The difficulties of finding the right participants for a clinical trial are intensified when that trial centres on a rare disease. We look at the unique challenges of developing clinical trials for orphan drug development.
Although rare diseases affect 300 million people worldwide1 – more than cancer and Alzheimer’s Disease combined – most of these conditions have limited or no treatment options.
One reason for this is that with around 10,000 known rare diseases, the pool of potential participants for individual trials is small and often widely dispersed geographically. Where conventional, parallel, randomised controlled trials are not feasible, researchers may need to work with regulatory agencies to develop acceptable trial parameters. This could be extending trial duration to increase the events captured per patient, selecting patients likely to respond to treatment, or using broad networks to maximise study access. A 2020 study published by the National Library of Medicine outlined four design options for rare diseases2.
Another issue is that there is often limited understanding of the underlying biology of rare diseases compared with more common diseases, making it difficult to identify potential ways to treat them. Many rare diseases do not have well-defined or validated outcome measures and biomarkers which are usually used to demonstrate impact and effectiveness in trials. With no or few clinical trials already undertaken in a particular area, there may be no established regulatory pathways.
One of the solutions to this lack of understanding is engaging closely with the patient communities themselves. For a successful trial it’s important to understand not only the biology but also the impact the disease has on the lives of patients and the unique challenges they face so that the trial can be designed in a way that suits them.
While drug development for rare diseases has historically been underfunded, this picture is changing. In 2022 over half of the novel drugs approved by the FDA were orphan drugs3 and there are increasingly financial incentives in place to encourage this area of research. In the UK, the National Institute of Health Research announced a series of new initiatives in 2023 including £790 million funding for research into rare conditions as part of the government’s Rare Disease Action Plan for England4. To translate research into approved clinical interventions which change lives, taking a patient-centric approach and engaging with rare disease communities will be vital.
