RWE Feasibility in Ultra-Rare Diseases: A Site Network Playbook

Ultra-rare disease studies — indications with fewer than 1 in 100,000 affected patients — fail on feasibility long before they fail on science. After 40+ rare-disease RWE deployments across 22 countries, we have codified a repeatable site-and-patient recruitment playbook that consistently cuts activation-to-first-patient time by more than half.

Feasibility Starts With Patient Advocacy, Not Sites

For ultra-rare indications, the site list does not drive recruitment — the patient registry and advocacy relationships do. The best-in-class rare-disease sponsors we work with sign data-access MOUs with key patient advocacy groups and reference centers before they finalize the protocol. This reverse-engineering of the eligible universe eliminates the most common cause of feasibility failure: discovering halfway through that the target prevalence was a literature guess.

The Four-Site Activation Checklist We Use Every Time

• Principal Investigator has authored or co-authored on the specific indication within the last 36 months
• Site has access to a confirmed patient registry or referral network covering ≥15% of the estimated national prevalence
• Local IRB/IEC has rare-disease fast-track pathway or prior precedent for the protocol design
• Site staff are trained on ePRO and remote SDV workflows — on-site visits are a luxury rare-disease studies rarely have time for

Results From a Recent ULTRA-Rare Deployment

A sponsor developing a first-in-class gene therapy for a pediatric neuro-metabolic indication (estimated EU prevalence ~1,200 patients) engaged RWEOne to run a prospective natural history RWE study. Here is what happened:

The Rare Disease Center of Excellence

In April 2026, RWEOne launched a dedicated Rare Disease Center of Excellence led by a scientific advisory board with deep expertise across 8 ultra-rare indications. The CoE maintains pre-qualified investigator pools, advocacy relationships, and rare-specific eCRF templates — turning a 6-month feasibility project into a 3-week kickoff.