Ask the Experts: Why Do Rare Disease Clinical Trials Require a Unique Approach?

According to the National Organization for Rare Disorders (NORD), 90% of rare disorders do not have an FDA-approved treatment. We spoke with Juliane Mills, Director within PRA’s Center for Rare Diseases, about why the R&D process needs to change to address the smaller patient populations in orphan or rare disease trials.

PRA Insights Team
PRA Insights Team

What are the main differences between rare disease clinical trials and traditional trials?

Every patient is a precious resource in clinical research. When conducting a clinical trial in a rare disease, there are by definition only a few eligible patients who can participate in a clinical trial. If someone drops out, there may not be anyone else to invite.

The way we engage with patients needs to be reflective of the value of their participation. This means doing all we can to make it easy to volunteer such as with plain-language communication, reimbursement for time and travel, and carefully planning visit procedures.

Rare disease trials are also different due to the statistical challenges when researching a low number of patients. Just as every patient is precious, every data point in a rare disease study is critically important. Because there are fewer patients, there are less data overall, and we may not have the statistical power in rare disease clinical studies to discriminate noise from a true signal.

To reduce ‘noise’ in the data set, the methods used to collect data need to be standardized. We need to make sure every trial site in a study is consistently using the same staff and the same methods to assess each patient. Every person involved, from the doctors administering the assessment to the study coordinators and site staff, must follow the same procedures.

Just as every patient is precious, every data point in a rare disease study is critically important.

Juliane Mills, Director within PRA’s Center for Rare Diseases

What can be done to mitigate misdiagnoses in orphan drug or rare disease clinical trials?

When patients are misdiagnosed or bounced around from doctor to doctor, it can certainly upend the doctor-patient relationship. Sometimes a diagnosis of a rare disease is a process of ruling out other diseases, which means a lot of tests, painful procedures, and time. The lack of answers can cause a patient's trust in the medical system to wobble, and many are motivated by this frustration to become an advocate for their own health and treatment (or their family member’s) in a way that might be a new experience.

Honesty on both sides of the patient-doctor relationship is a great way to move forward. Doctors need to be willing to hear and listen to what patients are telling them. Conversely, patients need to understand that doctors may not have all the answers. Doctors and patients are partners in the journey. Patients should be empowered to do their own reading, talk to other people who have the same symptoms, and share their ideas about treatment alternatives with their doctor. It's never a one-way street.

Registries are often set up by R&D companies, but more and more we see advocacy groups setting them up and encouraged to do so by regulatory authorities. When advocacy groups set up registries on their own, they can democratize ownership of the data, which can put control on sharing and access in the hands of patients. [DO2] By building registries populated with shareable observational data, we can establish consensus in rare disease research and form a better singular view into these patient populations, including symptoms and treatment outcomes.

As we share what we know about rare diseases, we find that some rare diseases operate in the same biological pathway but may manifest with very different symptoms. Even though these patients have the same disease pathway, different types of doctors may treat them depending on where the symptoms occur. Advocacy groups and the rare disease community have been bringing together doctors from all different specialties as well as academic researchers to build consensus on biomarkers, disease terminology, and treatments.

When advocacy groups set up registries on their own, they can democratize ownership of the data, which can put control on sharing and access in the hands of patients.

Juliane Mills, Director within PRA’s Center for Rare Diseases

By partnering with patients in your rare disease research, you can develop more meaningful treatment options. Learn how in our latest white paper.

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