Rarity is an attribute which finds contextual appreciation or criticism. A rare gem could be an object of utmost desire, but a rare genetic mutation which translates into the rare, incurable disease is not. A disease which shows particularly low prevalence as it affects a small number of individuals in a population classifies as a rare or orphan disease. Such diseases are yet to be captured in a single universal definition, as defining these diseases is a complex issue. It is because these diseases show symptomatic heterogeneity, influenced by the socioeconomic and demographic condition of the patient as well. Most of the definitions are therefore based on prevalence estimates, undermining the factors of geographic location, level of rarity, diagnostic prevalence, and ability to be studied. The global review of terminology and definitions of rare diseases advises avoiding the use of qualitative descriptors such as life-threatening in rare disease definitions. It is necessary to reduce uncertainty and promote standardized practices.
It is not just the conceptual complexities which find a relation with these diseases, but the intricacies of therapeutics and research as well. The complexities include having specific knowledge of each disease, nature of a disease, widely dispersed patient population, lack of biomarkers, clinical expertise and expert centers. In lieu of such complexities the rare diseases are rendered unsuitable for pathophysiologic studies, and drug development, casting them as orphan diseases. Correspondingly, rarity makes the diseases less attractive to pharmaceutical companies as well which shy away from investing in drug development, and the drugs are thus referred to as orphan drugs. The lack of recognition and negligence has paved a way to a parallel world of problematic issues, such as unrecognized disease burden, an absence of a policy framework, highly expensive and often inaccessible diagnostic and treatment procedures. Out of the 7000 known rare diseases, 80% are known to have a genetic origin, 75% are known to affect children, and 30% of affected patients die at an early age of 5 years. These diseases constitute a large group of diseased conditions resulting in serious social problems and tremendous economic burden on survivors. As these diseases comparatively find less degree of research, reliable quantitative data for a burden of disease is also missing. Furthermore, in developing countries like India, no defining criteria have been established for rare diseases.
A rarity of policies and initiatives in India
450 rare diseases are known to exist in the Indian population however the quantitative data regarding disease prevalence does not exist. The statistical estimations of the number of people suffering from rare diseases in Indian states, extrapolated from global prevalence rates, have been put forth by Foundation for Research on Rare Diseases and Disorders. Amongst the union territories, NCT of Delhi leads the population estimates for rare diseases and disorders with 1,005,194 people accounted to be affected by rare diseases. Out of the 450 diseases, the most common rare disease in the Indian population includes Thalassemia, Primary Immuno Deficiency diseases, Haemophilia, Lysosomal storage disorders, and Sickle-cell anemia. The lack of prevalence studies even led to the misinformed classification of diseases as rare conditions. For example, cystic fibrosis earlier thought to be a rare disease does not classify as one, as unveiled by the genetic analysis. A dearth of diagnostic procedures and experts such as genetic medicine specialist makes genetic disease as mysteries lost in the abyss.
The rare diseases continue to pose as critical public health issues. The high degree of heterogeneity and deficit of scientific and medical knowledge is accompanied with non-existent government policies. The initiatives to spread awareness and provide support to affected individuals mostly comprise of not for profit, non-political and non-governmental groups, established by the responsible stakeholders of the society. These organizations and charitable groups encompass different rare diseases such as the LSDSS group focuses on providing support and treatment for patients suffering from Lysosomal storage diseases.
The Rett Syndrome Foundation is a national level initiative of parents, families, scientists, health professionals, doctors, and caretakers, the organization strives to identify people with Rett syndrome, spread awareness, improve the quality of life of patients, and counsel families on the management of Rett syndrome. Many of these organizations are parent initiatives such as the Pompe foundation, the trust started by parents of a little girl suffering from Pompe’s disease, a rare and deadliest LSD, campaigns for early diagnosis of disease, besides availability of adequate, safe, and affordable therapies while extending support to families and caretakers concerned with related diseases.
Sjorgen’s India is a volunteer-led foundation which works toward patient empowerment by creating awareness about Sjogren syndrome, providing a platform for patient’s to interact with multi-specialty doctors, facilitating scientific research, and developing educational resources besides advocating for the issue concerning disease management. The scientific initiatives include Dystrophy Annihilation research Trust (DART) and GUaRDIAN. Indian Council of Medical Research (ICMR) also launched a registry for rare diseases on 27 April 2018 to determine the number of patients, the age of onset of symptoms, diagnosis, and course of the disease.
DART is a parent founded and funded research lab aimed towards finding a treatment option to help alleviate and reverse Duchenne Muscular Dystrophy at the genetic level, enhancing the quality of life of affected children. GUaRDIAN, on the other hand, is CSIR and Institute of Genomics & Integrative Biology (IGIB) initiative comprising of more than 100 clinicians and 25 medical research centers in a collaborative research programme which works towards understanding the genetic and molecular basis underlying the rare genetic disorders. Concerning promotion of orphan drug research and manufacture the Central Drugs Standard Control Organization (CDSCO) issued a notice concerning the waiver of a clinical trial for approval of new orphan drugs for rare diseases and diseases with no therapy. To address the issue of the policy framework, the central government finalized the National Policy on Treatment of Rare Diseases in May 2013. The interdisciplinary committee appointed for the formulation of policies made the below-mentioned recommendations.
