Illustration of a magnifying glass over a strand of DNA surrounded by people.

Rare-disease researchers pioneer a unique approach to clinical trials

Randomization and placebo groups are giving way to biomarkers, real-world data from wearables, and multi-center and adaptive trials.

By Mike May, Nature Medicine

In the development of new treatments for rare diseases, a crucial challenge lies in the name: rare. Despite their being rare, there are many of these diseases, with more than 7,000 diseases that each affect fewer than 200,000 Americans, according to the US Food and Drug Administration (FDA). Researchers are continually trying to develop safe and effective new treatments for thousands of rare diseases, but it is difficult. Some of the most promising approaches lie in modified clinical trials and making use of real-world data.

The European Medicines Agency (EMA) defines a disease as rare if it afflicts fewer than 5 people in 10,000. The list includes well-known diseases, such as sickle-cell disease, and more-obscure diseases, such as the neurodegenerative disease aceruloplasminemia, the autoimmune disorder Schnitzler syndrome, and Waldenström macroglobulinemia, a type of lymphoma.

Even within one rare disease, many subtypes can exist that require personalized approaches to therapy. As one example, EMA’s chief medical officer Steffen Thirstrup mentions cystic fibrosis, which affects around 1 in 2,500 babies born. “When I left medical school 30 years ago, we knew that cystic fibrosis was caused by a genetic defect, but now we know that different mutations in the genome can cause this disease,” he explains. “So now, you actually start to subsegment this rare disease, which adds additional complexity to finding patients and screening them to find out whether they’re eligible for a trial.” Read more …