Ultra-Rare Diseases: Decentralized Solutions To Tackle Challenging Clinical Studies

What is a rare disease? The answer seems obvious, yet there is not a universally agreed-upon definition. In fact, there are almost 300 different definitions from over 1,100 organizations with interest in rare diseases.(1) So it isn’t surprising that there is even less certainty about what constitutes an ultra-rare disease. 

What Is an Ultra-Rare Disease? 

As per the case with rare disease in general, there is no single definition of what constitutes an ultra-rare disease. That said, there are some guidelines that provide insight: 

• In Europe, a disease is generally considered to be ultra-rare if it affects one patient per 50,000 people (or fewer than 20 patients per million of population). (2,3) This is the definition used at THREAD 

• Other scholarly sources use < 1 patient per 100,000 as the definition (4) 

• Others define ultra-rare as even more scarce. For instance, The n-Lorem Foundation (5) defines ultra-rare as a disease that occurs either when a patient has a mutation unique to them or has a mutation that has been identified as causing disease in fewer than 30 patients worldwide and is therefore out of the reach of traditional commercial drug programs  

The total number of patients affected with ultra-rare diseases runs into the millions and that number grows each year as advances in genome sequencing improves the ability to diagnose them. Whatever definition is used, the extreme rarity of such patients presents unique challenges to their diagnosis and treatment paradigms. Further, the diseases that these patients experience are typically severe, often fatal, and frequently cause developmental delays, mobility difficulties, and other healthcare issues. In short, these patients are desperate and underserved.