The Indian Government still needs to tread the policy path further and bring into action relevant act concerning the development of orphan drugs.
Global Scenario of Rare Diseases
The primary issues for patients suffering from rare diseases and those who are at risk are the equitable and timely access to appropriate healthcare infrastructure. The easy access to timely diagnosis and treatment with sufficient supportive care can help rare disease patients lead a better life. To ensure that rare diseases are designated as a public health priority the International Rare Diseases Research Consortium (IRDiRC) has collaborated with relevant researchers and organizations to deliver 200 new therapies for rare diseases by 2020, with suitable diagnostic measures. The global initiatives reflect a better recognition of the compromised quality of life of those suffering from rare diseases. The initiatives aim towards implementation of patient-centered, appropriate, public policies, incorporating rare diseases into the healthcare system design strategies.
EURORDIS, the umbrella organization for rare diseases in Europe, represents 300 rare disease organizations in more than 30 countries across Europe covering more than 1000 rare diseases. The organization aims to empower patients by fighting for their right to timely diagnosis, quality health care and treatments, and equitable social involvement. Besides patient empowerment, the European law states that the “Patients suffering from rare conditions should be entitled to the same quality of treatment as other patients.” The European legislation, therefore, pays attention to orphan drug development and regulation 141/2000 provides commercial incentives for development of orphan drugs to stimulate their development by the pharmaceutical industry. Correspondingly, the Orphan Drug Act of 1983 enacted by the USA was the first orphan drug legislation and has been acclaimed with success in encouraging the development of orphan products. Other nations which have established orphan drug legislations include Japan, Singapore, and Australia. Some of the other significant global initiatives are as mentioned below.
|S. No.||Name of organization||What the organization strives to do?|
|1||National Organization for Rare Disorders (rarediseases.org)||A patient advocacy group working with more than 280 patient organization NORD works towards identification, treatment and cure of rare disorders through educational programs, research, advocacy, and patient services.|
|2||EURORDIS (eurordis.org)||A non-governmental patient-driven alliance of patient organizations and individuals active in the field of rare diseases in Europe.|
|3||IRDiRC (irdirc.org)||A global consortium spanning across Africa, Australia, Asia, North-America, and Europe, it unites the various national and international governmental bodies, advocacy groups, and researchers for collaboration and research in rare disease.|
|4||Orphanet (orpha.net)||A unique information resource, gathering and improving knowledge on rare diseases by providing high-quality information to improve diagnosis, care, and treatment of patients with rare diseases.|
|5||Office of rare diseases research||A division of National Center for Advancing Translational Sciences oversees the Rare Diseases Clinical Research Network and Genetic and Rare Diseases Information Center.|
|6||Rare genomics institute (raregenomics.org)||An organization working alongside patients and their families to provide the necessary tools, knowledge, and connection to help them better understand the disease.|
|7||In need of diagnosis (inod.org)||In Need Of Diagnosis, Inc. (INOD) advocates for increased
accuracy and timeliness of diagnoses and
is a resource center for those who suffer with
illnesses that have eluded diagnosis.
|8||Syndromes without a Name (swanaus.org.au)||Syndromes Without A Name (SWAN) Australia provides information and support to families who have a child with an undiagnosed or rare genetic condition.|
|9||Online Mendelian Inheritance in man (omim.org)||An open database, OMIM provides essential information regarding clinical features, phenotypes, genes, and other aspects of rare diseases. It is mainly intended for physicians, genetic researchers, and professionals to advance research and study of rare genetic diseases.|
|10||Rare diseases international||A global alliance of survivors of rare diseases, RDI works towards advocacy for rare diseases to be recognized as the international public health priority.|
Table 2: Global initiatives towards the betterment of life of people suffering from rare diseases
A long way to sustainability…
As evident from the existing state of public health policies, legislation, diagnostic, and treatment options the awareness and the need to recognize rare diseases as a public health priority continues to increase around the globe. In developing nations like India, there is a lack of awareness at the grassroots level, which often results in late diagnosis or no diagnosis at all. The Government of India has come to realize the importance of dedicated public policy concerning the treatment of rare diseases. However, the lack of legislation providing research and development incentives to pharmaceutical companies continues to fuel the negligence of orphan drugs and diagnostic procedures. This further poses a high economic burden on the patience to access the diagnostic and treatment procedures. The global scenario reflects a better image of rare disease initiatives with developed economies having well established legislative and policy frameworks to provide equitable and timely access to appropriate healthcare infrastructure to rare disease patients. However, there is still a lot to be achieved to fulfill the dearth of genetic specialists, establishing standardized measures of disease definition, and ensure that rare disease no longer remains orphan.