evaluation)
• By offering comprehensive insights into various aspects of the disease, like prevalence, patient distribution, and healthcare access, patient registries aid governments and non-profit organisations in making well-informed decisions about resource allocation and shaping public policy.

Government-led initiatives have been instrumental in advancing rare disease research through various means, such as promoting awareness programs to educate the public about rare diseases, offering legislative support, providing grants to support research endeavors and help with forming patient registries.

Awareness: GARD, which is a program of the National Institute of Health (NIH) 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”) take 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.

Legislative support: A notable example of Government initiative is the passing of the Orphan Drug Act in 1983. This legislation aimed to incentivize the pharmaceutical industry to invest in the development of therapies for rare diseases. It achieved this through tax incentives, market exclusivity, and exemptions from user fees. The implementation of this act led to a notable surge in research efforts focused on rare diseases.

Grants and funds: The government has been allocating funds and providing grants to support research projects focused on rare diseases. These financial resources help researchers investigate the underlying causes, develop new therapies, and improve patient care. One such example is FDA-funded research. FDA has different funding opportunities for rare disease research. With these funding opportunities, FDA expects to increase the number of approved treatments for rare diseases and exert a broad and positive impact on rare disease drug development. (Funding opportunities for rare diseases)

Patient registries – The government is also helping with forming a patient registry for rare diseases. NCATS (National Center for Advancing Translational Research) one of the centers of NIH launched the rare disease registry program website to provide the rare disease community with easily accessible guidance on how to set up and maintain high-quality registries so that rare disease patient groups support and promote patient focussed rare disease research.

International collaborations have been established to address the challenges associated with rare diseases – one example is the International rare disease research consortium with 60 member organisations from all continents, with funders, researchers, companies, and patient advocacy groups all under one umbrella, with a vision of enabling all people living with a rare disease to receive an accurate diagnosis, care, and available therapy within one year of coming to medical attention.

Apart from government, several nonprofits have been helping rare disease patients in various ways from raising donations and fundraising events to awareness campaigns. Government and nonprofits can work together through collaboration and partnership to achieve common goals and address various challenges in rare disease research.

Can government organisations and nonprofits join forces to establish patient registries and ensure successful clinical trials through collaborative efforts?

Patient registries are immensely valuable for rare disease patients, healthcare professionals, and researchers. Therefore, it is essential for governments to provide funding for the development of patient registries and implement standardized measures that facilitate smooth data sharing among various registries and research groups.

Nonprofits can help with the next crucial step in patient registry – spreading awareness about it and help with populating it with data. By partnering with patient advocacy groups, outreach programs can be conducted to promote the active involvement of patients, healthcare professionals, and researchers in the registries. This increased engagement will result in more extensive and valuable data, facilitating medical advancements and ultimately leading to improved patient outcomes.

Collaborating with governments, nonprofits can streamline regulatory processes for clinical trials and research on rare diseases, ensuring faster progress.

Nonprofits can also engage with patients through patient registries, address their concerns, update the disease progression, create and promote information collaterals, conduct seminars, and keep them abreast of clinical trials. Active participation in the registry will enable patients to recognize its value, leading to a reduction in patient drop-out rates.

The long-term development and sustainability of registries are of paramount importance. Securing additional funding from diverse sources, fostering collaborations with relevant stakeholders, and utilizing technology to streamline data entry and quality control processes can be some effective strategies to address these challenges and to bolster the stability and reliability of registries.

Patient registries can play a vital role in advancing medical research, treatment, and regulatory decision-making in the future benefitting millions of rare disease patients.

References

1. “Can a decision support system accelerate rare disease diagnosis? Evaluating the potential impact of Ada DX in a retrospective study” NCBI, 21 March 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427854/.
2. Rabiei, Reza. “National information system for rare diseases with an approach to data architecture: A systematic review.” NCBI, 20 August 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119672/.
3. “A guide for the diagnosis of rare and undiagnosed disease: beyond the exome – Genome Medicine” Genome Medicine, 28 February 2022, https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01026-w.
4. “Defining Patient Registries and Research Networks – Engaging Patients in Information Sharing and Data Collection.” NCBI, https://www.ncbi.nlm.nih.gov/books/NBK164514/.
5. “Patient Registries: An Underused Resource for Medicines Evaluation: Operational proposals for increasing the use of patient registries in regulatory assessments” NCBI, 13 July 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834729/.)
6. “Rare Disease Day at NIH 2023 | National Center for Advancing Translational Sciences.” National Center for Advancing Translational Sciences |, 22 March 2023, https://ncats.nih.gov/news/events/rdd.
7. “Funding opportunities for rare disease research.” FDA, 30 May 2023,https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/funding-opportunities-rare-disease-research. Accessed 12 July 2023.
8. Augustine, Erika F. “Clinical Trials in Rare Disease: Challenges and Opportunities.” NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964003/.
9. “The importance of international collaboration for rare diseases research: a European perspective.” NCBI, 27 July 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628265/.
10. “Rare Disease Registries – Registries for Evaluating Patient Outcomes.” NCBI, https://www.ncbi.nlm.nih.gov/books/NBK208609/.
11. “Rare Diseases FAQ.” National Human Genome Research Institute, 10 January 2020, https://www.genome.gov/FAQ/Rare-Diseases.
12. “Who we are – IRDiRC.” IRDiRC, https://irdirc.org/who-we-are-2/. Accessed 15 June 2023.

About the Author

Dr. Harsha Rajasimha is the Founder and Executive Chairman of IndoUSrare. IndoUSrare is a humanitarian nonprofit 501(c)(3) tax-exempt public charity organization based in the United States. Dr. Harsha Rajasimha, who lost a child to a rare disease in 2012, has been a rare disease advocate for more than 10 years. To address the unmet needs of diverse patients with rare diseases globally, the leadership team comprised of experienced professionals from research, advocacy, regulatory, and drug development seeks to build cross-border collaborations connecting stakeholders of rare diseases in low- and middle-income regions such as India, with their counterparts and clinical researchers in the United States to improve the diversity of clinical trial participants, accelerate research and development, and improve equitable access to life-saving therapies to diverse populations of rare disease patients. Visit https://indousrare.org.

About the Co-Author

Dr. Padma Rammoorthy is a medical consultant at Indo US Organisation for Rare Diseases (IndoUSrare – https://indousrare.org). Over a span of 26 years, she has transitioned from clinical practice to health education and lifestyle medicine in her career. In recognition of her efforts to raise awareness about maternal health and newborn care in India and worldwide through her social start-up, she has been honored with prestigious awards such as the India Innovation Growth Program and the World Summit Award.