Collectively, rare diseases affect a huge number of people: about 25 million in the US and 400 million globally. To qualify as a rare disease per the US standard, fewer than 200,000 Americans must be affected by the condition, or per the EU standard, fewer than 1 in 2000 Europeans must be affected. That is still a significant number of people.

Unfortunately, many rare diseases were previously treated as orphan diseases – or diseases whose drug development was halted because of the lack of a promising ROI – and have fallen behind in the pharmaceutical sector. That is changing now that pharmaceutical companies are realizing the many niches that have been left untouched; about 7,000 rare diseases have been classified up to this point.

Aside from a fear of a low ROI, pharmaceutical companies have been hesitant to take on rare disease drug development because the indications can be challenging to study.

Here are some common challenges experienced during the course of researching rare diseases:

  • It’s hard to find enough patients. Rare diseases are labeled “rare” for a reason. But this doesn’t mean it is impossible to find the patients; it just requires the right resources, a highly motivated research team, and a little bit of creativity. This challenge also means that there is a smaller pool of patients to draw from for phase II and III trials, but adaptive design trials can offer a way around this so that the same patients may be used for multiple phases.
  • The research is underdeveloped. Validated assessment tools and operational definitions are lacking because each indication is so unique. The disease etiologies are also often less understood at the basic science level because of the historical lack of resources set aside to study rare diseases. Legislation has attempted to change this, though.
  • Affected populations are often pediatric. Rare diseases, especially those that are of genetic origins, generally present early in life and thus affect pediatric populations. Children are often more challenging to study for many reasons, including additional ethical/regulatory constraints.
  • Clinical manifestations are heterogeneous. Within a single disease, each individual patient can have very different, seemingly disconnected symptoms. This challenge can delay a physician’s time to diagnosis, and a patient usually can’t participate in a trial until they have a confirmed diagnosis, meaning that recruiting physicians may have to rely on their current patients for recruitment rather than turning to other clinical data repositories. Better biomarkers are needed in order to more quickly and accurately diagnose each disease, which requires a better understanding of the basic science.

Although each rare disease is unique, some elements of the clinical operations of rare disease trials are consistent across indications. Anyone studying a rare disease needs to be good at working with pediatric populations, have a large network of physician researchers but can also standardize the large number of physicians to the protocol and clinical assessments, and be able to employ creative means of recruiting patients using multiple media. Virtual trials may be an appropriate means for reaching these targets, since they are designed to address these very challenges.

Keep an eye out for our white paper on this topic early next year! We will go into more depth about how rare diseases really are more similar than they are different.