Methods for Patient-Centered Endpoint Selection in Rare Disease Drug Development Programs

Rare disease research offers a lot for people in the world of clinical trials and drug development to think about.

Rare diseases are getting more and more attention, and I don’t know if it’s because of Orphan Drug Designations that regulatory agencies around the world offer and provide incentives for pharma; or it’s from the science side of breakthrough medicines that offer so much for patients with rare disorders; or it’s the patient voice and action that resonates with the public. But rare disease research offers a lot for people in the world of clinical trials and drug development to think about.

To that end, I watched an on-demand webinar from Pharmaceutical Executive titled “Methods for Patient-Centered Endpoint Selection in Rare Disease Drug Development Programs,” which was sponsored by Evidera.

Evidera experts, Kathleen Wyrwich, PhD, Senior Research Leader, and Margaret Vernon, PhD, Senior Research Scientist, offered insights into the rare disease space.

Wyrwich, shared this information: In the US, it takes an average of seven years to get a correct diagnosis for a rare disease. Before that, the patient will see up to eight doctors, four in primary care and four specialists, and receive two or three incorrect diagnosis. This is an excellent article from the New Yorker on a disorder that had never been discovered prior to the persistence of two parents who took to blogging to find other patients.

Vernon presented background on the definition of patient centered outcomes or PCOs. PCOs may include PROs or endpoints such as Clinical Outcomes Assessments (COA). And COAs further can include ClinRO (clinician-reported outcomes); observer-reported outcomes (obsRO—parents or caregivers that do not require clinical expertise) and performance outcomes (PerfO) based on tasks performed by a patient that are outlined by a healthcare professionals.

Why the need for PCOs? Number one, Vernon said there needs to be an understanding of the treatment and definition of the treatment based on a benefit and value. For some diseases, for which there are no other treatments (only 450 out of 7,000 rare disease have a drug treatment), finding the most appropriate endpoints requires a lot of background work. The challenges are that there is limited existing research on the disease, small numbers of patients that are geographically dispersed and small numbers of clinicians that are qualified and experienced in the disease.

Vernon suggested the following steps to understanding the PCO endpoints:

• Literature review (though it may be limited or relied on similar conditions)

• Gathering info from patient-centered sources

• Patient blogs/websites

• Data from patient registries

• Engaging in discussion with 1-2 Patient Advocacy Group leaders

• Endpoint Concept Validation

• Directly from patients/caregivers—logistically difficult spread out patients

• Focus groups

• Elicitation interviews

• Recruited through various methods including:

• Clinical sites

• Patient associations

• Conferences (patient education conferences)

Helpful advice: Wyrwich noted that when involved conferences, which are usually sponsored by an advocacy group, it is important to get the advocates’ involvement. Advocates are very aware of pharmaceutical research and its benefits, but also work primarily to protect patients and can be suspect of a sponsors’ motives.

Here’s an article about regulatory issues around the rare disease and orphan drug space on our web site.