RARE needs CARE! Indian Scenario

Rare diseases?are often serious, chronic, and life-threatening conditions. WHO defines a rare disease as often debilitating lifelong disease or disorder with a prevalence of 1 or less, per 1000 population. However, different countries have their definitions to suit their specific requirements and in the context of their population, the health care system, and resources. This has resulted in heterogeneity in rare disease definition and therefore consensus among nations does not exist. Nevertheless, it is generally accepted that a disease having fewer than 100 patients per 100,000 population is described as a rare disease and fewer than 2 patients per 100,000 are described as an ultra-rare disease. Ultra rare diseases are the rarest of rare diseases. Rare and ultra-rare diseases are sometimes referred to as orphan and ultra-orphan diseases, respectively.

Disease Prevalence Data:

The gross estimate of the number of rare or ultra-rare disease patients is 6 - 8% of the global population and is widely accepted by researchers. This consensus, fortunately, allows us to fathom the situation at hand and also helps provide geographic regional estimates. More than 70 million people of India suffer from the plethora of Rare Diseases, manifesting in childhood which remain with them throughout their lives. Registry is important for determining the precise number of patients, age of onset of symptoms, age of diagnosis (to determine for delay for making the diagnosis), the course of disease / natural history of disease. Here an attempt is made to derive ‘probable’ numbers for rare and ultra-rare disease patients in various South Asian countries based entirely on the officially reported current population of respective countries (Table 1). Similarly, rare disease patient numbers for individual states and territories in India are derived as well (Table 2).

Issues And Challenges

The field of rare diseases is complex and heterogeneous. The landscape of rare diseases is constantly changing, as there are new rare diseases and conditions being identified and reported regularly in medical literature. Apart from a few rare diseases, where significant progress has been made, the field is still at a nascent stage. For a long time, doctors, researchers and policy makers were unaware of rare diseases and until very recently there was no real research or public health policy concerning issues related to the field.

The formidable challenges in rare disease for developing a comprehensive policy are:

Screening & Diagnosis: Early diagnosis of rare diseases is a challenge owing to multiple factors that include lack of awareness among primary care physicians, lack of adequate screening and diagnostic facilities.

Many doctors lack appropriate training and awareness to be able to correctly and timely diagnose and treat these conditions. According to a recent report2, it takes patients in United States (US) an average of 7.6 years and patients in United Kingdom (UK) an average of 5.6 years to receive an accurate diagnosis, typically involving as many as eight physicians (four primary care and four specialists). In addition, two to three misdiagnoses are typical before arriving at a final diagnosis.

Delay in diagnosis or a wrong diagnosis increases the suffering of the patients exponentially. There is an immediate need to create awareness amongst general public, patients & their families and doctors, training of doctors for early and accurate diagnosis, standardization of diagnostic modalities and development of newer diagnostic and therapeutic tools.

Affordable & Accessible Treatment: Affordability and accessibility to medicines are important to reduce morbidity and mortality associated with rare diseases. Despite progress in recent years, effective or safe treatment is not available for most of the rare diseases. Hence, even when a correct diagnosis is made, there may not be an available therapy to treat the rare disease. There are between 7000 - 8000 rare diseases, but less than 5% have therapies available to treat them. About 95% rare diseases have no approved treatment3 and less than 1 in 10 patients receive disease specific treatment. Where drugs are available, they are prohibitively expensive, placing immense strain on resources.

Orphan Drug

As the number of persons suffering from individual rare diseases is small, they do not constitute a significant market for drug manufacturers to develop and bring to market drugs for them. For this reason, rare diseases are also called ‘orphan diseases’ and drugs to treat them are called “orphan drugs”.

At present, very few pharmaceutical companies are manufacturing drugs for rare diseases globally and there are no domestic manufacturers in India except for Food for Special Medical Purposes(FSMP) for small molecule inborn errors of metabolism. Due to the high cost of most therapies, the government has not been able to provide these for free. It is estimated that for a child weighing 10 kg, the annual cost of treatment for some rare diseases, may vary from Rupees 10 lakh to more than 1 crore per year with treatment being lifelong and drug dose and cost, increasing with age and weight. On the above onset of discussion, it's the high time to clear some of the myths regarding "orphan drugs" & The Orphan Drug Act, as rightly pointed out through the infographic bellow.         

These drugs have multiple indications, both orphan and non-orphan. For example, HUMIRA? has 12 indications, 4 of which are orphan. Of its $13.6 billion in total sales in 2016, only 3.8% were for orphan indications. Of the total drug sales of $450 billion in the U.S. in 2016, only 7.9% were for orphan designations of approved drugs. Specialty drugs are defined by special requirements (i.e., for storage or handling); how they are administered (i.e., by a professional or as an infusion); and how much they cost. While an orphan drug may be a specialty drug, not all specialty drugs are orphans. The Orphan Drug Act has helped drive innovation in many fields within medicine, including cancer treatment.

