A rare disease is typically defined as a condition affecting fewer than 200,000 people in the US or fewer than 5 in 10,000 people in the EU. There are over 7,000 known rare diseases, and most have limited or no approved treatments. Clinical trials are often the primary pathway to new therapies for rare disease patients. This guide covers the unique aspects of rare disease trials and how to find them.
Why Rare Disease Trials Are Different
The fundamental challenge in rare disease research is the small number of patients available. This affects every aspect of trial design:
• Smaller sample sizes — trials may enrol dozens of patients rather than thousands
• International recruitment — patients may need to travel to specialised centres, sometimes in other countries
• Longer enrolment periods — finding enough eligible participants takes more time
• Flexible trial designs — regulators may accept alternative study designs (such as single-arm trials or crossover designs) that would not be used for common diseases
• Natural history studies — because many rare diseases are poorly understood, trials may first study the disease itself before testing treatments
Regulatory Incentives for Rare Disease Research
Governments provide special incentives to encourage pharmaceutical companies to develop treatments for rare diseases:
Orphan Drug Designation (US/EU/AU): Provides tax credits, fee reductions, and market exclusivity (7 years in the US, 10 years in the EU) to companies developing rare disease treatments.
Fast Track, Breakthrough Therapy, and Accelerated Approval (US FDA): These pathways speed up the review process for drugs that treat serious conditions with unmet medical needs.
Priority Review (TGA, Australia): Similar expedited review for drugs addressing serious conditions.
These incentives have led to significant growth in rare disease drug development. Over 600 orphan drugs have been approved in the US since the Orphan Drug Act was passed in 1983.
How to Find Rare Disease Trials
Finding trials for rare diseases requires a more active search than for common conditions:
• Search ClinicalTrialsFinder.org or ClinicalTrials.gov using your specific condition name
• Contact patient advocacy organisations for your condition — they often maintain lists of ongoing trials and can connect you with researchers
• Reach out to academic medical centres that specialise in your condition
• Ask your specialist directly — doctors treating rare diseases are often connected to the research community
• Check international registries — trials for rare diseases are frequently conducted across multiple countries
Patient advocacy groups are particularly valuable for rare disease trials because they serve as information hubs connecting patients, researchers, and pharmaceutical companies.
Considerations for Rare Disease Patients
Travel may be required. Rare disease trials are often conducted at a small number of specialised centres. Some trials offer travel support or decentralised elements (such as remote monitoring or local lab work) to reduce the burden.
Expanded access programs may be available. If you do not qualify for a trial or if a trial is not currently recruiting, you may be able to access an investigational treatment through an expanded access (compassionate use) program. Your doctor can request this directly from the drug manufacturer.
Natural history studies matter. Even if a trial is not testing a treatment, participating in a natural history study contributes to understanding your condition and helps design future treatment trials.
Frequently Asked Questions
What is an orphan drug?
An orphan drug is a medication developed specifically to treat a rare disease. The term comes from the Orphan Drug Act (US, 1983), which provides incentives for pharmaceutical companies to develop treatments for conditions affecting small patient populations. Similar legislation exists in the EU, Australia, and Japan.
Are rare disease trials less safe?
Rare disease trials follow the same safety standards and regulatory oversight as all clinical trials. Ethics committee review, informed consent, and data safety monitoring are required regardless of the disease. The smaller sample sizes mean that rare side effects may be harder to detect, but the fundamental protections are the same.
What if there are no trials for my condition?
If no trials are currently available, contact patient advocacy organisations for your condition, reach out to academic researchers studying the disease, and ask your specialist about expanded access programs. You can also set up alerts on ClinicalTrialsFinder.org to be notified when new trials open for your condition.
Can I participate in a trial in another country?
Yes, many rare disease trials recruit internationally. Practical considerations include travel costs, visa requirements, insurance coverage abroad, and follow-up logistics. Some trial sponsors provide travel support for international participants. Discuss the feasibility with the study team.