How is a Rare disease defined? Well, it depends on the geography in question, since there is no universal definition, even so, the definition revolves around the point of prevalence or incidence of rare disease. If we talk about the United States, a rare disease affects fewer than 200,000 people (Orphan Drug Act). While in the European Union, a rare disease is a disease that affects fewer than 1 in 2,000 people. However, despite the changing attributes in the definition, there is one common ground every country faces‒challenges in mapping the patient pool, R&D, development of therapies, and investments & funding. Let us have a look at the unique challenges that Rare diseases pose that impact healthcare, regulatory agencies, but mainly patients. 

Lack of knowledge.

The first and foremost challenge is the struggle in identifying and understanding the pathophysiology of the disease. With varying demographics, race, and ethnicity, symptoms and causes may vary, and it often gives rise to chaos and frustration. Rare disease patients are vastly spread and heterogeneous in disease subtypes, symptoms, stages, and exposure to prior treatment. The limited number of patients who have reported the disease limits the number of medical practitioners dealing with it. Data recorded is restricted, and it does not offer the chance to fully examine and analyze the disease. 

Rare is frequent.

Rare diseases are individually rare, however, en masse, they are agreeably vast. Many times it takes years of consultations, hospital visits, and tests for an accurate diagnosis of any rare disease. According to reported data, there are around 7000 identified rare diseases, with several being discovered all the time. Rare diseases are difficult to diagnose. Many have non-specific symptoms; while others have unusual symptoms. Many progress gradually and slowly within the body. There is no way to find out when the journey will end unless the prescribed therapies start to improve the condition. 

Patients and their misery. 

For patients, the path towards an appropriate diagnosis is bleaker than any figure represents. The challenges to patients with a rare disease are that they keep on struggling with the disease, manifesting the symptoms, and find a knowledgeable physician who would accurately diagnose and prescribe treatment for it. Cases of misdiagnosis and prescription of wrong treatment regimen are umpteen. Further, after diagnosis, the huge cost of the treatment as well as long-distance travel to get specific treatment drill holes in their pockets. In the fullness of time, every second of wait or search can proportionate to a missed opportunity to save a life. 

Dilemma of physicians. 

The challenges to physicians attending rare disease patients mirror the concerns faced by the patients. We discussed how late and misdiagnoses of rare disease is a common sight, and how it adds to the medical bills, physical stress, and mental burden for the patients and their families. However, physicians find it equally challenging and difficult while dealing with rare diseases. The exposure any physician is ought to get with rare disease patients is not very high owing to the dispersed patient pool of rare diseases.  Knowledge and experience of the clinicians build over time while they deal with patients, which is not the case in rare diseases owing to fewer patients that report such diseases. 

Screening and diagnosing?

Despite technological and medical advances in recent years, misdiagnosis or underdiagnosis of rare diseases forms a significant challenge. Often patients spend years, however, many neither get the name right nor treatment. Diagnosed without treatment is better than being underdiagnosed or misdiagnosed because in former cases, at least, patients get a chance to undergo the right treatment than none at all. However, diagnostic tests themselves cost a lot. There is a clear lack of services, technology, and understanding of the diagnostics and screening methodologies that can accurately detect and differentiate among a myriad of rare diseases. 

Rare is costly.

In many cases, the treatment of rare diseases is extremely costly. Caretakers and families of patients shell out thousands of dollars yearly to buy orphan drugs, as designated by the USFDA. Pharmaceutical companies sell their orphan drugs at astronomical prices such that many patients are not able to afford them. Past years saw an increase in the entry of Orphan drugs in the market – at higher rates than ever before, and it is hurting the families and patients. 

Funding is an issue! 

A rare disease is a costly affair. High costs associated with launching a new drug in the market that has a limited patient pool discourages potential sponsors and pharma enterprises to invest in it. Therefore, rare disease patients were ‘orphaned’ by them and left without treatment. However unfortunate this is, it can be understood. Developing a new drug requires years of research, time, and money; and in cases where winds are against the market forces and profit margins appear shallow, conducting and bearing the cost for such trials can prove to be a pretty penny.  

Conducting clinical trials for rare diseases?

Conducting clinical trials for orphan diseases is as important as for any other disease, however, in this case, it is nothing but a tough row to hoe. The clinical trials and patient studies are vital to deciding on effective and ineffective treatments; however, given the minuscule patient populations, the designing of the trials, recruitment of patients in the trials, and evaluating the results is extremely difficult. It makes it hard to rely on results obtained from short cohorts. Further, it gets expensive both in terms of time and money to run trials for rare diseases whose patients are widely spread all over the world. 

Aftermath of clinical trials. 

The struggle continues even after the designing and conducting of trials. Mapping the journey through the trials, and deriving an outcome from it is equally challenging. Further, the nod from regulatory agencies to run the trial, post-approval process, and assessment of the drug play a greater role that can not be neglected or compromised. Studies demonstrate varying results owing to varying age, the pace of progression of the disease, ethnicity, race, age, and severity. Thus, lost in diversity of data, researchers often find themselves in turmoil while measuring clinical trial outcomes in rare disease patients. 

Thus, the crux of the matter is that lack of knowledge compounded with other challenges invariably lands patients, their caretakers, clinicians, and investigators in a difficult place. On the flipside, rare diseases project a shedload of opportunities as well. Medical research for orphan conditions has opened innumerable avenues to chart into the waters, explore the unexplored world of the rare disease, and emerge with novel therapies to lessen down their burden. Over time, several pharma companies such as Celgene, Takeda, Eli Lilly, Novartis, BMS, Alexion, Sanofi, Vertex Pharmaceuticals, Roche, bluebird bio, Amgen, Biogen, and many more have come up with novel approaches and novel orphan drugs that include oral, inhalable, and injectable therapies; drug-device combination products, novel gene therapies, diagnostics methods, and others to bring relief to the patients. 

The health regulatory agencies all over have issued several guidelines, released strategies, and amended regulations to expedite the drug delivery process in the rare disease market landscape. Keeping in mind unique challenges, including low patient numbers, limited understanding of disease pathology and progression, variability in disease presentation, and a lack of established endpoints, regulatory bodies, and advisory bodies have taken a flexible stance. Undoubtedly, strides of improvements are made in healthcare, however, there remains a lot to traverse.