Clinical Trials for Rare Diseases — Finding Hope in Research

What qualifies as a "rare disease"?

In the United States, a disease is classified as rare if it affects fewer than 200,000 people at any given time. In the European Union, the threshold is fewer than 1 in 2,000 people. These definitions matter because they determine whether a treatment qualifies for special regulatory incentives.

There are an estimated 7,000 to 10,000 rare diseases, and collectively they affect roughly 30 million Americans. About 80% of rare diseases have a genetic component. Many are diagnosed in childhood, though symptoms can appear at any age.

The rarity of each condition creates a fundamental challenge for research: there simply are not enough patients to run the large-scale trials that are standard for common diseases like diabetes or heart disease.

The Orphan Drug Act and why it matters

Before 1983, pharmaceutical companies had little financial incentive to develop treatments for rare diseases. The patient population was too small to recoup research costs. The Orphan Drug Act changed that by offering companies several incentives:

• Seven years of market exclusivity after approval, meaning no competing generic version can be sold during that period.
• Tax credits for clinical trial expenses.
• Reduced FDA fees and eligibility for research grants.
• Faster regulatory review pathways including Accelerated Approval and Breakthrough Therapy designation.

The impact has been significant. Before the Orphan Drug Act, fewer than 40 drugs had been developed for rare diseases. Since then, the FDA has approved more than 600 orphan drugs, and thousands more are in development.

The European Union adopted similar legislation in 2000, and Japan, Australia, and other countries have followed with their own orphan drug frameworks.

How rare disease trials are different

The small number of patients with any given rare disease forces researchers to adapt their study designs. Here are the key differences you may encounter:

Smaller enrollment

Where a Phase 3 trial for a common condition might enroll thousands of participants, a rare disease trial may include only 30 to 100 people. Some ultra-rare conditions have been studied with fewer than 20 participants. Regulatory agencies accept this when the disease is truly rare.

Single-arm studies

In a traditional trial, one group receives the treatment and another receives a placebo or standard care. When patients are scarce, researchers sometimes use a single-arm design where everyone receives the treatment. Results are compared against the patient's own baseline health or against historical data from untreated patients.

Natural history studies

Before a treatment can be tested, researchers need to understand how a rare disease progresses without intervention. Natural history studies follow patients over time to document this progression. Participating in a natural history study does not involve receiving any treatment, but the data collected is essential for designing future treatment trials.

Adaptive trial designs

Some rare disease trials use adaptive designs that allow researchers to modify the study as data accumulates, for example by adjusting dose levels or dropping an ineffective treatment arm. This approach maximizes the information gained from a small number of participants.

Expanded access and compassionate use

When a rare disease treatment shows early promise, patients who do not qualify for the trial may be able to access the drug through expanded access programs, sometimes called compassionate use. The FDA has streamlined the application process for these requests.

Finding trials for your rare condition

Locating a clinical trial for a rare disease requires a more proactive approach than for common conditions. Here are the most effective strategies:

• Search ClinicalTrials.gov using your specific diagnosis. Try different terms — the medical name, common name, and related gene names if applicable.
• Contact your disease-specific patient advocacy group. Organizations like NORD (National Organization for Rare Disorders), the Genetic Alliance, and condition-specific foundations often maintain curated lists of active trials and can connect you with researchers.
• Ask your specialist. If you see a doctor at a center of excellence for your condition, they may be conducting or connected to relevant research.
• Register with a patient registry. Many rare disease communities maintain registries that researchers use to identify potential trial participants. Enrolling in a registry does not obligate you to join a trial, but it means researchers can find you when a study opens.
• Search TrialFinder by your condition name. We translate eligibility criteria into plain English, so you can quickly assess whether a trial might be a match.

Patient advocacy groups and registries

Patient advocacy organizations play an outsized role in rare disease research. Many fund research directly, build patient registries, and even help design clinical trials. Some notable resources include:

• NORD (National Organization for Rare Disorders) — maintains a database of rare diseases, patient assistance programs, and research opportunities.
• NIH Genetic and Rare Diseases Information Center (GARD) — provides free information about more than 6,500 rare diseases, including links to clinical trials.
• Orphanet — a European reference portal for rare diseases with a global clinical trial database.
• Condition-specific foundations — organizations like the Cystic Fibrosis Foundation, the Muscular Dystrophy Association, and the Sickle Cell Disease Association fund and coordinate research for specific conditions.

Next steps

A rare disease diagnosis does not mean you are out of options. Researchers are actively studying treatments for thousands of rare conditions, and new trials open regularly.

If you are considering a trial, start with our guide on how to join a clinical trial for a step-by-step overview of the process. Understanding trial phases can also help you evaluate where a potential treatment stands in its development. And when you are ready to talk to a researcher, bring along our list of questions to ask.