Type of Disease in India

So far only limited number of diseases has been recorded in India from tertiary care hospitals that are globally considered as rare diseases though ambit may encompass from 7000 to 8000 disorders. The commonly reported diseases include Primary immunodeficiency disorders, Lysosomal storage disorders (Gaucher’s disease, Mucopolysaccharidoses, Pompe disease, Fabry disease etc.) small molecule inborn errors of metabolism (Maple Syrup urine disease, organic acidemias etc.), Cystic Fibrosis, osteogenesis imperfecta, certain forms of muscular dystrophies and spinal muscular atrophy, etc.

Rare Disease Policy 2021

In the circumstances, though framed with best intent, the policy had implementation challenges and gaps, including the issue of cost effectiveness of supporting such health interventions for limited resource situation, which made it not feasible to implement. Given the challenges in implementing the policy, the need for wider consultation and recommendations, a decision was taken to reframe the National Policy for Treatment of Rare Diseases. An Expert Committee was constituted by Ministry of Health and Family Welfare in November, 2018 to review the NPTRD, 2017.

The policy aims at lowering the incidence and prevalence of rare diseases based on an integrated and comprehensive preventive strategy encompassing awareness generation, premarital, post-marital, pre-conception and post-conception screening and counselling programmes to prevent births of children with rare diseases, and within the constraints on resources and competing health care priorities, enable access to affordable health care to patients of rare diseases which are amenable to one-time treatment or relatively low cost therapy.

Implementation Strategy

The Government will have a hospital based National Registry for Rare Diseases at ICMR with the objective of creating a database of various rare diseases. Steps have already been taken in this direction by ICMR. Over a period of time, the registry is expected to yield information on hospital based data and disease burden.

ii. The Government shall take steps to create awareness amongst all the levels of health care personnel as well as general public towards the rare diseases. This will encourage people to seek pre-marital genetic counselling, identification of high- risk couples & families and also result in prevention of births as well as early detection of cases of rare diseases. Simple standard protocols/algorithms would be developed for screening and diagnosis in order to avoid missing cases and provide best possible management.

iii. Public Health and hospitals being a State subject, the Central Government shall encourage and support the State Governments in implementation of a targeted preventive strategy.

iv. The Government shall provide financial assistance upto Rs. 20.00 lakh (under the Umbrella Scheme of Rashtriya Arogya Nidhi) to the entitled population, as per PMJAY norms, for their treatment in Government tertiary hospital, for rare diseases amenable to one-time treatment (identified under Group 1).

v. The State Governments may undertake treatment of disorders managed with special dietary formulae or food for special medical purposes (FSMP) and Disorders that are amenable to other forms of therapy (hormone/ specific drugs)- diseases covered under Group 2.

vi. The Government shall notify selected Centers of Excellence at premier government hospitals for comprehensive management of rare diseases. The Centers of Excellence will be provided one time grant subject to maximum of Rs. 5 crore each for infrastructure development for screening, tests, treatment, if such infrastructure is not available.

vii. The Government shall create a digital platform for bringing together notified Centers of Excellence where patients of rare diseases can receive treatment or come for treatment, on the one hand and prospective voluntary individual or corporate donors willing to support treatment of such patients. Funds received through this mechanism will be utilized for treatment of patients suffering from rare diseases.

viii. In order to maintain transparency of transactions in provision of funding under RAN/ crowd funding etc., the Centers of Excellence receiving the funds should have linkages with the ICMR registry.

ix. The Government shall facilitate the creation of an enabling environment that promotes research & development of diagnostic and therapeutic modalities within the Country. Consortium of Centers of Excellence shall be created so that research efforts are synchronized. AIIMS, Delhi will be nodal hospital to coordinate with other Centres of Excellence for various activities.

x. State Governments will be requested to create Department of Medical Genetics at least in one medical college in the State for imparting education and increasing awareness amongst health care professionals. This will strengthen manpower base in the country for managing Rare Diseases.

xi. Department of Pharmaceuticals, Department for Promotion of Industry and Internal Trade (DPIIT) will be requested to promote local development and manufacture of drugs for rare diseases by public and private sector pharmaceutical companies at affordable prices and take legal/legislative measures for creating conducive environment for indigenous manufacturing of drugs for rare diseases at affordable prices. PSUs could also be encouraged for local manufacturing of drugs for rare diseases.

xii. Ministry of Finance will be requested for reduction in custom duties on import of medicines related to rare diseases.

Let us take a pledge on the occasion of 'Rare Disease Day 2022', help the survivor like Rakesh to smile & join the main stream of life once gain.